@article {pmid39813598, year = {2025}, author = {Ren, M and Xia, Y and Pan, H and Zhou, X and Yu, M and Ji, F}, title = {Duodenal-jejunal bypass ameliorates MASLD in rats by regulating gut microbiota and bile acid metabolism through FXR pathways.}, journal = {Hepatology communications}, volume = {9}, number = {2}, pages = {}, pmid = {39813598}, issn = {2471-254X}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Receptors, Cytoplasmic and Nuclear/metabolism ; Rats ; *Bile Acids and Salts/metabolism ; *Duodenum/surgery/metabolism/microbiology ; Male ; *Fecal Microbiota Transplantation ; Jejunum/surgery/metabolism ; Rats, Sprague-Dawley ; Disease Models, Animal ; Fatty Liver/metabolism ; Anti-Bacterial Agents/pharmacology ; Diet, High-Fat ; Gastric Bypass ; Insulin Resistance ; }, abstract = {BACKGROUND: Although bariatric and metabolic surgical methods, including duodenal-jejunal bypass (DJB), were shown to improve metabolic dysfunction-associated steatotic liver disease (MASLD) in clinical trials and experimental rodent models, their underlying mechanisms remain unclear. The present study therefore evaluated the therapeutic effects and mechanisms of action of DJB in rats with MASLD.

METHODS: Rats with MASLD were randomly assigned to undergo DJB or sham surgery. Rats were orally administered a broad-spectrum antibiotic cocktail (Abx) or underwent fecal microbiota transplantation to assess the role of gut microbiota in DJB-induced improvement of MASLD. Gut microbiota were profiled by 16S rRNA gene sequencing and metagenomic sequencing, and bile acids (BAs) were analyzed by BA-targeted metabolomics.

RESULTS: DJB alleviated hepatic steatosis and insulin resistance in rats with diet-induced MASLD. Abx depletion of bacteria abrogated the ameliorating effects of DJB on MASLD. Fecal microbiota transplantation from rats that underwent DJB improved MASLD in high-fat diet-fed recipients by reshaping the gut microbiota, especially by significantly reducing the abundance of Clostridium. This, in turn, suppressed secondary BA biosynthesis and activated the hepatic BA receptor, farnesoid X receptor. Inhibition of farnesoid X receptor attenuated the ameliorative effects of post-DJB microbiota on MASLD.

CONCLUSIONS: DJB ameliorates MASLD by regulating gut microbiota and BA metabolism through hepatic farnesoid X receptor pathways.}, } @article {pmid39812804, year = {2025}, author = {Sobral, J and Empadinhas, N and Esteves, AR and Cardoso, SM}, title = {Impact of Nutrition on the Gut Microbiota: Implications for Parkinson's Disease.}, journal = {Nutrition reviews}, volume = {}, number = {}, pages = {}, doi = {10.1093/nutrit/nuae208}, pmid = {39812804}, issn = {1753-4887}, support = {//Portuguese national funds/ ; //FCT/ ; }, abstract = {Parkinson's disease (PD) is a multifactorial neurodegenerative disease that is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta and by the anomalous accumulation of α-synuclein aggregates into Lewy bodies and Lewy neurites. Research suggests 2 distinct subtypes of PD: the brain-first subtype if the pathology arises from the brain and then spreads to the peripheral nervous system (PNS) and the body-first subtype, where the pathological process begins in the PNS and then spreads to the central nervous system. This review primarily focuses on the body-first subtype. The influence of the gut microbiota on the development of PD has been the subject of growing interest among researchers. It has been suggested that gut inflammation may be closely associated with pathogenesis in PD, therefore leading to the hypothesis that gut microbiota modulation could play a significant role in this process. Nutrition can influence gut health and alter the risk and progression of PD by altering inflammatory markers. This review provides an overview of recent research that correlates variations in gut microbiota composition between patients with PD and healthy individuals with the impact of certain nutrients and dietary patterns, including the Mediterranean diet, the Western diet, and the ketogenic diet. It explores how these diets influence gut microbiota composition and, consequently, the risk of PD. Last, it examines fecal transplantation and the use of prebiotics, probiotics, or synbiotics as potential therapeutic strategies to balance the gut microbiome, aiming to reduce the risk or delay the progression of PD.}, } @article {pmid39812540, year = {2025}, author = {Cerna, C and Vidal-Herrera, N and Silva-Olivares, F and Álvarez, D and González-Arancibia, C and Hidalgo, M and Aguirre, P and González-Urra, J and Astudillo-Guerrero, C and Jara, M and Porras, O and Cruz, G and Hodar, C and Llanos, P and Urrutia, P and Ibacache-Quiroga, C and Nevzorova, Y and Cubero, FJ and Fuenzalida, M and Thomas-Valdés, S and Jorquera, G}, title = {Fecal Microbiota Transplantation from Young-Trained Donors Improves Cognitive Function in Old Mice Through Modulation of the Gut-Brain Axis.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2024.1089}, pmid = {39812540}, issn = {2152-5250}, abstract = {The gut-brain axis is a bidirectional communication pathway that modulates cognitive function. A dysfunctional gut-brain axis has been associated with cognitive impairments during aging. Therefore, we propose evaluating whether modulation of the gut microbiota through fecal microbiota transplantation (FMT) from young-trained donors (YT) to middle-aged or aged mice could enhance brain function and cognition in old age. Twelve-month-old male mice received an initial FMT from YT (YT-Tr) or age-matched donors (Auto-Tr) following antibiotic treatment. Three months later, the mice received a second FMT as reinforcement. Additionally, 18-month-old mice received Auto-Tr, YT-Tr, or FMT from young sedentary donors (YS-Tr). Cognitive function was assessed using novel object recognition and object location memory tests. Long-term potentiation (LTP) in hippocampal brain slices was studied, while neuroinflammation and synaptic plasticity were analyzed in hippocampal samples via qPCR and immunoblot. Gut permeability was evaluated in ileum and colon sections, serum samples were analyzed for cytokine levels, and fecal samples were used to measure short-chain fatty acid (SCFA) levels and perform 16S rRNA gene sequencing. We observed that YT-Tr, whether performed in middle age or old age, improved cognitive function in aged mice. Recognition and spatial memory were significantly enhanced in YT-Tr mice compared to Auto-Tr and YS-Tr groups. Intact LTP was observed in YT-Tr mice at 18 months of age, whereas LTP was impaired in the Auto-Tr group. Neuroinflammation was reduced, and synaptic plasticity modulators such as PSD-95 and FNDC5/Irisin were upregulated in the hippocampus of YT-Tr mice compared to both YS-Tr and Auto-Tr groups. A significant reduction in ileal and colon permeability was detected in YT-Tr animals, along with elevated cecal levels of butyrate and valerate compared to Auto-Tr. Moreover, YT-Tr decreased pro-inflammatory factors and increased anti-inflammatory factors in the serum of aged mice. Beta diversity analysis revealed significant differences in microbial community composition between YT-Tr and Auto-Tr animals, with higher abundances of Akkermansia, Prevotellaceae_UCG-001, and Odoribacter in YT-Tr mice. In conclusion, our study demonstrates that FMT from young-trained donors improves cognitive function and synaptic plasticity by modulating gut permeability, inflammation, SCFA levels, and gut microbiota composition in aged mice.}, } @article {pmid39812347, year = {2025}, author = {Gustafson, KL and Rodriguez, TR and McAdams, ZL and Coghill, LM and Ericsson, AC and Franklin, CL}, title = {Failure of colonization following gut microbiota transfer exacerbates DSS-induced colitis.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2447815}, pmid = {39812347}, issn = {1949-0984}, support = {T32 GM008396/GM/NIGMS NIH HHS/United States ; T32 OD011126/OD/NIH HHS/United States ; U42 OD010918/OD/NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Colitis/microbiology/chemically induced/pathology ; *Dextran Sulfate ; Mice ; *Disease Models, Animal ; *Mice, Inbred C57BL ; *Fecal Microbiota Transplantation ; Bacteria/classification/isolation & purification/genetics/metabolism ; Female ; Specific Pathogen-Free Organisms ; Feces/microbiology ; Inflammatory Bowel Diseases/microbiology ; Male ; }, abstract = {To study the impact of differing specific pathogen-free gut microbiomes (GMs) on a murine model of inflammatory bowel disease, selected GMs were transferred using embryo transfer (ET), cross-fostering (CF), and co-housing (CH). Prior work showed that the GM transfer method and the microbial composition of donor and recipient GMs can influence microbial colonization and disease phenotypes in dextran sodium sulfate-induced colitis. When a low richness GM was transferred to a recipient with a high richness GM via CH, the donor GM failed to successfully colonize, and a more severe disease phenotype resulted when compared to ET or CF, where colonization was successful. By comparing CH and gastric gavage for fecal material transfer, we isolated the microbial component of this effect and determined that differences in disease severity and survival were associated with microbial factors rather than the transfer method itself. Mice receiving a low richness GM via CH and gastric gavage exhibited greater disease severity and higher expression of pro-inflammatory immune mediators compared to those receiving a high richness GM. This study provides valuable insights into the role of GM composition and colonization in disease modulation.}, } @article {pmid39812329, year = {2025}, author = {Zhang, Y and Wang, A and Zhao, W and Qin, J and Zhang, Y and Liu, B and Yao, C and Long, J and Yuan, M and Yan, D}, title = {Microbial succinate promotes the response to metformin by upregulating secretory immunoglobulin a in intestinal immunity.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2450871}, pmid = {39812329}, issn = {1949-0984}, mesh = {*Metformin/pharmacology ; Animals ; *Immunoglobulin A, Secretory/metabolism ; Mice ; *Gastrointestinal Microbiome/drug effects ; Humans ; *Succinic Acid/metabolism ; Up-Regulation/drug effects ; Diabetes Mellitus, Type 2/immunology/drug therapy/metabolism/microbiology ; Bacteroides thetaiotaomicron/drug effects ; Intestines/immunology/microbiology/drug effects ; Male ; Fecal Microbiota Transplantation ; Female ; Hypoglycemic Agents/pharmacology ; Mice, Inbred C57BL ; Mice, Knockout ; }, abstract = {Metformin is the first-line pharmacotherapy for type 2 diabetes mellitus; however, many patients respond poorly to this drug in clinical practice. The potential involvement of microbiota-mediated intestinal immunity and related signals in metformin responsiveness has not been previously investigated. In this study, we successfully constructed a humanized mouse model by fecal transplantation of the gut microbiota from clinical metformin-treated - responders and non-responders, and reproduced the difference in clinical phenotypes of responsiveness to metformin. The abundance of Bacteroides thetaiotaomicron, considered a representative differential bacterium of metformin responsiveness, and the level of secretory immunoglobulin A (SIgA) in intestinal immunity increased significantly in responder recipient mice following metformin treatment. In contrast, no significant alterations in B. thetaiotaomicron and SIgA were observed in non-responder recipient mice. The study of IgA[-/-] mice confirmed that downregulated expression or deficiency of SIgA resulted in non-response to metformin, meaning that metformin was unable to improve dysfunctional glucose metabolism and reduce intestinal and adipose tissue inflammation, ultimately leading to systemic insulin resistance. Furthermore, supplementation with succinate, a microbial product of B. thetaiotaomicron, potentially reversed the non-response to metformin by inducing the production of SIgA. In conclusion, we demonstrated that upregulated SIgA, which could be regulated by succinate, was functionally involved in metformin response through its influence on immune cell-mediated inflammation and insulin resistance. Conversely, an inability to regulate SIgA may result in a lack of response to metformin.}, } @article {pmid39812000, year = {2025}, author = {Zhao, H and Fu, X and Wang, Y and Shang, Z and Li, B and Zhou, L and Liu, Y and Liu, D and Yi, B}, title = {Therapeutic Potential of Vanillic Acid in Ulcerative Colitis Through Microbiota and Macrophage Modulation.}, journal = {Molecular nutrition & food research}, volume = {}, number = {}, pages = {e202400785}, doi = {10.1002/mnfr.202400785}, pmid = {39812000}, issn = {1613-4133}, support = {81760587//National Natural Science Foundation of China/ ; 81760731)//National Natural Science Foundation of China/ ; }, abstract = {This study investigated the protective effects of the dietary polyphenol vanillic acid (VA) on dextran sulfate sodium-induced acute ulcerative colitis (UC) in mice, focusing on its impact on the gut microbiota and inflammatory responses. VA was supplemented following dextran sulfate sodium administration, and key indicators, including body weight, disease activity index, colon length, spleen index, and inflammatory markers, were assessed. VA supplementation significantly alleviated UC symptoms, preserved intestinal barrier integrity, and reduced pro-inflammatory cytokine levels. Additionally, VA positively altered the gut microbiota composition, promoting beneficial bacteria such as Akkermansia muciniphila while suppressing the arachidonic acid metabolism pathway. Fecal microbiota transplantation confirmed that the VA-modified gut microbiota contributed to these protective effects. VA also facilitated macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, further mitigating inflammation. These findings highlight the potential of VA as a natural dietary intervention for UC, emphasizing its role in regulating the gut microbiota and inflammatory pathways, which may have significant nutritional relevance in managing inflammatory bowel diseases.}, } @article {pmid39811933, year = {2025}, author = {Zhang, L and Wang, K and Huang, L and Deng, B and Chen, C and Zhao, K and Wang, W}, title = {Ganoderic Acid A Alleviates Severe Acute Pancreatitis by Modulating Gut Homeostasis and Inhibiting TLR4-NLRP3 Signaling.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {2}, pages = {1563-1579}, pmid = {39811933}, issn = {1520-5118}, mesh = {Animals ; *Toll-Like Receptor 4/metabolism/genetics ; Mice ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; *Signal Transduction/drug effects ; *Pancreatitis/drug therapy/metabolism/immunology ; Male ; *Mice, Inbred C57BL ; Humans ; *Gastrointestinal Microbiome/drug effects ; *Homeostasis/drug effects ; *Heptanoic Acids/pharmacology ; Mice, Knockout ; Pancreas/immunology/metabolism/drug effects ; Rats ; Lanosterol/analogs & derivatives ; }, abstract = {Background Severe acute pancreatitis (SAP) manifests as a critical state marked by acute abdominal symptoms, often associated with intestinal barrier dysfunction, exacerbating SAP retroactively. Ganoderic acid A (GAA) demonstrates anti-inflammatory properties in various inflammatory disorders. Nonetheless, its potential therapeutic impact on SAP and the underlying mechanisms remain unexplored. Methods In both wild-type and TLR4[-/-] mice, experimental SAP was induced using caerulein plus lipopolysaccharide. Caerulein injections were administered intraperitoneally following 7 days of intragastric GAA administration. Additionally, the potential mechanisms by which GAA ameliorates SAP were further investigated using fecal microbiota transplantation and TLR4-overexpressing IEC-6 cells. Results We observed that GAA treatment significantly ameliorated serum levels of amylase, lipase, and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in SAP mice. Pretreatment with GAA mitigated pathological injuries and reduced M1 macrophage and neutrophil infiltration in pancreatic or ileal tissues. Additionally, GAA treatment down-regulated TLR4-MAPK/NF-κB signaling and NLRP3 inflammasome activation in the pancreatic and ileal tissues of SAP mice. The results further revealed that the gavage of GAA decreased bacterial translocation (Escherichia coli and EUB338), repaired intestinal barrier dysfunction (ZO-1, occludin, DAO, and FITC), increased lysozyme and MUC2 expression, and raised the levels of short-chain fatty acids. Analysis of the gut microbiome showed that the beneficial effects of GAA treatment were associated with improvements in pancreatitis-associated gut microbiota dysbiosis, characterized by notable increases in α-diversity and the abundance of probiotics such as Akkermansia, GCA-900066575, and Parvibacter. Fecal transplantation experiments further confirmed that GAA exerts protective effects by modulating intestinal flora. The protective role of GAA in intestinal and pancreatic injuries is mediated by the inhibition of TLR4 signaling, as further evidenced in TLR4-deficient mice and TLR4-overexpressed IEC-6 cells. The results of docking indicated that GAA interacts with TLR4 via a hydrophobic interaction. Conclusions The study demonstrates that GAA significantly alleviates SAP through its anti-inflammatory and antioxidant capacities, as well as by restoring intestinal homeostasis, thereby providing insights into novel treatments for SAP.}, } @article {pmid39811913, year = {2025}, author = {Ribeiro, G and Schellekens, H and Cuesta-Marti, C and Maneschy, I and Ismael, S and Cuevas-Sierra, A and Martínez, JA and Silvestre, MP and Marques, C and Moreira-Rosário, A and Faria, A and Moreno, LA and Calhau, C}, title = {A Menu for Microbes: Unraveling Appetite Regulation and Weight Dynamics Through the Microbiota-Brain Connection Across the Lifespan.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpgi.00227.2024}, pmid = {39811913}, issn = {1522-1547}, support = {UIDB/4255/2020//Centro de Investigação em Tecnologias e Serviços de Saúde (CINTESIS)/ ; UIDP/4255/2020//Centro de Investigação em Tecnologias e Serviços de Saúde (CINTESIS)/ ; UIDP/04923/2020//Comprehensive Health Research Centre/ ; UIDB/04923/2020//Comprehensive Health Research Centre/ ; SFI/12/RC/2273 _P2//Science Foundation Ireland (SFI)/ ; TC20180025//Food for Health Ireland EI Technology Centre/ ; GOIPG/2023/4836//Irish Research Council (IrishResearch)/ ; CD22/00011//Ministerio de Ciencia e Innovación (MCIN)/ ; MV23/00115//Instituto Carlos III de Salud/ ; Y2020/6600//Comunidad de Madrid (Community of Madrid)/ ; 2020.06333.BD//Fundacao para a Ciencia e a Technologia/ ; }, abstract = {Appetite, as the internal drive for food intake, is often dysregulated in a broad spectrum of conditions associated with over- and under-nutrition across the lifespan. Appetite regulation is a complex, integrative process comprising psychological and behavioral events, peripheral and metabolic inputs, and central neurotransmitter and metabolic interactions. The microbiota-gut-brain axis has emerged as a critical mediator of multiple physiological processes, including energy metabolism, brain function, and behavior. Therefore, the role of the microbiota-gut-brain axis in appetite and obesity is receiving increased attention. Omics approaches such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics in appetite and weight regulation offer new opportunities for featuring obesity phenotypes. Furthermore, gut microbiota-targeted approaches such as pre- pro- post- and synbiotic, personalized nutrition, and fecal microbiota transplantation are novel avenues for precision treatments. The aim of this narrative review is (1) to provide an overview of the role of the microbiota-gut-brain-axis in appetite regulation across the lifespan and (2) to discuss the potential of omics and gut microbiota-targeted approaches to deepen understanding of appetite regulation and obesity.}, } @article {pmid39811513, year = {2025}, author = {Wang, Y and Liu, J}, title = {Interplay between creeping fat and gut microbiota: A brand-new perspective on fecal microbiota transplantation in Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {31}, number = {2}, pages = {100024}, pmid = {39811513}, issn = {2219-2840}, mesh = {*Crohn Disease/microbiology/therapy/immunology ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Animals ; *Dysbiosis ; Mice ; *Disease Models, Animal ; Mesentery ; Adipose Tissue ; Recurrence ; Permeability ; Treatment Outcome ; Intestinal Mucosa/microbiology ; }, abstract = {Inflammatory bowel disease, particularly Crohn's disease (CD), has been linked to modifications in mesenteric adipose tissue (MAT) and the phenomenon known as "creeping fat" (CrF). The presence of CrF is believed to serve as a predictor for early clinical recurrence following surgical intervention in patients with CD. Notably, the incorporation of the mesentery during ileocolic resection for CD has been correlated with a decrease in surgical recurrence, indicating the significant role of MAT in the pathogenesis of CD. While numerous studies have indicated that dysbiosis of the gut microbiota is a critical factor in the development of CD, the functional implications of translocated microbiota within the MAT of CD patients remain ambiguous. This manuscript commentary discusses a recent basic research conducted by Wu et al. In their study, intestinal bacteria from individuals were transplanted into CD model mice, revealing that fecal microbiota transplantation (FMT) from healthy donors alleviated CD symptoms, whereas FMT from CD patients exacerbated these symptoms. Importantly, FMT was found to affect intestinal permeability, barrier function, and the levels of proinflammatory factors and adipokines. Collectively, these findings suggest that targeting MAT and CrF may hold therapeutic potential for patients with CD. However, the study did not evaluate the composition of the intestinal microbiota of the donors or the subsequent alterations in the gut microbiota. Overall, the gut microbiota plays a crucial role in the histopathology of CD, and thus, targeting MAT and CrF may represent a promising avenue for treatment in this patient population.}, } @article {pmid39811502, year = {2025}, author = {Qiao, T and Wen, XH}, title = {Exploring gut microbiota as a novel therapeutic target in Crohn's disease: Insights and emerging strategies.}, journal = {World journal of gastroenterology}, volume = {31}, number = {2}, pages = {100827}, pmid = {39811502}, issn = {2219-2840}, mesh = {*Crohn Disease/microbiology/therapy/immunology ; Humans ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; *Dysbiosis ; Enteral Nutrition/methods ; Disease Progression ; Animals ; }, abstract = {Extensive research has investigated the etiology of Crohn's disease (CD), encompassing genetic predisposition, lifestyle factors, and environmental triggers. Recently, the gut microbiome, recognized as the human body's second-largest gene pool, has garnered significant attention for its crucial role in the pathogenesis of CD. This paper investigates the mechanisms underlying CD, focusing on the role of 'creeping fat' in disease progression and exploring emerging therapeutic strategies, including fecal microbiota transplantation, enteral nutrition, and therapeutic diets. Creeping fat has been identified as a unique pathological feature of CD and has recently been found to be associated with dysbiosis of the gut microbiome. We characterize this dysbiotic state by identifying key microbiome-bacteria, fungi, viruses, and archaea, and their contributions to CD pathogenesis. Additionally, this paper reviews contemporary therapies, emphasizing the potential of biological therapies like fecal microbiota transplantation and dietary interventions. By elucidating the complex interactions between host-microbiome dynamics and CD pathology, this article aims to advance our understanding of the disease and guide the development of more effective therapeutic strategies for managing CD.}, } @article {pmid39810863, year = {2024}, author = {Uździcki, AW and Wawrzynowicz-Syczewska, M}, title = {Impact of liver transplantation on intestinal and systemic inflammation markers in patients with colitis ulcerosa concomitant with primary sclerosing cholangitis.}, journal = {Przeglad gastroenterologiczny}, volume = {16}, number = {4}, pages = {439-445}, pmid = {39810863}, issn = {1895-5770}, abstract = {INTRODUCTION: Primary sclerosing cholangitis (PSC) is an uncommon, chronic liver disease characterised by fibrosis and strictures of a bile ducts, causing cholestasis. In the long term it can lead to complete stenosis leading in turn to liver cirrhosis. In patients with severe form of the disease, the recommended treatment is liver transplantation. Because PSC frequently coexists with ulcerative colitis (UC), it is crucial to determine the effect of liver transplantation on the course of UC.

AIM: The aim was to determine the impact of liver transplantation on intestinal and systemic inflammation markers with UC concomitant with PSC (PSC-UC).

MATERIAL AND METHODS: Sixty-three patients with PSC-UC were enrolled, 25 of whom underwent liver transplantation (OLTx) due to PSC progression. Clinical symptoms, faecal calprotectin levels, C-reactive protein (CRP) serum concentration, erythrocyte sedimentation rate, and white blood cell count (WBC) were obtained.

RESULTS: Faecal calprotectin was significantly higher in the post-OLTx group. Mean calprotectin values were 163% higher - 474 ng/ml and 180 ng/ml (p = 0.024) in the post-OLTx group and in the PSC-UC group without the transplantation, respectively. Calprotectin levels exceeded the upper limit of normal (defined as 200 ng/l) in 66% of liver recipients and in 18% of non-transplanted patients (OR = 9.33, p = 0.011). In the post-OLTx group, also CRP concentration (11.01 mg/l vs. 6.54 mg/l, p = 0.30) and WBC (7.58 K/ml vs. 5.72 K/ml, p = 0.006) were higher than in the PSC-UC group without transplantation.

CONCLUSIONS: We found significantly higher inflammation markers in PSC-UC patients who underwent liver transplantation due to PSC. The effect was strongest in faecal calprotectin levels. In PSC-UC patients after liver transplantation, intensification of UC treatment may be needed, despite the lack of worsening of clinical symptoms.}, } @article {pmid39809955, year = {2025}, author = {Kumar, D and Bishnoi, M and Kondepudi, KK and Sharma, SS}, title = {Gut Microbiota-Based Interventions for Parkinson's Disease: Neuroprotective Mechanisms and Current Perspective.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {39809955}, issn = {1867-1314}, abstract = {Recent evidence links gut microbiota alterations to neurodegenerative disorders, including Parkinson's disease (PD). Replenishing the abnormal composition of gut microbiota through gut microbiota-based interventions "prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT)" has shown beneficial effects in PD. These interventions increase gut metabolites like short-chain fatty acids (SCFAs) and glucagon-like peptide-1 (GLP-1), which may protect dopaminergic neurons via the gut-brain axis. Neuroprotective effects of these interventions are mediated by several mechanisms, including the enhancement of neurotrophin and activation of the PI3K/AKT/mTOR signaling pathway, GLP-1-mediated gut-brain axis signaling, Nrf2/ARE pathway, and autophagy. Other pathways, such as free fatty acid receptor activation, synaptic plasticity improvement, and blood-brain and gut barrier integrity maintenance, also contribute to neuroprotection. Furthermore, the inhibition of the TLR4/NF-кB pathway, MAPK pathway, GSK-3β signaling pathway, miR-155-5p-mediated neuroinflammation, and ferroptosis could account for their protective effects. Clinical studies involving gut microbiota-based interventions have shown therapeutic benefits in PD patients, particularly in improving gastrointestinal dysfunction and some neurological symptoms. However, the effectiveness in alleviating motor symptoms remains mild. Large-scale clinical trials are still needed to confirm these findings. This review emphasizes the neuroprotective mechanisms of gut microbiota-based interventions in PD as supported by both preclinical and clinical studies.}, } @article {pmid39806466, year = {2025}, author = {Khemiri, H and Ben Fraj, I and Lorusso, A and Mekki, N and Mangone, I and Gdoura, M and Di Pasqual, A and Cammà, C and Di Lollo, V and Cherni, A and Touzi, H and Sadraoui, A and Meddeb, Z and Hogga, N and Ben Mustapha, I and Barbouche, MR and Ouederni, M and Triki, H and Haddad-Boubaker, S}, title = {SARS-CoV-2 excretion and genetic evolution in nasopharyngeal and stool samples from primary immunodeficiency and immunocompetent pediatric patients.}, journal = {Virology journal}, volume = {22}, number = {1}, pages = {9}, pmid = {39806466}, issn = {1743-422X}, mesh = {Humans ; *SARS-CoV-2/genetics/immunology ; *Feces/virology ; *Nasopharynx/virology ; *COVID-19/virology/immunology ; Child ; Male ; Female ; Child, Preschool ; *RNA, Viral/genetics ; *Virus Shedding ; Infant ; Phylogeny ; Evolution, Molecular ; Primary Immunodeficiency Diseases/genetics ; Adolescent ; Whole Genome Sequencing ; }, abstract = {BACKGROUND: Primary Immunodeficiency disorders (PID) can increase the risk of severe COVID-19 and prolonged infection. This study investigates the duration of SARS-CoV-2 excretion and the genetic evolution of the virus in pediatric PID patients as compared to immunocompetent (IC) patients.

MATERIALS AND METHODS: A total of 40 nasopharyngeal and 24 stool samples were obtained from five PID and ten IC children. RNA detection was performed using RT-qPCR, and whole-genome sequencing was conducted with the NexSeq 1000 platform. Data analysis used the nextflow/viralrecon pipeline. Hotspot amino acid frequencies were investigated using GraphPad Prism v10. Phylodynamic analysis was conducted with BEAST software.

RESULTS: In IC children, the viral excretion period lasted up to 14 days in nasopharyngeal swabs, with an average duration of 7 days, and ranged from 7 to 14 days in stool samples. In PID patients, the viral RNA was detected in nasopharyngeal for periods between 7 and 28 days, with an average duration of 15 days, and up to 28 days in stool samples. Two SARS-CoV-2 variants were detected in PID patients: Delta (AY.122) and Omicron (BA.1.1). Patients with antibody and combined deficiencies, exhibited the most prolonged shedding periods in both nasopharyngeal and stool samples and one patient presented complications and fatal outcome. Specific Hotspot amino acid changes were detected in PID: A2821V and R550H (ORF1ab).

CONCLUSION: Our findings underscore the prolonged excretion of SARS-CoV-2 RNA in patients with antibody and combined deficiencies. Thus, specialized care is essential for effectively managing PID patients.}, } @article {pmid39805780, year = {2024}, author = {Ye, LJ and Xu, XF and Chen, SY and Zhang, H and Gan, YX and Meng, T and Ding, R and Li, J and Cao, G and Wang, KL}, title = {[Regulation of Bifidobacterium-short chain fatty acid metabolism and improvement of intestinal toxicity of vinegar-processed Euphorbiae Pekinensis Radix].}, journal = {Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica}, volume = {49}, number = {23}, pages = {6331-6341}, doi = {10.19540/j.cnki.cjcmm.20240912.301}, pmid = {39805780}, issn = {1001-5302}, mesh = {Mice ; Animals ; *Fatty Acids, Volatile/metabolism ; *Acetic Acid ; Humans ; Caco-2 Cells ; *Gastrointestinal Microbiome/drug effects ; *Drugs, Chinese Herbal/pharmacology/chemistry ; *Bifidobacterium/drug effects ; RAW 264.7 Cells ; Intestines/drug effects ; Male ; Intestinal Mucosa/metabolism/drug effects ; Feces/microbiology/chemistry ; }, abstract = {To explore the mechanism by which vinegar-processed Euphorbiae Pekinensis Radix regulates gut microbiota and reduces intestinal toxicity, this study aimed to identify key microbial communities related to vinegar-induced detoxification and verify their functions. Using a derivatization method, the study measured the content of short-chain fatty acids(SCFAs) in feces before and after vinegar-processing of Euphorbiae Pekinensis Radix. Combined with the results of previous gut microbiota sequencing, correlation analysis was used to identify key microbial communities related to SCFAs content. Through single-bacterium transplantation experiments, the role of key microbial communities in regulating SCFAs metabolism and alleviating the intestinal toxicity of Euphorbiae Pekinensis Radix was clarified. Fecal extracts were then added to a co-culture system of Caco-2 and RAW264.7 cells, and toxicity differences were evaluated using intestinal tight junction proteins and inflammatory factors as indicators. Additionally, the application of a SCFAs receptor blocker helped confirm the role of SCFAs in reducing intestinal toxicity during vinegar-processing of Euphorbiae Pekinensis Radix. The results of this study indicated that vinegar-processing of Euphorbiae Pekinensis Radix improved the decline in SCFAs content caused by the raw material. Correlation analysis revealed that Bifidobacterium was positively correlated with the levels of acetic acid, propionic acid, isobutyric acid, n-butyric acid, isovaleric acid, and n-valeric acid. RESULTS:: from single-bacterium transplantation experiments demonstrated that Bifidobacterium could mitigate the reduction in SCFAs content induced by raw Euphorbiae Pekinensis Radix, enhance the expression of tight junction proteins, and reduce intestinal inflammation. Similarly, cell experiment results confirmed that fecal extracts from Bifidobacterium-transplanted mice alleviated inflammation and increased the expression of tight junction proteins in intestinal epithelial cells. The use of the free fatty acid receptor-2 inhibitor GLPG0974 verified that this improvement effect was related to the SCFAs pathway. This study demonstrates that Bifidobacterium is the key microbial community responsible for reducing intestinal toxicity in vinegar-processed Euphorbiae Pekinensis Radix. Vinegar-processing increases the abundance of Bifidobacterium, elevates the intestinal SCFAs content, inhibits intestinal inflammation, and enhances the expression of tight junction proteins, thereby improving the intestinal toxicity of Euphorbiae Pekinensis Radix.}, } @article {pmid39804518, year = {2025}, author = {Claytor, JD and Lin, DL and Magnaye, KM and Guerrero, YS and Langelier, CR and Lynch, SV and El-Nachef, N}, title = {Effect of Fecal Microbiota Transplant on Antibiotic Resistance Genes Among Patients with Chronic Pouchitis.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {39804518}, issn = {1573-2568}, abstract = {BACKGROUND: Pouchitis is common among patients with ulcerative colitis (UC) who have had colectomy with ileal pouch-anal anastomosis. Antibiotics are first-line therapy for pouch inflammation, increasing the potential for gut colonization with multi-drug resistant organisms (MDRO). Fecal microbial transplant (FMT) is being studied in the treatment of pouchitis and in the eradication of MDRO. Prior work using aerobic antibiotic culture disks suggests that some patients with chronic pouchitis may regain fluoroquinolone sensitivity after FMT. However, gut MDRO include anaerobic, fastidious organisms that are difficult to culture using traditional methods.

AIM: We aimed to assess whether FMT reduced the abundance of antibiotic resistance genes (ARG) or affected resistome diversity, evenness, or richness in patients with chronic pouchitis.

METHODS: We collected clinical characteristics regarding infections and antibiotic exposures for 18 patients who had previously been enrolled in an observational study investigating FMT as a treatment for pouchitis. Twenty-six pre- and post-FMT stool samples were analyzed using FLASH (Finding Low Abundance Sequences by Hybridization), a CRISPR/Cas9-based shotgun metagenomic sequence enrichment technique that detects acquired and chromosomal bacterial ARGs. Wilcoxon rank sum tests were used to assess differences in clinical characteristics, ARG counts, resistome diversity and ARG richness, pre- and post-FMT.

RESULTS: All 13 of the patients with sufficient stool samples for analysis had recently received antibiotics for pouchitis prior to a single endoscopic FMT. Fecal microbiomes of all patients had evidence of multi-drug resistance genes and ESBL resistance genes at baseline; 62% encoded fluoroquinolone resistance genes. A numerical decrease in overall ARG counts was noted post-FMT, but no statistically significant differences were noted (P = 0.19). Richness and diversity were not significantly altered. Three patients developed infections during the 5-year follow-up period, none of which were associated with MDRO.

CONCLUSION: Antibiotic resistance genes are prevalent among antibiotic-exposed patients with chronic pouchitis. FMT led to a numerical decrease, but no statistically significant change in ARG, nor were there significant changes in the diversity, richness, or evenness of ARGs. Further investigations to improve FMT engraftment and to optimize FMT delivery in patients with inflammatory pouch disorders are warranted.}, } @article {pmid39801363, year = {2025}, author = {Chevalier, C and Tournier, BB and Marizzoni, M and Park, R and Paquis, A and Ceyzériat, K and Badina, AM and Lathuiliere, A and Saleri, S and Cillis, F and Cattaneo, A and Millet, P and Frisoni, GB}, title = {Fecal Microbiota Transplantation (FMT) From a Human at Low Risk for Alzheimer's Disease Improves Short-Term Recognition Memory and Increases Neuroinflammation in a 3xTg AD Mouse Model.}, journal = {Genes, brain, and behavior}, volume = {24}, number = {1}, pages = {e70012}, pmid = {39801363}, issn = {1601-183X}, support = {1216//Velux Stiftung/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation ; Mice ; *Alzheimer Disease/therapy/microbiology ; Humans ; Female ; *Gastrointestinal Microbiome ; Memory, Short-Term/physiology ; Neuroinflammatory Diseases/therapy/metabolism ; Disease Models, Animal ; Hippocampus/metabolism ; Aged ; }, abstract = {Human microbiota-associated murine models, using fecal microbiota transplantation (FMT) from human donors, help explore the microbiome's role in diseases like Alzheimer's disease (AD). This study examines how gut bacteria from donors with protective factors against AD influence behavior and brain pathology in an AD mouse model. Female 3xTgAD mice received weekly FMT for 2 months from (i) an 80-year-old AD patient (AD-FMT), (ii) a cognitively healthy 73-year-old with the protective APOEe2 allele (APOEe2-FMT), (iii) a 22-year-old healthy donor (Young-FMT), and (iv) untreated mice (Mice-FMT). Behavioral assessments included novel object recognition (NOR), Y-maze, open-field, and elevated plus maze tests; brain pathology (amyloid and tau), neuroinflammation (in situ autoradiography of the 18 kDa translocator protein in the hippocampus); and gut microbiota were analyzed. APOEe2-FMT improved short-term memory in the NOR test compared to AD-FMT, without significant changes in other behavioral tests. This was associated with increased neuroinflammation in the hippocampus, but no effect was detected on brain amyloidosis and tauopathy. Specific genera, such as Parabacteroides and Prevotellaceae_UGC001, were enriched in the APOEe2-FMT group and associated with neuroinflammation, while genera like Desulfovibrio were reduced and linked to decreased neuroinflammation. Gut microbiota from a donor with a protective factor against AD improved short-term memory and induced neuroinflammation in regions strategic to AD. The association of several genera with neuroinflammation in the APOEe2-FMT group suggests a collegial effect of the transplanted microbiome rather than a single-microbe driver effect. These data support an association between gut bacteria, glial cell activation, and cognitive function in AD.}, } @article {pmid39800714, year = {2025}, author = {Sall, I and Foxall, R and Felth, L and Maret, S and Rosa, Z and Gaur, A and Calawa, J and Pavlik, N and Whistler, JL and Whistler, CA}, title = {Gut dysbiosis was inevitable, but tolerance was not: temporal responses of the murine microbiota that maintain its capacity for butyrate production correlate with sustained antinociception to chronic morphine.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2446423}, pmid = {39800714}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Morphine/administration & dosage ; *Dysbiosis/microbiology ; Mice ; *Butyrates/metabolism ; Male ; *Fecal Microbiota Transplantation ; *Drug Tolerance ; *Analgesics, Opioid/administration & dosage/metabolism ; *Mice, Inbred C57BL ; Bacteria/metabolism/classification/genetics/drug effects ; Probiotics/administration & dosage ; }, abstract = {The therapeutic benefits of opioids are compromised by the development of analgesic tolerance, which necessitates higher dosing for pain management thereby increasing the liability for drug dependence and addiction. Rodent models indicate opposing roles of the gut microbiota in tolerance: morphine-induced gut dysbiosis exacerbates tolerance, whereas probiotics ameliorate tolerance. Not all individuals develop tolerance, which could be influenced by differences in microbiota, and yet no study design has capitalized upon this natural variation. We leveraged natural behavioral variation in a murine model of voluntary oral morphine self-administration to elucidate the mechanisms by which microbiota influences tolerance. Although all mice shared similar morphine-driven microbiota changes that largely masked informative associations with variability in tolerance, our high-resolution temporal analyses revealed a divergence in the progression of dysbiosis that best explained sustained antinociception. Mice that did not develop tolerance maintained a higher capacity for production of the short-chain fatty acid (SCFA) butyrate known to bolster intestinal barriers and promote neuronal homeostasis. Both fecal microbial transplantation (FMT) from donor mice that did not develop tolerance and dietary butyrate supplementation significantly reduced the development of tolerance independently of suppression of systemic inflammation. These findings could inform immediate therapies to extend the analgesic efficacy of opioids.}, } @article {pmid39800223, year = {2025}, author = {Lista, S and Munafò, A and Caraci, F and Imbimbo, C and Emanuele, E and Minoretti, P and Pinto-Fraga, J and Merino-País, M and Crespo-Escobar, P and López-Ortiz, S and Monteleone, G and Imbimbo, BP and Santos-Lozano, A}, title = {Gut microbiota in Alzheimer's disease: Understanding molecular pathways and potential therapeutic perspectives.}, journal = {Ageing research reviews}, volume = {104}, number = {}, pages = {102659}, doi = {10.1016/j.arr.2025.102659}, pmid = {39800223}, issn = {1872-9649}, abstract = {Accumulating evidence suggests that gut microbiota (GM) plays a crucial role in Alzheimer's disease (AD) pathogenesis and progression. This narrative review explores the complex interplay between GM, the immune system, and the central nervous system in AD. We discuss mechanisms through which GM dysbiosis can compromise intestinal barrier integrity, enabling pro-inflammatory molecules and metabolites to enter systemic circulation and the brain, potentially contributing to AD hallmarks. Additionally, we examine other pathophysiological mechanisms by which GM may influence AD risk, including the production of short-chain fatty acids, secondary bile acids, and tryptophan metabolites. The role of the vagus nerve in gut-brain communication is also addressed. We highlight potential therapeutic implications of targeting GM in AD, focusing on antibiotics, probiotics, prebiotics, postbiotics, phytochemicals, and fecal microbiota transplantation. While preclinical studies showed promise, clinical evidence remains limited and inconsistent. We critically assess clinical trials, emphasizing challenges in translating GM-based therapies to AD patients. The reviewed evidence underscores the need for further research to elucidate precise molecular mechanisms linking GM to AD and determine whether GM dysbiosis is a contributing factor or consequence of AD pathology. Future studies should focus on large-scale clinical trials to validate GM-based interventions' efficacy and safety in AD.}, } @article {pmid39800192, year = {2025}, author = {Bajaj, JS and Fagan, A and Gavis, EA and Sterling, RK and Gallagher, ML and Lee, H and Matherly, SC and Siddiqui, MS and Bartels, A and Mousel, T and Davis, BC and Puri, P and Fuchs, M and Moutsoglou, DM and Thacker, LR and Sikaroodi, M and Gillevet, PM and Khoruts, A}, title = {Microbiota transplant for hepatic encephalopathy in cirrhosis: The THEMATIC trial.}, journal = {Journal of hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhep.2024.12.047}, pmid = {39800192}, issn = {1600-0641}, abstract = {BACKGROUND: Preventing hepatic encephalopathy (HE) recurrence in cirrhosis, which is associated with an altered gut-liver-brain axis, is an unmet need. Fecal microbiota transplantation (FMT) is beneficial in phase-1 studies, but route and dose-related questions remain.

METHODS: We performed a phase-2 randomized, placebo-controlled, double-blind, clinical trial of capsule and enema FMT in cirrhosis and HE on lactulose and rifaximin. Subjects were randomized into 4 groups receiving 3 active and 0-placebo, 2 active and 1-placebo, 1 active and 2-placebo, or all 3-placebo doses. Each patient received two capsule and one enema FMT and were followed for six months.

PRIMARY OUTCOME: FMT-related serious adverse events/AEs using intention-to-treat analysis. Secondary outcomes were HE recurrence, all-cause hospitalizations, death, donor engraftment, and quality-of-life (QOL). FMT was from a vegan or omnivorous donor.

RESULTS: 60 patients (15/group) with similar baseline characteristics were enrolled.

PRIMARY OUTCOMES: FMT was safe without any FMT-related SAEs/ AEs.

SECONDARY OUTCOMES: Overall SAEs (p=0.96) or death (p=1.0) were similar. There were significant differences in HE recurrence between groups (p=0.035, Cramer's V=0.39). Post-hoc, recurrence was highest in all-placebo vs FMT [40% vs 9%, OR:0.15 (95% CI: 0.04, 0.64)]. Within FMT, HE-recurrence rates were similar regardless of route, doses, or donor type. QOL improved in FMT-recipient groups. Engraftment was highest in those with high pre-FMT Lachnospiraceae and lower in those whose HE recurred.

CONCLUSIONS: In a Phase 2 double-blind, placebo-controlled, randomized clinical trial in cirrhosis with HE on maximal therapy, FMT regardless of dose, route, or donor was safe without any FMT-related adverse events. On post-hoc analysis, groups differed on HE recurrence, which was highest in the placebo-only group and linked with lower baseline Lachnospiraceae and reduced donor engraftment.}, } @article {pmid39798925, year = {2025}, author = {Aleksandrova, RR and Nieuwenhuis, LM and Karmi, N and Zhang, S and Swarte, JC and Björk, JR and Gacesa, R and Blokzijl, H and Connelly, MA and Weersma, RK and Lisman, T and Festen, EAM and de Meijer, VE and , }, title = {Gut microbiome dysbiosis is not associated with portal vein thrombosis in patients with end-stage liver disease: a cross-sectional study.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtha.2024.12.036}, pmid = {39798925}, issn = {1538-7836}, abstract = {BACKGROUND: Portal vein thrombosis (PVT) is a common complication in patients with end-stage liver disease (ESLD). The portal vein in ESLD patients is proposedly an inflammatory vascular bed due to translocation of endotoxins and cytokines from the gut. We hypothesized that a pro-inflammatory gut microbiome and elevated trimethylamine N-oxide (TMAO), a driver of thrombosis, may contribute to PVT development.

OBJECTIVES: We investigated whether gut microbiome diversity, bacterial species, metabolic pathways, and TMAO levels are associated with PVT in ESLD patients.

METHODS: Fecal samples, plasma samples and data from ESLD patients and healthy controls were collected through the TransplantLines Biobank and Cohort Study. PVT was defined as a thrombus in the portal vein within a year prior to or after fecal sample collection. Fecal samples were analyzed using Shotgun Metagenomic Sequencing, and TMAO levels were measured in plasma using a Vantera® Clinical Analyzer.

RESULTS: 102 ESLD patients, of which 23 with PVT, and 246 healthy controls were included. No significant difference in gut microbiome diversity was found between patients with PVT and without PVT (P=0.18). Both ESLD groups had significantly lower alpha-diversity compared with controls. Bacteroides fragilis and three Clostridiales species were increased in patients with PVT compared to without PVT. TMAO levels between the three groups were not significantly different.

CONCLUSION: We observed profound differences in gut microbiota between ESLD patients and controls, but minimal differences between ESLD patients with or without PVT. In our cohort, a gut-derived pro-inflammatory state was not associated with presence of PVT in ESLD patients.}, } @article {pmid39797102, year = {2024}, author = {Díez-Madueño, K and de la Cueva Dobao, P and Torres-Rojas, I and Fernández-Gosende, M and Hidalgo-Cantabrana, C and Coto-Segura, P}, title = {Gut Dysbiosis and Adult Atopic Dermatitis: A Systematic Review.}, journal = {Journal of clinical medicine}, volume = {14}, number = {1}, pages = {}, pmid = {39797102}, issn = {2077-0383}, abstract = {Background/Objectives: Research on the relationship between gut microbiota (GM) and atopic dermatitis (AD) has seen a growing interest in recent years. The aim of this systematic review was to determine whether differences exist between the GM of adults with AD and that of healthy adults (gut dysbiosis). Methods: We conducted a systematic review based on the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The search was performed using PubMed, EMBASE, and Web of Science. Observational and interventional studies were analyzed. Results: Although the studies showed heterogeneous results, some distinguishing characteristics were found in the intestinal microbial composition of adults with dermatitis. Even though no significant differences in diversity were found between healthy and affected adults, certain microorganisms, such as Bacteroidales, Enterobacteriaceae, and Clostridium (perfringens), were more characteristic of the fecal microbiota in adults with AD. Healthy individuals exhibited lower abundances of aerobic bacteria and higher abundances of short-chain fatty acid-producing species and polyamines. Clinical trials showed that the consumption of probiotics (Bifidobacterium and/or Lactobacillus), fecal microbiota transplants, and balneotherapy modified the fecal microbiota composition of participants and were associated with significant improvements in disease management. Conclusions: In anticipation of forthcoming clinical trials, it is essential to conduct meta-analyses that comprehensively evaluate the effectiveness and safety of interventions designed to modify intestinal flora in the context of AD. Preliminary evidence suggests that certain interventions may enhance adult AD management.}, } @article {pmid39796717, year = {2024}, author = {Kumari, S and Srilatha, M and Nagaraju, GP}, title = {Effect of Gut Dysbiosis on Onset of GI Cancers.}, journal = {Cancers}, volume = {17}, number = {1}, pages = {}, pmid = {39796717}, issn = {2072-6694}, abstract = {Dysbiosis in the gut microbiota plays a significant role in GI cancer development by influencing immune function and disrupting metabolic functions. Dysbiosis can drive carcinogenesis through pathways like immune dysregulation and the release of carcinogenic metabolites, and altered metabolism, genetic instability, and pro-inflammatory signalling, contributing to GI cancer initiation and progression. Helicobacter pylori infection and genotoxins released from dysbiosis, lifestyle and dietary habits are other factors that contribute to GI cancer development. Emerging diagnostic and therapeutic approaches show promise in colorectal cancer treatment, including the multitarget faecal immunochemical test (mtFIT), standard FIT, and faecal microbiota transplantation (FMT) combined with PD-1 inhibitors. We used search engine databases like PubMed, Scopus, and Web of Science. This review discusses the role of dysbiosis in GI cancer onset and explores strategies such as FMT, probiotics, and prebiotics to enhance the immune response and improve cancer therapy outcomes.}, } @article {pmid39796536, year = {2024}, author = {Cuffaro, F and Lamminpää, I and Niccolai, E and Amedei, A}, title = {Nutritional and Microbiota-Based Approaches in Amyotrophic Lateral Sclerosis: From Prevention to Treatment.}, journal = {Nutrients}, volume = {17}, number = {1}, pages = {}, pmid = {39796536}, issn = {2072-6643}, support = {PNRR-MAD-2022-12375798//Ministero della Salute/ ; PE0000006//Ministry of University and Research (MUR)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; *Gastrointestinal Microbiome ; *Dysbiosis/therapy ; Probiotics/therapeutic use ; Brain-Gut Axis/physiology ; Fecal Microbiota Transplantation ; Fatty Acids, Omega-3 ; Prebiotics/administration & dosage ; Oxidative Stress ; Nutritional Status ; Diet, Mediterranean ; Antioxidants ; }, abstract = {Metabolic alterations, including hypermetabolism, lipid imbalances, and glucose dysregulation, are pivotal contributors to the onset and progression of Amyotrophic Lateral Sclerosis (ALS). These changes exacerbate systemic energy deficits, heighten oxidative stress, and fuel neuroinflammation. Simultaneously, gastrointestinal dysfunction and gut microbiota (GM) dysbiosis intensify disease pathology by driving immune dysregulation, compromising the intestinal barrier, and altering gut-brain axis (GBA) signaling, and lastly advancing neurodegeneration. Therapeutic and preventive strategies focused on nutrition offer promising opportunities to address these interconnected pathophysiological mechanisms. Diets enriched with antioxidants, omega-3 fatty acids, and anti-inflammatory compounds-such as the Mediterranean diet-have shown potential in reducing oxidative stress and systemic inflammation. Additionally, microbiota-targeted approaches, including probiotics, prebiotics, postbiotics, and fecal microbiota transplantation, are emerging as innovative tools to restore microbial balance, strengthen gut integrity, and optimize GBA function. This review highlights the critical need for personalized strategies integrating immunonutrition and microbiota modulation to slow ALS progression, improve quality of life, and develop preventive measures for neurodegenerative and neuroinflammatory diseases. Future research should prioritize comprehensive dietary and microbiota-based interventions to uncover their therapeutic potential and establish evidence-based guidelines for managing ALS and related disorders.}, } @article {pmid39796390, year = {2025}, author = {Yu, R and Zhang, H and Chen, R and Lin, Y and Xu, J and Fang, Z and Ru, Y and Fan, C and Wu, G}, title = {Fecal Microbiota Transplantation from Methionine-Restricted Diet Mouse Donors Improves Alzheimer's Learning and Memory Abilities Through Short-Chain Fatty Acids.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {1}, pages = {}, pmid = {39796390}, issn = {2304-8158}, support = {LQ22H260002//Natural Science Foundation of Zhejiang Province/ ; 82103836//National Natural Science Foundation of China/ ; }, abstract = {Alzheimer's disease (AD) is marked by impaired cognitive functions, particularly in learning and memory, owing to complex and diverse mechanisms. Methionine restriction (MR) has been found to exert a mitigating effect on brain oxidative stress to improve AD. However, the bidirectional crosstalk between the gut and brain through which MR enhances learning and memory in AD, as well as the effects of fecal microbiota transplantation (FMT) from MR mice on AD mice, remains underexplored. In this study, APP/PS1 double transgenic AD mice were used and an FMT experiment was conducted. 16S rRNA gene sequencing, targeted metabolomics, and microbial metabolite short-chain fatty acids (SCFAs) of feces samples were analyzed. The results showed that MR reversed the reduction in SCFAs induced by AD, and further activated the free fatty acid receptors, FFAR2 and FFAR3, as well as the transport protein MCT1, thereby signaling to the brain to mitigate inflammation and enhance the learning and memory capabilities. Furthermore, the FMT experiment from methionine-restricted diet mouse donors showed that mice receiving FMT ameliorated Alzheimer's learning and memory ability through SCFAs. This study offers novel non-pharmaceutical intervention strategies for AD prevention.}, } @article {pmid39795549, year = {2024}, author = {Tsuji, K and Uchida, N and Nakanoh, H and Fukushima, K and Haraguchi, S and Kitamura, S and Wada, J}, title = {The Gut-Kidney Axis in Chronic Kidney Diseases.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, pmid = {39795549}, issn = {2075-4418}, support = {24K11411//the Japanese Society for the Promotion of Science (JSPS)/Grant-in-Aid for Young Scientists/ ; }, abstract = {The gut-kidney axis represents the complex interactions between the gut microbiota and kidney, which significantly impact the progression of chronic kidney disease (CKD) and overall patient health. In CKD patients, imbalances in the gut microbiota promote the production of uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, which impair renal function and contribute to systemic inflammation. Mechanisms like endotoxemia, immune activation and oxidative stress worsen renal damage by activating pro-inflammatory and oxidative pathways. Insights into these mechanisms highlight the impact of gut-derived metabolites, bacterial translocation, and immune response changes on kidney health, suggesting new potential approaches for CKD treatment. Clinical applications, such as dietary interventions, prebiotics, probiotics and fecal microbiota transplantation, are promising in adjusting the gut microbiota to alleviate CKD symptoms and slow disease progression. Current research highlights the clinical relevance of the gut-kidney axis, but further study is essential to clarify these mechanisms' diagnostic biomarkers and optimize therapeutic interventions. This review emphasizes the importance of an integrated approach to CKD management, focusing on the gut microbiota as a therapeutic target to limit kidney injury.}, } @article {pmid39792405, year = {2024}, author = {Guo, Z and He, M and Shao, L and Li, Y and Xiang, X and Wang, Q}, title = {The role of fecal microbiota transplantation in the treatment of acute graft-versus-host disease.}, journal = {Journal of cancer research and therapeutics}, volume = {20}, number = {7}, pages = {1964-1973}, doi = {10.4103/jcrt.jcrt_33_24}, pmid = {39792405}, issn = {1998-4138}, mesh = {Humans ; *Graft vs Host Disease/therapy/etiology/microbiology ; *Fecal Microbiota Transplantation/methods ; *Hematopoietic Stem Cell Transplantation/adverse effects/methods ; *Gastrointestinal Microbiome ; Transplantation, Homologous/methods ; Acute Disease ; Treatment Outcome ; }, abstract = {Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most important methods for treating a wide range of hematologic malignancies and bone marrow failure diseases. However, graft-versus-host disease (GVHD), a major complication associated with this method, can seriously affect the survival and quality of life of patients. Acute GVHD (aGVHD) occurs within 100 days after transplantation, and gastrointestinal aGVHD (GI-aGVHD) is one of the leading causes of nonrecurrent death after allo-HSCT. In recent years, fecal microbiota transplantation (FMT) has been attempted as an emerging treatment method for various diseases, including aGVHD after HSCT. Studies have shown encouraging preliminary clinical results after the application of FMT in aGVHD, particularly steroid-resistant aGVHD. Additionally, several studies have demonstrated that the gut microbiota plays an important immunomodulatory role in the pathogenesis of GVHD. Consensus guidelines recommend FMT as a secondary option for the treatment of aGVHD. This article aims to review FMT treatment for GI-aGVHD after allo-HSCT.}, } @article {pmid39791180, year = {2025}, author = {Shakya, R and Sivakumar, PM and Prabhakar, PK}, title = {Gut Microbiota and Diabetes: Pioneering New Treatment Frontiers.}, journal = {Endocrine, metabolic & immune disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715303342579241119155225}, pmid = {39791180}, issn = {2212-3873}, abstract = {Diabetes Mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia and poses significant global health challenges. Conventional treatments, such as insulin therapy and lifestyle modifications, have shown limited efficacy in addressing the multifactorial nature of DM. Emerging evidence suggests that gut microbiota, a diverse community of microorganisms critical for metabolism and immune function, plays a pivotal role in metabolic health. Dysbiosis, an imbalance in gut microbiota composition, has been linked to insulin resistance, obesity, and DM. Gut microbiota influences glucose metabolism through mechanisms, including short-chain fatty acid production, gut permeability regulation, and immune system interactions, indicating a bidirectional relationship between microbial health and metabolism. Clinical and experimental studies demonstrate that modulating gut microbiota through dietary interventions (prebiotics, probiotics, synbiotics) improves glycemic control and insulin sensitivity in DM patients. Fecal Microbiota Transplantation (FMT) has also shown promise in restoring healthy gut microbiota and alleviating DM-related metabolic disturbances. However, challenges remain, including the need for personalized treatments due to individual microbiota variability and the unknown long-term effects of these interventions. Future research should focus on elucidating the mechanisms by which gut microbiota influences metabolism and refining personalized approaches to enhance DM management.}, } @article {pmid39791141, year = {2025}, author = {Li, X and Sun, B and Qin, Y and Yue, F and Lü, X}, title = {Amelioration of Obesity-Related Disorders in High-Fat Diet-Fed C57BL/6 Mice Following Fecal Microbiota Transplantation From DL-Norvaline-Dosed Mice.}, journal = {Molecular nutrition & food research}, volume = {}, number = {}, pages = {e202400577}, doi = {10.1002/mnfr.202400577}, pmid = {39791141}, issn = {1613-4133}, support = {2023-ZDLNY-35//Shaanxi Province Science and Technology Plan Project/ ; 2022A02006//Major Scientific and Technological Special Project of Xinjiang Uygur Autonomous Region/ ; }, abstract = {Fecal microbiota transplantation (FMT) could significantly alter the recipient's gut bacteria composition and attenuate obesity and obesity-related metabolic syndromes. DL-norvaline is a nonproteinogenic amino acid and possesses anti-obesity potential. However, the specific mechanisms by which gut microbiota might mediate beneficial effects of DL-norvaline have not been completely elucidated. In this study, DL-norvaline-mediated FMT upregulated the beneficial bacteria (Clostridia_UCG_014, Christensenellales, Bacilli, Ileibacterium, Dubosiella, Lactobacillus, Muribaculaceae, and Bacteroidaceae) and downregulated the harmful bacteria (Tuzzerella and Marinifilaceae), further intestinal inflammation, oxidative stress, and intestinal barrier were alleviated as well as short chain fatty acids levels were increased, thus alleviating glucose and insulin metabolism, improving biochemical indexes and energy metabolism and decreasing body weight gain and tissue weight. However, heat-inactivated FMT did not demonstrate any of those improvements in obese mice. Notably, both DL-norvaline-mediated FMT and heat-inactivated FMT increased Bacteroidaceae and Muribaculaceae, this being a signature of alterations to the gut microbiota marker caused by DL-norvaline. Therefore, the beneficial effects of DL-norvaline were transmissible via FMT. This study highlighted the pivotal involvement of the gut microbiota in the development of obesity and provided a novel insight into the underlying mechanisms of FMT, thereby potentially enhancing the efficacy and refinement of FMT utilization.}, } @article {pmid39736240, year = {2025}, author = {Qiu, M and Geng, H and Zou, C and Zhao, X and Zhao, C and Xie, J and Wang, J and Zhang, N and Hu, Y and Fu, Y and Wang, J and Hu, X}, title = {Intestinal inflammation exacerbates endometritis through succinate production by gut microbiota and SUCNR1-mediated proinflammatory response.}, journal = {International immunopharmacology}, volume = {146}, number = {}, pages = {113919}, doi = {10.1016/j.intimp.2024.113919}, pmid = {39736240}, issn = {1878-1705}, mesh = {Animals ; Female ; *Gastrointestinal Microbiome ; *Endometritis/microbiology/immunology/pathology/metabolism ; *Succinic Acid/metabolism ; Mice ; *Lipopolysaccharides/immunology ; *Mice, Inbred C57BL ; Dysbiosis/immunology ; Receptors, G-Protein-Coupled/metabolism/genetics ; Dextran Sulfate ; Uterus/pathology/immunology/microbiology/metabolism ; Inflammation/immunology ; Disease Models, Animal ; Intestines/immunology/microbiology/pathology ; Fecal Microbiota Transplantation ; Humans ; }, abstract = {Endometritis poses higher health risks to women. Clinical practice has found that gastrointestinal dysfunction is more likely to lead to the occurrence of endometritis. However, the mechanism is unclear. This study explored the influence and mechanism of DSS-induced intestinal inflammation on endometritis. Our findings demonstrate that DSS-induced intestinal inflammation can worsen LPS-induced endometritis in mice, and this effect is dependent on the gut microbiota, as depleting the gut microbiota eliminates this protective effect. Similarly, FMT from DSS-treated mice to recipient mice exacerbates LPS-induced endometritis. In addition, treatment of DSS disrupted an imbalance of succinate-producing and succinate-consuming bacteria and increased the levels of succinate in the gut and uterine tissues. Furthermore, treatment with succinate aggravates LPS-induced endometritis by activating the succinate receptor 1 (SUCNR1), evidenced by inhibition of the activation of SUCNR1 reversed the inflammatory response in uterine tissues induced by succinate during endometritis induced by LPS. Collectively, the results suggested that dysbiosis of the gut microbiota exacerbates LPS-induced endometritis by production and migration of succinate from gut to uterine tissues via the gut-uterus axis, then activates the SUCNR1. This identifies gut-derived succinate as a novel target for treating endometritis, and it indicates that targeting the gut microbiota and its metabolism could be a potential strategy for intervention in endometritis.}, } @article {pmid39791120, year = {2024}, author = {Huang, H and Yang, Y and Wang, X and Wen, B and Yang, X and Zhong, W and Wang, Q and He, F and Li, J}, title = {Gut virome dysbiosis impairs antitumor immunity and reduces 5-fluorouracil treatment efficacy for colorectal cancer.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1501981}, pmid = {39791120}, issn = {2234-943X}, abstract = {INTRODUCTION: Despite the established influence of gut bacteria, the role of the gut virome in modulating colorectal cancer (CRC) patient chemotherapy response remains poorly understood. In this study, we investigated the impact of antiviral (AV) drug-induced gut virome dysbiosis on the efficacy of 5-FU in CRC treatment.

METHODS: Using a subcutaneous CRC mouse model, we assessed tumor growth and immune responses following AV treatment, fecal microbiota transplantation (FMT), and 5-FU administration.

RESULTS: AV therapy reduced the abundance of gut DNA and RNA viruses, leading to accelerated tumor growth, shortened survival, and diminished chemotherapy efficacy. FMT restored the gut virome, improving tumor suppression and extending the survival of 5-FU-treated mice. Metagenomic sequencing revealed significant changes in virome composition, AV treatment expanded Kahnovirus, Petivirales, and Enterogokushovirus, whereas FMT enriched Peduovirus STYP1, Mahlunavirus rarus, and Jouyvirus ev207. AV treatment reduced the number of dendritic cells and CD8+ T cells in peripheral blood and tumor tissues, impairing antitumor immunity, FMT reversed these deficiencies. To further investigate the underlying mechanisms, we examined the TLR3-IRF3-IFN-β pathway, essential for recognizing viral RNA and triggering immune responses. AV treatment downregulated this pathway, impairing immune cell recruitment and reducing chemotherapy efficacy, while activation of TLR3 with Poly(I:C) restored pathway function and enhanced the effectiveness of 5-FU.

DISCUSSION: These findings suggest the importance of maintaining gut virome integrity or activating TLR3 as adjunct strategies to enhance chemotherapy outcomes in CRC patients.}, } @article {pmid39791110, year = {2025}, author = {Høyer, KL and Dahl Baunwall, SM and Kornum, DS and Klinge, MW and Drewes, AM and Yderstræde, KB and Thingholm, LB and Mortensen, MS and Mikkelsen, S and Erikstrup, C and Hvas, CL and Krogh, K}, title = {Faecal microbiota transplantation for patients with diabetes type 1 and severe gastrointestinal neuropathy (FADIGAS): a randomised, double-blinded, placebo-controlled trial.}, journal = {EClinicalMedicine}, volume = {79}, number = {}, pages = {103000}, pmid = {39791110}, issn = {2589-5370}, abstract = {BACKGROUND: Diabetic gastroenteropathy is associated with nausea, vomiting, bloating, pain, constipation, and diarrhoea. Current therapies are scarce. We tested faecal microbiota transplantation (FMT) for patients with type 1 diabetes and gastroenteropathy.

METHODS: In a randomised, double-blinded, placebo-controlled pilot trial, adults with type 1 diabetes and moderate-to-severe gastrointestinal symptoms were randomised (1:1) to encapsulated FMT or placebo. Each patient received around 25 capsules containing 50 g of faeces, administered in a single dose. The placebo capsules contained glycerol, saline and food colouring. All patients received FMT as a second intervention. The primary endpoint was number of adverse events of severity grade 2 or more assessed by the Common Terminology Criteria for Adverse Events during the week following the first intervention. Secondary endpoints included gastrointestinal symptoms and quality of life assessed four weeks after treatment. Public trial registration, ClinicalTrials.govNCT04749030.

FINDINGS: We randomised 20 patients to FMT or placebo. Following this intervention, 26 adverse events of grade 2 or more occurred. Four patients in the FMT group reported seven adverse events, and five patients in the placebo group reported 19, with no differences between the groups. The most frequent adverse events were diarrhoea, bloating, and abdominal pain. No serious adverse events were related to the treatment. Patients who received FMT reduced their median Gastrointestinal Symptom Rating Scale-Irritable Bowel Syndrome score from 58 (IQR 54-65) to 35 (32-48), whereas patients receiving placebo reduced their score from 64 (55-70) to 56 (50-77) (p = 0.01). The Irritable Bowel Syndrome Impact Scale score improved from 108 (101-123) to 140 (124-161) with FMT and 77 (53-129) to 92 (54-142) with placebo (p = 0.02). The Patient Assessment of Gastrointestinal Symptom Severity Index declined from a median of 42 (28-47) to 25 (14-31) after FMT and 47 (31-69) to 41 (36-64) after placebo (p = 0.03).

INTERPRETATION: FMT was safe and improved clinical outcomes for patients with type 1 diabetes suffering from bowel symptoms.

FUNDING: Steno Collaborative Grant.}, } @article {pmid39788762, year = {2025}, author = {Augustijn, QJJ and Grefhorst, A and de Groen, P and Wortelboer, K and Seegers, JFM and Gül, IS and Suenaert, P and Verheij, J and de Vos, WM and Herrema, H and Nieuwdorp, M and Holleboom, AG}, title = {Randomised double-blind placebo-controlled trial protocol to evaluate the therapeutic efficacy of lyophilised faecal microbiota capsules amended with next-generation beneficial bacteria in individuals with metabolic dysfunction-associated steatohepatitis.}, journal = {BMJ open}, volume = {15}, number = {1}, pages = {e088290}, doi = {10.1136/bmjopen-2024-088290}, pmid = {39788762}, issn = {2044-6055}, mesh = {Humans ; Double-Blind Method ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Adult ; Male ; Randomized Controlled Trials as Topic ; Capsules ; Female ; Middle Aged ; Fatty Liver/therapy ; Feces/microbiology ; Freeze Drying ; }, abstract = {BACKGROUND: The spectrum of metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent, affecting 30% of the world's population, with a significant risk of hepatic and cardiometabolic complications. Different stages of MASLD are accompanied by distinct gut microbial profiles, and several microbial components have been implicated in MASLD pathophysiology. Indeed, earlier studies demonstrated that hepatic necroinflammation was reduced in individuals with MASLD after allogenic faecal microbiota transplantation (FMT) from healthy donors on a vegan diet. Here, we further investigate the therapeutic potential of gut microbiome modulation using a syntrophic combination of next-generation beneficial bacteria with FMT in individuals with advanced MASLD.

METHODS AND ANALYSIS: This trial is a randomised, double-blind, placebo-controlled study investigating the therapeutic potential of lyophilised faecal microbiota capsules (LFMCs) in individuals with metabolic dysfunction-associated steatohepatitis. In this study, 48 participants will be randomised 1:1 to receive either healthy vegan donor LFMCs or placebo for 24 weeks. In addition, all participants will be supplemented with a set of next-generation beneficial bacteria, including Anaerobutyricum soehngenii, pasteurised Akkermansia muciniphila and Bifidobacterium animalis subsp. lactis, as well as fructo-oligosaccharides. A liver biopsy will be performed at baseline and at the end of the trial. In addition, participants will be assessed through MRI, FibroScan, blood tests, faecal samples and continuous glucose monitoring. The first participant was enrolled on 25 April 2023.

ETHICS AND DISSEMINATION: Ethical approval was obtained from the Medical Ethics Committee of the University Medical Centre of Amsterdam. The results of this study will be disseminated through peer-reviewed journals.

TRIAL REGISTRATION NUMBER: The trial is registered on clinicaltrials.gov (NCT05821010).}, } @article {pmid39788096, year = {2025}, author = {Wang, W and Pi, Z and Yu, Y and Zhang, F}, title = {The butterfly effect of the strain richness influences the efficacy of microbiota transplantation.}, journal = {Cell host & microbe}, volume = {33}, number = {1}, pages = {3-5}, doi = {10.1016/j.chom.2024.12.010}, pmid = {39788096}, issn = {1934-6069}, mesh = {*Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Animals ; Feces/microbiology ; Bacteria/classification ; }, abstract = {Strain-level variation in the gut microbiome modulates its impact on host health. Recently in Nature, Chen-Liaw et al. propose that strain richness is a crucial element in the gut ecosystem, thus influencing efficacy of fecal microbiota transplantation, and provide a theoretical foundation for optimizing microbiota-based treatments and developing microbiota medicine.}, } @article {pmid39787138, year = {2025}, author = {Luo, Y and Zhou, S and Zhang, X and Lin, Y and Liu, J and Cheng, W and Zeng, Y}, title = {The role of the microbiota and metabolites in the treatment of pulmonary fibrosis with UC-MSCs: Integrating fecal metabolomics and 16S rDNA analysis.}, journal = {PloS one}, volume = {20}, number = {1}, pages = {e0313989}, pmid = {39787138}, issn = {1932-6203}, mesh = {Animals ; Mice ; *Pulmonary Fibrosis/therapy/metabolism/pathology/microbiology ; *Metabolomics/methods ; *Feces/microbiology ; *RNA, Ribosomal, 16S/genetics ; Mesenchymal Stem Cell Transplantation/methods ; Mesenchymal Stem Cells/metabolism ; Gastrointestinal Microbiome ; Male ; DNA, Ribosomal/genetics ; Mice, Inbred C57BL ; Disease Models, Animal ; Lung/pathology/metabolism/microbiology ; Bleomycin ; Microbiota ; Cytokines/metabolism ; }, abstract = {INTRODUCTION: Pulmonary fibrosis (PF) is a chronic and irreversible interstitial lung disease characterized by a lack of effective therapies. Mesenchymal stem cells (MSCs) have garnered significant interest in the realm of lung regeneration due to their abundant availability, ease of isolation, and capacity for expansion. The objective of our study was to investigate the potential therapeutic role of umbilical cord-derived MSCs (UC-MSCs) in the management of PF, with a focus on the alterations in the gut microbiota and its metabolites during the use of UC-MSCs for the treatment of pulmonary fibrosis, as well as the possible mechanisms involved.

METHODS: Bleomycin injection was utilized to establish a mouse model of lung fibrosis, followed by the application of 16S rDNA sequencing and LC-MS/MS metabolomics to explore the underlying mechanism of UC-MSC treatment for lung fibrosis. Seventy-five mice were allocated into five groups, namely Control, Model, and low/medium/high dose of UC-MSCs groups, and survival metrics, lung morphology, and the levels of the inflammatory cytokines TNF-α, IL-1β, IL-6, and TGF-β1 were subsequently evaluated. Fecal samples from six mice in each of the Control group, Model group, and UC-MSCs-M groups were collected randomly for 16S rDNA sequencing to analyze the gut microbiota and nontargeted metabolomics.

RESULTS: In comparison to IPF model mice, the three treatment groups exhibited increased survival rates, restored alveolar morphology, and reduced levels of the inflammatory cytokines TNF-α, IL-1β, IL-6, and TGF-β1, confirming the anti-inflammatory properties of UC-MSCs in IPF treatment. The findings from the 16S rDNA assay indicate that UC-MSCs treatment effectively lower α-diversity induced such as Chao 1 and ACE, as well as β-diversity, leading to a decrease in microbiota abundance. The findings from the metabolomics analysis revealed that the metabolites exhibiting notable variances were primarily composed of Lipids and lipid-like molecules, Organoheterocyclic compounds, Organic acids and derivatives, and Benzenoids, indicating the potential of UC-MSCs to exert antifibrotic effects via these metabolic pathways.

CONCLUSION: Umbilical cord-derived mesenchymal stem cells (UC-MSCs) ameliorate bleomycin-induced pulmonary fibrosis symptoms in mice by exerting anti-inflammatory effects and mitigating pulmonary fibrosis through the modulation of gut microbiota disorders and their metabolism. These findings offer novel insights into the potential mechanisms and clinical utility of stem cell therapy for pulmonary fibrosis.}, } @article {pmid39786379, year = {2024}, author = {Yang, Q and Zhu, Y and Jian, X and Qiu, Y and Zhu, Y and Zhao, L and He, Y and An, G and Qiu, L and Guo, J and He, N and Abudumijiti, H and Hu, C and Chen, X and Huang, S and Feng, X and Li, X and Liu, J and Xu, Y and Zhou, W}, title = {Targeting Enterobacter cloacae attenuates osteolysis by reducing ammonium in multiple myeloma.}, journal = {Blood}, volume = {}, number = {}, pages = {}, doi = {10.1182/blood.2024025694}, pmid = {39786379}, issn = {1528-0020}, abstract = {Multiple myeloma (MM)-induced bone disease affects not only patients' quality of life but also their overall survival. Our previous work demonstrated that the gut microbiome plays a crucial role in MM progression and drug resistance. However, the role of altered gut microbiota in MM bone disease remains unclear. In this study, we show that intestinal E. cloacae is significantly enriched in MM patients with osteolysis. Through fecal microbial transplantation and single bacterial colonization experiments in a 5TGM1 MM mouse model, we found that intestinal colonization of E. cloacae promotes osteolysis by increasing circulating ammonium levels. Elevated ammonium promotes osteoclastogenesis by increasing Trap protein levels in osteoclast precursors and by acetylating and stabilizing CCL3 protein in MM cells. Inhibition of ammonium synthesis, using E. cloacae with a deleted dcd gene, along with probiotic supplementation, alleviated osteolysis in MM. Overall, our work suggests that E. cloacae promotes osteolysis in MM by synthesizing ammonium. This establishes a novel mechanism and potential intervention strategy for managing MM with osteolysis.}, } @article {pmid39780269, year = {2025}, author = {Li, X and Ding, Q and Wan, X and Wu, Q and Ye, S and Lou, Y}, title = {Fecal microbiota transplantation attenuates Alzheimer's disease symptoms in APP/PS1 transgenic mice via inhibition of the TLR4-MyD88-NF-κB signaling pathway-mediated inflammation.}, journal = {Behavioral and brain functions : BBF}, volume = {21}, number = {1}, pages = {2}, pmid = {39780269}, issn = {1744-9081}, support = {Grant No. Y20220029//Health Project of the Science and Technology Department of Wenzhou/ ; 231104408302408//Industry-university Cooperative education program of Ministry of Education/ ; First Class, Category A//the Key Discipline of Zhejiang Province in Medical Technology/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Myeloid Differentiation Factor 88/metabolism ; Mice ; *Alzheimer Disease/therapy/microbiology ; *Mice, Transgenic ; *Toll-Like Receptor 4/metabolism ; *NF-kappa B/metabolism ; *Signal Transduction/physiology ; *Presenilin-1/genetics ; Amyloid beta-Protein Precursor/genetics ; Gastrointestinal Microbiome/physiology ; Inflammation/therapy/metabolism ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {Alzheimer's disease (AD) is a prevalent and progressive neurodegenerative disorder that is the leading cause of dementia. The underlying mechanisms of AD have not yet been completely explored. Neuroinflammation, an inflammatory response mediated by certain mediators, has been exhibited to play a crucial role in the pathogenesis of AD. Additionally, disruption of the gut microbiota has been found to be associated with AD, and fecal microbiota transplantation (FMT) has emerged as a potential therapeutic approach. However, the precise mechanism of FMT in the treatment of AD remains elusive. In this study, FMT was performed by transplanting fecal microbiota from healthy wild-type mice into APP/PS1 mice (APPswe, PSEN1dE9) to assess the effectiveness of FMT in mitigating AD-associated inflammation and to reveal its precise mechanism of action. The results demonstrated that FMT treatment improved cognitive function and reduced the expression levels of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway in mice, which was accompanied by the restoration of gut microbial dysbiosis. These findings suggest that FMT has the potential to ameliorate AD symptoms and delay the disease progression in APP/PS1 mice.}, } @article {pmid39779925, year = {2025}, author = {He, X and Hu, M and Xu, Y and Xia, F and Tan, Y and Wang, Y and Xiang, H and Wu, H and Ji, T and Xu, Q and Wang, L and Huang, Z and Sun, M and Wan, Y and Cui, P and Liang, S and Pan, Y and Xiao, S and He, Y and Song, R and Yan, J and Quan, X and Wei, Y and Hong, C and Liao, W and Li, F and El-Omar, E and Chen, J and Qi, X and Gao, J and Zhou, H}, title = {The gut-brain axis underlying hepatic encephalopathy in liver cirrhosis.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, pmid = {39779925}, issn = {1546-170X}, support = {82372305//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Up to 50-70% of patients with liver cirrhosis develop hepatic encephalopathy (HE), which is closely related to gut microbiota dysbiosis, with an unclear mechanism. Here, by constructing gut-brain modules to assess bacterial neurotoxins from metagenomic datasets, we found that phenylalanine decarboxylase (PDC) genes, mainly from Ruminococcus gnavus, increased approximately tenfold in patients with cirrhosis and higher in patients with HE. Cirrhotic, not healthy, mice colonized with R. gnavus showed brain phenylethylamine (PEA) accumulation, along with memory impairment, symmetrical tremors and cortex-specific neuron loss, typically found in patients with HE. This accumulation of PEA was primarily driven by decreased monoamine oxidase-B activity in both the liver and serum due to cirrhosis. Targeting PDC or PEA reversed the neurological symptoms induced by R. gnavus. Furthermore, fecal microbiota transplantation from patients with HE to germ-free cirrhotic mice replicated these symptoms and further corroborated the efficacy of targeting PDC or PEA. Clinically, high baseline PEA levels were linked to a sevenfold increased risk of HE after intrahepatic portosystemic shunt procedures. Our findings expand the understanding of the gut-liver-brain axis and identify a promising therapeutic and predictive target for HE.}, } @article {pmid39779878, year = {2025}, author = {Keskey, RC and Xiao, J and Hyoju, S and Lam, A and Kim, D and Sidebottom, AM and Zaborin, A and Dijkstra, A and Meltzer, R and Thakur, A and Zhang, K and Chen, HJ and Beloborodova, NV and Pautova, AK and Wolfe, K and Patel, B and Thewissen, R and Zaborina, O and Alverdy, JC}, title = {Enterobactin inhibits microbiota-dependent activation of AhR to promote bacterial sepsis in mice.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, pmid = {39779878}, issn = {2058-5276}, support = {R01GMO62344-22//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; }, abstract = {Sepsis is a major cause of morbidity and mortality, but our understanding of the mechanisms underlying survival or susceptibility is limited. Here, as pathogens often subvert host defence mechanisms, we hypothesized that this might influence the outcome of sepsis. We used microbiota analysis, faecal microbiota transplantation, antibiotic treatment and caecal metabolite analysis to show that gut-microbiota-derived tryptophan metabolites including indoles increased host survival in a mouse model of Serratia marcescens sepsis. Infection in macrophage-specific aryl hydrocarbon receptor (AhR) knockout mice revealed that AhR activation induced transcriptional reprogramming in macrophages and increased bacterial clearance and host survival. However, culture supernatants from multiple bacterial pathogens inhibited AhR activation in vitro. We showed that the secreted siderophore, enterobactin, inhibited AhR activation in vitro and increased sepsis mortality in vivo. By contrast, oral or systemic tryptophan supplementation increased survival. These findings show that sepsis survival depends upon the interplay between pathogen inhibition and the activation of AhR by a microbiota-derived metabolite.}, } @article {pmid39779854, year = {2025}, author = {Won, TH and Arifuzzaman, M and Parkhurst, CN and Miranda, IC and Zhang, B and Hu, E and Kashyap, S and Letourneau, J and Jin, WB and Fu, Y and Guzior, DV and , and Quinn, RA and Guo, CJ and David, LA and Artis, D and Schroeder, FC}, title = {Host metabolism balances microbial regulation of bile acid signalling.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {39779854}, issn = {1476-4687}, abstract = {Metabolites derived from the intestinal microbiota, including bile acids (BA), extensively modulate vertebrate physiology, including development[1], metabolism[2-4], immune responses[5-7] and cognitive function[8]. However, to what extent host responses balance the physiological effects of microbiota-derived metabolites remains unclear[9,10]. Here, using untargeted metabolomics of mouse tissues, we identified a family of BA-methylcysteamine (BA-MCY) conjugates that are abundant in the intestine and dependent on vanin 1 (VNN1), a pantetheinase highly expressed in intestinal tissues. This host-dependent MCY conjugation inverts BA function in the hepatobiliary system. Whereas microbiota-derived free BAs function as agonists of the farnesoid X receptor (FXR) and negatively regulate BA production, BA-MCYs act as potent antagonists of FXR and promote expression of BA biosynthesis genes in vivo. Supplementation with stable-isotope-labelled BA-MCY increased BA production in an FXR-dependent manner, and BA-MCY supplementation in a mouse model of hypercholesteraemia decreased lipid accumulation in the liver, consistent with BA-MCYs acting as intestinal FXR antagonists. The levels of BA-MCY were reduced in microbiota-deficient mice and restored by transplantation of human faecal microbiota. Dietary intervention with inulin fibre further increased levels of both free BAs and BA-MCY levels, indicating that BA-MCY production by the host is regulated by levels of microbiota-derived free BAs. We further show that diverse BA-MCYs are also present in human serum. Together, our results indicate that BA-MCY conjugation by the host balances host-dependent and microbiota-dependent metabolic pathways that regulate FXR-dependent physiology.}, } @article {pmid39779737, year = {2025}, author = {Corcione, S and Ferrocino, I and Lupia, T and Busca, A and Bianco, G and Dellacasa, C and Giaccone, L and Brunello, L and Butera, S and Costa, C and Bruno, B and De Rosa, FG}, title = {Influence of ESBL colonization status on gut microbiota composition during allogenic hematopoietic stem cell transplantation.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {1275}, pmid = {39779737}, issn = {2045-2322}, support = {Project no. PE00000007, INF-ACT//EU funding within the MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Male ; Female ; Middle Aged ; Adult ; Prospective Studies ; Pilot Projects ; *beta-Lactamases/metabolism ; *Transplantation, Homologous/adverse effects ; Aged ; Feces/microbiology ; Italy ; Anti-Bacterial Agents/therapeutic use/pharmacology ; }, abstract = {After allogeneic HSCT (allo-HSCT), the diversity of the intestinal microbiota significantly decreases. The changes can be rapid and are thought to be caused by chemotherapy, antibiotics, or intestinal inflammation. Most patients are exposed to prophylactic and therapeutic antibiotics during neutropenia and several patients are colonized by ESBL bacteria. We investigated the changes in gut microbiota composition in allo-HSCT, aiming at investigating if the acquisition of ESBL colonization may affect gut microbiome diversity during allo-HSCT. This was a single-center prospective pilot study. All patients consecutively admitted to the Haematological Unit of the City of Health and Science, Molinette Hospital in Turin, Italy, and undergoing allo-HSCT between August 2017 to August 2020 were enrolled in the study. Microbiome analysis on fecal samples were collected every 7 days from hospital admission to discharge and until 1 year after HSCT. 48 patients were enrolled in the study. At baseline 14 patients (29.16%) were colonized by MDR bacteria, mostly extended-spectrum beta-lactamase (ESBL)-producing gram negatives (N = 11; 78.57%). During allo-HSCT, one patient had a positive rectal swab for a carbapenemase-producing Klebsiella pneumoniae and eight patients lost the colonization during the hospital stay. Microbiota composition was compared between patients colonized by ESBL at baseline and non-colonized patients. Patients colonized by ESBL had a greater abundances of Bifidobacterium, Blautia, Clostridium, Coprococcus, L-Ruminococcus Mogibacteriaceae, Peptostreptococceae and Oscillospira, while non-colonized ESBL patients had a greater abundance of Actinomycetales, Staphylococcus and Sutterella. Moreover, microbiota composition of colonized by ESBL that retained colonization after HSCT showed an increased in abundances of Akkermansia, Dialister, Erysipelotrichaceae and Methanobrevibacter when compared with patients that become negative at rectal swabs. From a clinical perspective, the evolution of this prospective pilot study will be to investigate markers of gut barrier functions, SCFA productions and to correlate the predictivity of these parameters with risk of invasive infections and clinical outcomes in allo-HSCT population.}, } @article {pmid39778887, year = {2025}, author = {Pérez-Accino, J and Salavati, M and Glendinning, L and Salavati Schmitz, S}, title = {Effect of a single rectal fecal microbiota transplantation on clinical severity and fecal microbial communities in dogs with chronic inflammatory enteropathy.}, journal = {Journal of veterinary internal medicine}, volume = {39}, number = {1}, pages = {e17264}, pmid = {39778887}, issn = {1939-1676}, support = {//Fiona and Ian Russel Fund/ ; }, mesh = {Animals ; Dogs ; *Dog Diseases/therapy/microbiology ; *Fecal Microbiota Transplantation/veterinary ; *Feces/microbiology ; Male ; Female ; Inflammatory Bowel Diseases/veterinary/therapy/microbiology ; RNA, Ribosomal, 16S/genetics ; Gastrointestinal Microbiome ; Chronic Disease ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been advocated as a treatment for chronic enteropathy (CE) in dogs. However, so far only short-term clinical effects have been reported whereas the effect on the microbiota remains unexplored.

HYPOTHESIS/OBJECTIVES: Assess if a single FMT enema can lead to clinical improvement in dogs with CE when accompanied by presumed favorable microbiota changes. The effect of glycerol as a cryopreservative when storing FMT preparations also was assessed.

ANIMALS: Seven dogs with CE that received FMTs from 2 healthy donor dogs.

MATERIALS AND METHODS: Six dogs received a single FMT, 1 dog received 3 consecutive FMTs. Canine chronic enteropathy clinical activity index (CCECAI) and fecal samples were obtained before (Day 0), and 7, 30 and 90 days after FMT. Samples were stored with and without 10% glycerol. Sequencing of microbiota (16S rRNA, Illumina) was performed and compared by accepted analysis pipelines.

RESULTS: Median CCECAI before FMT was 8 (range, 5-14), decreased to a median of 3 (range, 1-12) within 1 week and a median of 1 (range, 0-12) by Day 30 (P < .01), with an average duration of response of approximately 10 weeks. Significant variation in the donors' microbiota composition was observed across different donations. Recipient microbiota composition or diversity did not change over time. Glycerol addition was associated with a difference in microbiota composition (P ≤ .001).

A single FMT can be considered an appropriate treatment in dogs with CE, but consistent microbiota changes were not observed.}, } @article {pmid39778639, year = {2025}, author = {Chen, C and Wang, J and Cheng, M and Xie, H and Li, W and Zhang, C}, title = {Muribaculum intestinale-derived 3-hydroxybutyric acid from Heterophyllin B attenuated pulmonary fibrosis through IDO1-mediated ferroptosis.}, journal = {Pharmacological research}, volume = {212}, number = {}, pages = {107587}, doi = {10.1016/j.phrs.2025.107587}, pmid = {39778639}, issn = {1096-1186}, abstract = {Pulmonary fibrosis (PF) is a fatal disease with increasing incidence, poor prognosis, and unclear pathogenesis. Our previous research demonstrated the beneficial effects of the natural cyclopeptide Heterophyllin B (HB) in PF. However, the precise mechanism by which HB exerts its effects in PF remains unclear. Our study revealed HB's beneficial effects in alleviating PF symptoms and restoring the intestinal mucosal barrier. Subsequently, the microbiota-dependent antifibrotic efficacy of HB was verified using various delivery routes, antibiotic treatments, and faecal microbiota transplantation. Functionally, 16S rRNA sequencing, untargeted metabolomics, and co-incubation experiments revealed that the antifibrotic efficacy of HB was primarily contingent on the enrichment of Muribaculum intestinale and its metabolite, 3-hydroxybutyric acid. Mechanistically, indoleamine 2,3- dioxygenase 1 (IDO1)-mediated ferroptosis was identified as a pivotal process in initiating PF, and the anti-fibrotic efficacy of HB relies on suppressing IDO1-mediated ferroptosis. Conversely, IDO1 deficiency alleviated the symptoms of bleomycin-induced PF and ferroptosis in mice. Coincidentally, both IDO1 overexpression and ferroptosis were observed in the pulmonary tissue of patients with idiopathic PF. Collectively, this study revealed that HB alleviates PF by eliminating intestinal microecology and metabolism and highlights the feasibility of targeting IDO1 for PF treatment.}, } @article {pmid39777251, year = {2025}, author = {Quaglio, AE and Magro, DO and Imbrizi, M and De Oliveira, EC and Di Stasi, LC and Sassaki, LY}, title = {Creeping fat and gut microbiota in Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {31}, number = {1}, pages = {102042}, pmid = {39777251}, issn = {2219-2840}, mesh = {*Crohn Disease/microbiology/immunology/therapy ; Humans ; *Gastrointestinal Microbiome/physiology/immunology ; *Dysbiosis/immunology ; *Fecal Microbiota Transplantation ; *Intra-Abdominal Fat/immunology ; *Probiotics/therapeutic use ; *Disease Progression ; Prebiotics/administration & dosage ; Fibrosis ; Animals ; Mesentery ; }, abstract = {In this article, we explored the role of adipose tissue, especially mesenteric adipose tissue and creeping fat, and its association with the gut microbiota in the pathophysiology and progression of Crohn's disease (CD). CD is a form of inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal tract, influenced by genetic predisposition, gut microbiota dysbiosis, and environmental factors. Gut microbiota plays a crucial role in modulating immune response and intestinal inflammation and is associated with the onset and progression of CD. Further, visceral adipose tissue, particularly creeping fat, a mesenteric adipose tissue characterized by hypertrophy and fibrosis, has been implicated in CD pathogenesis, inflammation, and fibrosis. The bacteria from the gut microbiota may translocate into mesenteric adipose tissue, contributing to the formation of creeping fat and influencing CD progression. Although creeping fat may be a protective barrier against bacterial invasion, its expansion can damage adjacent tissues, leading to complications. Modulating gut microbiota through interventions such as fecal microbiota transplantation, probiotics, and prebiotics has shown potential in managing CD. However, more research is needed to clarify the mechanisms linking gut dysbiosis, creeping fat, and CD progression and develop targeted therapies for microbiota modulation and fat-related complications in patients with CD.}, } @article {pmid39777148, year = {2024}, author = {An, Y and He, L and Xu, X and Piao, M and Wang, B and Liu, T and Cao, H}, title = {Gut microbiota in post-acute COVID-19 syndrome: not the end of the story.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1500890}, pmid = {39777148}, issn = {1664-302X}, abstract = {The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has led to major global health concern. However, the focus on immediate effects was assumed as the tip of iceberg due to the symptoms following acute infection, which was defined as post-acute COVID-19 syndrome (PACS). Gut microbiota alterations even after disease resolution and the gastrointestinal symptoms are the key features of PACS. Gut microbiota and derived metabolites disorders may play a crucial role in inflammatory and immune response after SARS-CoV-2 infection through the gut-lung axis. Diet is one of the modifiable factors closely related to gut microbiota and COVID-19. In this review, we described the reciprocal crosstalk between gut and lung, highlighting the participation of diet and gut microbiota in and after COVID-19 by destroying the gut barrier, perturbing the metabolism and regulating the immune system. Therefore, bolstering beneficial species by dietary supplements, probiotics or prebiotics and fecal microbiota transplantation (FMT) may be a novel avenue for COVID-19 and PACS prevention. This review provides a better understanding of the association between gut microbiota and the long-term consequences of COVID-19, which indicates modulating gut dysbiosis may be a potentiality for addressing this multifaceted condition.}, } @article {pmid39776845, year = {2024}, author = {Zhuang, L and You, Y and Zeng, S and Yu, Z and Wang, H and Chen, M and Wen, W}, title = {Fecal microbiota transplantation in severe pneumonia: a case report on overcoming pan-drug resistant Klebsiella pneumoniae infection.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1451751}, pmid = {39776845}, issn = {2296-858X}, abstract = {OBJECTIVE: To evaluate the therapeutic potential of fecal microbiota transplantation (FMT) in treating severe pneumonia patients with concurrent pan-drug resistant Klebsiella pneumoniae infection.

METHODS: A case report of a 95-year-old female patient with severe pneumonia, complicated by pan-resistant bacterial infections, is presented. The patient was diagnosed with severe pneumonia caused by COVID-19, along with co-infections of Staphylococcus hominis, Enterococcus faecalis, Candida tropicalis, Pseudomonas aeruginosa, ESBL-producing pan-drug resistant Klebsiella pneumoniae and pan-resistant Acinetobacter baumannii. During hospitalization, the patient underwent comprehensive treatments, including antimicrobials, mechanical ventilation, and fiberoptic bronchoscopic alveolar lavage. FMT was administered following the failure of conventional treatments to resolve recurrent diarrhea, increased sputum production, and persistent pan-drug resistant Klebsiella pneumoniae infection.

RESULTS: Post-FMT, the patient exhibited significant clinical improvement, including reduced sputum production, cessation of diarrhea, and the normalization of respiratory symptoms. Gut microbiota analysis revealed that FMT enhanced the abundance of beneficial microbiota and suppressed Klebsiella pneumoniae, and the patient was successfully discharged after 133 days of hospitalization.

CONCLUSION: FMT emerged as a pivotal intervention in the management of this severe pneumonia case, suggesting its efficacy in restoring gut microbiota balance and aiding recovery from multi-drug-resistant infections. This case underscores the potential of FMT as a therapeutic option in severe pulmonary infections, especially in the context of antibiotic resistance in severe pneumonia patients.}, } @article {pmid39776440, year = {2024}, author = {Fang, L and Ning, J}, title = {Recent advances in gut microbiota and thyroid disease: pathogenesis and therapeutics in autoimmune, neoplastic, and nodular conditions.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1465928}, pmid = {39776440}, issn = {2235-2988}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Probiotics/therapeutic use ; *Thyroid Diseases/therapy/microbiology ; *Fecal Microbiota Transplantation ; Animals ; Bacteria/classification/metabolism ; Neoplasms/therapy/microbiology ; Dysbiosis/therapy/microbiology ; }, abstract = {This review synthesizes key findings from the past five years of experimental literature, elucidating the gut microbiome's significant influence on the pathogenesis of thyroid diseases. A pronounced shift in the gut microbiota composition has been consistently observed, with a significant reduction in bacteria such as Bifidobacterium, Bacillaceae, Megamonas, and Clostridium, and a notable increase in bacteria, including Bacteroides, Proteobacteria, Actinobacteria, Desulfobacterota, and Klebsiella. These alterations are implicated in the development and progression of thyroid diseases by impacting metabolic pathways including bile acid and cytokine production, including a decrease in short-chain fatty acids (SCFAs) that are crucial for immune regulation and thyroid hormone homeostasis. The review also highlights the therapeutic implications of probiotics in managing thyroid conditions. Evidence suggests that probiotic adjunct therapy can modulate the gut microbiota, leading to improvements in thyroid function and patient outcomes. The use of specific probiotic strains, such as Lactiplantibacillus plantarum 299v and Bifidobacterium longum, has demonstrated potential in enhancing the effects of traditional treatments and possibly restoring a balanced gut microbiota. Notably, fecal microbiota transplantation (FMT) has emerged as a promising intervention in Graves' Disease (GD), demonstrating the potential to recalibrate the gut microbiota, thereby influencing neurotransmitters and trace elements via the gut-brain and gut-thyroid axes. The integration of microbiome-based therapies with traditional treatments is anticipated to usher in a new era of personalized thyroid disease management, offering a more nuanced approach to patient care. By integrating this body of work, the review offers an innovative perspective on the gut microbiome's broad impact on thyroid diseases and the therapeutic applications of probiotics.}, } @article {pmid39775925, year = {2025}, author = {Bloem, MN and Baaleman, DF and Thapar, N and Roberts, SE and Koppen, IJN and Benninga, MA}, title = {Prevalence of functional defecation disorders in European children: A systematic review and meta-analysis.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1002/jpn3.12437}, pmid = {39775925}, issn = {1536-4801}, support = {//None/ ; }, abstract = {OBJECTIVES: Functional defecation disorders (FDDs) are common among children worldwide. The prevalence of these disorders has not been clearly described in Europe. This study performed a systematic review and meta-analysis on the prevalence of FDD in European children and assessed geographical, age, and sex distribution and associated factors.

METHODS: PubMed, Embase, Psycinfo, Cochrane Library, and Cinahl were searched from 1999 to July 2023. Included studies were (1) prospective or cross-sectional studies of European population-based samples; (2) reporting the prevalence of infant dyschezia (ID) according to Rome II, III, or IV criteria or functional constipation (FC) or functional non-retentive fecal incontinence (FNRFI) according to Rome III or IV criteria; (3) aged 0-18 years; and (4) published in English, Dutch or Spanish. PRISMA guidelines for extracting data and assessing data quality were followed.

RESULTS: Twenty-eight studies were included. Pooled prevalence was 6.9% (95% confidence interval [CI]: 3.1%-11.9%) for ID in infants 0-12 months (9 studies, n = 5611), 8.17% (95% CI: 6.33%-10.22%) for FC in children <4 years (25 studies, n = 35,189), 11.39% (95% CI: 9.34%-14.11%) for FC in children 4-18 years, and 0.24% (95% CI: 0.07%-0.49%) for FNRFI in children 4-18 years (7 studies, n = 16,873). No sex predominance was found for FC. FC prevalence did not differ significantly when diagnosed according to Rome III versus IV. FC prevalence differed between countries, with greatest rates in Italy, Germany, and Spain. No meta-analysis could be performed on other factors associated with FDD.

CONCLUSIONS: FDD is common in European children. Future longitudinal studies are needed to provide better insight into associated factors in pathogenesis.}, } @article {pmid39775370, year = {2025}, author = {Lai, Y and Qiu, R and Zhou, J and Ren, L and Qu, Y and Zhang, G}, title = {Fecal Microbiota Transplantation Alleviates Airway Inflammation in Asthmatic Rats by Increasing the Level of Short-Chain Fatty Acids in the Intestine.}, journal = {Inflammation}, volume = {}, number = {}, pages = {}, pmid = {39775370}, issn = {1573-2576}, support = {(No. 2021JJ30513, No. 2017JJ3245)//Natural Science Foundation of Hunan Province/ ; No. 20B444//Education Department of Hunan Province/ ; (No. 81603705)//National Natural Science Foundation of China/ ; (No. 2017M612567)//Postdoctoral Science Foundation of China/ ; (2024XJZA008)//Hunan University of Chinese Medicine research project/ ; }, abstract = {Asthma is a prevalent chronic inflammatory disorder of the respiratory tract that not only manifests with respiratory symptoms but also often involves intestinal flora disorders and gastrointestinal dysfunction. Recent studies have confirmed the close relationship between the gut and lungs, known as the "gut-lung axis" theory. Fecal microbiota transplantation (FMT), a method for restoring normal intestinal flora, has shown promise in treating common gastrointestinal diseases. The "gut-lung axis" theory suggests that FMT may have significant therapeutic potential for asthma. In this study, we established an Ovalbumin (OVA)-induced rat model of asthma to investigate the protective effect of FMT on airway inflammation and the restoration of intestinal short-chain fatty acids (SCFAs), aiming to explore its underlying mechanism. Rats in the Control group underwent fecal treatment via gavage (Control-FMT, C-FMT group), while rats in the Asthma group underwent fecal treatment via gavage after asthma induction (Asthma-FMT, A-FMT group). Following a two-week period of continuous intragastric administration, various measurements were conducted to assess pulmonary function, peripheral blood neutrophil, lymphocyte, and eosinophil content, lung tissue pathology, and collagen fiber deposition in the lungs. Additionally, neutrophil and eosinophil content in bronchoalveolar lavage fluid (BALF), expression levels of Interleukin-4 (IL-4), IL-5, IL-13, IL-17, IL-33, leukotrienes (LT), thymic stromal lymphopoietin (TSLP), prostaglandin D2 (PGD2) protein and mRNA in lung tissue, and SCFAs content in stool were evaluated. In the C-FMT group, lung function significantly improved, inflammatory cell content in peripheral blood and BALF decreased, lung tissue pathology and collagen fiber deposition significantly improved, the protein and mRNA levels of lung inflammatory factors IL-4, IL-5, IL-13, IL-17, IL-33, LT, TSLP, PGD2 were significantly decreased, and SCFAs such as acetate (C2), propionate (C3), butyrate (C4), isobutyric acid (I-C4), valeric acid (C5), and isovaleric acid (I-C5) content in stool significantly increased. However, the indexes in the A-FMT group did not show significant recovery, and the treatment effect on asthma symptoms in rats was inferior to that in the C-FMT group. Asthma induced intestinal flora disorders in rats, and FMT treatment improved the inflammatory response in asthmatic rat models and corrected their intestinal SCFAs disorders. Encouraging the recovery of intestinal SCFAs may play a significant role, and beneficial bacteria present in feces may improve asthma symptoms by promoting the remodeling of intestinal flora. This experiment provides further scientific evidence supporting the "gut-lung axis" theory.}, } @article {pmid39773995, year = {2024}, author = {Mullish, BH and Innes, AJ and Roberts, LA and Anim-Burton, S and Webber, L and Johnson, NA and Ghani, R and Farshi, P and Khan, AB and Kinsella, F and Kottaridis, P and Krishnamurthy, P and Nicholson, E and Palanicawandar, R and Wheeler, G and Davies, F and Marchesi, JR and Pavlů, J}, title = {Intestinal Microbiota Transplant Prior to Allogeneic Stem Cell Transplant (MAST) trial: study protocol for a multicentre, double-blinded, placebo-controlled, phase IIa trial.}, journal = {BMJ open}, volume = {14}, number = {12}, pages = {e093120}, doi = {10.1136/bmjopen-2024-093120}, pmid = {39773995}, issn = {2044-6055}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation ; Double-Blind Method ; *Transplantation, Homologous ; Multicenter Studies as Topic ; Clinical Trials, Phase II as Topic ; Adult ; Randomized Controlled Trials as Topic ; Transplantation Conditioning/methods ; Fecal Microbiota Transplantation/methods ; Hematologic Neoplasms/therapy ; Female ; Male ; }, abstract = {INTRODUCTION: Lower diversity of the gut microbiome prior to allogeneic haematopoietic cell transplantation (HCT) correlates with reduced survival after the intervention. Most patients undergoing HCT for a haematological malignancy have previously received intensive chemotherapy, resulting in prolonged neutropenic episodes requiring broad-spectrum antibiotics; use of these has been linked to reduced microbiome diversity. Intestinal microbiota transplant (IMT) is a novel treatment approach that restores this diversity. We hypothesised that IMT performed prior to initiation of HCT conditioning restores microbiome diversity during the early stages of HCT, leading to decreased frequency of complications and improved outcomes of HCT.

METHODS AND ANALYSIS: 50 adult patients receiving allogeneic HCT will be recruited into this phase IIa trial and randomised 1:1 to receive capsulised IMT or matched placebo shortly prior to initiation of HCT conditioning and followed for up to 12 months. The primary outcome will be to assess the increase in alpha diversity between pre-IMT and that measured at ~42 days after IMT administration (day +28 of HCT), comparing the difference between patients receiving IMT compared with placebo. Secondary outcomes will include tolerability, the dynamics of gut microbiome diversity metrics and taxonomy over all time points assessed, as well as clinical outcomes (including burden of invasive infections, days of fever, admission to intensive care, development of graft-vs-host disease and mortality).

ETHICS AND DISSEMINATION: This study was approved by a UK Research Ethics Committee (REC reference: 23/NE/0105). Dissemination of results will be in concert with patient and public involvement group input and is expected to be primarily via abstract presentation at conferences and manuscripts in peer-reviewed journals.

TRIAL REGISTRATION NUMBERS: NCT6355583; EudraCT: 2022-003617-10.}, } @article {pmid39773319, year = {2025}, author = {Prince, N and Peralta Marzal, LN and Roussin, L and Monnoye, M and Philippe, C and Maximin, E and Ahmed, S and Salenius, K and Lin, J and Autio, R and Adolfs, Y and Pasterkamp, RJ and Garssen, J and Naudon, L and Rabot, S and Kraneveld, AD and Perez-Pardo, P}, title = {Mouse strain-specific responses along the gut-brain axis upon fecal microbiota transplantation from children with autism.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2447822}, doi = {10.1080/19490976.2024.2447822}, pmid = {39773319}, issn = {1949-0984}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Mice ; Male ; *Mice, Inbred C57BL ; *Brain-Gut Axis/physiology ; *Mice, Inbred BALB C ; Child ; Autism Spectrum Disorder/microbiology ; Dysbiosis/microbiology ; Feces/microbiology ; Disease Models, Animal ; Autistic Disorder/microbiology/physiopathology ; Female ; Social Behavior ; Species Specificity ; Bacteria/classification/isolation & purification/genetics/metabolism ; }, abstract = {Several factors are linked to the pathophysiology of autism spectrum disorders (ASD); however, the molecular mechanisms of the condition remain unknown. As intestinal problems and gut microbiota dysbiosis are associated with ASD development and severity, recent studies have focused on elucidating the microbiota-gut-brain axis' involvement. This study aims to explore mechanisms through which gut microbiota might influence ASD. Briefly, we depleted the microbiota of conventional male BALB/cAnNCrl (Balb/c) and C57BL/6J (BL/6) mice prior to human fecal microbiota transplantation (hFMT) with samples from children with ASD or their neurotypical siblings. We found mouse strain-specific responses to ASD hFMT. Notably, Balb/c mice exhibit decreased exploratory and social behavior, and show evidence of intestinal, systemic, and central inflammation accompanied with metabolic shifts. BL/6 mice show less changes after hFMT. Our results reveal that gut microbiota alone induce changes in ASD-like behavior, and highlight the importance of mouse strain selection when investigating multifactorial conditions like ASD.}, } @article {pmid39772953, year = {2025}, author = {Teigen, LM and Hoeg, A and Zehra, H and Shah, P and Johnson, R and Hutchison, K and Kocher, M and Lin, AW and Johnson, AJ and Vaughn, BP}, title = {Nutritional optimization of fecal microbiota transplantation in humans: a scoping review.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2446378}, doi = {10.1080/19490976.2024.2446378}, pmid = {39772953}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Diet ; Clostridium Infections/therapy/microbiology ; Feces/microbiology ; Dietary Supplements ; }, abstract = {Diet constitutes a major source of nutrient flow to the gut microbes. As such, it can be used to help shape the gut microbiome. Fecal microbiota transplantation (FMT) is an increasingly promising therapy in disease states beyond recurrent Clostridioides difficile infection, but diet is largely overlooked for its potential to help optimize this therapy. Therefore, the aim of this scoping review is to present the literature landscape that captures pre- and post-FMT dietary intake in humans, identify research gaps, and provide recommendations for future research. A comprehensive search strategy was developed and searches were run in five databases. Studies were included if they discussed adults who underwent FMT for any recognized treatment indication and had dietary intake as a study objective, this search encompassed studies with interventions that included foods and dietary supplements. The initial screening identified a total of 7721 articles, of which 18 met the inclusion criteria for this review. Studies were heterogeneous, but taken together, they introduce a framework that defines important nutritional considerations for both donors and FMT recipients in the period around FMT dosing. This framework is summarized with this review and highlights the opportunities available to develop FMT-based precision nutrition strategies to optimize its clinical efficacy.}, } @article {pmid39772388, year = {2025}, author = {Wouters, S and Moors, H and Verslegers, M and Leys, N and Malhotra-Kumar, S and Kumar-Singh, S and Mysara, M}, title = {Protocol for fecal microbiota transplantation: A microaerophilic approach for mice housed in a specific pathogen-free facility.}, journal = {STAR protocols}, volume = {6}, number = {1}, pages = {103517}, doi = {10.1016/j.xpro.2024.103517}, pmid = {39772388}, issn = {2666-1667}, abstract = {Recently, studies have emerged exploring the potential application of fecal microbiota transplantation (FMT) in pre-clinical settings. Here, we present a protocol for FMT for mice housed in a specific pathogen-free (SPF) facility. We describe steps for sample collection, microaerophilic processing of freshly collected fecal pellets, and administration through oral gavage. We then detail procedures for the engraftment of the bacterial community. This protocol focuses on age- and gender-matched, healthy donor mice using a mobile and cost-effective alternative to an anoxic cabinet.}, } @article {pmid39771031, year = {2024}, author = {Olga, B and Boicean, A and Fleacă, SR and Blanca, G and Florin, S and Corina, RF and Iulian, RF and Adelaida, S and Sabrina, B and Dura, H and Corina, P and Cristian, A and Onisor, DM}, title = {Importance of Fecal Microbiota Transplantation and Molecular Regulation as Therapeutic Strategies in Inflammatory Bowel Diseases.}, journal = {Nutrients}, volume = {16}, number = {24}, pages = {}, pmid = {39771031}, issn = {2072-6643}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Inflammatory Bowel Diseases/therapy/microbiology/immunology ; *MicroRNAs/metabolism ; *Gastrointestinal Microbiome ; Gene Expression Regulation ; Animals ; Intestinal Mucosa/microbiology/metabolism/immunology ; }, abstract = {Noncoding RNAs, particularly microRNAs (miRNAs) and small interfering RNAs (siRNAs), have emerged as key players in the pathogenesis and therapeutic strategies for inflammatory bowel disease (IBD). MiRNAs, small endogenous RNA molecules that silence target mRNAs to regulate gene expression, are closely linked to immune responses and inflammatory pathways in IBD. Notably, miR-21, miR-146a, and miR-155 are consistently upregulated in IBD, influencing immune cell modulation, cytokine production, and the intestinal epithelial barrier. These miRNAs serve as biomarkers for disease progression and severity, as well as therapeutic targets for controlling inflammation. This comprehensive review highlights the intricate interplay between the gut microbiota, fecal microbiota transplantation (FMT), and miRNA regulation. It concludes that microbiota and FMT influence miRNA activity, presenting a promising avenue for personalized IBD treatment.}, } @article {pmid39771027, year = {2024}, author = {Gruenbaum, BF and Merchant, KS and Zlotnik, A and Boyko, M}, title = {Gut Microbiome Modulation of Glutamate Dynamics: Implications for Brain Health and Neurotoxicity.}, journal = {Nutrients}, volume = {16}, number = {24}, pages = {}, doi = {10.3390/nu16244405}, pmid = {39771027}, issn = {2072-6643}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Glutamic Acid/metabolism ; *Brain-Gut Axis/physiology ; *Brain/metabolism ; Animals ; Fecal Microbiota Transplantation ; Blood-Brain Barrier/metabolism ; Neurotoxicity Syndromes/etiology/metabolism ; Depression/metabolism/microbiology ; }, abstract = {The gut-brain axis plays an integral role in maintaining overall health, with growing evidence suggesting its impact on the development of various neuropsychiatric disorders, including depression. This review explores the complex relationship between gut microbiota and glutamate (Glu) regulation, highlighting its effect on brain health, particularly in the context of depression following certain neurological insults. We discuss how microbial populations can either facilitate or limit Glu uptake, influencing its bioavailability and predisposing to neuroinflammation and neurotoxicity. Additionally, we examine the role of gut metabolites and their influence on the blood-brain barrier and neurotransmitter systems involved in mood regulation. The therapeutic potential of microbiome-targeted interventions, such as fecal microbiota transplantation, is also highlighted. While much research has explored the role of Glu in major depressive disorders and other neurological diseases, the contribution of gut microbiota in post-neurological depression remains underexplored. Future research should focus on explaining the mechanisms linking the gut microbiota to neuropsychiatric outcomes, particularly in conditions such as post-stroke depression, post-traumatic brain-injury depression, and epilepsy-associated depression. Systematic reviews and human clinical studies are needed to establish causal relationships and assess the efficacy of microbiome-targeted therapies in improving the neuropsychiatric sequalae after neurological insults.}, } @article {pmid39770958, year = {2024}, author = {Puca, P and Del Gaudio, A and Becherucci, G and Sacchetti, F and Sofo, L and Lopetuso, LR and Papa, A and Cammarota, G and Scaldaferri, F}, title = {Diet and Microbiota Modulation for Chronic Pouchitis: Evidence, Challenges, and Opportunities.}, journal = {Nutrients}, volume = {16}, number = {24}, pages = {}, doi = {10.3390/nu16244337}, pmid = {39770958}, issn = {2072-6643}, mesh = {*Pouchitis/therapy/microbiology ; Humans ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Chronic Disease ; *Probiotics/therapeutic use ; *Prebiotics/administration & dosage ; Colitis, Ulcerative/microbiology/therapy ; Proctocolectomy, Restorative/adverse effects ; Diet/methods ; Diet, Mediterranean ; }, abstract = {Chronic pouchitis occurs in about 50% of patients undergoing a restorative proctocolectomy for ulcerative colitis. This affection represents a significant therapeutic challenge, particularly for symptomatic patients who do not respond to antibiotic treatments and biologic therapies. Several dietary approaches, including low FODMAP diets and the Mediterranean diet, have shown promising results in improving symptoms and disease burden. The rationale for dietary intervention lies in the reduction in inflammation and modulation of gut microbiota. However, conflicting results and methodological heterogeneity jeopardize the transition of these approaches from the field of research to clinical practice. Together with a nutritional approach, innovative methods of microbiota modulation, including probiotics and fecal microbiota transplantation, are emerging as safe and effective strategies in managing chronic pouchitis. This narrative review analyzes recent advancements in nutritional therapies and microbiota modulation as innovative and complementary approaches for managing chronic pouchitis. After examining microbiota modulation strategies, specifically the effectiveness of probiotics, prebiotics, and fecal microbiota transplantation in restoring microbial diversity and their potential role in alleviating symptoms, the review assesses the available clinical evidence concerning dietary interventions and their impact on gut microbiota. A comprehensive understanding of interventions aimed at modulating the microbiota is crucial for enhancing the effectiveness of conventional therapies. Such strategies may lead to significant improvements in patients' quality of life and their perception of the disease. However, the variability in microbiota composition, the use of restrictive diets, and the lack of standardized methods for evaluating these interventions remain significant challenges. Future research is essential to improve our understanding of the underlying mechanisms and optimize clinical application.}, } @article {pmid39770742, year = {2024}, author = {Park, SH and Lee, JH and Lee, S and Shin, J and Cha, B and Hong, JT and Kwon, KS}, title = {Factors for Treatment Failure After Fecal Microbiota Transplantation in Clostridioides difficile Infection.}, journal = {Microorganisms}, volume = {12}, number = {12}, pages = {}, doi = {10.3390/microorganisms12122539}, pmid = {39770742}, issn = {2076-2607}, support = {2023AR05//Seoul Clinical Laboratories/ ; }, abstract = {Recently, fecal microbiota transplantation (FMT) has been introduced as an effective treatment option for Clostridioides difficile infection (CDI). However, the risk factors associated with FMT treatment failure have not been well demonstrated. Therefore, we aimed to investigate the risk factors of treatment failure or recurrence after FMT for CDI. This retrospective study included 124 patients with CDI who underwent FMT at Inha University Hospital between November 2017 and August 2021 and were followed up for 8 weeks after FMT for symptoms of CDI. FMT failure was defined as diarrhea recurrence or a positive stool test. We assessed the risk factors for treatment failure, including comorbidities, antibiotic use pre- and post-FMT, and the number of CDI episodes before FMT. Ninety-three patients (75%) experienced symptom improvement <7 days after FMT, while treatment failure occurred in 40 patients (32.3%). Multivariate analysis revealed that males had a lower symptom improvement rate <7 days after FMT (p = 0.049). Patients using antibiotics after FMT showed a higher rate of recurrence or treatment failure in <8 weeks (p = 0.032). Patients requiring antibiotics after FMT should be considered at higher risk of treatment failure. Careful antibiotic stewardship, particularly minimizing non-essential antibiotic use before and after FMT, may significantly enhance treatment outcomes. Further large-scale prospective studies are warranted to confirm these findings and develop targeted antibiotic management protocols for improving the efficacy of FMT in CDI treatment.}, } @article {pmid39770703, year = {2024}, author = {Islam, MZ and Jozipovic, D and Lopez, PA and Krych, L and Correia, BSB and Bertram, HC and Hansen, AK and Hansen, CHF}, title = {Wild-Mouse-Derived Gut Microbiome Transplantation in Laboratory Mice Partly Alleviates House-Dust-Mite-Induced Allergic Airway Inflammation.}, journal = {Microorganisms}, volume = {12}, number = {12}, pages = {}, doi = {10.3390/microorganisms12122499}, pmid = {39770703}, issn = {2076-2607}, support = {R288-2018-1123//Lundbeck Foundation/ ; N/A//Sigrid Rigmor Morans Mindefond/ ; }, abstract = {Laboratory mice are instrumental for preclinical research but there are serious concerns that the use of a clean standardized environment for specific-pathogen-free (SPF) mice results in poor bench-to-bedside translation due to their immature immune system. The aim of the present study was to test the importance of the gut microbiota in wild vs. SPF mice for evaluating host immune responses in a house-dust-mite-induced allergic airway inflammation model without the influence of pathogens. The wild mouse microbiome reduced histopathological changes and TNF-α in the lungs and serum when transplanted to microbiota-depleted mice compared to mice transplanted with the microbiome from SPF mice. Moreover, the colonic gene expression of Gata3 was significantly lower in the wild microbiome-associated mice, whereas Muc1 was more highly expressed in both the ileum and colon. Intestinal microbiome and metabolomic analyses revealed distinct profiles associated with the wild-derived microbiome. The wild-mouse microbiome thus partly reduced sensitivity to house-dust-mite-induced allergic airway inflammation compared to the SPF mouse microbiome, and preclinical studies using this model should consider using both 'dirty' rewilded and SPF mice for testing new therapeutic compounds due to the significant effects of their respective microbiomes and derived metabolites on host immune responses.}, } @article {pmid39770634, year = {2024}, author = {Chun, M and Tun, KM and Vongsavath, T and Verma, R and Batra, K and Limsui, D and Jenkins, E}, title = {Fecal Microbiota Transplantation for Chronic Pouchitis: A Systematic Review and Meta-Analysis.}, journal = {Microorganisms}, volume = {12}, number = {12}, pages = {}, doi = {10.3390/microorganisms12122430}, pmid = {39770634}, issn = {2076-2607}, abstract = {Pouchitis is a common complication after ileal-pouch anal anastomosis in patients with medically refractory ulcerative colitis. There has been a lack of high-level evidence focusing on the safety and efficacy outcomes of fecal microbiota transplantation (FMT). We aim to evaluate outcomes and complications of fecal microbiota transplantation (FMT) for chronic pouchitis. Databases were systematically searched to retrieve English-only, original studies, published from inception to 31 March 2024, investigating chronic pouchitis only. Primary outcomes included overall remission, clinical response, remission, relapse, and complications. Seven studies with 94 patients were included. The pooled overall remission rate was 15% (95% CI: 0-29%, p < 0.001), the clinical response rate was 33% (95% CI: 19-46%, p = 0.14), the clinical remission rate was 14% (95% CI: 19-46%, p < 0.001), and the clinical relapse rate was 36% (95% CI: 16-55%, p = 0.11). The pooled proportion of patients with mild adverse events after FMT treatment was 39% (95% CI: 6-71%, p < 0.001). No severe adverse events or deaths were reported. Although FMT is an effective treatment for chronic pouchitis, there is still a high rate of mild adverse events. High-level evidence for FMT is still sparse, limiting recommendations for clinical use.}, } @article {pmid39767682, year = {2024}, author = {Farhadi Rad, H and Tahmasebi, H and Javani, S and Hemati, M and Zakerhamidi, D and Hosseini, M and Alibabaei, F and Banihashemian, SZ and Oksenych, V and Eslami, M}, title = {Microbiota and Cytokine Modulation: Innovations in Enhancing Anticancer Immunity and Personalized Cancer Therapies.}, journal = {Biomedicines}, volume = {12}, number = {12}, pages = {}, doi = {10.3390/biomedicines12122776}, pmid = {39767682}, issn = {2227-9059}, abstract = {The gut microbiota plays a crucial role in modulating anticancer immunity, significantly impacting the effectiveness of various cancer therapies, including immunotherapy, chemotherapy, and radiotherapy. Its impact on the development of cancer is complex; certain bacteria, like Fusobacterium nucleatum and Bacteroides fragilis, can stimulate the growth of tumors by causing immunological evasion and inflammation, while advantageous strains, like Faecalibaculum rodentium, have the ability to suppress tumors by modifying immune responses. Cytokine activity and immune system regulation are intimately related. Cytokines including TGF-β, IL-6, and IL-10 promote tumor development by inhibiting efficient immune surveillance. The gut microbiome exhibits a delicate balance between pro- and anti-tumorigenic factors, as evidenced by the enhancement of anti-tumor immunity by cytokines such as IL-12 and IFN-γ. Improved immunotherapy responses are linked to a diverse microbiota, which is correlated with higher tumor infiltration and cytotoxic T-cell activation. Because microbial metabolites, especially short-chain fatty acids, affect cytokine expression and immune cell activation inside the tumor microenvironment, this link highlights the need to maintain microbial balance for optimal treatment effects. Additionally, through stimulating T-cell activation, bacteria like Lactobacillus rhamnosus and Bifidobacterium bifidum increase cytokine production and improve the efficacy of immune checkpoint inhibitors (ICIs). An option for overcoming ICI resistance is fecal microbiota transplantation (FMT), since research suggests that it improves melanoma outcomes by increasing CD8+ T-cell activation. This complex interaction provides an opportunity for novel cancer therapies by highlighting the possibility of microbiome modification as a therapeutic approach in personalized oncology approaches.}, } @article {pmid39767577, year = {2024}, author = {Munteanu, C and Onose, G and Rotariu, M and Poștaru, M and Turnea, M and Galaction, AI}, title = {Role of Microbiota-Derived Hydrogen Sulfide (H2S) in Modulating the Gut-Brain Axis: Implications for Alzheimer's and Parkinson's Disease Pathogenesis.}, journal = {Biomedicines}, volume = {12}, number = {12}, pages = {}, doi = {10.3390/biomedicines12122670}, pmid = {39767577}, issn = {2227-9059}, support = {CNFIS - FDI - 2024 - F - 0099//Supporting the institutional capacity for research and innovation through transdisciplinary biotechnologies (InovBiotech)/ ; }, abstract = {Microbiota-derived hydrogen sulfide (H2S) plays a crucial role in modulating the gut-brain axis, with significant implications for neurodegenerative diseases such as Alzheimer's and Parkinson's. H2S is produced by sulfate-reducing bacteria in the gut and acts as a critical signaling molecule influencing brain health via various pathways, including regulating inflammation, oxidative stress, and immune responses. H2S maintains gut barrier integrity at physiological levels and prevents systemic inflammation, which could impact neuroinflammation. However, as H2S has a dual role or a Janus face, excessive H2S production, often resulting from gut dysbiosis, can compromise the intestinal barrier and exacerbate neurodegenerative processes by promoting neuroinflammation and glial cell dysfunction. This imbalance is linked to the early pathogenesis of Alzheimer's and Parkinson's diseases, where the overproduction of H2S exacerbates beta-amyloid deposition, tau hyperphosphorylation, and alpha-synuclein aggregation, driving neuroinflammatory responses and neuronal damage. Targeting gut microbiota to restore H2S homeostasis through dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation presents a promising therapeutic approach. By rebalancing the microbiota-derived H2S, these strategies may mitigate neurodegeneration and offer novel treatments for Alzheimer's and Parkinson's diseases, underscoring the critical role of the gut-brain axis in maintaining central nervous system health.}, } @article {pmid39766423, year = {2024}, author = {Menezes, AA and Shah, ZA}, title = {A Review of the Consequences of Gut Microbiota in Neurodegenerative Disorders and Aging.}, journal = {Brain sciences}, volume = {14}, number = {12}, pages = {}, doi = {10.3390/brainsci14121224}, pmid = {39766423}, issn = {2076-3425}, support = {R01NS112642/NS/NINDS NIH HHS/United States ; }, abstract = {Age-associated alterations in the brain lead to cognitive deterioration and neurodegenerative disorders (NDDs). This review with a particular focus on Alzheimer's disease (AD), emphasizes the burgeoning significance of the gut microbiota (GMB) in neuroinflammation and its impact on the gut-brain axis (GBA), a communication conduit between the gut and the central nervous system (CNS). Changes in the gut microbiome, including diminished microbial diversity and the prevalence of pro-inflammatory bacteria, are associated with AD pathogenesis. Promising therapies, such as fecal microbiota transplantation (FMT), probiotics, and prebiotics, may restore gut health and enhance cognitive performance. Clinical data remain insufficient, necessitating further research to elucidate causes, enhance therapy, and consider individual variances. This integrative approach may yield innovative therapies aimed at the GMB to improve cognitive function and brain health in older people.}, } @article {pmid39766170, year = {2024}, author = {Ciernikova, S and Sevcikova, A and Novisedlakova, M and Mego, M}, title = {Insights into the Relationship Between the Gut Microbiome and Immune Checkpoint Inhibitors in Solid Tumors.}, journal = {Cancers}, volume = {16}, number = {24}, pages = {}, doi = {10.3390/cancers16244271}, pmid = {39766170}, issn = {2072-6694}, support = {1/0071/24//Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; 2/0069/22//Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; }, abstract = {Immunotherapy with immune checkpoint inhibitors represents a revolutionary approach to the treatment of solid tumors, including malignant melanoma, lung cancer, and gastrointestinal malignancies. Anti-CTLA-4 and anti-PD-1/PDL-1 therapies provide prolonged survival for cancer patients, but their efficacy and safety are highly variable. This review focuses on the crucial role of the gut microbiome in modulating the efficacy and toxicity of immune checkpoint blockade. Studies suggest that the composition of the gut microbiome may influence the response to immunotherapy, with specific bacterial strains able to promote an anti-tumor immune response. On the other hand, dysbiosis may increase the risk of adverse effects, such as immune-mediated colitis. Interventions aimed at modulating the microbiome, including the use of probiotics, prebiotics, fecal microbial transplantation, or dietary modifications, represent promising strategies to increase treatment efficacy and reduce toxicity. The combination of immunotherapy with the microbiome-based strategy opens up new possibilities for personalized treatment. In addition, factors such as physical activity and nutritional supplementation may indirectly influence the gut ecosystem and consequently improve treatment outcomes in refractory patients, leading to enhanced patient responses and prolonged survival.}, } @article {pmid39766032, year = {2024}, author = {Altrawy, A and Khalifa, MM and Abdelmaksoud, A and Khaled, Y and Saleh, ZM and Sobhy, H and Abdel-Ghany, S and Alqosaibi, A and Al-Muhanna, A and Almulhim, J and El-Hashash, A and Sabit, H and Arneth, B}, title = {Metabolites in the Dance: Deciphering Gut-Microbiota-Mediated Metabolic Reprogramming of the Breast Tumor Microenvironment.}, journal = {Cancers}, volume = {16}, number = {24}, pages = {}, doi = {10.3390/cancers16244132}, pmid = {39766032}, issn = {2072-6694}, abstract = {Breast cancer (BC), a major cause of death among women worldwide, has traditionally been linked to genetic and environmental factors. However, emerging research highlights the gut microbiome's significant role in shaping BC development, progression, and treatment outcomes. This review explores the intricate relationship between the gut microbiota and the breast tumor microenvironment, emphasizing how these microbes influence immune responses, inflammation, and metabolic pathways. Certain bacterial species in the gut either contribute to or hinder BC progression by producing metabolites that affect hormone metabolism, immune system pathways, and cellular signaling. An imbalance in gut bacteria, known as dysbiosis, has been associated with a heightened risk of BC, with metabolites like short-chain fatty acids (SCFAs) and enzymes such as β-glucuronidase playing key roles in this process. Additionally, the gut microbiota can impact the effectiveness of chemotherapy, as certain bacteria can degrade drugs like gemcitabine and irinotecan, leading to reduced treatment efficacy. Understanding the complex interactions between gut bacteria and BC may pave the way for innovative treatment approaches, including personalized microbiome-targeted therapies, such as probiotics and fecal microbiota transplants, offering new hope for more effective prevention, diagnosis, and treatment of BC.}, } @article {pmid39765038, year = {2024}, author = {Wang, C and Peng, M and Gao, Z and Fu, F and Li, G and Su, D and Huang, L and Guo, J and Shan, Y}, title = {Citrus aurantium 'Changshan-huyou' physiological premature fruit drop: A promising prebiotic to tackle obesity.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {136}, number = {}, pages = {156347}, doi = {10.1016/j.phymed.2024.156347}, pmid = {39765038}, issn = {1618-095X}, abstract = {BACKGROUND: Presently, the mitigation and governance of obesity have surfaced as significant public health dilemmas on a global scale. A wealth of studies indicated that the host gut microbiota is instrumental in regulating the interplay between high-fat diet (HFD) intake and the pathogenesis of obesity. Physiological premature fruit drop, a major byproduct of citrus, is rich in a variety of bioactive constituents, yet its potential has remained underutilized for an extended period.

PURPOSE: The objective of this investigation is to examine the chemical constituents of Citrus aurantium'Changshan-huyou' premature fruit drop (HYFD) and investigate its anti-obesity effects, elucidating its potential pathways.

METHODS: Volatile compounds and flavonoids in HYFD were analyzed using chromatographic and mass spectrometric techniques. Furthermore, this study utilized biochemical assays and histopathological examinations to evaluate the effects of HYFD on HFD-fed mice. The impact of HYFD on the gut microbiota of the mice was examined through 16S rRNA gene sequencing, and fecal microbiota transplantation was employed to validate the role of the gut microbial community in host obesity prevention. Concurrently, transcriptome was employed to identify differentially expressed genes, providing further insights into the molecular mechanisms through which HYFD manifests its anti-obesity effects.

RESULTS: Our findings demonstrated that HYFD supplementation significantly alleviated adiposity and ameliorated the dysbiosis of gut microbiota in HFD-induced mice. HYFD rectified the HFD-induced gut microbiota dysregulation, enhanced the presence of beneficial microbial taxa linked to lipid metabolism, including Parabacteroides and Alistipes, and elevated concentrations of the anti-obesity short-chain fatty acids, comprising caproic acid and isocaproic acid. Additionally, transcriptomic analyses confirmed that HYFD prevented obesity in mice by enhancing fatty acid catabolism via the activation of the AMPK/PPARα/CPT1a signaling pathway.

CONCLUSION: Our results provided novel insights into the mechanism of citrus physiological premature fruit drop and its potential role in preventing obesity, while sparking greater interest in leveraging more biomass waste.}, } @article {pmid39764653, year = {2024}, author = {Mao, Y and Huang, Y and Zhang, W and Liang, H and Liu, F and Luo, Q and Xu, C and Qin, Y and Liu, J and Tang, S and Liu, H and Ge, X}, title = {FMT reduces systemic inflammatory response in severe acute pancreatitis by increasing the abundance of intestinal Bifidobacteria and fecal bacteria.}, journal = {Biomolecules & biomedicine}, volume = {}, number = {}, pages = {}, doi = {10.17305/bb.2024.11445}, pmid = {39764653}, issn = {2831-090X}, abstract = {Severe acute pancreatitis (SAP) is one of the leading causes of hospital admissions for gastrointestinal diseases, with a rising incidence worldwide. Intestinal microbiota dysbiosis caused by SAP exacerbates systemic inflammatory response syndrome and organ dysfunction. Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic option for gastrointestinal diseases. In this study, fecal samples from healthy, control, and FMT-treated groups were analyzed using 16S rRNA sequencing to assess microbiome abundance and diversity. Composition and functional prediction analyses were conducted to explore the mechanisms underlying FMT in SAP. FMT significantly improved clinical parameters in SAP patients, including leukocyte count, C-reactive protein (CRP), neutrophil granulocyte count, lactate dehydrogenase (LDH), and calcitonin (P < 0.05). Organ failure rates significantly increased in the control group but decreased in the FMT group after treatment (P < 0.05). Fecal microbiota sequencing revealed that FMT significantly upregulated the abundance of Bifidobacterium longum among all SAP patients (P < 0.05). Receiver operating characteristic (ROC) curve analysis indicated that Bifidobacterium longum might play a critical role in the efficacy of FMT, with an area under the curve (AUC) value of 0.84. Additionally, there was a negative correlation between Bifidobacterium longum abundance and procalcitonin (PCT) levels, as well as a negative correlation between Escherichia coli abundance and both CT and Ca values (P < 0.05). The relative abundances of Bifidobacterium longum and Escherichia coli were significantly higher in the FMT group compared to the Bifidobacterium triple viable group (P < 0.05). In conclusion, this research supports FMT as a safe and effective intervention for treating SAP patients.}, } @article {pmid39764615, year = {2025}, author = {Harris, SC and Bajaj, JS}, title = {Interaction of the Gut-Liver-Brain Axis and the sterolbiome with sexual dysfunction in patients with cirrhosis.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2446390}, doi = {10.1080/19490976.2024.2446390}, pmid = {39764615}, issn = {1949-0984}, mesh = {Humans ; *Liver Cirrhosis/complications/metabolism ; *Gastrointestinal Microbiome ; *Brain-Gut Axis/physiology ; *Sexual Dysfunction, Physiological/metabolism/etiology/physiopathology ; *Liver/metabolism ; Sterols/metabolism ; Brain/metabolism ; Gonadal Steroid Hormones/metabolism ; Animals ; Quality of Life ; }, abstract = {There is a complex interplay between the gut microbes, liver, and central nervous system, a gut-liver-brain axis, where the brain impacts intestinal and hepatic function while the gut and liver can impact cognition and mental status. Dysregulation of this axis can be seen in numerous diseases. Hepatic encephalopathy, a consequence of cirrhosis, is perhaps the best studied perturbation of this system. However, patients with cirrhosis have been shown to have increased incidence of other disorders of mental health which may be otherwise less clinically identifiable. Sexual dysfunction affects a large proportion of patients with cirrhosis and is associated with decreased quality of life. Screening for sexual dysfunction in patients with cirrhosis is often overlooked, and even when identified, treatment options are limited, particularly in patients with advanced liver disease. The mechanism by which patients with cirrhosis develop sexual dysfunction is multifactorial, but a key driver of this clinical manifestation is alterations in circulating sex hormones. In patients with cirrhosis, low serum sex hormones have been shown to be associated with higher mortality regardless of MELD score. The gut microbiome has been shown to have an immense metabolic capacity to metabolize steroid hormones. This "sterolbiome" has already been implicated in other disease processes and has been linked to low circulating sex hormones, suggesting a new mechanism by which sex hormones may be altered in disease states where the gut-liver-brain axis is disrupted. The aim of this review is to cover sex hormone changes and sexual dysfunction in cirrhosis, examine the gut microbiome and its metabolic capacity, particularly for steroid hormones, and consider how microbial changes using fecal microbiota transplant could modulate sexual dysfunction.}, } @article {pmid39764447, year = {2024}, author = {Wang, J and Zhuang, P and Lin, B and Zheng, J and Li, H and Tang, W and Ye, W and Chen, X and Zheng, M}, title = {Comparative analysis of gut microbiota in metabolic syndrome and obese children from Southeastern China.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1503302}, pmid = {39764447}, issn = {1664-302X}, abstract = {The prevalence of childhood obesity is rising globally, with some obese children progressing to develop metabolic syndrome (MS). However, the specific differences between these groups remain unclear. To investigate the differences in gut microbiota, we conducted physiological and biochemical assessments, alongside 16S rRNA sequencing, in a cohort of 32 children from Southeastern China, which included 4 normal-weight children, 5 with mild obesity, 9 with moderate obesity, 9 with severe obesity, and 5 with metabolic syndrome. Our results indicated that waist circumference, serum triglycerides, total cholesterol, non-HDL levels, and the prevalence of fatty liver were significantly elevated in both obese and MS children compared to their normal-weight peers, with the MS group exhibiting more pronounced abnormalities. Conversely, HDL levels showed a contrasting trend. Additionally, alpha diversity of gut microbiota increased with weight, while beta diversity analysis revealed significant compositional differences between children with MS and those who were normal weight or obese. At the class and genus levels, we found that the relative abundance of c_Gammaproteobacteria increased with weight, whereas c_Bacteroidia and g_Bacteroides decreased. Notably, g_Faecalibacterium was significantly less abundant in the MS group compared to the other cohorts. LEfSe and functional analyses identified distinct gut microbiota and functional differences between children with MS and those with normal weight or obesity. Furthermore, gavage experiments in mice showed that gut microbiota from obese and MS subjects significantly increased serum triglycerides and cholesterol levels, leading to hepatocellular damage. In contrast, fecal gavage from normal-weight individuals into obese model mice significantly reduced serum triglycerides and the number of degenerative liver cells, as well as the extent of fat accumulation. These findings provide critical insights into the understanding and management of obesity and metabolic syndrome in pediatric populations.}, } @article {pmid39762283, year = {2025}, author = {Feng, C and Wu, Y and Zhang, X and Wang, S and Wang, J and Yang, H}, title = {Maternal milk fat globule membrane enriched gut L. murinus and circulating SCFAs to improve placental efficiency and fetal development in intrauterine growth restricted mice model.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2449095}, doi = {10.1080/19490976.2024.2449095}, pmid = {39762283}, issn = {1949-0984}, mesh = {Animals ; Female ; Pregnancy ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Placenta/metabolism ; *Fetal Growth Retardation/metabolism ; *Glycoproteins/metabolism ; *Fatty Acids, Volatile/metabolism ; *Lipid Droplets/metabolism ; *Glycolipids/metabolism ; *Fetal Development/drug effects ; *Disease Models, Animal ; Lactobacillus ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; }, abstract = {Intrauterine growth restriction (IUGR) caused by placental dysfunctions leads to fetal growth defects. Maternal microbiome and its metabolites have been reported to promote placental development. Milk fat globule membrane (MFGM) is known for its diverse bioactive functions, while the effects of gestational MFGM supplementation on the maternal gut microbiota, placental efficiency, and fetal development remained unclear. In this study, low protein diet-induced IUGR decreased the litter birth weight, fetal birth weight, and the fetal/placental ratio in pregnant mice, while gestational MFGM supplementation restored these impairments. Meanwhile, MFGM supplementation during gestation enriched intestinal Lactobacillus murinus (L. murinus) and increased luminal and circulating short chain fatty acids (SCFAs) in IUGR pregnant mice, which improved placental efficiency and fetal development due to an enhanced antioxidant capacity and a decreased inflammation. In addition, fecal microbiota transplantation (FMT) with MFGM-derived microbiota reprinted the promoted phenotypes of maternal litter characteristics, gut L. murinus enrichment, placental efficiency, and fetal gut development in MFGM-fed pregnant mice, which were also recapitulated by exogenous administration with L. murinus or SCFAs cocktail. Mechanically, MFGM, MFGM-derived microbiota, L. murinus, or SCFAs cocktail activated IUGR-induced depressive phosphorylation of PI3K-Akt signaling in the placenta. Moreover, in vitro placental cells cultivation under amino acid shortage model (AAS) or oxygen-glucose shortage model (OGS) was used to validate that MFGM-derived key microbial and circulating SCFAs cocktails can alleviate placental oxidative stress and inflammation via activating PI3K/Akt signaling. Taken together, gestational MFGM supplementation enriched intestinal L. murinus and circulating SCFAs of IUGR pregnant mice, thereby improving placental efficiency, fetal growth, and intestinal functions of IUGR fetus. Our findings will provide theoretical support for the application of MFGM in the maternal-placental-fetal nutrition to address pregnancy malnutrition-induced IUGR.}, } @article {pmid39762111, year = {2025}, author = {Al-Shakhshir, S and Quraishi, MN and Mullish, B and Patel, A and Vince, A and Rowe, A and Homer, V and Jackson, N and Gyimah, D and Shabir, S and Manzoor, S and Cooney, R and Alrubaiy, L and Quince, C and van Schaik, W and Hares, M and Beggs, AD and Efstathiou, E and Rimmer, P and Weston, C and Iqbal, T and Trivedi, PJ}, title = {FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO): study protocol for a randomised, multicentre, phase IIa, placebo-controlled trial.}, journal = {BMJ open}, volume = {15}, number = {1}, pages = {e095392}, doi = {10.1136/bmjopen-2024-095392}, pmid = {39762111}, issn = {2044-6055}, mesh = {Adult ; Female ; Humans ; Male ; *Cholangitis, Sclerosing/therapy ; Clinical Trials, Phase II as Topic ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; Inflammatory Bowel Diseases/therapy/microbiology ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {INTRODUCTION: Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). The strong association between gut and liver inflammation has driven several pathogenic hypotheses to which the intestinal microbiome is proposed to contribute. Pilot studies of faecal microbiota transplantation (FMT) in PSC and IBD are demonstrated to be safe and associated with increased gut bacterial diversity. However, the longevity of such changes and the impact on markers of disease activity and disease progression have not been studied. The aim of this clinical trial is to determine the effects of repeated FMT as a treatment for PSC-IBD.

METHODS AND ANALYSIS: FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO) is a phase IIa randomised placebo-controlled trial to assess the efficacy and safety of repeated colonic administration of FMT in patients with non-cirrhotic PSC-IBD. Fifty-eight patients will be recruited from six sites across England and randomised in a 1:1 ratio between active FMT or FMT placebo arms. FMT will be manufactured by the University of Birmingham Microbiome Treatment Centre, using stool collected from rigorously screened healthy donors. A total of 8 weekly treatments will be delivered; the first through colonoscopic administration (week 1) and the remaining seven via once-weekly enema (up to week 8). Participants will then be followed on a 12-weekly basis until week 48 from the first treatment visit. The primary efficacy outcome will be to determine the effect of FMT on serum alkaline phosphatase values over time (end of study at 48 weeks). Key secondary outcomes will be to evaluate the impact of FMT on other liver biochemical parameters, PSC risk scores, circulating and imaging markers of liver fibrosis, health-related quality of life measures, IBD activity and the incidence of PSC-related clinical events. Key translational objectives will be to identify mucosal metagenomic, metatranscriptomic, metabolomic and immunological pathways associated with the administration of FMT.

ETHICS AND DISSEMINATION: The protocol was approved by the South Central-Hampshire B Research Ethics Committee (REC 23/SC/0147). Participants will be required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.

TRIAL REGISTRATION NUMBER: The trial was registered at ClinicalTrials.gov on 23 February 2024 (NCT06286709). Weblink: Study Details | FAecal Microbiota Transplantation in primaRy sclerosinG chOlangitis | ClinicalTrials.gov.}, } @article {pmid39761011, year = {2024}, author = {Jain, V and Dalby, MJ and Alexander, EC and Burford, C and Acford-Palmer, H and Serghiou, IR and Teng, NMY and Kiu, R and Gerasimidis, K and Zafeiropoulou, K and Logan, M and Verma, A and Davenport, M and Hall, LJ and Dhawan, A}, title = {Association of gut microbiota and gut metabolites and adverse outcomes in biliary atresia: A longitudinal prospective study.}, journal = {Hepatology communications}, volume = {8}, number = {11}, pages = {}, pmid = {39761011}, issn = {2471-254X}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Biliary Atresia/surgery/microbiology/metabolism ; *Feces/microbiology ; Male ; Female ; Prospective Studies ; Infant ; Longitudinal Studies ; Portoenterostomy, Hepatic ; RNA, Ribosomal, 16S/genetics ; Enterococcus ; Case-Control Studies ; Infant, Newborn ; Bifidobacterium/isolation & purification ; }, abstract = {BACKGROUND: The Kasai portoenterostomy (KPE) aims to re-establish bile flow in biliary atresia (BA); however, BA remains the commonest indication for liver transplantation in pediatrics. Gut microbiota-host interplay is increasingly associated with outcomes in chronic liver disease. This study characterized fecal microbiota and fatty acid metabolites in BA.

METHODS: Fecal samples were prospectively collected in newly diagnosed BA infants (n = 55) before and after KPE. Age-matched healthy control (n = 19) and cholestatic control (n = 21) fecal samples were collected. Fecal 16S rRNA gene amplicon sequencing for gut microbiota and gas chromatography for fecal fatty acids was performed.

RESULTS: Increased abundance of Enterococcus in pre-KPE BA and cholestatic control infants, compared to healthy infants, was demonstrated. At the early post-KPE time points, increased alpha diversity was revealed in BA versus healthy cohorts. A lower relative abundance of Bifidobacterium and increased Enterococcus, Clostridium, Fusobacterium, and Pseudomonas was seen in infants with BA. Fecal acetate was reduced, and fecal butyrate and propionate were elevated in early post-KPE BA infants. Higher post-KPE alpha diversity was associated with nonfavorable clinical outcomes (6-month jaundice and liver transplantation). A higher relative abundance of post-KPE Streptococcus and Fusobacterium and a lower relative abundance of Dorea, Blautia, and Oscillospira were associated with nonfavorable clinical outcomes. Blautia inversely correlated to liver disease severity, and Bifidobacterium inversely correlated to fibrosis biomarkers. Bifidobacterium abundance was significantly lower in infants experiencing cholangitis within 6 months after KPE.

CONCLUSIONS: Increased diversity, enrichment of pathogenic, and depletion of beneficial microbiota early post-KPE are all factors associated with nonfavorable BA outcomes. Manipulation of gut microbiota in the early postsurgical period could provide therapeutic potential.}, } @article {pmid39760535, year = {2025}, author = {Saha, S and Schnabl, B}, title = {Modulating the microbiome in chronic liver diseases- current evidence on the role of fecal microbiota transplantation.}, journal = {Expert review of gastroenterology & hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1080/17474124.2025.2450707}, pmid = {39760535}, issn = {1747-4132}, abstract = {INTRODUCTION: The gut microbiota has a complex relationship with the human host and is key to maintaining health. Disruption of the healthy diverse gut microbial milieu plays an important role in the pathogenesis of several diseases including Clostridioides difficile infection (CDI), inflammatory bowel disease, irritable bowel syndrome, alcohol-related liver disease and metabolic-dysfunction associated steatotic liver disease (MASLD). Fecal microbiota transplantation (FMT) is highly effective in treating CDI, though its utility in other diseases is still being explored.

AREAS COVERED: In this narrative review, we explore the role of gut microbiota in liver diseases, focusing on key changes in the microbial composition and function. We summarize current evidence on the role of FMT, identifying gaps in current research and outlining future directions for investigation. We comprehensively searched PubMed through 15 October 2024 to identify relevant studies.

EXPERT OPINION: While data from available studies shows promise, more research is necessary before we can use FMT for liver diseases. Key areas that require further study are- determining the optimal FMT regimen for each disease, establishing efficacy and safety with larger clinical trials, ensuring safe and equitable access to the FMT product and mechanistic insights into the reasons for success or failure of FMT.}, } @article {pmid39759692, year = {2024}, author = {Muzaffer, M and Masarath, A and Mohammed, F}, title = {Biliary Atresia: A Case Report.}, journal = {Cureus}, volume = {16}, number = {12}, pages = {e75087}, pmid = {39759692}, issn = {2168-8184}, abstract = {Biliary atresia (BA) is a serious hepatobiliary disorder that occurs due to progressive inflammation and scarring obstruction in the bile ducts, posing a threat to life. This condition usually appears in infants, and timely identification is fundamental for a better prognosis. If left untreated, individuals will inevitably experience liver damage and mortality. This case report describes a nine-month-old female infant presenting with jaundice, icteric sclera, yellowish skin, acholic feces, and hepatomegaly. Elevated liver enzymes and a hepatobiliary iminodiacetic acid (HIDA) scan confirmed BA. Histopathological examination revealed fibrosis, cholestatic disease, and an atretic gallbladder. A modified Kasai portoenterostomy (KPE) with Roux-en-Y jejunojejunostomy was performed, and the infant was discharged with supportive care. However, seven months post-Kasai portoenterostomy, the infant presented with persistent jaundice and progressive deterioration of liver function, indicative of a failed Kasai procedure. Consequently, she was scheduled to undergo liver transplantation (LT) as a definitive treatment. BA is a rare disorder that is observed across nearly all ethnic groups, though the incidence rates vary significantly. This case highlights the efficacy of liver transplantation in treating failed Kasai procedures and demonstrates the potential for enhanced outcomes in infants with end-stage liver disease.}, } @article {pmid39758967, year = {2025}, author = {Thorndal, C and Kragsnaes, MS and Nilsson, AC and Holm, DK and dePont Christensen, R and Ellingsen, T and Kjeldsen, J and Bjørsum-Meyer, T}, title = {Safety and efficacy of faecal microbiota transplantation in patients with acute uncomplicated diverticulitis: study protocol for a randomised placebo-controlled trial.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848241309868}, pmid = {39758967}, issn = {1756-283X}, abstract = {BACKGROUND: Little is known about the involvement of gut microbiota in the disease course of diverticulitis and the potential benefits of manipulating the gut milieu. We propose to conduct a randomised placebo-controlled feasibility trial of faecal microbiota transplantation (FMT) given as capsules to patients with acute uncomplicated diverticulitis.

OBJECTIVES: The objective is primarily to investigate the feasibility of clinical safety, explore efficacy associated with FMT in this patient population, and examine changes in patient-reported quality of life and the composition and function of the gut microbiota.

DESIGN: Study protocol for a randomised placebo-controlled trial.

METHODS AND ANALYSIS: Participants with acute, uncomplicated diverticulitis, as confirmed by computed tomography (CT) scan, will be recruited from Odense University Hospital (Denmark) and randomly assigned to either the intervention group or the control group. The intervention group will consist of 20 patients who receive encapsulated FMT. The control group will also consist of 20 patients, receiving placebo capsules. Primary safety endpoint: Patient safety is monitored by (a) the number of re-admissions and (b) the number of adverse events within 3 months of FMT/placebo; Primary efficacy endpoint: Reduction in the proportion of patients treated with antibiotics within 3 months following FMT/placebo; Secondary outcome: Change from baseline to 3 months in the GI-QLI questionnaire. Results will be analysed using an intention-to-treat approach. Adverse events or unintended consequences will be reported.

ETHICS AND DISCUSSION: This is the first study to investigate the safety and efficacy of FMT in patients with acute uncomplicated diverticulitis. The project has the potential to broaden the knowledge and literature on the role of the intestinal microbiota in diverticulitis, and we believe it will elevate our understanding of cause and effect.

TRIAL REGISTRATION: Informed consent is obtained from all participants. The study is approved by the regional ethics committee (ref. S-20230023) and the Danish Data Protection Agency (ref. 24/2435). The trial was registered on clinicaltrials.gov (NCT06254625) on 10th February 2024.}, } @article {pmid39758313, year = {2024}, author = {Liu, B and Zhang, Z and Zhao, J and Li, X and Wang, Y and Liu, L and Qiao, W and Chen, L}, title = {Lactiplantibacillus plantarum HM-P2 influences gestational gut microbiome and microbial metabolism.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1489359}, pmid = {39758313}, issn = {2296-861X}, abstract = {INTRODUCTION: Human milk-derived probiotics are beneficial bacteria that provide gestational health benefits, for both pregnant women and their offspring. The study aims to investigate whether the administration of human milk-derived probiotic L. plantarum HM-P2 could effectively influence gestational health.

METHODS: The gestational humanized microbiome model was built by fecal microbiome transplant from gestational women into germ-free (GF) mice.

RESULTS: HM-P2 was successfully planted and increased the top crypt depth of the colon, and microbes such as L. reuteri, Anaerofilum sp. An201, and Gemmiger were up-regulated in the HM-P2 group throughout gestation. HM-P2 significantly promoted the contents of intestinal caproic acid, bile acids, and tryptophan catabolites such as serotonin. Gut microbes were associated with these bile acids and tryptophans.

DISCUSSION: HM-P2 could modulate the microbial community and microbial metabolites in gestational humanized GF mice. This probiotic strain could be a potential gestational dietary supplement with health benefits.}, } @article {pmid39757809, year = {2025}, author = {Huang, ST and Hu, YH and Gao, YC and Zhou, DD and Chen, MY and Wang, L and Song, JY and Zhou, HH and Zhang, W and Huang, WH}, title = {Hypoglycemic Effect of Ginsenoside Compound K Mediated by N-Acetylserotonin Derived From Gut Microbiota.}, journal = {Phytotherapy research : PTR}, volume = {}, number = {}, pages = {}, doi = {10.1002/ptr.8385}, pmid = {39757809}, issn = {1099-1573}, support = {82074000//National Natural Science Foundation of China/ ; 82073945//National Natural Science Foundation of China/ ; 81874329//National Natural Science Foundation of China/ ; 2023YFC3405200//National Key Research and Development Program of China/ ; 2021YFA1301200//National Key Research and Development Program of China/ ; 2024JJ5585//Hunan Provincial Natural Science Foundation of China/ ; 2023SK2083//Scientific Research Project of Furong Laboratory of Central South University/ ; }, abstract = {Ginsenoside compound K (GCK) has been proved to have great hypoglycemic effect pertinent to gut microbiota. However, the improvement of high-fat-diet (HFD)-induced type 2 diabetes (T2D) as well as the mechanism of GCK mediated by gut microbiota is not well-known. This study aimed to investigate the hypoglycemic effects and mechanism of GCK on a HFD-induced diabetic mouse model. HFD-induced pseudo-germ free (GF) T2D mice model and fecal microbiota transplantation (FMT) experiments were performed to clarify the role of gut microbiota in the hypoglycemic effect of GCK. Differential metabolites were screened by untargeted metabolomics analysis and their functions were verified by suppling to T2D mice. The level of glucagon-like peptide-1 (GLP-1) in plasma was detected by ELISA analysis to explore the potential hypoglycemic mechanism of GCK. The results showed GCK alleviated metabolic disorders and altered gut microbiota in HFD-induced diabetic mice, which was transmitted to pseudo-GF diabetic mice via FMT experiment to reproduce the hypoglycemic effect. Non-targeted metabolites analysis on cecal content samples indicated that N-acetylserotonin (NAS) was markedly increased after GCK treatment. Moreover, gavage with NAS improved insulin sensitivity and increased the secretion of GLP-1 in HFD mice. Our study showed that GCK had hypoglycemic effect through modifying gut microbiota profiling.}, } @article {pmid39757609, year = {2024}, author = {Bhat, MM and Hussain, MS and Bisht, AS and Agrawal, M and Sultana, A and Khurrana, N and Kumar, R}, title = {Frontiers in Pulmonary Hypertension: A Comprehensive Insight of Etiological Advances.}, journal = {Current reviews in clinical and experimental pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/0127724328325178241210174545}, pmid = {39757609}, issn = {2772-4336}, abstract = {Pulmonary hypertension (PH) is a severe, progressive disorder characterized by elevated pulmonary arterial pressure, leading to right ventricular failure and increased mortality. Despite advancements in management, the median survival for PH patients remains 5-7 years, with an inhospital mortality rate of approximately 6%. The core pathological feature of PH is pulmonary vascular remodeling (PVR), a multifactorial process involving endothelial dysfunction, inflammation, and aberrant immune responses. While current therapies target endothelial dysfunction, they fall short of preventing PVR or halting disease progression. Emerging research highlights the potential of immune-inflammatory pathways, oxygen-sensing mechanisms, and gut microbiota modulation as therapeutic targets. Integrating nutritional strategies, probiotics, and fecal microbiota transplantation (FMT) as adjunctive therapies also shows promise. These factors may collectively influence PVR, offering novel insights into therapeutic avenues for PH management in the future.}, } @article {pmid39756658, year = {2025}, author = {Chen, Q and Liu, F and Zhang, G and Qu, Q and Chen, Y and Li, M and Huang, Q and Fu, H and Zhu, X and He, Y and Huang, X and Zhang, X}, title = {Progesterone Regulates Gut Microbiota Mediating Bone Marrow MSCs Injury in ITP Patients during Pregnancy.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtha.2024.12.027}, pmid = {39756658}, issn = {1538-7836}, abstract = {BACKGROUND: Immune thrombocytopenia during pregnancy (PITP) is the most common cause of platelet reduction in early and mid-pregnancy. However, the pathogenesis of PITP is still unclear.

OBJECTIVES: To determine the characteristics of bone marrow mesenchymal stem cells (BM-MSCs) in PITP patients and to explore the associations between metabolites, the gut microbiota, and BM-MSCs in PITP.

METHODS: The characteristics of BM-MSCs were detected through in vitro and in vivo experiments. Non-targeted metabolomics was used to screen metabolites. The features of the gut microbiota were analyzed by 16S rDNA sequencing. PITP and a fecal microbiota transplantation (FMT) mouse model were established to explore the associations between metabolites, the gut microbiota, and BM-MSCs.

RESULTS: BM-MSCs from PITP patients had significant senescence and apoptosis, as well as impaired immunoregulatory function. Metabolomic analysis indicated that progesterone was the most significant specific metabolite in PITP patients. In vivo studies showed that progesterone mediated the MSCs injury. Further analysis of the gut microbiota and FMT experiments revealed that progesterone mediated BM-MSCs injury by regulating the the composition of the gut microbiota in the PITP. RNA-seq analysis of BM-MSCs from FMT mice revealed abnormal expression of genes related to cell aging and the NOD-like receptor signaling pathway.

CONCLUSION: In conclusion, BM-MSCs in the PITP were significantly impaired, which was associated with increased progesterone and changes in the gut microbiota regulated by progesterone. Intervening with the gut microbiota may become a new treatment for PITP.}, } @article {pmid39754054, year = {2025}, author = {Azhar Ud Din, M and Lin, Y and Lyu, C and Yi, C and Fang, A and Mao, F}, title = {Advancing therapeutic strategies for graft-versus-host disease by targeting gut microbiome dynamics in allogeneic hematopoietic stem cell transplantation: current evidence and future directions.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {31}, number = {1}, pages = {2}, pmid = {39754054}, issn = {1528-3658}, mesh = {*Graft vs Host Disease/etiology/microbiology ; Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Gastrointestinal Microbiome ; *Transplantation, Homologous ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; }, abstract = {Hematopoietic stem cell transplantation (HSCT) is a highly effective therapy for malignant blood illnesses that pose a high risk, as well as diseases that are at risk due to other variables, such as genetics. However, the prevalence of graft-versus-host disease (GVHD) has impeded its widespread use. Ensuring the stability of microbial varieties and associated metabolites is crucial for supporting metabolic processes, preventing pathogen intrusion, and modulating the immune system. Consequently, it significantly affects the overall well-being and susceptibility of the host to disease. Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) may experience a disruption in the balance between the immune system and gut bacteria when treated with medicines and foreign cells. This can lead to secondary intestinal inflammation and GVHD. Thus, GM is both a reliable indicator of post-transplant mortality and a means of enhancing GVHD prevention and treatment after allo-HSCT. This can be achieved through various strategies, including nutritional support, probiotics, selective use of antibiotics, and fecal microbiota transplantation (FMT) to target gut microbes. This review examines research advancements and the practical use of intestinal bacteria in GVHD following allo-HSCT. These findings may offer novel insights into the prevention and treatment of GVHD after allo-HSCT.}, } @article {pmid39747695, year = {2025}, author = {Wang, X and Fang, Y and Liang, W and Cai, Y and Wong, CC and Wang, J and Wang, N and Lau, HC and Jiao, Y and Zhou, X and Ye, L and Mo, M and Yang, T and Fan, M and Song, L and Zhou, H and Zhao, Q and Chu, ES and Liang, M and Liu, W and Liu, X and Zhang, S and Shang, H and Wei, H and Li, X and Xu, L and Liao, B and Sung, JJY and Kuang, M and Yu, J}, title = {Gut-liver translocation of pathogen Klebsiella pneumoniae promotes hepatocellular carcinoma in mice.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, pmid = {39747695}, issn = {2058-5276}, support = {82173191//National Science Foundation of China | National Natural Science Foundation of China-Yunnan Joint Fund (NSFC-Yunnan Joint Fund)/ ; }, abstract = {Hepatocellular carcinoma (HCC) is accompanied by an altered gut microbiota but whether the latter contributes to carcinogenesis is unclear. Here we show that faecal microbiota transplantation (FMT) using stool samples from patients with HCC spontaneously initiate liver inflammation, fibrosis and dysplasia in wild-type mice, and accelerate disease progression in a mouse model of HCC. We find that HCC-FMT results in gut barrier injury and translocation of live bacteria to the liver. Metagenomic analyses and bacterial culture of liver tissues reveal enrichment of the gut pathogen Klebsiella pneumoniae in patients with HCC and mice transplanted with the HCC microbiota. Moreover, K. pneumoniae monocolonization recapitulates the effect of HCC-FMT in promoting liver inflammation and hepatocarcinogenesis. Mechanistically, K. pneumoniae surface protein PBP1B interacts with and activates TLR4 on HCC cells, leading to increased cell proliferation and activation of oncogenic signalling. Targeting gut colonization using K. oxytoca or TLR4 inhibition represses K. pneumoniae-induced HCC progression. These findings indicate a role for an altered gut microbiota in hepatocarcinogenesis.}, } @article {pmid39746875, year = {2025}, author = {Faith, JJ}, title = {Assessing live microbial therapeutic transmission.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2447836}, doi = {10.1080/19490976.2024.2447836}, pmid = {39746875}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Clostridium Infections/microbiology/therapy/drug therapy ; *Clostridioides difficile/drug effects/physiology/genetics ; *Gastrointestinal Microbiome ; Feces/microbiology ; Animals ; }, abstract = {The development of fecal microbiota transplantation and defined live biotherapeutic products for the treatment of human disease has been an empirically driven process yielding a notable success of approved drugs for the treatment of recurrent Clostridioides difficile infection. Assessing the potential of this therapeutic modality in other indications with mixed clinical results would benefit from consistent quantitative frameworks to characterize drug potency and composition and to assess the impact of dose and composition on the frequency and duration of strain engraftment. Monitoring these drug properties and engraftment outcomes would help identify minimally sufficient sets of microbial strains to treat disease and provide insights into the intersection between microbial function and host physiology. Broad and correct usage of strain detection methods is essential to this advancement. This article describes strain detection approaches, where they are best applied, what data they require, and clinical trial designs that are best suited to their application.}, } @article {pmid39746695, year = {2024}, author = {He, H and Zhang, JP and Wei, ZJ and Lu, Y and Zhao, YL and Sun, RJ}, title = {[Role of human herpesvirus infection in refractory gastrointestinal graft-versus-host-disease after hematopoietic stem cell transplantation and the diagnosis and treatment thereof].}, journal = {Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi}, volume = {45}, number = {11}, pages = {1016-1021}, doi = {10.3760/cma.j.cn121090-20240906-00339}, pmid = {39746695}, issn = {0253-2727}, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Male ; Female ; Adult ; Middle Aged ; *Graft vs Host Disease/diagnosis/etiology ; Retrospective Studies ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Herpesviridae Infections/diagnosis ; Transplantation, Homologous ; Cytomegalovirus/isolation & purification ; Herpesvirus 6, Human/isolation & purification ; }, abstract = {Objective: This study aimed to investigate the role of human herpesvirus (HHV) infection in refractory intestinal graft-versus-host disease (GI-GVHD) after hematopoietic stem cell transplantation (HSCT) and its diagnosis and treatment. Methods: This study retrospectively analyzed patients presenting with refractory GI-GVHD after allogeneic HSCT (allo-HSCT) with concomitant colonoscopy and mucosal biopsy at Lu Daopei Hospital, Yanda, Hebei, from March 2022 to July 2024. Human herpesvirus 6 (HHV6), HHV7, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) detection with the RQ-PCR method. The intestinal mucosa was pathologically assessed and immunohistochemistry was utilized to detect the CMV early antigen, CMV late antigen, and EBV by in situ hybridization. Results: This study included 42 patients, consisting of 25 males and 17 females with a median age of 26 (1-59) years. All were histopathologically diagnosed as GI-GVHD. Among them, 34 (81.0%) cases had combined viral enteritis, with 52.4% positive for EBV, 38.1% positive for HHV6, 26.2% positive for CMV, and 14.3% positive for HHV7. Further, 17 (40.5%) cases had mixed viral infections, including 5 EBV+ HHV6, 3 CMV+HHV6, 3 CMV+EBV, 2 CMV+EBV+HHV6, 2 EBV+HHV6+HHV7, 1 EBV+HHV7, and 1 HHV6 + HHV7 cases. Furthermore, 17 (40.5%) had a single viral infection, including 9 EBV, 3 CMV, 3 HHV6, and 2 HHV7 cases. Moreover, 17 (40.5%) patients exhibited a positive histopathological viral test, including 7 (16.6%) CMV-positive and 12 (28.5%) EBV-positive cases. The same positive virus was detected in the feces of all 34 patients with positive tissue homogenate virus, and the positive rate of the same virus in the blood was 17.6%. Tissue homogenized virus testing was utilized as the diagnostic criterion for enterocolitis: blood tests for CMV, EBV, HHV6, and HHV7 demonstrated a sensitivity of 45.4%, 4.5%, 6.3%, and 0%, and specificity of 90.3%, 95%, 100%, and 110%, respectively. Additionally, fecal tests for CMV, EBV, HHV6, and HHV7 demonstrated a sensitivity and specificity of 100%. Treatment based on etiology caused ORR and CR rates for diarrhea of 76.1% (32/42) and 66.6% (28/42), respectively. The median follow-up of 42 patients was 13 (1 - 49) months, and 28 patients survived, with an expected 2-year survival rate of 61.9%. Conclusion: In addition to GVHD itself, intestinal human herpesvirus infection is one of the reasons for the refractory nature of GI-GVHD. Viral testing in blood and tissues reveals significant segregation, and the possibility of comorbid viral enteritis cannot be excluded even if a patient with GI-GVHD tests negative for blood viruses.}, } @article {pmid39744736, year = {2024}, author = {Jeyaraman, N and Jeyaraman, M and Dhanpal, P and Ramasubramanian, S and Ragavanandam, L and Muthu, S and Santos, GS and da Fonseca, LF and Lana, JF}, title = {Gut microbiome and orthopaedic health: Bridging the divide between digestion and bone integrity.}, journal = {World journal of orthopedics}, volume = {15}, number = {12}, pages = {1135-1145}, pmid = {39744736}, issn = {2218-5836}, abstract = {The gut microbiome, a complex ecosystem of microorganisms in the digestive tract, has emerged as a critical factor in human health, influencing metabolic, immune, and neurological functions. This review explores the connection between the gut microbiome and orthopedic health, examining how gut microbes impact bone density, joint integrity, and skeletal health. It highlights mechanisms linking gut dysbiosis to inflammation in conditions such as rheumatoid arthritis and osteoarthritis, suggesting microbiome modulation as a potential therapeutic strategy. Key findings include the microbiome's role in bone metabolism through hormone regulation and production of short-chain fatty acids, crucial for mineral absorption. The review also considers the effects of diet, probiotics, and fecal microbiota transplantation on gut microbiome composition and their implications for orthopedic health. While promising, challenges in translating microbiome research into clinical practice persist, necessitating further exploration and ethical consideration of microbiome-based therapies. This interdisciplinary research aims to link digestive health with musculoskeletal integrity, offering new insights into the prevention and management of bone and joint diseases.}, } @article {pmid39744230, year = {2025}, author = {Singh, A and Chandrasekar, SV and Valappil, VT and Scaria, J and Ranjan, A}, title = {Tumor immunomodulation by nanoparticle and focused ultrasound alters gut microbiome in a sexually dimorphic manner.}, journal = {Theranostics}, volume = {15}, number = {1}, pages = {216-232}, pmid = {39744230}, issn = {1838-7640}, mesh = {Animals ; Female ; Male ; *Gastrointestinal Microbiome/immunology ; Mice ; *Nanoparticles/administration & dosage ; *Immunomodulation ; Calreticulin/metabolism ; Cell Line, Tumor ; Immunogenic Cell Death/drug effects ; Mice, Inbred C57BL ; Mouth Neoplasms/immunology/microbiology/therapy ; Sex Characteristics ; Cytokines/metabolism ; }, abstract = {Background: Local immunomodulation with nanoparticles (NPs) and focused ultrasound (FUS) is recognized for triggering anti-tumor immunity. However, the impact of these tumor immunomodulations on sex-specific microbiome diversity at distant sites and their correlation with therapeutic effectiveness remains unknown. Here, we conducted local intratumoral therapy using immunogenic cell death-enhancing Calreticulin-Nanoparticles (CRT-NPs) and FUS in male and female mice. We identified immune-related microbiome populations, aiming to translate our findings into clinical applications. Methods: CRT-NPs were synthesized by loading CRT-delivering plasmids into cationic liposomes. Local tumor therapy was performed using CRT-NP and FUS-based histotripsy (HT) on poorly immunogenic Mouse Oral Squamous Cell Carcinoma (MOC2) in the flank regions of male and female mice. Fecal samples were collected and analyzed before and three weeks post-treatment. The microbiome features were then correlated with immune cell dynamics within tumors and systemic cytokine responses to identify prognostic biomarkers in both male and female subjects. Results: Intratumorally administered CRT-NP induced tumor remission and immune cell activation in both male and female mice, whereas HT was ineffective in males and showed efficacy only in females. Turicibacter and Peptococcus inversely correlated with tumor growth, while Enterorhabdus, Subdologranulum, Desulfovibrio, and Aldercreutzia-Asaccharobacter showed direct correlations with tumor growth. HT induced higher levels of Turicibacter in MOC2-bearing females, while males displayed increased Enterorhabdus and Streptococcus populations. Independent of sex, treatments promoting CD4+ T helper cells, functional CD8+ T cells, and total macrophage infiltration correlated with higher levels of Gastrophilales, Romboutsia, Turicibacter, and Peptococcus. Alternatively, Enterorhabdus, Desulfovibrio, Streptococcus, and Staphylococcus corresponded to poor treatment outcomes in both sexes. Conclusion: An enhanced abundance of Enterorhabdus, Desulfovibrio, Streptococcus, and Staphylococcus in response to immunomodulatory therapies could serve as predictive biomarkers in a sex-independent manner. These findings could also be potentially extended to the realm of personalized interventions through fecal transplantations to reverse immunosuppressive phenotypes in males and improve patient outcomes.}, } @article {pmid39741383, year = {2024}, author = {van Rheenen, PF and Kolho, KL and Russell, RK and Aloi, M and Deganello, A and Hussey, S and Junge, N and De Laffolie, J and Deneau, MR and Fitzpatrick, E and Griffiths, AM and Hojsak, I and Nicastro, E and Nita, A and Pakarinen, M and Ricciuto, A and de Ridder, L and Sonzogni, A and Tenca, A and Samyn, M and Indolfi, G}, title = {Primary sclerosing cholangitis in children with inflammatory bowel disease: An ESPGHAN position paper from the Hepatology Committee and the IBD Porto group.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1002/jpn3.12378}, pmid = {39741383}, issn = {1536-4801}, support = {//European Society for Paediatric Gastroenterology Hepatology and Nutrition/ ; }, abstract = {OBJECTIVE: We aimed to provide an evidence-supported approach to diagnose, monitor, and treat children with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC).

METHODS: The core group formulated seven PICO-structured clinical questions. A systematic literature search from inception to December 2022 was conducted by a medical librarian using MEDLINE and EMBASE. Core messages from the literature were phrased as position statements and then circulated to a sounding board composed of international experts in pediatric gastroenterology and hepatology, histopathology, adult gastroenterology and hepatology, radiology, and surgery. Statements reaching at least 80% agreement were considered as final. The other statements were refined and then subjected to a second online vote or rejection.

RESULTS: Regular screening for gamma-glutamyltransferase (GGT) is essential for detecting possible biliary disease in children with IBD. MR cholangiopancreatography is the radiological modality of choice for establishing the diagnosis of PSC. Liver biopsy is relevant in the evaluation of small duct PSC or autoimmune hepatitis. Children who do not have known IBD at the time of PSC diagnosis should undergo initial screening with fecal calprotectin for asymptomatic colitis, and then at least once yearly thereafter. Children with a cholestatic liver enzyme profile can be considered for treatment with ursodeoxycholic acid and can continue if there is a meaningful reduction or normalization in GGT. Oral vancomycin may have a beneficial effect on GGT and intestinal inflammation, but judicious use is recommended due to the lack of long-term studies. Children with PSC-IBD combined with convincing features of autoimmune hepatitis may benefit from corticosteroids and antimetabolites.

CONCLUSIONS: We present state-of-the-art guidance on the diagnostic criteria, follow-up strategies, and therapeutic strategies and point out research gaps in children and adolescents with PSC-IBD.}, } @article {pmid39739648, year = {2024}, author = {Lei, J and Lv, L and Zhong, L and Xu, F and Su, W and Chen, Y and Wu, Z and He, S and Chen, Y}, title = {The Gut Microbiota Affects Anti-TNF Responsiveness by Activating the NAD[+] Salvage Pathway in Ulcerative Colitis.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2413128}, doi = {10.1002/advs.202413128}, pmid = {39739648}, issn = {2198-3844}, support = {82100548//National Natural Science Foundation of China/ ; CSTB2022NSCQ-MSX0094//Natural Science Foundation of Chongqing Municipality/ ; }, abstract = {Approximately 50% of the patients with ulcerative colitis (UC) are primarily nonresponsive to anti-tumor necrosis factor (TNF) therapy or lose their responsiveness over time. The gut microbiota plays an important role in the resistance of UC to anti-TNF therapy; however, the underlying mechanism remains unknown. Here, it is found that the transplantation of gut fecal microbiota from patients with UC alters the diversity of the gut microbiota in dextran sulfate sodium-induced colitis mice and may affect the therapeutic responsiveness of mice to infliximab. Furthermore, the abundances of Romboutsia and Fusobacterium increase in the tissues of patients with UC who do not respond to anti-TNF therapy. Differentially abundant metabolites are mainly enriched in nicotinate and nicotinamide metabolism in NCM460 cells after Fusobacterium nucleatum infection. Mechanistically, F. nucleatum promotes the nicotinamide adenine dinucleotide (NAD[+]) salvage pathway by upregulating NAMPT expression, which subsequently leads to the activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway and promotes the secretion of inflammatory factors, ultimately inhibiting the therapeutic response to anti-TNF drugs. These findings demonstrate that the gut microbiota can influence the response to anti-TNF therapy in patients with UC and highlight the therapeutic potential of targeting F. nucleatum and its associated pathways for preventing and treating drug resistance in UC.}, } @article {pmid39738016, year = {2024}, author = {Li, Z and Gu, M and Zaparte, A and Fu, X and Mahen, K and Mrdjen, M and Li, XS and Yang, Z and Ma, J and Thoudam, T and Chandler, K and Hesler, M and Heathers, L and Gorse, K and Van, TT and Wong, D and Gibson, AM and Wang, Z and Taylor, CM and Quijada, P and Makarewich, CA and Hazen, SL and Liangpunsakul, S and Brown, JM and Lefer, DJ and Welsh, DA and Sharp, TE}, title = {Alcohol-induced gut microbial reorganization and associated overproduction of phenylacetylglutamine promotes cardiovascular disease.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {10788}, pmid = {39738016}, issn = {2041-1723}, support = {R01 AA029984/AA/NIAAA NIH HHS/United States ; P50 AA024333/AA/NIAAA NIH HHS/United States ; UH2 AA026226/AA/NIAAA NIH HHS/United States ; P60 AA009803/AA/NIAAA NIH HHS/United States ; R21 AA027199/AA/NIAAA NIH HHS/United States ; U01 AA026917/AA/NIAAA NIH HHS/United States ; UH3 AA026903/AA/NIAAA NIH HHS/United States ; R01AA030312//U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA)/ ; T32 AR065972/AR/NIAMS NIH HHS/United States ; T32 HL069766/HL/NHLBI NIH HHS/United States ; R25 HL145817/HL/NHLBI NIH HHS/United States ; HL160569//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; HL171221//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; P01 HL147823/HL/NHLBI NIH HHS/United States ; R01 HL103866/HL/NHLBI NIH HHS/United States ; R01 HL167831/HL/NHLBI NIH HHS/United States ; P01 HL147823/HL/NHLBI NIH HHS/United States ; R01 HL146098/HL/NHLBI NIH HHS/United States ; R01 HL146514/HL/NHLBI NIH HHS/United States ; R01 HL151398/HL/NHLBI NIH HHS/United States ; NSF 2018936//National Science Foundation (NSF)/ ; RF1 NS133812/NS/NINDS NIH HHS/United States ; P20 GM103424/GM/NIGMS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; U24 DK1132746//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; R01 DK130227/DK/NIDDK NIH HHS/United States ; R01 DK120679/DK/NIDDK NIH HHS/United States ; KC2210163//U.S. Department of Defense (United States Department of Defense)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Male ; *Glutamine/metabolism/analogs & derivatives ; *Cardiovascular Diseases/metabolism/microbiology/etiology ; Mice ; Humans ; Mice, Inbred C57BL ; Myocytes, Cardiac/metabolism/drug effects ; Ethanol/pharmacology/metabolism ; Oxidative Stress/drug effects ; Fecal Microbiota Transplantation ; Alcoholism/metabolism ; Disease Models, Animal ; Female ; Glutamates/metabolism ; Endothelial Cells/metabolism/drug effects ; Middle Aged ; }, abstract = {The mechanism(s) underlying gut microbial metabolite (GMM) contribution towards alcohol-mediated cardiovascular disease (CVD) is unknown. Herein we observe elevation in circulating phenylacetylglutamine (PAGln), a known CVD-associated GMM, in individuals living with alcohol use disorder. In a male murine binge-on-chronic alcohol model, we confirm gut microbial reorganization, elevation in PAGln levels, and the presence of cardiovascular pathophysiology. Fecal microbiota transplantation from pair-/alcohol-fed mice into naïve male mice demonstrates the transmissibility of PAGln production and the CVD phenotype. Independent of alcohol exposure, pharmacological-mediated increases in PAGln elicits direct cardiac and vascular dysfunction. PAGln induced hypercontractility and altered calcium cycling in isolated cardiomyocytes providing evidence of improper relaxation which corresponds to elevated filling pressures observed in vivo. Furthermore, PAGln directly induces vascular endothelial cell activation through induction of oxidative stress leading to endothelial cell dysfunction. We thus reveal that the alcohol-induced microbial reorganization and resultant GMM elevation, specifically PAGln, directly contributes to CVD.}, } @article {pmid39736988, year = {2024}, author = {Wang, F and Wang, Z and Qu, L}, title = {The changes of intestinal flora and metabolites in atopic dermatitis mice.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1462491}, pmid = {39736988}, issn = {1664-302X}, abstract = {INTRODUCTION: Atopic dermatitis (AD) is an allergic disease caused by various factors that can affect an individual's appearance and cause psychological stress. Therefore, it is necessary to investigate the underlying mechanisms and develop effective treatment strategies. The gut microbiota and bacterial metabolism play crucial roles in human diseases. However, their specific role in AD remains unclear.

METHODS: In this study, we established a mouse model of AD and found that 2,4-dinitrofluorobenzene disrupted the skin barrier in mice. The species composition of intestinal bacteria was then analyzed by fecal 16s rRNA sequencing. The metabolic level of mice was analyzed by untargeted and targeted metabolomics in stool.

RESULTS: The levels of filaggrin and aquaporin 3 proteins in the model mice and total superoxide dismutase, catalase and malondialdehyde levels were significantly altered. Additionally, inflammatory factors such as tumor necrosis factor-alpha showed a significant increase. Using 16S rRNA gene sequencing, we identified 270 bacterial species with altered abundances of Ruminococcaceae and Bifidobacteriaceae. The untargeted metabolomic analysis detected 1,299 metabolites. Targeted analysis of free fatty acids revealed 49 metabolites with notable increases in linoleic and linolenic acid levels. Fecal bacterial transplantation experiments have demonstrated that oxidative stress, inflammation, and skin barrier damage were alleviated after transplantation.

DISCUSSION: These findings suggested that the metabolite linoleic acid negatively correlated with Ruminococcaceae and Bifidobacteriaceae may influence AD development. Perturbations in the intestinal bacteria and flora contributed to the development of AD, and the mouse model could serve as a valuable tool for further investigation of therapeutic approaches for managing ADS.}, } @article {pmid39736924, year = {2025}, author = {Yuan, C}, title = {Molecular mechanisms and therapeutic strategies of gut microbiota modulation in Sarcopenia (Review).}, journal = {Oncology letters}, volume = {29}, number = {3}, pages = {104}, pmid = {39736924}, issn = {1792-1082}, abstract = {Sarcopenia is an age-related disease that is characterized by a decline in muscle mass and function with significant epidemiological and clinical implications. In recent years, gut microbiota has gained attention as an important regulatory factor in human health. To the best of our knowledge, this is the first study to introduce the definition and epidemiological background of sarcopenia and analyze the potential impact of the gut microbiota on muscle metabolism and growth, including aspects such as gut microbiota metabolites, muscle protein synthesis and energy metabolism. Additionally, this article summarizes the current research progress in gut microbiota interventions for the treatment of sarcopenia, such as probiotics, prebiotics and fecal microbiota transplantation and discusses future research directions and potential therapeutic strategies.}, } @article {pmid39735707, year = {2024}, author = {Chu, C and Behera, TR and Huang, Y and Qiu, W and Chen, J and Shen, Q}, title = {Research progress of gut microbiome and diabetic nephropathy.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1490314}, pmid = {39735707}, issn = {2296-858X}, abstract = {Diabetic nephropathy is an important complication of diabetic microvascular injury, and it is also an important cause of end-stage renal disease. Its high prevalence and disability rate significantly impacts patients' quality of life while imposing substantial social and economic burdens. Gut microbiota affects host metabolism, multiple organ functions, and regulates host health throughout the life cycle. With the rapid development of technology, researchers have found that gut microbiota is closely related to the progression of diabetic kidney disease. This review explores the role of gut microbiome in diabetic nephropathy summarizing proposed mechanisms of progression and focusing on microbial metabolites, intestinal barrier disruption, inflammation, filtration barrier damage and renal fibrosis. This review also examines the mechanism and limitations of current treatments, including drugs, fecal microbiota transplantation, and lifestyle changes, offering new perspectives on prevention and treatment.}, } @article {pmid39735647, year = {2024}, author = {Wang, H and Li, S and Zhang, L and Zhang, N}, title = {The role of fecal microbiota transplantation in type 2 diabetes mellitus treatment.}, journal = {Frontiers in endocrinology}, volume = {15}, number = {}, pages = {1469165}, pmid = {39735647}, issn = {1664-2392}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Diabetes Mellitus, Type 2/therapy/microbiology ; *Gastrointestinal Microbiome ; Animals ; }, abstract = {In contemporary microbial research, the exploration of interactions between microorganisms and multicellular hosts constitutes a burgeoning field. The gut microbiota is increasingly acknowledged as a pivotal contributor to various disorders within the endocrine system, encompassing conditions such as diabetes and thyroid diseases. A surge in research activities has been witnessed in recent years, elucidating the intricate interplay between the gut microbiota and disorders of the endocrine system. Simultaneously, fecal microbiota transplantation (FMT) has emerged as a focal point, garnering substantial attention in both biomedical and clinical spheres. Research endeavors have uncovered the remarkable therapeutic efficacy of FMT across diverse diseases, with particular emphasis on its application in addressing type 2 diabetes mellitus (T2DM) and associated com-plications. Consequently, this manuscript accentuates the intimate connection between the gut microbiota and disorders within the endocrine system, with a specific focus on exploring the potential of FMT as an intervention in the therapeutic landscape of T2DM and its complications. Furthermore, the article scrutinizes concerns inherent in treatment modalities centered around the gut microbiota, proposing viable solutions to address these issues.}, } @article {pmid39735273, year = {2024}, author = {Patnaik, S and Durairajan, SSK and Singh, AK and Krishnamoorthi, S and Iyaswamy, A and Mandavi, SP and Jeewon, R and Williams, LL}, title = {Role of Candida species in pathogenesis, immune regulation, and prognostic tools for managing ulcerative colitis and Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {30}, number = {48}, pages = {5212-5220}, pmid = {39735273}, issn = {2219-2840}, mesh = {Humans ; *Crohn Disease/immunology/microbiology/therapy ; *Gastrointestinal Microbiome/immunology ; *Colitis, Ulcerative/microbiology/immunology/diagnosis/therapy ; *Dysbiosis/immunology/microbiology ; Prognosis ; Candida albicans/immunology/pathogenicity/isolation & purification ; Immunity, Mucosal ; Candida/immunology/pathogenicity/isolation & purification ; Candidiasis/immunology/microbiology/diagnosis ; Host-Pathogen Interactions ; Intestinal Mucosa/microbiology/immunology ; }, abstract = {The gut microbiome plays a key role in the pathogenesis and disease activity of inflammatory bowel disease (IBD). While research has focused on the bacterial microbiome, recent studies have shifted towards host genetics and host-fungal interactions. The mycobiota is a vital component of the gastrointestinal microbial community and plays a significant role in immune regulation. Among fungi, Candida species, particularly Candida albicans (C. albicans), have been extensively studied due to their dual role as gut commensals and invasive pathogens. Recent findings indicate that various strains of C. albicans exhibit considerable differences in virulence factors, impacting IBD's pathophysiology. Intestinal fungal dysbiosis and antifungal mucosal immunity may be associated to IBD, especially Crohn's disease (CD). This article discusses intestinal fungal dysbiosis and antifungal immunity in healthy individuals and CD patients. It discusses factors influencing the mycobiome's role in IBD pathogenesis and highlights significant contributions from the scientific community aimed at enhancing understanding of the mycobiome and encouraging further research and targeted intervention studies on specific fungal populations. Our article also provided insights into a recent study by Wu et al in the World Journal of Gastroenterology regarding the role of the gut microbiota in the pathogenesis of CD.}, } @article {pmid39735176, year = {2025}, author = {Bhatia, Z and Kumar, S and Seshadri, S}, title = {Fecal microbiota transplantation as a potential therapeutic approach to improve impaired glucose tolerance via gut microbiota modulation in rat model.}, journal = {Journal of diabetes and metabolic disorders}, volume = {24}, number = {1}, pages = {28}, pmid = {39735176}, issn = {2251-6581}, abstract = {OBJECTIVES: To investigate the impact of diet-induced gut microbiota alterations on type 2 diabetes and assess the therapeutic potential of Fecal Microbiota Transplantation (FMT) in restoring a balanced gut microenvironment.

METHODS: To induce type 2 diabetes, rats were fed a high-sugar high-fat diet (HSFD) for 90 days. After diabetes induction, animals were divided into an HSFD control group, a metformin group (100 mg/kg), and an FMT group (100 mg/kg), receiving treatment for an additional 90 days. Fasting blood glucose levels, glucose tolerance, serum markers (HbA1C, free fatty acids, lipopolysaccharides, pro-inflammatory and anti-inflammatory cytokines), and gut microbiota profiles via cecal metagenome sequencing were analyzed post-treatment.

RESULTS: FMT effectively restored gut microbiota composition to a profile similar to healthy controls, rebalancing the Firmicutes/Bacteroidetes ratio and increasing beneficial taxa, including Prevotella ruminicola, Akkermansia muciniphila, Roseburia, and Faecalibacterium prausnitzii. These microbial shifts corresponded with significant metabolic improvements: FMT reduced inflammatory markers (LPS and FFA), lowered HbA1c, and improved glucose tolerance. Enhanced gut barrier integrity observed in FMT-treated animals likely contributed to reduced endotoxemia and systemic inflammation, distinguishing FMT's metabolic effects from those of metformin. Notably, FMT addressed the dysbiosis associated with HSFD, promoting microbial resilience and mitigating the metabolic disruptions linked to type 2 diabetes.

CONCLUSION: These findings underscore the potential of FMT as a targeted therapeutic approach to modulate gut microbiota composition and mitigate metabolic dysregulation induced by high sugar high fat diet.}, } @article {pmid39733842, year = {2024}, author = {Mamun, AA and Geng, P and Wang, S and Shao, C and Xiao, J}, title = {IUPHAR review: Targeted therapies of signaling pathways based on the gut microbiome in autism spectrum disorders: Mechanistic and therapeutic applications.}, journal = {Pharmacological research}, volume = {211}, number = {}, pages = {107559}, doi = {10.1016/j.phrs.2024.107559}, pmid = {39733842}, issn = {1096-1186}, abstract = {Autism spectrum disorders (ASD) are complex neurodevelopmental disorders characterized by impairments in social interaction, communication and repetitive activities. Gut microbiota significantly influences behavior and neurodevelopment by regulating the gut-brain axis. This review explores gut microbiota-influenced treatments for ASD, focusing on their therapeutic applications and mechanistic insights. In addition, this review discusses the interactions between gut microbiota and the immune, metabolic and neuroendocrine systems, focusing on crucial microbial metabolites including short-chain fatty acids (SCFAs) and several neurotransmitters. Furthermore, the review explores various therapy methods including fecal microbiota transplantation, dietary modifications, probiotics and prebiotics and evaluates their safety and efficacy in reducing ASD symptoms. The discussion shows the potential of customized microbiome-based therapeutics and the integration of multi-omics methods to understand the underlying mechanisms. Moreover, the review explores the intricate relationship between gut microbiota and ASD, aiming to develop innovative therapies that utilize the gut microbiome to improve the clinical outcomes of ASD patients. Microbial metabolites such as neurotransmitter precursors, tryptophan metabolites and SCFAs affect brain development and behavior. Symptoms of ASD are linked to changes in these metabolites. Dysbiosis in the gut microbiome may impact neuroinflammatory processes linked to autism, negatively affecting immune signaling pathways. Research indicates that probiotics and prebiotics can improve gut microbiota and alleviate symptoms in ASD patients. Fecal microbiota transplantation may also improve behavioral symptoms and restore gut microbiota balance. The review emphasizes the need for further research on gut microbiota modification as a potential therapeutic approach for ASD, highlighting its potential in clinical settings.}, } @article {pmid39733798, year = {2024}, author = {Luo, Y and Li, M and Luo, D and Tang, B}, title = {Gut Microbiota: An Important Participant in Childhood Obesity.}, journal = {Advances in nutrition (Bethesda, Md.)}, volume = {}, number = {}, pages = {100362}, doi = {10.1016/j.advnut.2024.100362}, pmid = {39733798}, issn = {2156-5376}, abstract = {Increasing prevalence of childhood obesity has emerged as a critical global public health concern. Recent studies have challenged the previous belief that obesity was solely a result of excessive caloric intake. Alterations in early-life gut microbiota can contribute to childhood obesity through their influence on nutrient absorption and metabolism, initiation of inflammatory responses, and regulation of gut-brain communication. The gut microbiota is increasingly acknowledged to play a crucial role in human health, as certain beneficial bacteria have been scientifically proven to possess the capacity to reduce body fat content and enhance intestinal barrier function, and their metabolic products to exhibit anti-inflammatory effect. Examples of such microbes include bifidobacteria, Akkermansia muciniphila, and Lactobacillus reuteri. In contrast, an increase in Enterobacteriaceae and Propionate-producing bacteria (Prevotellaceae and Veillonellaceae) has been implicated in the induction of low-grade systemic inflammation and disturbances in lipid metabolism, which can predispose individuals to obesity. Studies have demonstrated that modulating the gut microbiota through diet, lifestyle changes, prebiotics, probiotics, or fecal microbiota transplantation may contribute to gut homeostasis and the management of obesity and its associated comorbidities. This review elucidates the impact of alterations in gut microbiota composition during early-life on childhood obesity and explores the mechanisms by which gut microbiota contributes to the pathogenesis of obesity, and specifically focuses on recent advances in utilizing short-chain fatty acids for regulating gut microbiota and ameliorating obesity. Additionally, it discusses the therapeutic strategies for childhood obesity from the perspective of gut microbiota, aiming to provide a theoretical foundation for interventions targeting pediatric obesity based on gut microbiota. Statement of Significance: We provide a summary of the factors, mechanisms, and therapeutic strategies pertaining to the impact of gut microbiota alterations on childhood obesity, with particularly emphasis recent advancements in leveraging short-chain fatty acids for modulating gut microbiota composition and ameliorating obesity-related concerns.}, } @article {pmid39732757, year = {2024}, author = {Jasiński, M and Biliński, J and Maciejewska, M and Ostrowska, K and Rusicka-Krzewska, P and Konarski, W and Podsiadły, E and Snarski, E and Basak, GW}, title = {Impact of gut colonization by antibiotic-resistant bacteria on the outcomes of autologous stem cell transplantation in multiple myeloma.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {31221}, pmid = {39732757}, issn = {2045-2322}, mesh = {Humans ; *Multiple Myeloma/therapy/microbiology ; Male ; Middle Aged ; Female ; *Transplantation, Autologous ; Aged ; Retrospective Studies ; *Gastrointestinal Microbiome ; Adult ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Drug Resistance, Bacterial ; Treatment Outcome ; }, abstract = {Patients undergoing autologous stem cell transplantation (auto-SCT) face elevated risks of infections. Additionally, patients colonized in the gastrointestinal tract with antibiotic-resistant bacteria (ARB) are at higher risk of infection with ARB and other infections. Therefore, patients colonized with ARB before auto-SCT should present with an exceptionally high incidence of infections. According to current literature, ARB colonization is the surrogate marker for dysbiosis, which is known to be associated with a diagnosis of multiple myeloma (MM). Given that, this retrospective study aimed to assess the influence of ARB colonization on infection rates, hematopoiesis regeneration, mucositis, overall survival, and progression-free survival following auto-SCT in MM. Data from 138 MM patients undergoing 141 auto-SCT were analyzed, with 15% showing ARB colonization. Among colonized patients, ESBL-producing gram-negative rods predominated. Patients with gut ARB colonization had significantly higher infection rates than non-colonized individuals (52 vs. 26%, P = 0.02), particularly bloodstream infections (43% vs. 14%, P = 0.004). Colonized patients also tended to exhibit shorter survival rates although there was no statistical significance (1-year and 2-year OS; non-colonized vs. colonized; 97 and 92% vs. 90 and 86%; p = 0.054). Based on our results, gut colonization before auto-SCT negatively affects treatment outcomes.}, } @article {pmid39732731, year = {2024}, author = {Lu, Y and Huangfu, S and Ma, C and Ding, Y and Zhang, Y and Zhou, C and Liao, L and Li, M and You, J and Chen, Y and Wang, D and Chen, A and Jiang, B}, title = {Exosomes derived from umbilical cord mesenchymal stem cells promote healing of complex perianal fistulas in rats.}, journal = {Stem cell research & therapy}, volume = {15}, number = {1}, pages = {414}, pmid = {39732731}, issn = {1757-6512}, support = {BE2022674//General Program of Jiangsu Province Social Development-oriented Special Fund Project/ ; No. 82004365//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Exosomes/metabolism ; Rats ; *Mesenchymal Stem Cells/metabolism/cytology ; *Wound Healing ; *Rats, Sprague-Dawley ; *Umbilical Cord/cytology ; *Rectal Fistula/therapy/metabolism ; Humans ; Signal Transduction ; Transforming Growth Factor beta/metabolism ; Disease Models, Animal ; Male ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; Mesenchymal Stem Cell Transplantation/methods ; }, abstract = {BACKGROUND: Complex perianal fistulas, challenging to treat and prone to recurrence, often require surgical intervention that may cause fecal incontinence and lower quality of life due to large surgical wounds and potential sphincter damage. Human umbilical cord-derived MSCs (hUC-MSCs) and their exosomes (hUCMSCs-Exo) may promote wound healing.

METHODS: This study assessed the efficacy, mechanisms, and safety of these exosomes in treating complex perianal fistulas in SD rats. We established a rat model, divided rats with fistulas into the control and the exosome groups. We assessed treatment efficacy through ultrasound, clinical observations, and histopathological analysis. We also evaluated the activation of the HIF-1α/TGF-β/Smad signaling pathway via PCR and Western blot and assessed serological markers for HIF-1α and inflammatory indices through ELISA. We analyzed gut microbiota and the systemic metabolic environment via untargeted metabolomics.

RESULTS: The hUCMSCs-Exo effectively promoted healing of wound, regulated the immune balance enhanced collagen synthesis and angiogenesis in the perianal fistulas model of rats, and regulated the gut microbiota and metabolomic profiles. Results of PCR and Western blot analyses indicated that the exosomes activated HIF-1α/TGF-β/Smad signaling pathways. To the dosages tested, the 10ug/100ul concentration (medium dose) was found to be the most effective to the treatment of complex perianal fistulas.

CONCLUSIONS: The hUCMSCs-Exo significantly promoted the healing of wound in perianal fistulas of rats and demonstrated higher safety. The underlying mechanism facilitating the healing process was likely associated with the activation of the HIF-1α/TGF-β/Smad signaling pathway.}, } @article {pmid39732352, year = {2024}, author = {Kamath, S and Sokolenko, E and Collins, K and Chan, NSL and Mills, N and Clark, SR and Marques, FZ and Joyce, P}, title = {IUPHAR themed review: The gut microbiome in schizophrenia.}, journal = {Pharmacological research}, volume = {211}, number = {}, pages = {107561}, doi = {10.1016/j.phrs.2024.107561}, pmid = {39732352}, issn = {1096-1186}, abstract = {Gut microbial dysbiosis or altered gut microbial consortium, in schizophrenia suggests a pathogenic role through the gut-brain axis, influencing neuroinflammatory and neurotransmitter pathways critical to psychotic, affective, and cognitive symptoms. Paradoxically, conventional psychotropic interventions may exacerbate this dysbiosis, with antipsychotics, particularly olanzapine, demonstrating profound effects on microbial architecture through disruption of bacterial phyla ratios, diminished taxonomic diversity, and attenuated short-chain fatty acid synthesis. To address these challenges, novel therapeutic strategies targeting the gut microbiome, encompassing probiotic supplementation, prebiotic compounds, faecal microbiota transplantation, and rationalised co-pharmacotherapy, show promise in attenuating antipsychotic-induced metabolic disruptions while enhancing therapeutic efficacy. Harnessing such insights, precision medicine approaches promise to transform antipsychotic prescribing practices by identifying patients at risk of metabolic side effects based on their microbial profiles. This IUPHAR review collates the current literature landscape of the gut-brain axis and its intricate relationship with schizophrenia while advocating for integrating microbiome assessments and therapeutic management. Such a fundamental shift in proposing microbiome-informed psychotropic prescriptions to optimise therapeutic efficacy and reduce adverse metabolic impacts would align antipsychotic treatments with microbiome safety, prioritising 'gut-neutral' or gut-favourable drugs to safeguard long-term patient outcomes in schizophrenia therapy.}, } @article {pmid39731142, year = {2024}, author = {Yang, Y and Wang, L and Zhuang, T and Xu, T and Ji, M and Wang, Q}, title = {Washed microbiota transplantation stopped recurrent sepsis in a patient with myelofibrosis: a case report.}, journal = {Gut pathogens}, volume = {16}, number = {1}, pages = {78}, pmid = {39731142}, issn = {1757-4749}, abstract = {BACKGROUND: Sepsis represents the most prevalent infectious complication and the primary cause of mortality in myeloproliferative neoplasms (MPN). The risk of sepsis and the difficulty of treatment are significantly increased in MPN patients due to the need for immunomodulators and antibiotics.

CASE PRESENTATION: On June 9, 2023, a 69-year-old male was admitted to the hospital. Following a battery of tests, the diagnosis of sepsis due to Escherichia coli was ultimately established. The patient was administered amoxicillin clavulanate potassium intravenously. In light of the patient's recurrent sepsis and the likelihood that the source of infection is the intestinal tract, we advised that the patient undergo washed microbiota transplantation (WMT) via a colonic transendoscopic enteral tube (TET).

CONCLUSIONS: WMT as the new method of fecal microbiota transplantation (FMT) successfully cured the recurrent sepsis in this case, indicating the novel option for challenging the refractory or serious infections.}, } @article {pmid39729440, year = {2024}, author = {Cibulkova, I and Rehorova, V and Soukupova, H and Waldauf, P and Cahova, M and Manak, J and Matejovic, M and Duska, F}, title = {Allogenic faecal microbiota transplantation for antibiotic-associated diarrhoea in critically ill patients (FEBATRICE)-Study protocol for a multi-centre randomised controlled trial (phase II).}, journal = {PloS one}, volume = {19}, number = {12}, pages = {e0310180}, pmid = {39729440}, issn = {1932-6203}, mesh = {Female ; Humans ; Male ; *Anti-Bacterial Agents/adverse effects/therapeutic use ; *Critical Illness ; *Diarrhea/therapy/microbiology ; Dysbiosis/therapy/microbiology ; *Fecal Microbiota Transplantation/methods/adverse effects ; Feces/microbiology ; *Gastrointestinal Microbiome/drug effects ; Prospective Studies ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic ; Clinical Trials, Phase II as Topic ; }, abstract = {BACKGROUND: Exposure of critically ill patients to antibiotics lead to intestinal dysbiosis, which often manifests as antibiotic-associated diarrhoea. Faecal microbiota transplantation restores gut microbiota and may lead to faster resolution of diarrhoea.

METHODS: Into this prospective, multi-centre, randomized controlled trial we will enrol 36 critically ill patients with antibiotic-associated diarrhoea. We will exclude patients with ongoing sepsis, need of systemic antibiotics, or those after recent bowel surgery or any other reason that prevents the FMT. Randomisation will be in 1:1 ratio. Patients in the control group will receive standard treatment based on oral diosmectite. In the intervention group, patients will receive, in addition to the standard of care, faecal microbiota transplantation via rectal tube, in the form of a preparation mixed from 7 thawed aliquots (50 mL) made from fresh stool of 7 healthy unrelated donors and quarantined deep frozen for 3 to 12 months. Primary outcome is treatment failure defined as intervention not delivered or diarrhoea persisting at day 7 after randomisation. Secondary outcomes include safety measures such as systemic inflammatory response, adverse events, and also diarrhoea recurrence within 28 days. Exploratory outcomes focus on gut barrier function and composition of intestinal microbiota.

DISCUSSION: Faecal microbiota transplantation has been effective for dysbiosis in non-critically ill patients with recurrent C. difficile infections and it is plausible to hypothesize that it will be equally effective for symptoms of dysbiosis in the critically ill patients. In addition, animal experiments and observational data suggest other benefits such as reduced colonization with multi-drug resistant bacteria and improved gut barrier and immune function. The frozen faeces from unrelated donors are immediately available when needed, unlike those from the relatives, who require lengthy investigation. Using multiple donors maximises graft microbiota diversity. Nonetheless, in vulnerable critically ill patients, Faecal microbiota transplantation might lead to bacterial translocation and unforeseen complications. From growing number of case series it is clear that its off label use in the critically ill patients is increasing and that there is a burning need to objectively assess its efficacy and safety, which this trial aims.

TRIAL REGISTRATION: www.clinicaltrials.gov (NCT05430269).}, } @article {pmid39728458, year = {2024}, author = {Voziki, A and Deda, O and Kachrimanidou, M}, title = {The Efficacy of Fecal Microbiota Transplantation in Mouse Models Infected with Clostridioides difficile from the Perspective of Metabolic Profiling: A Systematic Review.}, journal = {Metabolites}, volume = {14}, number = {12}, pages = {}, pmid = {39728458}, issn = {2218-1989}, abstract = {Objectives: This systematic review evaluates the effectiveness of fecal microbiota transplantation (FMT) in treating Clostridioides difficile infection (CDI) in mouse models using a metabolomics-based approach. Methods: A comprehensive search was conducted in three databases (PubMed, Scopus, Google Scholar) from 10 April 2024 to 17 June 2024. Out of the 460 research studies reviewed and subjected to exclusion criteria, only 5 studies met all the inclusion criteria and were analyzed. Results: These studies consistently showed that FMT effectively restored gut microbiota and altered metabolic profiles, particularly increasing short-chain fatty acids (SCFAs) and secondary bile acids, which inhibited C. difficile growth. FMT proved superior to antibiotic and probiotic treatments in re-establishing a healthy gut microbiome, as evidenced by significant changes in the amino acid and carbohydrate levels. Despite its promise, variability in the outcomes-due to factors such as immune status, treatment protocols, and donor microbiome differences-underscores the need for standardization. Rather than pursuing immediate standardization, the documentation of factors such as donor and recipient microbiome profiles, preparation methods, and administration details could help identify optimal configurations for specific contexts and patient needs. In all the studies, FMT was successful in restoring the metabolic profile in mice. Conclusions: These findings align with the clinical data from CDI patients, suggesting that FMT holds potential as a therapeutic strategy for gut health restoration and CDI management. Further studies could pave the way for adoption in clinical practice.}, } @article {pmid39726974, year = {2024}, author = {Ebrahimi, R and Farsi, Y and Nejadghaderi, SA}, title = {Fecal microbiota transplantation for glaucoma; a potential emerging treatment strategy.}, journal = {Current research in microbial sciences}, volume = {7}, number = {}, pages = {100314}, pmid = {39726974}, issn = {2666-5174}, abstract = {Glaucoma is the primary cause of irreversible blindness globally. Different glaucoma subtypes are identified by their underlying mechanisms, and treatment options differ by its pathogenesis. Current management includes topical medications to lower intraocular pressure and surgical procedures like trabeculoplasty and glaucoma drainage implants. Fecal microbiota transplantation (FMT) is an almost effective and safe treatment option for recurrent Clostridium difficile infection. The relationship between bacterial populations, metabolites, and inflammatory pathways in retinal diseases indicates possible therapeutic strategies. Thus, incorporating host microbiota-based therapies could offer an additional treatment option for glaucoma patients. Here, we propose that combining FMT with standard glaucoma treatments may benefit those affected by this condition. Also, the potential safety, efficacy, cost-effectiveness and clinical applications are discussed.}, } @article {pmid39726854, year = {2025}, author = {Minerbi, A and Khoutorsky, A and Shir, Y}, title = {Decoding the connection: unraveling the role of gut microbiome in fibromyalgia.}, journal = {Pain reports}, volume = {10}, number = {1}, pages = {e1224}, pmid = {39726854}, issn = {2471-2531}, abstract = {The gut microbiome is emerging as a critical player in the pathophysiology of fibromyalgia, offering mechanistic insights as well as potential diagnostic and therapeutic applications.}, } @article {pmid39725607, year = {2025}, author = {Wang, P and Wang, R and Zhao, W and Zhao, Y and Wang, D and Zhao, S and Ge, Z and Ma, Y and Zhao, X}, title = {Gut microbiota-derived 4-hydroxyphenylacetic acid from resveratrol supplementation prevents obesity through SIRT1 signaling activation.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2446391}, doi = {10.1080/19490976.2024.2446391}, pmid = {39725607}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Sirtuin 1/metabolism ; *Obesity/metabolism/prevention & control/microbiology ; *Resveratrol/pharmacology/administration & dosage ; Mice ; *Phenylacetates/pharmacology/metabolism ; *Signal Transduction/drug effects ; *Diet, High-Fat/adverse effects ; Male ; *Mice, Inbred C57BL ; Dysbiosis/microbiology/prevention & control ; Adipose Tissue, White/metabolism/drug effects ; Anti-Obesity Agents/pharmacology/administration & dosage ; Dietary Supplements ; Bacteria/classification/metabolism/drug effects/genetics ; Fecal Microbiota Transplantation ; }, abstract = {Resveratrol (RSV), a natural polyphenol, has been suggested to influence glucose and lipid metabolism. However, the underlying molecular mechanism of its action remains largely unknown due to its multiple biological targets and low bioavailability. In this study, we demonstrate that RSV supplementation ameliorates high-fat-diet (HFD)-induced gut microbiota dysbiosis, enhancing the abundance of anti-obesity bacterial strains such as Akkermansia, Bacteroides and Blautia. The critical role of gut microbiota in RSV-mediated anti-obesity effects was confirmed through antibiotic-induced microbiome depletion and fecal microbiota transplantation (FMT), which showed that RSV treatment effectively mitigates body weight, histopathological damage, glucose dysregulation and systematic inflammation associated with HFD. Metabolomics analysis revealed that RSV supplementation significantly increases the levels of the gut microbial flavonoid catabolite 4-hydroxyphenylacetic acid (4-HPA). Notably, 4-HPA was sufficient to reverse obesity and glucose intolerance in HFD-fed mice. Mechanistically,4-HPA treatment markedly regulates SIRT1 signaling pathways and induces the expression of beige fat and thermogenesis-specific markers in white adipose tissue (WAT). These beneficial effects of 4-HPA are partially abolished by EX527, a known SIRT1 inhibitor. Collectively, our findings indicate that RSV improve obesity through a gut microbiota-derived 4-HPA-SIRT1 axis, highlighting gut microbiota metabolites as a promising target for obesity prevention.}, } @article {pmid39725475, year = {2024}, author = {Yang, RF and Wu, W and Zhang, P}, title = {Research Progress on Obesity-Associated Kidney Diseases.}, journal = {Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae}, volume = {}, number = {}, pages = {}, doi = {10.3881/j.issn.1000-503X.16098}, pmid = {39725475}, issn = {1000-503X}, abstract = {The pathogenesis of obesity-associated kidney disease (OAKD) involves many aspects,including the overactivation of the renin-angiotensin-aldosterone system,insulin resistance,chronic inflammation,disorder of lipid metabolism and imbalance of gut microecology.Treatment strategies for OAKD focus on lifestyle adjustments,pharmacotherapy,bariatric surgery,and fecal microbiota transplantation.A deeper understanding of the hazards of OAKD and its pathogenesis will contribute to the development of personalized and precise strategies for prevention,diagnosis and treatment of OAKD in the future.}, } @article {pmid39724461, year = {2024}, author = {Mahmoudian, F and Gheshlagh, SR and Hemati, M and Farhadi, S and Eslami, M}, title = {The influence of microbiota on the efficacy and toxicity of immunotherapy in cancer treatment.}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {86}, pmid = {39724461}, issn = {1573-4978}, mesh = {Animals ; Humans ; *Dysbiosis/immunology/microbiology/therapy ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/immunology ; *Immunotherapy/methods/adverse effects ; *Neoplasms/immunology/microbiology/therapy ; }, abstract = {Immunotherapy, which uses the body's immune system to fight cancer cells, has gained attention recently as a breakthrough in cancer treatment. Although significant progress has been made, obstacles still exist since cancers are skilled at avoiding immune monitoring. The gut microbiota is being looked at more and more in modern research as a critical component in improving the results of immunotherapy. Through modulating both innate and adaptive immune responses, the gut microbiome has a significant impact on cancer immunotherapy. The effectiveness of treatment and the way the immune system responds are significantly influenced by some microorganisms and the metabolites they produce, especially short-chain fatty acids. On the other hand, dysbiosis and persistent inflammation in the gut environment might unintentionally accelerate the growth of tumors, which makes the complex relationship between the makeup of the microbiota and cancer treatment more challenging. Gut microbiota plays a crucial role in immunotherapy effectiveness. Improved microbial diversity leads to better treatment responses, with some taxa like Bacteroides and Ruminococcaceae being linked to better responses to immune checkpoint inhibitors. Dysbiotic conditions can worsen immune-related side effects and reduce treatment effectiveness. Strategies manipulating gut microbiota, such as fecal microbiota transplantation, antibiotic therapies, and dietary interventions, could optimize immunotherapy response and prognosis. However, standardizing these interventions for different cancer types and patient populations is challenging due to individual microbiome differences. Future research should combine microbiome research with AI and rigorous clinical trials for individualized cancer treatments.}, } @article {pmid39717506, year = {2025}, author = {Bloom, PP and Chung, RT}, title = {The future of clinical trials of gut microbiome therapeutics in cirrhosis.}, journal = {JHEP reports : innovation in hepatology}, volume = {7}, number = {1}, pages = {101234}, pmid = {39717506}, issn = {2589-5559}, abstract = {The last two decades have witnessed an explosion of microbiome research, including in hepatology, with studies demonstrating altered microbial composition in liver disease. More recently, efforts have been made to understand the association of microbiome features with clinical outcomes and to develop therapeutics targeting the microbiome. While microbiome therapeutics hold much promise, their unique features pose certain challenges for the design and conduct of clinical trials. Herein, we will briefly review indications for microbiome therapeutics in cirrhosis, currently available microbiome therapeutics, and the biological pathways targeted by these therapies. We will then focus on the best practices and important considerations for clinical trials of gut microbiome therapeutics in cirrhosis.}, } @article {pmid39716346, year = {2024}, author = {Li, Y and Wang, K and Shen, D and Liu, J and Li, S and Liu, L and Nagaoka, K and Li, C}, title = {Mogroside V protects Lipopolysaccharides-induced lung inflammation chicken via suppressing inflammation mediated by the Th17 through the gut-lung axis.}, journal = {Journal of animal science}, volume = {}, number = {}, pages = {}, doi = {10.1093/jas/skae388}, pmid = {39716346}, issn = {1525-3163}, abstract = {Lipopolysaccharide (LPS) exposure triggers pulmonary inflammation, leading to compromised lung function in broiler. As amplified by policy restrictions on antibiotic usage, seeking antibiotic alternatives has become imperative. Mogroside V (MGV) has been reported to have a beneficial role in livestock and poultry production due to its remarkable anti-inflammatory effects. Despite evidence showcasing MGV's efficacy against LPS-triggered lung inflammation, its precise mechanism of action remains elusive. In this study, we transplanted normal fecal microbiota (CF), fecal microbiota modified by MGV (MF), and sterile fecal filtrate (MS) into broiler with LPS-induced pneumonia. The results showed that through fecal microbiota transplantation, transplanting MGV-induced microbial populations significantly mitigated tissue damage induced by LPS and enhanced the mRNA level of pulmonary tight junction proteins and mucoprotein (P < 0.01). The expression levels of RORα (P < 0.001), Foxp3 (P < 0.01) and PD-L1 (P < 0.01) were significantly increased in the MF group than CF group. The concentrations of IL-6 and IL-17 in broilers lung tissue of MF group were lower than those in broilers of CF group (P < 0.05). Furthermore, the concentration of TGF-β in broilers serum of MS and MF groups was higher than those in broilers of control group (P < 0.05). Microbial community analysis demonstrated that at genus level, the harmful bacterial populations Escherichia-shigella and Helicobacter following FMT treatment was significantly reduced in MF group (P < 0.05), potentially mediating its protective effects. Compared with CF group, valerate content and FFAR2 mRNA expression levels in MF group were significantly increased (P < 0.05). The study suggests that MGV via the gut-lung axis, attenuates Th17-mediated inflammation, offering promise as a therapeutic strategy against LPS-induced lung inflammation in chickens.}, } @article {pmid39715825, year = {2024}, author = {Bornbusch, SL and Crosier, A and Gentry, L and Delaski, KM and Maslanka, M and Muletz-Wolz, CR}, title = {Fecal microbiota transplants facilitate post-antibiotic recovery of gut microbiota in cheetahs (Acinonyx jubatus).}, journal = {Communications biology}, volume = {7}, number = {1}, pages = {1689}, pmid = {39715825}, issn = {2399-3642}, support = {NSF IOS-2131060//National Science Foundation (NSF)/ ; }, mesh = {*Acinonyx ; *Gastrointestinal Microbiome ; Animals ; *Anti-Bacterial Agents/pharmacology ; *Fecal Microbiota Transplantation ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Male ; Female ; }, abstract = {Burgeoning study of host-associated microbiomes has accelerated the development of microbial therapies, including fecal microbiota transplants (FMTs). FMTs provide host-specific microbial supplementation, with applicability across host species. Studying FMTs can simultaneously provide comparative frameworks for understanding microbial therapies in diverse microbial systems and improve the health of managed wildlife. Ex-situ carnivores, including cheetahs (Acinonyx jubatus), often suffer from intractable gut infections similar to those treated with antibiotics and FMTs in humans, providing a valuable system for testing FMT efficacy. Using an experimental approach in 21 cheetahs, we tested whether autologous FMTs facilitated post-antibiotic recovery of gut microbiota. We used 16S rRNA sequencing and microbial source tracking to characterize antibiotic-induced microbial extirpations and signatures of FMT engraftment for single versus multiple FMTs. We found that antibiotics extirpated abundant bacteria and FMTs quickened post-antibiotic recovery via engraftment of bacteria that may facilitate protein digestion and butyrate production (Fusobacterium). Although multiple FMTs better sustained microbial recovery compared to a single FMT, one FMT improved recovery compared to antibiotics alone. This study elucidated the dynamics of microbiome modulation in a non-model system and improves foundations for reproducible, low-cost, low-dose, and minimally invasive FMT protocols, emphasizing the scientific and applied value of FMTs across species.}, } @article {pmid39715151, year = {2024}, author = {Nie, P and Hu, L and You, T and Jia, T and Xu, H}, title = {Lead Mediated Lipopolysaccharides Exacerbates Fatty Liver Processes in High-Fat Diets-Induced Mice.}, journal = {Environmental toxicology}, volume = {}, number = {}, pages = {}, doi = {10.1002/tox.24463}, pmid = {39715151}, issn = {1522-7278}, support = {82060606//National Natural Science Foundation of China/ ; }, abstract = {Obesity leads to a variety of health risks, and lead, which is ranked second in Agency for Toxic Substances and Disease Registry's priority list of harmful substances, may be more harmful to individuals that are obese. C57BL/6 mice were fed a normal diet or a high-fat diet with or without exposure to 1 g/L lead exposure in drinking water for 8 consecutive weeks. Serum and hepatic biochemistry analysis, histopathological observation, and RT-qPCR were used to explore the potential mechanism of liver damage in obese individuals after Pb exposure, and fecal microbiota transplantation was performed to investigate the role of the gut microbiota in the progression of fatty liver disease. We found that the progression of fatty liver disease induced by high-fat diets was accelerated by chronic lead intake. In addition, the occurrences of liver injury in recipient mice suggested the role of the gut microbiota. These findings indicated that the combination of lead and a HFD exacerbated hepatic lipotoxicity by activating LPS-mediated inflammation, and that gut microbiota disorders and impaired intestinal barrier function play pivotal roles in the progression of fatty liver disease.}, } @article {pmid39714951, year = {2024}, author = {Li, W and Wang, Y and Shi, Y and He, F and Zhao, Z and Liu, J and Gao, Z and Zhang, J and Shen, X}, title = {The gut microbiota mediates memory impairment under high-altitude hypoxia via the gut-brain axis in mice.}, journal = {The FEBS journal}, volume = {}, number = {}, pages = {}, doi = {10.1111/febs.17365}, pmid = {39714951}, issn = {1742-4658}, support = {81973073//National Natural Science Foundation of China/ ; 82173481//National Natural Science Foundation of China/ ; 82204089//National Natural Science Foundation of China/ ; }, abstract = {Hypoxia is a predominant risk factor at high altitudes, and evidence suggests that high-altitude hypoxia alters the gut microbiota, which plays an essential regulatory role in memory function. However, the causal relationship between the gut microbiota and memory impairment under hypoxic conditions remains unclear. In this study, we employed a high-altitude hypoxia model combined with fecal microbiota transplantation (FMT) approach in mice to explore the effects of the gut microbiota on memory impairment in a hypoxic environment. We observed that high-altitude hypoxia exposure reduced short- and long-term memory and hippocampus-dependent fear memory abilities, along with decreased relative abundance of Ligilactobacillus and Muribaculum. Moreover, hypoxic conditions increased intestinal and blood-brain barrier permeability. FMT from hypoxia-exposed mice into naïve antibiotic-treated mice resulted in similar memory impairments, Ligilactobacillus and Muribaculum abundance changes, and increased intestinal/blood-brain barrier permeability. Correlation analysis showed a robust positive association between Ligilactobacillus and Muribaculum with hippocampus-dependent contextual fear memory. Likewise, Ligilactobacillus was positively correlated with short-term memory. Therefore, Ligilactobacillus and Muribaculum may be key microbes in reducing memory ability in hypoxia, with the intestinal and blood-brain barriers as primary pathways. Our findings provide further evidence for the potential regulatory mechanism by which gut microbiota dysbiosis may contribute to memory impairment in a high-altitude environment.}, } @article {pmid39712898, year = {2024}, author = {Tang, M and Wu, Y and Liang, J and Yang, S and Huang, Z and Hu, J and Yang, Q and Liu, F and Li, S}, title = {Gut microbiota has important roles in the obstructive sleep apnea-induced inflammation and consequent neurocognitive impairment.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1457348}, pmid = {39712898}, issn = {1664-302X}, abstract = {Obstructive sleep apnea (OSA) is a state of sleep disorder, characterized by repetitive episodes of apnea and chronic intermittent hypoxia. OSA has an extremely high prevalence worldwide and represents a serious challenge to public health, yet its severity is frequently underestimated. It is now well established that neurocognitive dysfunction, manifested as deficits in attention, memory, and executive functions, is a common complication observed in patients with OSA, whereas the specific pathogenesis remains poorly understood, despite the likelihood of involvement of inflammation. Here, we provide an overview of the current state of the art, demonstrating the intimacy of OSA with inflammation and cognitive impairment. Subsequently, we present the recent findings on the investigation of gut microbiota alteration in the OSA conditions, based on both patients-based clinical studies and animal models of OSA. We present an insightful discussion on the role of changes in the abundance of specific gut microbial members, including short-chain fatty acid (SCFA)-producers and/or microbes with pathogenic potential, in the pathogenesis of inflammation and further cognitive dysfunction. The transplantation of fecal microbiota from the mouse model of OSA can elicit inflammation and neurobehavioral disorders in naïve mice, thereby validating the causal relationship to inflammation and cognitive abnormality. This work calls for greater attention on OSA and the associated inflammation, which require timely and effective therapy to protect the brain from irreversible damage. This work also suggests that modification of the gut microbiota using prebiotics, probiotics or fecal microbiota transplantation may represent a potential adjuvant therapy for OSA.}, } @article {pmid39712559, year = {2024}, author = {Özdemir, Ö}, title = {Relation between dysbiosis and inborn errors of immunity.}, journal = {World journal of methodology}, volume = {14}, number = {4}, pages = {96380}, pmid = {39712559}, issn = {2222-0682}, abstract = {Inborn errors of immunity (IEI) disorders, formerly primary immune deficiency diseases, are a heterogeneous group of disorders with variable hereditary transitions, clinical manifestations, complications and varying disease severity. Many of the clinical symptoms, signs and complications in IEI patients can be attributed to inflammatory and immune dysregulatory processes due to loss of microbial diversity (dysbiosis). For example, in common variable immunodeficiency patients, the diversity of bacteria, but not fungi, in the gut microbiota has been found to be reduced and significantly altered. Again, this was associated with a more severe disease phenotype. Compromise of the STAT3/Th17 pathway in hyper-IgE syndrome may lead to dysbiosis of the oral microbiota in these patients, causing Candida albicans to switch from commensal to pathogenic. Modification of the microbiota can be used as a therapeutic approach in patients with IEI. Prebiotics, probiotics, postbiotics and fecal microbiota transplantation can be used to restore the balance of the gut microbiota and reduce pathogenicity in IEI patients. Clinical trials are currently underway to understand the impact of this dysbiosis on the phenotype of IEI diseases and its role in their treatment.}, } @article {pmid39712189, year = {2024}, author = {Lusk, S and Memos, NK and Rauschmayer, A and Ray, RS}, title = {The microbiome is dispensable for normal respiratory function and chemoreflexes in mice.}, journal = {Frontiers in physiology}, volume = {15}, number = {}, pages = {1481394}, pmid = {39712189}, issn = {1664-042X}, abstract = {Increasing evidence indicates an association between microbiome composition and respiratory homeostasis and disease, particularly disordered breathing, such as obstructive sleep apnea. Previous work showing respiratory disruption is limited by the methodology employed to disrupt, eliminate, or remove the microbiome by antibiotic depletion. Our work utilized germ-free mice born without a microbiome and described respiratory alterations. We used whole-body flow through barometric plethysmography to assay conscious and unrestrained C57BL/6J germ-free (GF, n = 24) and specific-pathogen-free (SPF, n = 28) adult mice (with an intact microbiome) in normoxic (21% O2,79% N2) conditions and during challenges in hypercapnic (5% CO2, 21% O2, 74% N2) and hypoxic (10% O2, 90% N2) environments. Following initial plethysmography analysis, we performed fecal transplants to test the ability of gut microbiome establishment to rescue any observed phenotypes. Data were comprehensively analyzed using our newly published respiratory analysis software, Breathe Easy, to identify alterations in respiratory parameters, including ventilatory frequency, tidal volume, ventilation, apnea frequency, and sigh frequency. We also considered possible metabolic changes by analyzing oxygen consumption, carbon dioxide production, and ventilatory equivalents of oxygen. We also assayed GF and SPF neonates in an autoresuscitation assay to understand the effects of the microbiome on cardiorespiratory stressors in early development. We found several differences in baseline and recovery cardiorespiratory parameters in the neonates and differences in body weight at both ages studied. However, there was no difference in the overall survival of the neonates, and in contrast to prior studies utilizing gut microbial depletion, we found no consequential respiratory alterations in GF versus SPF adult mice at baseline or following fecal transplant in any groups. Interestingly, we did see alterations in oxygen consumption in the GF adult mice, which suggests an altered metabolic demand. Results from this study suggest that microbiome alteration in mice may not play as large a role in respiratory outcomes when a less severe methodology to eliminate the microbiome is utilized.}, } @article {pmid39711145, year = {2024}, author = {Qian, M and Jiang, Z and Xu, C and Wang, L and Hu, N}, title = {Changes in the gut microbiota and derived fecal metabolites may play a role in tacrolimus-induced diabetes in mice.}, journal = {Future microbiology}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/17460913.2024.2444761}, pmid = {39711145}, issn = {1746-0921}, abstract = {AIMS: A notable scarcity of research has focused on examining alterations in gut microbiota and its metabolites within tacrolimus (TAC)-induced diabetes models.

METHODS: Tacrolimus-induced changes in glucose and lipid metabolism indices were analyzed through different routes of administration. The potential role of gut microbiota and its metabolites in TAC-induced diabetes was investigated using 16S rRNA sequencing and non-targeted metabolomics.

RESULTS: After intraperitoneal(ip) and oral(po) administration of TAC, the α-diversity index of gut microbiota was significantly increased. The gut microbiota of the three groups of mice was significantly separated, and there were significant changes in composition and functional genes. Fecal metabolites changed significantly after TAC administration by different routes, and 53 metabolites (38 down-regulated and 15 up-regulated) were identified (CON vs. TACip). Similarly, 29 metabolites (8 down-regulated and 21 up-regulated) were identified (CON vs. TACpo). KEGG pathway analysis identified 4 and 13 significantly altered metabolic pathways, respectively. Correlation analysis suggested that microbiota and metabolites were involved in the pathogenesis of TAC-induced diabetes.

CONCLUSION: This study investigated the alterations in gut microbiota and fecal metabolites in TAC-induced diabetic mice and evaluated the correlation between these changes. These findings provide valuable insights into potential biomarkers in the development of TAC-induced diabetes.}, } @article {pmid39710789, year = {2024}, author = {Wang, Y and Bai, M and Peng, Q and Li, L and Tian, F and Guo, Y and Jing, C}, title = {Angiogenesis, a key point in the association of gut microbiota and its metabolites with disease.}, journal = {European journal of medical research}, volume = {29}, number = {1}, pages = {614}, pmid = {39710789}, issn = {2047-783X}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Neovascularization, Pathologic/metabolism/microbiology ; Neoplasms/microbiology/metabolism/immunology ; Inflammation/metabolism ; Cardiovascular Diseases/microbiology/metabolism/etiology ; Animals ; Neurodegenerative Diseases/microbiology/metabolism ; Angiogenesis ; }, abstract = {The gut microbiota is a complex and dynamic ecosystem that plays a crucial role in human health and disease, including obesity, diabetes, cardiovascular diseases, neurodegenerative diseases, inflammatory bowel disease, and cancer. Chronic inflammation is a common feature of these diseases and is closely related to angiogenesis (the process of forming new blood vessels), which is often dysregulated in pathological conditions. Inflammation potentially acts as a central mediator. This abstract aims to elucidate the connection between the gut microbiota and angiogenesis in various diseases. The gut microbiota influences angiogenesis through various mechanisms, including the production of metabolites that directly or indirectly affect vascularization. For example, short-chain fatty acids (SCFAs) such as butyrate, propionate, and acetate are known to regulate immune responses and inflammation, thereby affecting angiogenesis. In the context of cardiovascular diseases, the gut microbiota promotes atherosclerosis and vascular dysfunction by producing trimethylamine N-oxide (TMAO) and other metabolites that promote inflammation and endothelial dysfunction. Similarly, in neurodegenerative diseases, the gut microbiota may influence neuroinflammation and the integrity of the blood-brain barrier, thereby affecting angiogenesis. In cases of fractures and wound healing, the gut microbiota promotes angiogenesis by activating inflammatory responses and immune effects, facilitating the healing of tissue damage. In cancer, the gut microbiota can either inhibit or promote tumor growth and angiogenesis, depending on the specific bacterial composition and their metabolites. For instance, some bacteria can activate inflammasomes, leading to the production of inflammatory factors that alter the tumor immune microenvironment and activate angiogenesis-related signaling pathways, affecting tumor angiogenesis and metastasis. Some bacteria can directly interact with tumor cells, activating angiogenesis-related signaling pathways. Diet, as a modifiable factor, significantly influences angiogenesis through diet-derived microbial metabolites. Diet can rapidly alter the composition of the microbiota and its metabolic activity, thereby changing the concentration of microbial-derived metabolites and profoundly affecting the host's immune response and angiogenesis. For example, a high animal protein diet promotes the production of pro-atherogenic metabolites like TMAO, activating inflammatory pathways and interfering with platelet function, which is associated with the severity of coronary artery plaques, peripheral artery disease, and cardiovascular diseases. A diet rich in dietary fiber promotes the production of SCFAs, which act as ligands for cell surface or intracellular receptors, regulating various biological processes, including inflammation, tissue homeostasis, and immune responses, thereby influencing angiogenesis. In summary, the role of the gut microbiota in angiogenesis is multifaceted, playing an important role in disease progression by affecting various biological processes such as inflammation, immune responses, and multiple signaling pathways. Diet-derived microbial metabolites play a crucial role in linking the gut microbiota and angiogenesis. Understanding the complex interactions between diet, the gut microbiota, and angiogenesis has the potential to uncover novel therapeutic targets for managing these conditions. Therefore, interventions targeting the gut microbiota and its metabolites, such as through fecal microbiota transplantation (FMT) and the application of probiotics to alter the composition of the gut microbiota and enhance the production of beneficial metabolites, present a promising therapeutic strategy.}, } @article {pmid39710683, year = {2024}, author = {Yarahmadi, A and Afkhami, H and Javadi, A and Kashfi, M}, title = {Understanding the complex function of gut microbiota: its impact on the pathogenesis of obesity and beyond: a comprehensive review.}, journal = {Diabetology & metabolic syndrome}, volume = {16}, number = {1}, pages = {308}, pmid = {39710683}, issn = {1758-5996}, abstract = {Obesity is a multifactorial condition influenced by genetic, environmental, and microbiome-related factors. The gut microbiome plays a vital role in maintaining intestinal health, increasing mucus creation, helping the intestinal epithelium mend, and regulating short-chain fatty acid (SCFA) production. These tasks are vital for managing metabolism and maintaining energy balance. Dysbiosis-an imbalance in the microbiome-leads to increased appetite and the rise of metabolic disorders, both fuel obesity and its issues. Furthermore, childhood obesity connects with unique shifts in gut microbiota makeup. For instance, there is a surge in pro-inflammatory bacteria compared to children who are not obese. Considering the intricate nature and variety of the gut microbiota, additional investigations are necessary to clarify its exact involvement in the beginnings and advancement of obesity and related metabolic dilemmas. Currently, therapeutic methods like probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), dietary interventions like Mediterranean and ketogenic diets, and physical activity show potential in adjusting the gut microbiome to fight obesity and aid weight loss. Furthermore, the review underscores the integration of microbial metabolites with pharmacological agents such as orlistat and semaglutide in restoring microbial homeostasis. However, more clinical tests are essential to refine the doses, frequency, and lasting effectiveness of these treatments. This narrative overview compiles the existing knowledge on the multifaceted role of gut microbiota in obesity and much more, showcasing possible treatment strategies for addressing these health challenges.}, } @article {pmid39706182, year = {2024}, author = {Jiang, Y and Huang, Z and Sun, W and Huang, J and Xu, Y and Liao, Y and Jin, T and Li, Q and Ho, IHT and Zou, Y and Zhu, W and Li, Q and Qin, F and Zhang, X and Shi, S and Zhang, N and Yang, S and Xie, W and Wu, S and Tan, L and Zhang, L and Chen, H and Gin, T and Chan, MTV and Wu, WKK and Xiao, L and Liu, X}, title = {Roseburia intestinalis-derived butyrate alleviates neuropathic pain.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2024.11.013}, pmid = {39706182}, issn = {1934-6069}, abstract = {Approximately 20% of patients with shingles develop postherpetic neuralgia (PHN). We investigated the role of gut microbiota in shingle- and PHN-related pain. Patients with shingles or PHN exhibited significant alterations in their gut microbiota with microbial markers predicting PHN development among patients with shingles. Functionally, fecal microbiota transplantation from patients with PHN to mice heightened pain sensitivity. Administration of Roseburia intestinalis, a bacterium both depleted in patients with shingles and PHN, alleviated peripheral nerve injury-induced pain in mice. R. intestinalis enhanced vagal neurotransmission to the nucleus tractus solitarius (NTS) to suppress the central amygdala (CeA), a brain region involved in pain perception. R. intestinalis-generated butyrate activated vagal neurons through the receptor, G protein-coupled receptor 41 (GPR41). Vagal knockout of Gpr41 abolished the effects of R. intestinalis on the NTS-CeA circuit and reduced pain behaviors. Overall, we established a microbiota-based model for PHN risk assessment and identified R. intestinalis as a potential pain-alleviating probiotic.}, } @article {pmid39703540, year = {2024}, author = {Finnegan, YE and Neill, HR and Prpa, EJ and Pot, B}, title = {"Gut" to grips with the science of the microbiome - a symposium report.}, journal = {Gut microbiome (Cambridge, England)}, volume = {5}, number = {}, pages = {e11}, pmid = {39703540}, issn = {2632-2897}, abstract = {The latest Yakult Science Study Day was held virtually on 2 November 2023. Aimed at healthcare professionals, researchers, and students, a variety of experts explored the latest gut microbiome research and what it means in practice. The morning sessions discussed the role of the microbiome in health and disease, the rapid advancements in DNA sequencing and implications for personalised nutrition, the current state of evidence on health benefits associated with fermented foods, prebiotics and probiotics and the challenges involved in interpreting research in this area. The afternoon session considered the emerging research on the microbiota-gut-brain axis in mediating effects of food on mood, the bidirectional impact of menopause on the gut microbiota, and the interplay between the gut and skin with implications for the treatment of rare and common skin disorders. The session ended with an update on the use of faecal microbiota transplant in both research and clinical practice. Undoubtedly, the gut microbiome is emerging as a key conductor of human health, both in relation to gastrointestinal and non-gastrointestinal outcomes. As research continues to elucidate mechanisms of action and confirm their effects in human trials, the gut microbiome should be a key consideration within a holistic approach to health moving forward.}, } @article {pmid39703374, year = {2024}, author = {Chen, T and Wang, N and Hao, Y and Fu, L}, title = {Fecal microbiota transplantation from postmenopausal osteoporosis human donors accelerated bone mass loss in mice.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1488017}, pmid = {39703374}, issn = {2235-2988}, mesh = {Animals ; *Fecal Microbiota Transplantation ; Humans ; Mice ; *Gastrointestinal Microbiome ; Female ; *Feces/microbiology ; *Osteoporosis, Postmenopausal/microbiology ; Disease Models, Animal ; Bacteria/classification/isolation & purification/genetics ; Bone Density ; Middle Aged ; Zonula Occludens-1 Protein/metabolism ; Mice, Inbred C57BL ; }, abstract = {OBJECTIVES: To investigate the effect of gut microbiota from postmenopausal osteoporosis patients on bone mass in mice.

METHODS: Fecal samples were collected from postmenopausal women with normal bone mass (Con, n=5) and postmenopausal women with osteoporosis (Op, n=5). Microbial composition was identified by shallow shotgun sequencing. Then fecal samples were transplanted into pseudo-sterile mice previously treated with antibiotics for 4 weeks. These mice were categorized into two groups: the Vehicle group (n=7) received fecal samples from individuals with normal bone mass, and the FMT group (n=7) received fecal samples from individuals with osteoporosis. After 8 weeks, bone mass, intestinal microbial composition, intestinal permeability and inflammation were assessed, followed by a correlation analysis.

RESULTS: The bone mass was significantly reduced in the FMT group. Microbiota sequencing showed that Shannon index (p < 0.05) and Simpson index (p < 0.05) were significantly increased in Op groups, and β diversity showed significant differences. the recipient mice were similar. linear discriminant analysis effect size (LEfSe) analysis of mice showed that Halobiforma, Enterorhabdus, Alistipes, and Butyricimonas were significantly enriched in the FMT group. Lachnospiraceae and Oscillibacter were significantly enriched in the Vehicle group. H&E staining of intestinal tissues showed obvious intestinal mucosal injury in mice. Intestinal immunohistochemistry showed that the expression of Claudin and ZO-1 in the intestinal tissue of the FMT group mice was decreased. The FITC-Dextran (FD-4) absorption rate and serum soluble CD14 (sCD14) content were increased in FMT mice. Correlation analysis showed that these dominant genera were significantly associated with bone metabolism and intestinal permeability, and were associated with the enrichment of specific enzymes. Serum and bone tissue inflammatory cytokines detection showed that the expression of TNF-α and IL-17A in the FMT group were significantly increased.

CONCLUSION: Overall, our findings suggested gut microbiota from postmenopausal osteoporosis patients accelerate bone mass loss in mice. Aberrant gut microbiota might play a causal role in the process of bone mass loss mediated by inflammation after the destruction of the intestinal barrier.}, } @article {pmid39702789, year = {2024}, author = {Kaur, S and Patel, BCK and Collen, A and Malhotra, R}, title = {The microbiome and the eye: a new era in ophthalmology.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {39702789}, issn = {1476-5454}, abstract = {The human microbiome has progressively been recognised for its role in various disease processes. In ophthalmology, complex interactions between the gut and distinct ocular microbiota within each structure and microenvironment of the eye has advanced our knowledge on the multi-directional relationships of these ecosystems. Increasingly, studies have shown that modulation of the microbiome can be achieved through faecal microbiota transplantation and synbiotics producing favourable outcomes for ophthalmic diseases. As ophthalmologists, we are obliged to educate our patients on measures to cultivate a healthy gut microbiome through a range of holistic measures. Further integrative studies combining microbial metagenomics, metatranscriptomics and metabolomics are necessary to fully characterise the human microbiome and enable targeted therapeutic interventions.}, } @article {pmid39701930, year = {2024}, author = {Wen, J and Wang, S and Sun, K and Wang, H and Yuan, Z and Deng, W}, title = {Chang-Wei-Qing Combined with PD-1 Inhibitor Alleviates Colitis-Associated Colorectal Tumorigenesis by Modulating the Gut Microbiota and Restoring Intestinal Barrier.}, journal = {Biological procedures online}, volume = {26}, number = {1}, pages = {32}, pmid = {39701930}, issn = {1480-9222}, support = {ptkwws202002//Shanghai Putuo District Health and Health System Science and Technology Innovation Project/ ; 2021tszk01//Shanghai Putuo District Health and Health System Clinical Specialty Construction Project/ ; ZY[2021-2023]-0302//Shanghai Municipal Health Commission's Shanghai Further Accelerating Traditional Chinese Medicine Development Three-Year Action Plan Project/ ; }, abstract = {Chang-Wei-Qing (CWQ) is a widely recognized Traditional Chinese Medicine (TCM) formulation composed of Astragalus, Codonopsis, Atractylodes, Poria, Coix seed, Akebia trifoliata Koidz, Sargentodoxa cuneata, and Vitis quinquangularis Rehd. This formulation has garnered significant interest for its positive effects in mitigating colorectal cancer, and when combined with PD-1, it affects some gut microbiota associated with tumor infiltrating lymphocytes cells. However, the biological rationale underlying the suppression of colitis-associated colorectal cancer (CAC) in AOM/DSS-treated mice by CWQ combined with PD-1 inhibitor remains to be explored. Our aim is to explore the chemopreventive effect of CWQ combined with PD-1 inhibitor on CAC, with a focus on modulating the gut microbiota. A mouse model of CAC was established using azoxymethane (AOM) and dextran sulfate sodium (DSS) treatment. Pathological evaluation of tissue samples included immunohistochemistry and hematoxylin and eosin staining. Intestinal barrier function was assessed by transmission electron microscopy. Fecal microbiota and metabolites were analyzed through 16 S rRNA gene sequencing and liquid chromatography-mass spectrometry, respectively. Mice treated with antibiotics served as models for fecal microbiota transplantation. CWQ combined with PD-1 inhibitor suppressed CAC in AOM/DSS-treated mice. This combined therapy effectively alleviated gut dysbiosis in the CAC model by increasing microbial diversity, enriching probiotic populations such as Limosilactobacillus and Bifidobacterium, and reducing pathogenic bacteria like Desulfovibrio. Additionally, CWQ combined with PD-1 inhibitor downregulated metabolites associated with the NF-kappa B signaling pathway. The combined treatment also significantly improved intestinal barrier function in CAC mice. Transmission electron microscopy of the CWQ combined with PD-1 inhibitor group showed enhanced cellular integrity, a relatively normal mitochondrial structure with intact membranes, and a more abundant, unexpanded endoplasmic reticulum, underscoring the protective effects of this combination on intestinal barrier integrity. Transcriptomic analysis further demonstrated that the combined therapy upregulated genes involved in tight and adherens junctions, while downregulating genes linked to innate immune responses. CWQ combined with PD-1 inhibitor can ameliorate dysbiosis in the AOM/DSS mouse model, with the metabolites of the gut microbiome potentially possessing anti-inflammatory activity. Moreover, CWQ combined with PD-1 inhibitor improves intestinal barrier function, thereby effectively inhibiting the occurrence and development of CAC.}, } @article {pmid39699275, year = {2024}, author = {Wang, Y and Xue, Y and Xu, H and Zhu, Q and Qin, K and He, Z and Huang, A and Mu, M and Tao, X}, title = {Pediococcus acidilactici Y01 reduces HFD-induced obesity via altering gut microbiota and metabolomic profiles and modulating adipose tissue macrophage M1/M2 polarization.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d4fo04301d}, pmid = {39699275}, issn = {2042-650X}, abstract = {Obesity-related metabolic syndrome is intimately associated with infiltrated adipose tissue macrophages (ATMs), gut microbiota, and metabolic disorders. Pediococcus acidilactici holds the potential to mitigate obesity; however, there exist strain-specific functionalities and diverse mechanisms, which deserve extensive exploration. This study aims to explore the potential of P. acidilactici Y01, isolated from traditional sour whey, in alleviating HFD-induced metabolic syndrome in mice and elucidating its underlying mechanism. The results showed that P. acidilactici Y01 could inhibit the increase of body weight gain, the deposition of fat, lipid disorders and chronic low-grade inflammation, improve glucose tolerance and insulin resistance, and could reduce adipose tissue inflammation by decreasing M1-type ATMs and increasing M2-type ATMs. Meanwhile, P. acidilactici Y01 significantly increased the abundance of potentially beneficial intestinal bacteria, such as Akkermansia, Alistipes, Bifidobacterium, Lachnospiraceae_NK4A136_group, Lactobacillus, norank_f__Muribaculaceae, and Parabacteroides, and partially restored the levels of metabolites, such as phosphatidylcholines, glycerophosphocholines, sphingolipids and unsaturated fatty acids. The fecal microbiota transplantation experiment demonstrated that P. acidilactici Y01 ameliorated obesity-related metabolic syndrome by modulating the polarization of M1/M2 ATMs mediated by gut microbiota. Overall, as a dietary supplement, P. acidilactici Y01 has good potential in the prevention and treatment of obesity.}, } @article {pmid39699220, year = {2024}, author = {Li, T and Hu, G and Fu, S and Qin, D and Song, Z}, title = {Phillyrin ameliorates DSS-induced colitis in mice via modulating the gut microbiota and inhibiting the NF-κB/MLCK pathway.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0200624}, doi = {10.1128/spectrum.02006-24}, pmid = {39699220}, issn = {2165-0497}, abstract = {Phillyrin (PHY), also known as forsythin, is an active constituent isolated from the fruit of Forsythia suspensa (Thunb.) Vahl (Oleaceae). It exhibits anti-inflammatory, anti-viral, and antioxidant properties. However, the precise impact of PHY on colitis induced by dextran sodium sulfate (DSS) and its mechanism remain elusive. The present investigation revealed that PHY (12.5, 25.0, and 50.0 mg/kg) exhibited significant therapeutic efficacy in protecting mice against DSS-induced colitis. This effect was manifested as reduced weight loss, a shortened colon, increased secretion of inflammatory factors, increased intestinal permeability, and an enhanced disease activity index in mice with ulcerative colitis (UC). Molecular investigations have determined that PHY mitigates the nuclear translocation of nuclear factor kappa B, thereby downregulating myosin light-chain kinase-driven myosin light-chain phosphorylation. This mechanism results in the preservation of the integrity of the intestinal barrier. The outcomes of 16S rRNA sequencing suggest that PHY (50 mg/kg) augmented the relative abundance of certain probiotic strains, including Lactobacillaceae and Lachnospiraceae. Additionally, PHY supplementation elevated the short-chain fatty acid contents within the intestinal contents of mice with UC. In conclusion, pre-treatment with PHY may ameliorate the DSS-induced UC in mice by lowering the expression of inflammatory factors, protecting intestinal barrier function, and enhancing the structure of the intestinal flora.IMPORTANCEThe protective effect of phillyrin on DSS-induced colitis was explained for the first time, and the anti-inflammatory effect of phillyrin was demonstrated by fecal microbiota transplantation experiments mainly through intestinal flora.}, } @article {pmid38659831, year = {2024}, author = {Sall, IJ and Foxall, R and Felth, L and Maret, S and Rosa, Z and Gaur, A and Calawa, J and Pavlik, N and Whistler, J and Whistler, CA}, title = {Gut dysbiosis was inevitable, but tolerance was not: temporal responses of the murine microbiota that maintain its capacity for butyrate production correlate with sustained antinociception to chronic morphine.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.04.15.589671}, pmid = {38659831}, issn = {2692-8205}, support = {F31 DA056222/DA/NIDA NIH HHS/United States ; P20 GM103506/GM/NIGMS NIH HHS/United States ; R15 DA058187/DA/NIDA NIH HHS/United States ; R21 DA049565/DA/NIDA NIH HHS/United States ; }, abstract = {The therapeutic benefits of opioids are compromised by the development of analgesic tolerance, which necessitates higher dosing for pain management thereby increasing the liability for drug dependence and addiction. Rodent models indicate opposing roles of the gut microbiota in tolerance: morphine-induced gut dysbiosis exacerbates tolerance, whereas probiotics ameliorate tolerance. Not all individuals develop tolerance which could be influenced by differences in microbiota, and yet no study design has capitalized upon this natural variation. We leveraged natural behavioral variation in a murine model of voluntary oral morphine self-administration to elucidate the mechanisms by which microbiota influences tolerance. Although all mice shared similar morphine-driven microbiota changes that largely masked informative associations with variability in tolerance, our high-resolution temporal analyses revealed a divergence in the progression of dysbiosis that best explained sustained antinociception. Mice that did not develop tolerance maintained a higher capacity for production of the short-chain fatty acid (SCFA) butyrate known to bolster intestinal barriers and promote neuronal homeostasis. Both fecal microbial transplantation (FMT) from donor mice that did not develop tolerance and dietary butyrate supplementation significantly reduced the development of tolerance independently of suppression of systemic inflammation. These findings could inform immediate therapies to extend the analgesic efficacy of opioids.}, } @article {pmid39694919, year = {2025}, author = {Zhang, Y and Ji, X and Chang, K and Yin, H and Zhao, M and Zhao, L}, title = {The regulatory effect of chitooligosaccharides on islet inflammation in T2D individuals after islet cell transplantation: the mechanism behind Candida albicans abundance and macrophage polarization.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2442051}, pmid = {39694919}, issn = {1949-0984}, mesh = {Animals ; *Candida albicans/drug effects ; *Oligosaccharides/pharmacology ; Mice ; *Gastrointestinal Microbiome/drug effects ; Humans ; *Macrophages/drug effects/immunology ; *Diabetes Mellitus, Type 2/microbiology ; *Islets of Langerhans Transplantation ; *Myeloid Differentiation Factor 88/metabolism/genetics ; *Inflammation ; Male ; Mice, Inbred C57BL ; Chitosan/pharmacology ; Islets of Langerhans/drug effects ; STAT6 Transcription Factor/metabolism/genetics ; NF-kappa B/metabolism/genetics ; }, abstract = {Islet cell transplantation (ICT) represents a promising therapeutic approach for addressing diabetes mellitus. However, the islet inflammation during transplantation significantly reduces the surgical outcome rate, which is related to the polarization of macrophages. Chitooligosaccharides (COS) was previously reported which could modulate the immune system, alleviate inflammation, regulate gut microecology, and repair the intestinal barrier. Therefore, we hypothesized COS could relieve pancreatic inflammation by regulating macrophage polarization and gut microbiota. First, 18S rDNA gene sequencing was performed on fecal samples from the ICT population, showing abnormally increased amount of Candida albicans, possibly causing pancreatic inflammation. Functional oligosaccharides responsible for regulating macrophage polarization and inhibiting the growth of Candida albicans were screened. Afterwards, human flora-associated T2D (HMA-T2D) mouse models of gut microbiota were established, and the ability of the selected oligosaccharides were validated in vivo to alleviate inflammation and regulate gut microbiota. The results indicated that ICT significantly decreased the alpha diversity of gut fungal, altered fungal community structures, and increased Candida albicans abundance. Moreover, Candida albicans promoted M1 macrophage polarization, leading to islet inflammation. COS inhibited Candida albicans growth, suppressed the MyD88-NF-κB pathway, activated STAT6, inhibited M1, and promoted M2 macrophage polarization. Furthermore, COS-treated HMA-T2D mice displayed lower M1 macrophage differentiation and higher M2 macrophage numbers. Additionally, COS also enhanced ZO-1 and Occludin mRNA expression, reduced Candida albicans abundance, and balanced gut microecology. This study illustrated that COS modulated macrophage polarization via the MyD88/NF-κB and STAT6 pathways, repaired the intestinal barrier, and reduced Candida albicans abundance to alleviate islet inflammation.}, } @article {pmid39691426, year = {2024}, author = {Yu, J and Chen, YX and Wang, JW and Wu, HT}, title = {Research progress on the relationship between traumatic brain injury and brain-gut-microbial axis.}, journal = {Ibrain}, volume = {10}, number = {4}, pages = {477-487}, pmid = {39691426}, issn = {2769-2795}, abstract = {Traumatic brain injury (TBI) is a common disease with a high rate of death and disability, which poses a serious threat to human health; thus, the effective treatment of TBI has been a high priority. The brain-gut-microbial (BGM) axis, as a bidirectional communication network for information exchange between the brain and gut, plays a crucial role in neurological diseases. This article comprehensively explores the interrelationship between the BGM axis and TBI, including its physiological effects, basic pathophysiology, and potential therapeutic strategies. It highlights how the bidirectional regulatory pathways of the BGM axis could provide new insights into clinical TBI treatment and underscores the necessity for advanced research and development of innovative clinical treatments for TBI.}, } @article {pmid39686442, year = {2024}, author = {Liu, F and Zhang, H and Fan, L and Yu, Q and Wang, S}, title = {Hotspots and development trends of gut microbiota in atopic dermatitis: A bibliometric analysis from 1988 to 2024.}, journal = {Medicine}, volume = {103}, number = {50}, pages = {e40931}, pmid = {39686442}, issn = {1536-5964}, mesh = {*Dermatitis, Atopic/microbiology/therapy ; *Gastrointestinal Microbiome ; Humans ; *Bibliometrics ; Probiotics/therapeutic use ; Prebiotics ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Atopic dermatitis (AD) is a prevalent inflammatory skin condition that commonly occurs in children. More and more scientific evidence suggests that gut microbiota plays an important role in the pathogenesis of AD, whereas there is no article providing a comprehensive summary and analysis. We aimed to analyze documents on AD and gut microbiota and identify hotspots and development trends in this field.

METHODS: Articles and reviews in the field of AD and gut microbiota from January 1, 1988 to October 20, 2024 were obtained from the Web of Science Core Collection database. Biblioshiny was utilized for evaluating and visualizing the core authors, journals, countries, documents, trend topics, and hotspots in this field.

RESULTS: Among 1672 documents, it indicated that the number of annual publications generally increased. The United States had the highest production, impact, and international collaboration. Journal of Allergy and Clinical Immunology was the journal of the maximum publications. Based on keyword co-occurrence and clustering analysis, "stratum-corneum lipids," "probiotics," "prebiotics," "fecal microbiota transplantation," "phage therapy," "short chain fatty-acids," "biologic therapy," and "skin inflammation" represented current trend topics. The pathological and molecular mechanisms and associated therapeutic methods for AD and gut microbiota were the research hotspots. The incorporation of microbiota-based therapies alongside conventional treatments can contribute to better clinical outcomes.

CONCLUSION: We highlighted that gut microbiota may exacerbate symptoms of AD through various aspects, including immunity, metabolites, and neuroendocrine pathways. More efforts are required to investigate the safety and efficacy of gut microbial management methods for the prevention and treatment of AD.}, } @article {pmid39684918, year = {2024}, author = {Li, C and Chen, S and Wang, Y and Su, Q}, title = {Microbiome-Based Therapeutics for Insomnia.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684918}, issn = {1422-0067}, mesh = {Humans ; *Sleep Initiation and Maintenance Disorders/therapy/microbiology ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation/methods ; *Probiotics/therapeutic use ; *Prebiotics/administration & dosage ; Animals ; Synbiotics ; }, abstract = {Insomnia poses considerable risks to both physical and mental health, leading to cognitive impairment, weakened immune function, metabolic dysfunction, cardiovascular issues, and reduced quality of life. Given the significant global increase in insomnia and the growing scientific evidence connecting gut microbiota to this disorder, targeting gut microbiota as an intervention for insomnia has gained popularity. In this review, we summarize current microbiome-based therapeutics for insomnia, including dietary modifications; probiotic, prebiotic, postbiotic, and synbiotic interventions; and fecal microbiota transplantation. Moreover, we assess the capabilities and weaknesses of these technologies to offer valuable insights for future studies.}, } @article {pmid39684788, year = {2024}, author = {Moreno, RJ and Ashwood, P}, title = {An Update on Microbial Interventions in Autism Spectrum Disorder with Gastrointestinal Symptoms.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684788}, issn = {1422-0067}, support = {HD090214/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; *Autism Spectrum Disorder/therapy/microbiology ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation/methods ; *Dysbiosis/therapy/microbiology ; *Prebiotics ; Gastrointestinal Diseases/therapy/microbiology ; Anti-Bacterial Agents/therapeutic use ; Animals ; }, abstract = {In the United States, autism spectrum disorder (ASD) affects 1 in 33 children and is characterized by atypical social interactions, communication difficulties, and intense, restricted interests. Microbial dysbiosis in the gastrointestinal (GI) tract is frequently observed in individuals with ASD, potentially contributing to behavioral manifestations and correlating with worsening severity. Moreover, dysbiosis may contribute to the increased prevalence of GI comorbidities in the ASD population and exacerbate immune dysregulation, further worsening dysbiosis. Over the past 25 years, research on the impact of microbial manipulation on ASD outcomes has gained substantial interest. Various approaches to microbial manipulation have been preclinically and clinically tested, including antibiotic treatment, dietary modifications, prebiotics, probiotics, and fecal microbiota transplantation. Each method has shown varying degrees of success in reducing the severity of ASD behaviors and/or GI symptoms and varying long-term efficacy. In this review, we discuss these microbiome manipulation methods and their outcomes. We also discuss potential microbiome manipulation early in life, as this is a critical period for neurodevelopment.}, } @article {pmid39682952, year = {2024}, author = {Ma, H and Mueed, A and Ma, Y and Ibrahim, M and Su, L and Wang, Q}, title = {Fecal Microbiota Transplantation Activity of Floccularia luteovirens Polysaccharides and Their Protective Effect on Cyclophosphamide-Induced Immunosuppression and Intestinal Injury in Mice.}, journal = {Foods (Basel, Switzerland)}, volume = {13}, number = {23}, pages = {}, pmid = {39682952}, issn = {2304-8158}, support = {2021YFD1600401//National Key Research and Development Program of China/ ; }, abstract = {Floccularia luteovirens polysaccharides (FLP1s) have potential biological activities. Our previous study showed that FLP1s positively regulated gut immunity and microbiota. However, it is still unclear whether FLP1s mediate gut microbiota in immunosuppressed mice. This research aims to explore the relationship between FLP1-mediated gut microbes and intestinal immunity in immunosuppressed mice through fecal microbiota transplantation (FMT). The results demonstrated that FLP1s exhibited prebiotic and anti-immunosuppressive effects on CTX-induced immunosuppressed mice. FFLP1 treatment (microbiota transplantation from the fecal sample) remarkably elevated the production of sIgA and secretion of the anti-inflammatory cytokines IL-4, TNF-α, and IFN-γ in the intestine of CTX-treated mice, inducing activation of the MAPK pathway. Moreover, FFLP1s mitigated oxidative stress by activating the Nrf2/Keap1 signaling pathway and strengthened the intestinal barrier function by upregulating the expression level of tight junction proteins (occludin, claudin-1, MUC-2, and ZO-1). Furthermore, FFPL1s restored gut dysbiosis in CTX-treated immunosuppressed mice by increasing the abundance of Alloprevotella, Lachnospiraceae, and Bacteroides. They also modified the composition of fecal metabolites, leading to enhanced regulation of lipolysis in adipocytes, the cGMP-PKG pathway, the Rap1 signaling pathway, and ovarian steroidogenesis, as indicated by KEGG pathway analysis. These findings indicate that FLP1s could modulate the response of the intestinal immune system through regulation of the gut microbiota, thus promoting immune activation in CTX-treated immunosuppressed mice. FLP1s can serve as a natural protective agent against CTX-induced immune injury.}, } @article {pmid39682542, year = {2024}, author = {Morales, C and Ballestero, L and Del Río, P and Barbero-Herranz, R and Olavarrieta, L and Gómez-Artíguez, L and Galeano, J and Avendaño-Ortiz, J and Basterra, J and Del Campo, R}, title = {Should the Faecal Microbiota Composition Be Determined to Certify a Faecal Donor?.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {23}, pages = {}, pmid = {39682542}, issn = {2075-4418}, support = {XX//Mikrobiomik/ ; }, abstract = {BACKGROUND/OBJECTIVES: Faecal microbiota transplantation (FMT) is considered a safe and effective therapy for recurrent Clostridioides difficile infection. It is the only current clinical indication for this technique, although numerous clinical research studies and trials propose its potential usefulness for treating other pathologies. Donor selection is a very rigorous process, based on a personal lifestyle interview and the absence of known pathogens in faeces and serum, leading to only a few volunteers finally achieving the corresponding certification. However, despite the high amount of data generated from the ongoing research studies relating microbiota and health, there is not yet a consensus defining what is a "healthy" microbiota. To date, knowledge of the composition of the microbiota is not a requirement to be a faecal donor. The aim of this work was to evaluate whether the analysis of the composition of the microbiota by massive sequencing of 16S rDNA could be useful in the selection of the faecal donors.

METHODS: Samples from 10 certified donors from Mikrobiomik Healthcare Company were collected and sequenced using 16S rDNA in a MiSeq (Illumina) platform. Alpha (Chao1 and Shannon indices) and beta diversity (Bray-Curtis) were performed using the bioinformatic web server Microbiome Analyst. The differences in microbial composition at the genera and phyla levels among the donors were evaluated.

RESULTS: The microbial diversity metric by alpha diversity indexes showed that most donors exhibited a similar microbial diversity and richness, whereas beta diversity by 16S rDNA sequencing revealed significant inter-donor differences, with a more stable microbial composition over time in some donors. The phyla Bacillota and Bacteroidota were predominant in all donors, while the density of other phyla, such as Actinomycota and Pseudomonota, varied among individuals. Each donor exhibited a characteristic genera distribution pattern; however, it was possible to define a microbiome core consisting of the genera Agathobacter, Eubacterium, Bacteroides, Clostridia UCG-014 and Akkermansia. Conclusions: The results suggest that donor certification does not need to rely exclusively on their microbiota composition, as it is unique to each donor. While one donor showed greater microbial diversity and richness, clear criteria for microbial normality and health have yet to be established. Therefore, donor certification should focus more on clinical and lifestyle aspects.}, } @article {pmid39681213, year = {2024}, author = {Liu, X and Tan, X and Yu, Y and Niu, J and Zhao, B and Wang, Q}, title = {Short chain fatty acids mediates complement C1q pathway alleviation of perioperative neurocognitive disorders.}, journal = {Neuropharmacology}, volume = {265}, number = {}, pages = {110266}, doi = {10.1016/j.neuropharm.2024.110266}, pmid = {39681213}, issn = {1873-7064}, abstract = {Perioperative neurocognitive disorders (PND) is one of the most common postoperative complications, which can lead to a harmful impact on self-dependence, longer hospital stays, increased medical costs, morbidity, and mortality amongst older adults. Microglia can modulate synapse elimination involved in the complement component protein 1q (C1q) pathway to induce cognitive dysfunction, which is significantly improved by short chain fatty acids (SCFAs) treatment. Here we investigate the effects of SCFAs treatment on PND via mediating C1q complement pathway. High-throughput sequencing of 16S rDNA from fecal samples of male SD rats was applied to assess the changes in gut microbiota. Fecal microbiota transplantation (FMT) was performed to investigate whether gut microbiota from PND rats could alter cognitive impairment. The blood from the rat tail vein was collected to measure the SCFAs concentrations. Hippocampal and brain tissue samples were obtained to perform Western blots, Golgi and immunofluorescence staining. Primary microglia treated with SCFAs or Histone deacetylase inhibitor were cultured to measure microglial activation states and the expression of acetylated histone. The 16S rDNA sequencing results showed that PND rats had the significant changes in the species diversity of the gut microbiota and the metabolite of specifc species. Gut microbiota from PND rats could alter spatial learning and memory, and meanwhile, the changed SCFAs concentrations in plasma were involved. The synapse elimination in PND rats was strikingly reversed by SCFAs treatment involved in modulation complement C1q via suppressing neuroinflammation. This suggests that a link between gut microbiota dysbiosis and cognitive function impairment is involved in synapse elimination via mediating complement C1q pathway. SCFAs treatment can alleviate PND, the mechanisms of which may be associated with regulating complement C1q pathway.}, } @article {pmid39680691, year = {2024}, author = {Yang, JC and Lagishetty, V and Aja, E and Arias-Jayo, N and Chang, C and Hauer, M and Katzka, W and Zhou, Y and Sedighian, F and Koletic, C and Liang, F and Dong, TS and Situ, J and Troutman, R and Buri, H and Bhute, S and Simpson, CA and Braun, J and Jacob, N and Jacobs, JP}, title = {Biogeographical distribution of gut microbiome composition and function is partially recapitulated by fecal transplantation into germ-free mice.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/ismejo/wrae250}, pmid = {39680691}, issn = {1751-7370}, abstract = {Fecal microbiota transplantation has been vital for establishing whether host phenotypes can be conferred through the microbiome. However, whether the existing microbial ecology along the mouse gastrointestinal tract can be recapitulated in germ-free mice colonized with stool remains unknown. We first identified microbes and their predicted functions specific to each of six intestinal regions in three cohorts of specific pathogen-free mice spanning two facilities. Of these region-specific microbes, the health-linked genus Akkermansia was consistently enriched in the lumen of the small intestine compared to the colon. Predictive functional modeling on 16S rRNA gene amplicon sequencing data recapitulated in shotgun sequencing data revealed increased microbial central metabolism, lipolytic fermentation, and cross-feeding in the small intestine, whereas butyrate synthesis was colon-enriched. Neuroactive compound metabolism also demonstrated regional specificity, including small intestine-enriched gamma-aminobutyric acid degradation and colon-enriched tryptophan degradation. Specifically, the jejunum and ileum stood out as sites with high predicted metabolic and neuromodulation activity. Differences between luminal and mucosal microbiomes within each site of the gastrointestinal tract were largely facility-specific, though there were a few consistent patterns in microbial metabolism in specific pathogen-free mice. These included luminal enrichment of central metabolism and cross-feeding within both the small intestine and the colon, and mucosal enrichment of butyrate synthesis within the colon. Across three cohorts of germ-free mice colonized with mice or human stool, compositional and functional region specificity were inconsistently reproduced. These results underscore the importance of investigating the spatial variation of the gut microbiome to better understand its impact on host physiology.}, } @article {pmid39680624, year = {2024}, author = {Zuo, H and Jiang, W and Gao, J and Ma, Z and Li, C and Peng, Y and Jin, J and Zhan, X and Lv, W and Liu, X and Hu, J and Zhang, M and Jia, Y and Xu, Z and Tang, J and Zheng, R and Zuo, B}, title = {SYISL Knockout Promotes Embryonic Muscle Development of Offspring by Modulating Maternal Gut Microbiota and Fetal Myogenic Cell Dynamics.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2410953}, doi = {10.1002/advs.202410953}, pmid = {39680624}, issn = {2198-3844}, support = {32221005//National Natural Science Foundation of China/ ; 31900448//National Natural Science Foundation of China/ ; 2021YFA0805903//National Key Research and Development Program of China/ ; 2021CFA018//Natural Science Foundation of Hubei Province/ ; 2021-620-000-001-030//Agricultural Innovation Fund of Hubei Province/ ; 2022ESOF007//Open Fund of Hubei Key Laboratory of Embryonic Stem Cell Research/ ; 2023ZD04072//Biological Breeding-National Science and Technology Major Project/ ; }, abstract = {Embryonic muscle fiber formation determines post-birth muscle fiber totals. The previous research shows SYISL knockout significantly increases muscle fiber numbers and mass in mice, but the mechanism remains unclear. This study confirms that the SYISL gene, maternal gut microbiota, and their interaction significantly affect the number of muscle fibers in mouse embryos through distinct mechanisms, as SYISL knockout alters maternal gut microbiota composition and boosts butyrate levels in embryonic serum. Both fecal microbiota transplantation and butyrate feeding significantly increase muscle fiber numbers in offspring, with butyrate inhibiting histone deacetylases and increasing histone acetylation in embryonic muscle. Combined analysis of RNA-seq between wild-type and SYISL knockout mice with ChIP-seq for H3K9ac and H3K27ac reveals that SYISL and maternal microbiota interaction regulates myogenesis via the butyrate-HDAC-H3K9ac/H3K27ac pathway. Furthermore, scRNA-seq analysis shows that SYISL knockout alone significantly increases the number and proportion of myogenic cells and their dynamics, independently of regulating histone acetylation levels. Cell communication analysis suggests that this may be due to the downregulation of signaling pathways such as MSTN and TGFβ. Overall, multiple pathways are highlighted through which SYISL influences embryonic muscle development, offering valuable insights for treating muscle diseases and improving livestock production.}, } @article {pmid39679941, year = {2024}, author = {Wu, Q and Wang, J and Tu, C and Chen, P and Deng, Y and Yu, L and Xu, X and Fang, X and Li, W}, title = {Gut microbiota of patients insusceptible to olanzapine-induced fatty liver disease relieves hepatic steatosis in rat.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpgi.00167.2024}, pmid = {39679941}, issn = {1522-1547}, support = {82173903//MOST | National Natural Science Foundation of China (NSFC)/ ; 81903686//Natural Science Foundation for Young Scientists of Shanxi Province (Young Scientists Fund of the National Natural Science Foundation of China)/ ; }, abstract = {Olanzapine-induced fatty liver disease continues to pose vital therapeutic challenges in the treatment of psychiatric disorders. In addition, we observed that some patients were less prone to hepatic steatosis induced by olanzapine. Therefore, we aimed to investigate the role and the underlying mechanism of the intestinal flora in olanzapine-mediated hepatic side effects and explore the possible countermeasures. Our results showed that patients with different susceptibilities to olanzapine-induced fatty liver disease had different gut microbial diversity and composition. Furthermore, we performed fecal microbiota treatment (FMT), and confirmed that the gut microbiome of patients less prone to the fatty liver caused by olanzapine exhibited an alleviation against fatty liver disease in rats. In terms of mechanism, we revealed that the crosstalk of leptin with the gut-short-chain fatty acid (SCFA)-liver axis play a critical role in olanzapine-related fatty degeneration in liver. These findings propose a promising strategy for overcoming the issues associated with olanzapine application and will hopefully inspire future in-depth research of fecal microbiota-based therapy in olanzapine-induced fatty liver disease.}, } @article {pmid39679465, year = {2024}, author = {Wang, M and Ma, Y and Zeng, B and Yang, W and Huang, C and Tang, B}, title = {Influence of the Gut Microbiota, Metabolism and Environment on Neuropsychiatric Disorders.}, journal = {Current reviews in clinical and experimental pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/0127724328335219241202142003}, pmid = {39679465}, issn = {2772-4336}, abstract = {The two-way communication between intestinal microbiota and the central nervous system (the microbiota-gut-brain axis) is involved in the regulation of brain function, neurodevelopment, and aging. The microbiota-gut-brain axis dysfunction may be a predisposition factor for Parkinson's disease (PD), Alzheimer's disease (AD), Autism spectrum disorder (ASD), and other neurological diseases. However, it is not clear whether gut microbiota dysfunction contributes to neuropsychiatric disorders. Changes in the gut microbiota may modulate or modify the effects of environmental factors on neuropsychiatric disorders. Factors that impact neuropsychiatric disorders also influence the gut microbiota, including diet patterns, exercise, stress and functional gastrointestinal disorders. These factors change microbiome composition and function, along with the metabolism and immune responses that cause neuropsychiatric disorders. In this review, we summarized epidemiological and laboratory evidence for the influence of the gut microbiota, metabolism and environmental factors on neuropsychiatric disorders incidence and outcomes. Furthermore, the role of gut microbiota in the two-way interaction between the gut and the brain was also reviewed, including the vagus nerve, microbial metabolism, and immuno-inflammatory responses. We also considered the therapeutic strategies that target gut microbiota in the treatment of neuropsychiatric disorders, including prebiotics, probiotics, Fecal microbiota transplant (FMT), and antibiotics. Based on these data, possible strategies for microbiota-targeted intervention could improve people's lives and prevent neuropsychiatric disorders in the future.}, } @article {pmid39679306, year = {2024}, author = {Hasnaoui, A and Trigui, R and Giuffrida, M}, title = {Gut microbiota and mesenteric adipose tissue interactions in shaping phenotypes and treatment strategies for Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {30}, number = {46}, pages = {4969-4976}, pmid = {39679306}, issn = {2219-2840}, mesh = {*Crohn Disease/microbiology/immunology/therapy ; Humans ; *Gastrointestinal Microbiome/immunology ; *Dysbiosis/immunology ; *Fecal Microbiota Transplantation ; *Phenotype ; *Mesentery ; Adipose Tissue/immunology/microbiology/metabolism ; Bacterial Translocation ; Cytokines/metabolism ; }, abstract = {In this letter, we commented on the article by Wu et al. We examined the interactions between mesenteric adipose tissue, creeping fat, and gut microbiota in Crohn's disease (CD), a condition marked by chronic gastrointestinal inflammation with a rising global incidence. The pathogenesis of CD involves complex genetic, environmental, and microbial factors. Dysbiosis, which is an imbalance in gut microbial communities, is frequently observed in CD patients, highlighting the pivotal role of the gut microbiota in disease progression and the inflammatory response. Recent studies have shown that mesenteric adipose tissue and creeping fat actively contribute to inflammation by producing proinflammatory cytokines. The relationship between creeping fat and altered microbiota can shift from a potentially protective role to one that encourages bacterial translocation, further complicating disease management. Recent research has suggested that fecal microbiota transplantation could help restore microbial balance, offering a promising therapeutic strategy to improve clinical disease response.}, } @article {pmid39679283, year = {2024}, author = {Chen, J and Yang, H and Qin, Y and Zhou, X and Ma, Q}, title = {Tryptophan Ameliorates Metabolic Syndrome by Inhibiting Intestinal Farnesoid X Receptor Signaling: The Role of Gut Microbiota-Bile Acid Crosstalk.}, journal = {Research (Washington, D.C.)}, volume = {7}, number = {}, pages = {0515}, pmid = {39679283}, issn = {2639-5274}, abstract = {Background and Aims: Metabolic syndrome (MS) is a progressive metabolic disease characterized by obesity and multiple metabolic disorders. Tryptophan (Trp) is an essential amino acid, and its metabolism is linked to numerous physiological functions and diseases. However, the mechanisms by which Trp affects MS are not fully understood. Methods and Results: In this study, experiments involving a high-fat diet (HFD) and fecal microbiota transplantation (FMT) were conducted to investigate the role of Trp in regulating metabolic disorders. In a mouse model, Trp supplementation inhibited intestinal farnesoid X receptor (FXR) signaling and promoted hepatic bile acid (BA) synthesis and excretion, accompanied by elevated levels of conjugated BAs and the ratio of non-12-OH to 12-OH BAs in hepatic and fecal BA profiles. As Trp alters the gut microbiota and the abundance of bile salt hydrolase (BSH)-enriched microbes, we collected fresh feces from Trp-supplemented mice and performed FMT and sterile fecal filtrate (SFF) inoculations in HFD-treated mice. FMT and SFF not only displayed lipid-lowering properties but also inhibited intestinal FXR signaling and increased hepatic BA synthesis. This suggests that the gut microbiota play a beneficial role in improving BA metabolism through Trp. Furthermore, fexaramine (a gut-specific FXR agonist) reversed the therapeutic effects of Trp, suggesting that Trp acts through the FXR signaling pathway. Finally, validation in a finishing pig model revealed that Trp improved lipid metabolism, enlarged the hepatic BA pool, and altered numerous glycerophospholipid molecules in the hepatic lipid profile. Conclusion: Our studies suggest that Trp inhibits intestinal FXR signaling mediated by the gut microbiota-BA crosstalk, which in turn promotes hepatic BA synthesis, thereby ameliorating MS.}, } @article {pmid39679259, year = {2024}, author = {Feng, M and Zou, Z and Shou, P and Peng, W and Liu, M and Li, X}, title = {Gut microbiota and Parkinson's disease: potential links and the role of fecal microbiota transplantation.}, journal = {Frontiers in aging neuroscience}, volume = {16}, number = {}, pages = {1479343}, pmid = {39679259}, issn = {1663-4365}, abstract = {Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide and seriously affects the quality of life of elderly patients. PD is characterized by the loss of dopaminergic neurons in the substantia nigra as well as abnormal accumulation of α-synuclein in neurons. Recent research has deepened our understanding of the gut microbiota, revealing that it participates in the pathological process of PD through the gut-brain axis, suggesting that the gut may be the source of PD. Therefore, studying the relationship between gut microbiota and PD is crucial for improving our understanding of the disease's prevention, diagnosis, and treatment. In this review, we first describe the bidirectional regulation of the gut-brain axis by the gut microbiota and the mechanisms underlying the involvement of gut microbiota and their metabolites in PD. We then summarize the different species of gut microbiota found in patients with PD and their correlations with clinical symptoms. Finally, we review the most comprehensive animal and human studies on treating PD through fecal microbiota transplantation (FMT), discussing the challenges and considerations associated with this treatment approach.}, } @article {pmid39677507, year = {2024}, author = {Li, Y and Xiao, P and Ding, H and Wang, H and Xu, Q and Wang, R and Zheng, L and Song, X and Wang, Y and Zhang, T}, title = {Fecal Microbiota Transplantation in Children with Autism.}, journal = {Neuropsychiatric disease and treatment}, volume = {20}, number = {}, pages = {2391-2400}, pmid = {39677507}, issn = {1176-6328}, abstract = {PURPOSE: This research aimed to explore the clinical efficacy of fecal microbiota transplantation (FMT) in treating children with autism spectrum disorder (ASD).

METHODS: In this single-arm prospective study, every participant received FMT therapy, followed by an 8-week follow-up. Children unable to swallow lyophilized capsules (Caps) received fecal solution through transendoscopic enteral tube (TET) or nasal jejunal tube (NJT) approaches. All participants underwent assessments of ASD core symptoms, gastrointestinal (GI) symptoms and sleep status initially, after treatment and during follow-up. The study outcomes included the changes in scores of the Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), Gastrointestinal Symptoms Rating Scale (GSRS) and Sleep Disturbance Scale for Children (SDSC), as well as the adverse events (AEs).

RESULTS: 98 participants were involved, consisting of 80 males and 18 females, with a median age of 7 years. 73 children received the FMT in the form of Caps, while 13 patients underwent the procedure through TET and 12 patients via NJT. Improvements were observed in all outcome measures for Caps and NJT groups at both the post-treatment and 8-week follow-up evaluations. Adjusted between-group analyses at post-treatment and follow-up showed that Caps and NJT group had greater reduction in ABC, CARS and SRS scores compared with TET group, while NJT group had greater reduction in SDSC scores compared with Caps and TET group. The incidence of AEs was 8.2% in the Caps group, 23.1% in the TET group, and 8.3% in the NJT group, with no serious AEs reported.

CONCLUSION: FMT treatment can improve the core symptoms, GI symptoms and sleep disturbances in children with ASD. The upper GI tract routes, including Caps and NJT, may be more effective and safe compared to the lower GI tract route of TET.}, } @article {pmid39265742, year = {2025}, author = {Herner, A and Nennstiel, S and Ramser, M and Turina, M and Schlag, C}, title = {New therapeutic approach for anastomotic leaks after ileoanal J-pouch construction in patients with ulcerative colitis.}, journal = {Gastrointestinal endoscopy}, volume = {101}, number = {1}, pages = {222-223}, doi = {10.1016/j.gie.2024.09.004}, pmid = {39265742}, issn = {1097-6779}, } @article {pmid39674485, year = {2024}, author = {Ni, Z and Chen, L and Qian, X and Yong, Y and Wu, M and Yihao, L and Li, J and Wang, Y and Li, L and Shao, Y and Chen, A}, title = {Preliminary characterization of Ramaria botrytoides polysaccharide RB-P1-1 and analysis of its hypoglycemic effects by altering the gut microbiota and metabolites in mice with type 2 diabetes mellitus.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {138774}, doi = {10.1016/j.ijbiomac.2024.138774}, pmid = {39674485}, issn = {1879-0003}, abstract = {Gut microbiota has a symbiotic relationship with the host and is closely linked to the development of type 2 diabetes mellitus (T2DM). Polysaccharides are natural bioactive compounds with beneficial effects on T2DM; however, the mechanisms underlying their effects remain unclear. This study investigated the hypoglycemic effects of a purified polysaccharide, RB-P1-1, from Ramaria botrytoides and assessed its association with gut microbiota and metabolite changes using 16S rDNA sequencing and liquid chromatography-mass spectrometry, respectively. Hypoglycemic effects were evaluated after microbial community restoration via fecal microbiota transplantation. RB-P1-1 significantly improved hyperglycemia profiles and reshaped gut microbiota, increasing the abundance of Alistipes, Bacteroides, Ruminococcus, Odoribacter, Akkermansia, and Turicibacter. RB-P1-1 modulated microbiota metabolites associated with hypoglycemic effects, including pyridoxamine, L-histidine, quercetin, 3-phosphonopropionic acid, oleoylethanolamide, 3-ketocholanic acid, 4-phenylbutyric acid, LysoPC(P-16:0/0:0), LysoPC(18:2), and short-chain fatty acids, and altered various metabolic pathways involved in T2DM development. Gut microbiota that showed altered abundance were correlated with metabolites that showed altered concentration. Gut microbiota isolated from the RB-P1-1-treated group alleviated the symptoms associated with T2DM. These results suggest RB-P1-1 is an effective active ingredient in the treatment of T2DM by modulating gut microbiota and metabolites.}, } @article {pmid39674267, year = {2024}, author = {Cheng, X and Yang, J and Wang, Z and Zhou, K and An, X and Xu, ZZ and Lu, H}, title = {Modulating intestinal viruses: A potential avenue for improving metabolic diseases with unresolved challenges.}, journal = {Life sciences}, volume = {361}, number = {}, pages = {123309}, doi = {10.1016/j.lfs.2024.123309}, pmid = {39674267}, issn = {1879-0631}, abstract = {The gut microbiome affects the occurrence and development of metabolic diseases, with a significant amount of research focused on intestinal bacteria. As an important part of the gut microbiome, gut viruses were studied recently, particularly through fecal virome transplantation (FVT), revealing manipulating the gut virus could reverse overweight and glucose intolerance in mice. And human cohort studies found gut virome changed significantly in patients with metabolic disease. By summarizing those studies, we compared the research and analytical methods, as well as the similarities and differences in their results, and analyzed the reasons for these discrepancies. FVT provided potential value to improve metabolic diseases, but the mechanisms involved and the effect of FVT on humans should be investigated further. The potential methods of regulating intestinal virome composition and the possible mechanisms of intestinal virome changes affecting metabolic diseases were also discussed.}, } @article {pmid39672770, year = {2024}, author = {Facchin, S and Cardin, R and Patuzzi, I and Carlotto, C and Minotto, M and Barberio, B and Zingone, F and Besutti, VM and Castagliuolo, I and Cattelan, A and Savarino, EV}, title = {Long-term stability and efficacy of frozen fecal microbiota transplant (FMT) product at 24 months.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.dld.2024.11.025}, pmid = {39672770}, issn = {1878-3562}, abstract = {BACKGROUND: Freezing donor fecal microbiota has improved fecal microbiota transplantation (FMT) for recurrent C. difficile infection (CDI), achieving short-term effectiveness similar to fresh-samples. Research shows frozen fecal matter remains effective for up to 12-months at -80 °C.

OBJECTIVE: To assess how long-term-freezing and thawing affect the viability, microbial composition, and clinical efficacy of frozen-stools for FMT.

METHODS: Stool samples from three donors were processed into 18 aliquots, thawed at intervals over two years, and analyzed for cell viability and microbial load. Microbiota composition was assessed through 16S-sequencing, with diversity evaluated using the Shannon-index and Principal-Coordinates-Analysis based on Bray-Curtis-distance (α/β-diversity). The same donors provided fecal material for a total of 23 FMT procedures, including 15 for CDI and 8 off-label.

RESULTS: We found that donor stools frozen for two years contained viable bacteria comparable to fresh samples, with anaerobic and aerobic species remaining viable for 24 months. Despite a reduction in colony-forming-units, FMT was successful in 71.4 % and 100 % of the cases at one year and at the end of follow-up, respectively. Most bacterial changes occurred among anaerobic species (Blautia producta and Bifidobacterium adolescentis), increasing post-thawing. Notably, specific taxa, (C. aerofaciens and Erysipelotrichaceae_Cc115), showed significant unexplained increase.

CONCLUSION: Long-term-stool-storage enhances FMT accessibility without compromising its success, despite taxonomic changes after 24 months.}, } @article {pmid39672439, year = {2024}, author = {Chen, P and Chen, F and Hou, T and Hu, X and Xia, C and Zhang, J and Shen, S and Li, C and Li, K}, title = {Administration time modify the anxiolytic and antidepressant effects of inulin via gut-brain axis.}, journal = {International journal of biological macromolecules}, volume = {288}, number = {}, pages = {138698}, doi = {10.1016/j.ijbiomac.2024.138698}, pmid = {39672439}, issn = {1879-0003}, abstract = {An imbalance in the microbiota-gut-brain axis exerts an essential effect on the pathophysiology of depressive and anxiety disorders. Our previous research revealed that the timing of inulin administration altered its effects on chronic unpredictable mild stress (CUMS)-induced anxiety and depression. However, it is still unclear if the gut-brain axis is primarily responsible for these effects. In this study, fecal microbiota transplantation (FMT) confirmed that inulin administration at different times alleviated CUMS-induced anxiety- and depression-like behaviors via the gut-brain axis. The time of administration seemed to modify the anxiolytic and antidepressant effects of inulin, and inulin intervention in the evening was more pronounced in inhibiting the inflammatory responses than that of morning inulin intervention. Serum metabolomics analysis showed that the main differential metabolites, including fenofibric acid, 4'-Hydroxyfenoprofen glucuronide and 5-(4-Hydroxybenzyl)thiazolidine-2,4-dione may be vital for the anxiolytic and antidepressant effects of different inulin treatment times. Our results suggested that inulin administration in the evening was more effective in alleviating the inflammatory responses and improving amino acids metabolism. This study provides a new potential link between the microbiota-gut-brain axis and chrono-nutrition, demonstrating that a more appropriate administration time results in a better intervention effect.}, } @article {pmid39672393, year = {2024}, author = {He, P and He, H and Su, C and Liu, Y and Wang, J and Wu, Y and Wang, B and Wang, S and Zhao, J}, title = {Amomum villosum Lour. alleviates pre-eclampsia by inducing enrichment of Bifidobacterium bifidum through vanillic acid to inhibit placental ferroptosis.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {119217}, doi = {10.1016/j.jep.2024.119217}, pmid = {39672393}, issn = {1872-7573}, abstract = {Amomum villosum Lour. (AVL), a traditional Chinese medicine, is widely used to pregnancy-related vomiting and prevent miscarriage. Pre-eclampsia (PE) is a severe pregnancy syndrome. Recent studies have demonstrated interactions between PE and the digestive system. However, it is uncertain that AVL against PE was associated with the gut.

AIM OF THE STUDY: The current research examined the curative impact of AVL on PE and underly mechanisms based on the gut-placenta axis.

MATERIALS AND METHODS: A water decoction of AVL (WOA) was extracted in boiling water, and then the decoction was converted into dried particles by freeze drying. An NG-nitro-L-arginine methyl ester (L-NAME)-induced PE mouse model was established and the preventative activity of WOA was evaluated. Furthermore, the gut microbial composition and structure were analyzed using 16S rRNA gene sequencing. Fecal microbiota transplantation (FMT) experiment was applied to confirm the efficacy of gut microbiota remodeled by WOA.

RESULTS: WOA presented protective efficacy against PE. Notably, WOA induced a significant decrease in maternal hypertension and urine protein levels and promoted fetal intrauterine growth in a dose-dependent manner, thereby improving adverse pregnancy outcomes. Moreover, WOA modulated the angiogenic imbalance by decreasing the ratio between sFlt-1 (soluble fms-like tyrosine kinase 1) and PlGF (placental growth factor) to repair placental injury and inhibited placental ferroptosis by increasing the protein levels of FPN1, FTH1, xCT, and GPX4. Tight junction proteins (ZO-1, Occludin, Claudin1) in the placenta and colon were significantly upregulated by WOA, leading to enhanced placental and gut barriers. WOA rescued intestinal dysbiosis by enriching Bifidobacterium and Akkermansia. Fecal microbiota transplantation (FMT) experiments revealed that the protection of WOA on placenta and gut were dependent on the gut microbial composition. Furthermore, supplementation with both Bifidobacterium bifidum (B. bifidum) and vanillic acid (VA, the major component of WOA) ameliorated PE symptoms. Intriguingly, results from both in vivo and in vitro analyses indicated that the B. bifidum population was enriched by VA.

CONCLUSIONS: This research is the first to demonstrate that WOA prevents PE by enriching Bifidobacterium bifidum, strengthening the gut-placenta barrier, and inhibiting placental ferroptosis. Our findings provide compelling evidence for the vital involvement of the gut-placental axis in the protection of AVL on PE, presenting a novel target for the clinic.}, } @article {pmid39671402, year = {2024}, author = {, }, title = {Retraction: Fecal microbiota transplantation for treatment of recurrent C. difficile infection: An updated randomized controlled trial meta-analysis.}, journal = {PloS one}, volume = {19}, number = {12}, pages = {e0316040}, pmid = {39671402}, issn = {1932-6203}, } @article {pmid39670752, year = {2024}, author = {Peterson, D and Weidenmaier, C and Timberlake, S and Gura Sadovsky, R}, title = {Depletion of key gut bacteria predicts disrupted bile acid metabolism in inflammatory bowel disease.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0199924}, doi = {10.1128/spectrum.01999-24}, pmid = {39670752}, issn = {2165-0497}, abstract = {The gut microbiome plays a key role in bile acid (BA) metabolism, where a diversity of metabolic products contribute to human health and disease. In particular, Inflammatory Bowel Disease (IBD) is characterized by a low concentration of secondary bile acids (SBAs), whose transformation from primary bile acids (PBAs) is an essential function performed solely by gut bacteria. BA-transformation activity mediated by the bile acid inducible (bai) operon has been functionally characterized in the genus Clostridium, and homologous bai gene sequences have been found in metagenome-assembled genomes (MAGs) belonging to other taxa in the human gut, but it is unclear which species of bai-carrying bacteria perform physiologically significant amounts of bile acid transformation in healthy and sick individuals. Here, we analyzed hundreds of stool samples with paired metagenomic and metabolomic data from IBD patients and controls and found that the abundance of the bai operon in metagenomic samples was highly predictive of that sample's high- or low-SBA metabolic state. We further found that bai genes from the Clostridium species best characterized as BA transformers were more prevalent in IBD patients than in non-IBD controls, while bai genes from uncharacterized taxa known only from MAGs were much more physiologically relevant in non-IBD samples. These un-isolated clades of BA-transforming bacteria merit further research; as beyond their prevalence in the human population, we found some cases in which they engrafted in IBD patients who had undergone fecal microbiota transplantation and experienced a clinical response.IMPORTANCEIn this paper, we identify specific bacteria that perform an important metabolic function in the human gut and demonstrate that in the guts of a large subset of patients with IBD, these bacteria are missing and the function is defective. This is a rare example where the correlation between the absence of specific bacteria and the dysfunction of metabolism is directly observed, not in mice nor in the lab, but in physiologic microbial communities in the human gut. Our results point to a path for studying how a small but important set of bacteria is affected by conditions in the IBD gut and perhaps to the development of interventions to mitigate the loss of these bacteria in IBD.}, } @article {pmid39669573, year = {2024}, author = {Yan, J and Yang, L and Ren, Q and Zhu, C and Du, H and Wang, Z and Qi, Y and Xian, X and Chen, D}, title = {Gut microbiota as a biomarker and modulator of anti-tumor immunotherapy outcomes.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1471273}, pmid = {39669573}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Neoplasms/therapy/immunology ; *Immunotherapy/methods ; *Immune Checkpoint Inhibitors/therapeutic use ; Animals ; Biomarkers, Tumor ; Probiotics/therapeutic use ; Treatment Outcome ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; }, abstract = {Although immune-checkpoint inhibitors (ICIs) have significantly improved cancer treatment, their effectiveness is limited by primary or acquired resistance in many patients. The gut microbiota, through its production of metabolites and regulation of immune cell functions, plays a vital role in maintaining immune balance and influencing the response to cancer immunotherapies. This review highlights evidence linking specific gut microbial characteristics to increased therapeutic efficacy in a variety of cancers, such as gastrointestinal cancers, melanoma, lung cancer, urinary system cancers, and reproductive system cancers, suggesting the gut microbiota's potential as a predictive biomarker for ICI responsiveness. It also explores the possibility of enhancing ICI effectiveness through fecal microbiota transplantation, probiotics, prebiotics, synbiotics, postbiotics, and dietary modifications. Moreover, the review underscores the need for extensive randomized controlled trials to confirm the gut microbiota's predictive value and to establish guidelines for microbiota-targeted interventions in immunotherapy. In summary, the article suggests that a balanced gut microbiota is key to maximizing immunotherapy benefits and calls for further research to optimize microbiota modulation strategies for cancer treatment. It advocates for a deeper comprehension of the complex interactions between gut microbiota, host immunity, and cancer therapy, aiming for more personalized and effective treatment options.}, } @article {pmid39668679, year = {2024}, author = {Vitarelli, A and Minafra, P and Vulpi, M and Piana, A and Torre, G and Carbonara, U and Divenuto, L and Papapicco, G and Chiaradia, F and Alba, S and Lucarelli, G and Battaglia, M and Ditonno, P}, title = {A new approach to repair recurrent vescicourethral anastomotic strictures after radical prostatectomy: The use of prerectal access.}, journal = {Urologia}, volume = {}, number = {}, pages = {3915603241300877}, doi = {10.1177/03915603241300877}, pmid = {39668679}, issn = {1724-6075}, abstract = {BACKGROUND: Vesicourethral anastomosis stenosis (VUAS) is a well-known complication of prostate cancer treatments, observed in up to 26% of the cases after radical prostatectomy. Conservative management, with single or even repeated transurethral dilation or endoscopic incision of the stenosis, is successful in many cases, but up to 9% of patients are destined to fail after endoscopic treatment. In these cases, a revision of the vesicourethral anastomosis is necessary and can be realized with different surgical approaches. We aim to describe the technique and the outcomes of a new prerectal approach for VUAS repair.

METHODS: Twelve patients with recalcitrant VUAS following radical prostatectomy were enrolled between May 2014 and September 2018 for prerectal transperineal re-anastomosis. The evaluated outcomes were: the rate of successful anatomical repair at 3 months after surgery and at the last follow-up, postoperative incontinence and complications rate, and the need for further treatments.

RESULTS: No major intraoperative complications occurred. After a median follow-up of 46 months (IQR 36-55), 10 patients (83.3%) achieved a good anatomical repair even if one man required an endoscopic urethrotomy, while two patients (16.67%) with a history of pelvic radiotherapy developed a surgical site infection that required toilette and external urinary diversion. Among the others, nine (75%) developed severe stress urinary incontinence, with resolution of their condition. No patient reported significant postoperative pain or fecal incontinence.

CONCLUSIONS: The prerectal approach to VUAS repair allows direct access to the posterior urethra and the anastomosis, providing a better mobilization of the bladder neck for tension-free anastomosis. However, patients with a history of pelvic radiotherapy have a higher risk of complications. Postoperative incontinence is very common, but urinary continence could be restored with subsequent artificial urinary sphincter placement.}, } @article {pmid39667939, year = {2024}, author = {Dang, H and Feng, P and Zhang, S and Peng, L and Xing, S and Li, Y and Wen, X and Zhou, L and Goswami, S and Xiao, M and Barker, N and Sansonetti, P and Kundu, P}, title = {Maternal gut microbiota influence stem cell function in offspring.}, journal = {Cell stem cell}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.stem.2024.10.003}, pmid = {39667939}, issn = {1875-9777}, abstract = {The maternal microbiome influences child health. However, its impact on a given offspring's stem cells, which regulate development, remains poorly understood. To investigate the role of the maternal microbiome in conditioning the offspring's stem cells, we manipulated maternal microbiota using Akkermansia muciniphila. Different maternal microbiomes had distinct effects on proliferation and differentiation of neuronal and intestinal stem cells in the offspring, influencing their developmental trajectory, physiology, and long-term health. Transplantation of altered maternal microbiota into germ-free mice transmitted these stem cell phenotypes to the recipients' offspring. The progeny of germ-free mice selectively colonized with Akkermansia did not display these stem cell traits, emphasizing the importance of microbiome diversity. Metabolically more active maternal microbiomes enriched the levels of circulating short-chain fatty acids (SCFAs) and amino acids, leaving distinct transcriptomic imprints on the mTOR pathway of offsprings' stem cells. Blocking mTOR signaling during pregnancy eliminated the maternal-microbiome-mediated effects on stem cells. These results suggest a fundamental role of the maternal microbiome in programming offsprings' stem cells and represent a promising target for interventions.}, } @article {pmid39667762, year = {2024}, author = {Zhang, QW and Yang, MJ and Liao, CY and Taha, R and Li, QY and Abdelmotalab, MI and Zhao, SY and Xu, Y and Jiang, ZZ and Chu, CH and Huang, X and Jiao, CH and Sun, LX}, title = {Atractylodes macrocephala Koidz polysaccharide ameliorates DSS-induced colitis in mice by regulating the gut microbiota and tryptophan metabolism.}, journal = {British journal of pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1111/bph.17409}, pmid = {39667762}, issn = {1476-5381}, support = {82074115//National Natural Science Foundation of China/ ; 82174072//National Natural Science Foundation of China/ ; JSPH-MB-2022-2 supporting//Clinical Capability Enhancement Project Medical/ ; JSPH-MB-2022-2//Clinical Capability Enhancement Project/ ; }, abstract = {BACKGROUND AND PURPOSE: Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease, and the range of current clinical treatments is not ideal. We previously found that polysaccharide of Atractylodes macrocephala Koidz (PAMK) is beneficial in DSS-induced colitis, and we aimed to investigate the underlying mechanisms in this study.

EXPERIMENTAL APPROACH: PAMK was used to treat DSS-induced colitis in mice, 16S rRNA sequencing analysis was used to detect changes in the intestinal microbiota, targeted metabolomics analysis was used to determine the content of tryptophan-metabolizing bacteria, and western blotting was used to determine aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR) levels. Furthermore, antibiotic-mediated depletion of gut microbiota and faecal microbiota transplantation were performed to assess the role of the gut microbiota in PAMK alleviation of colitis.

KEY RESULTS: PAMK treatment relieved intestinal microbiota dysbiosis in mice with colitis, contributed to the proliferation of tryptophan-metabolizing bacteria, and increased the levels of tryptophan metabolites, resulting in a significant increase in the nuclear translocation of PXR and expression of PXR and its target genes, but not AhR. The gut microbiota is important in PAMK treatment of colitis, including in the alleviation of symptoms, inhibition of inflammation, maintenance of the integrity of the intestinal barrier, and the regulation of the Th17/Treg cell balance.

CONCLUSION AND IMPLICATIONS: Based on our findings, we elucidate a novel mechanism by which PAMK alleviates DSS-induced colitis and thus provides evidence to support the potential development of PAMK as a new clinical drug against UC.}, } @article {pmid39667450, year = {2024}, author = {Fu, Q and Yang, Y and Tian, Q and Zhu, Y and Xu, H and Wang, J and Huang, Q}, title = {Exploring the mechanism of Paotianxiong polysaccharide in the treatment of chronic kidney disease combining metabolomics and microbiomics technologies.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {138629}, doi = {10.1016/j.ijbiomac.2024.138629}, pmid = {39667450}, issn = {1879-0003}, abstract = {A close relationship between the pathogenesis of chronic kidney disease (CKD) and abnormalities in the gut-kidney axis. Paotianxiong polysaccharides (PTXP) that have demonstrated therapeutic effects on CKD. However, the specific mechanism by which PTXP ameliorates CKD through the gut-kidney axis remains to be explored. In this study, the microbiomes and metabolomics were combined to investigate the impact of PTXP on intestinal flora structure and metabolism, further unveiling the relationship through correlation analysis. The results showed that PTXP intervention significantly modulated renal function abnormalities in CKD rats and significantly modulates gut microbial disorders, evidenced by an increased abundance of Lactobacillus murinus, Bacteroides fragilis, and a decreased abundance of Bifidobacterium pseudolongum. Furthermore, PTXP reversed the changes in intestinal metabolites, such as linoleic acid and docosahexaenoic acid, induced by CKD and identified unsaturated fatty acid metabolism as a key metabolic pathway. Correlation analyses also revealed associations among gut microorganisms, metabolites, and renal function indexes, confirming that PTXP alleviated CKD through the gut-kidney axis. Moreover, the above conclusions were verified by fecal bacteria transplantation experiments. These findings provide insights into the mechanism of PTXP for the treatment of CKD and provide new targets for the treatment of CKD.}, } @article {pmid39666007, year = {2025}, author = {Shang, J and Del Valle, DM and Britton, GJ and Mead, KR and Rajpal, U and Chen-Liaw, A and Mogno, I and Li, Z and Menon, R and Gonzalez-Kozlova, E and Elkrief, A and Peled, JU and Gonsalves, TR and Shah, NJ and Postow, M and Colombel, JF and Gnjatic, S and Faleck, DM and Faith, JJ}, title = {Baseline colitogenicity and acute perturbations of gut microbiota in immunotherapy-related colitis.}, journal = {The Journal of experimental medicine}, volume = {222}, number = {1}, pages = {}, pmid = {39666007}, issn = {1540-9538}, support = {U24 CA224319/CA/NCI NIH HHS/United States ; U01 DK124165/DK/NIDDK NIH HHS/United States ; R01 DK112978/DK/NIDDK NIH HHS/United States ; F30 CA261144/CA/NCI NIH HHS/United States ; //Memorial Sloan-Kettering Cancer Center/ ; K08 HL143189/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; K08HL143189/NH/NIH HHS/United States ; }, mesh = {*Gastrointestinal Microbiome/immunology/drug effects ; Animals ; Humans ; *Colitis/microbiology/immunology/chemically induced ; Mice ; *Immunotherapy/adverse effects/methods ; Female ; Male ; Immune Checkpoint Inhibitors/adverse effects/pharmacology ; Mice, Inbred C57BL ; Middle Aged ; Aged ; Feces/microbiology ; Neoplasms/immunology/microbiology/therapy/drug therapy ; }, abstract = {Immunotherapy-related colitis (irC) frequently emerges as an immune-related adverse event during immune checkpoint inhibitor therapy and is presumably influenced by the gut microbiota. We longitudinally studied microbiomes from 38 ICI-treated cancer patients. We compared 13 ICI-treated subjects who developed irC against 25 ICI-treated subjects who remained irC-free, along with a validation cohort. Leveraging a preclinical mouse model, predisease stools from irC subjects induced greater colitigenicity upon transfer to mice. The microbiota during the first 10 days of irC closely resembled inflammatory bowel disease microbiomes, with reduced diversity, increased Proteobacteria and Veillonella, and decreased Faecalibacterium, which normalized before irC remission. These findings highlight the irC gut microbiota as functionally distinct but phylogenetically similar to non-irC and healthy microbiomes, with the exception of an acute, transient disruption early in irC. We underscore the significance of longitudinal microbiome profiling in developing clinical avenues to detect, monitor, and mitigate irC in ICI therapy cancer patients.}, } @article {pmid39664442, year = {2024}, author = {Chen, L and Zhang, K and Liu, J and Li, X and Liu, Y and Ma, H and Yang, J and Li, J and Chen, L and Hsu, C and Zeng, J and Xie, X and Wang, Q}, title = {The role of the microbiota-gut-brain axis in methamphetamine-induced neurotoxicity: Disruption of microbial composition and short-chain fatty acid metabolism.}, journal = {Acta pharmaceutica Sinica. B}, volume = {14}, number = {11}, pages = {4832-4857}, pmid = {39664442}, issn = {2211-3835}, abstract = {Methamphetamine (METH) abuse is associated with significant neurotoxicity, high addiction potential, and behavioral abnormalities. Recent studies have identified a connection between the gut microbiota and METH-induced neurotoxicity and behavioral disorders. However, the underlying causal mechanisms linking the gut microbiota to METH pathophysiology remain largely unexplored. In this study, we employed fecal microbiota transplantation (FMT) and antibiotic (Abx) intervention to manipulate the gut microbiota in mice administered METH. Furthermore, we supplemented METH-treated mice with short-chain fatty acids (SCFAs) and pioglitazone (Pio) to determine the protective effects on gut microbiota metabolism. Finally, we assessed the underlying mechanisms of the gut-brain neural circuit in vagotomized mice. Our data provide compelling evidence that modulation of the gut microbiome through FMT or microbiome knockdown by Abx plays a crucial role in METH-induced neurotoxicity, behavioral disorders, gut microbiota disturbances, and intestinal barrier impairment. Furthermore, our findings highlight a novel prevention strategy for mitigating the risks to both the nervous and intestinal systems caused by METH, which involves supplementation with SCFAs or Pio.}, } @article {pmid39664063, year = {2024}, author = {Li, L and Cai, F and Guo, C and Liu, Z and Qin, J and Huang, J}, title = {Gut microbiome and NAFLD: impact and therapeutic potential.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1500453}, pmid = {39664063}, issn = {1664-302X}, abstract = {Non-Alcoholic Fatty Liver Disease (NAFLD) affects approximately 32.4% of the global population and poses a significant health concern. Emerging evidence underscores the pivotal role of the gut microbiota-including bacteria, viruses, fungi, and parasites-in the development and progression of NAFLD. Dysbiosis among gut bacteria alters key biological pathways that contribute to liver fat accumulation and inflammation. The gut virome, comprising bacteriophages and eukaryotic viruses, significantly shapes microbial community dynamics and impacts host metabolism through complex interactions. Similarly, gut fungi maintain a symbiotic relationship with bacteria; the relationship between gut fungi and bacteria is crucial for overall host health, with certain fungal species such as Candida in NAFLD patients showing detrimental associations with metabolic markers and liver function. Additionally, the "hygiene hypothesis" suggests that reduced exposure to gut parasites may affect immune regulation and metabolic processes, potentially influencing conditions like obesity and insulin resistance. This review synthesizes current knowledge on the intricate interactions within the gut microbiota and their associations with NAFLD. We highlight the therapeutic potential of targeting these microbial communities through interventions such as probiotics, prebiotics, and fecal microbiota transplantation. Addressing the complexities of NAFLD requires comprehensive strategies that consider the multifaceted roles of gut microorganisms in disease pathology.}, } @article {pmid39664050, year = {2024}, author = {Alhamlan, FS and Albadawi, IA and Al-Qahtani, AA and Awartani, KA and Obeid, DA and Tulbah, AM}, title = {Cervicovaginal and gastrointestinal microbiomes in gynecological cancers and their roles in therapeutic intervention.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1489942}, pmid = {39664050}, issn = {1664-302X}, abstract = {Cancer remains a significant global health concern, and understanding factors that regulate cancer development is important. The microbiome, with its potential role in cancer development, progression, and treatment, has garnered increasing attention in recent years. The cervicovaginal and gastrointestinal microbiomes in females constitute complex biological ecosystems. Although the gut microbiome has been extensively studied, little is known about the cervicovaginal microbiome. The microbiome plays a crucial role in maintaining local microenvironments and tissue homeostasis, but dysbiosis can disrupt this fine balance and contribute to pathological ramifications leading to cancer. This review explores the current understanding of the microbiome's correlation with gynecological cancers and highlights the potential of microbiome-based interventions to improve outcomes in these cancers. In addition, this review underscores the gaps and limitations in the literature, such as findings in specific ethnicities compared with understudied ethnicities. In addition, discrepancies in molecular techniques and terminology (microbiome vs. microbiota) used in the literature are addressed. Emerging evidence linking gynecological cancers and dysbiosis underscores microbiota as a potential target for cancer prevention and therapy. Manipulating the microbiome, such as through the use of probiotics, prebiotics, antibiotics, or vaginal and fecal transplantation, has demonstrated benefits in the treatment of chronic and inflammatory conditions. Further translational research in this field is needed to integrate the benefits of beneficial microorganisms in the fight against gynecological cancers.}, } @article {pmid39662821, year = {2024}, author = {Groenewegen, B and van Lingen, E and Kovynev, A and van den Berg, AJ and Berssenbrugge, EKL and Sanders, IMJG and van Prehn, J and van Nood, E and Goorhuis, A and Kuijper, EJ and Smits, WK and Wiese, M and Keller, JJ and Ducarmon, QR and Terveer, EM and , }, title = {The presence of Clostridioides difficile in faeces before and after faecal microbiota transplantation and its relation with recurrent C. difficile infection and the gut microbiota in a Dutch cohort.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2024.12.003}, pmid = {39662821}, issn = {1469-0691}, abstract = {OBJECTIVES: To study the presence of Clostridioides difficile in faeces of patients with recurrent C. difficile infection (rCDI) before and after faecal microbiota transplantation (FMT) and to identify risk factors for faecal C. difficile and CDI recurrence.

METHODS: N=83 faecal sample triads (pre-FMT (∼one day), post-FMT (∼three weeks), and a corresponding FMT donor sample), and n=22 long-term (∼1-3 years) follow-up faecal samples (LTFU) were collected from FMT-treated patients. The presence of C. difficile in faeces was assessed by enrichment broth culture and PCR (tcdB gene) and associated with patient characteristics, FMT outcome, duration of pre-FMT vancomycin, FMT donor, post-FMT antibiotic use, and faecal microbiota composition (shotgun metagenomics).

RESULTS: The FMT cure rate for rCDI was 92.8% (77/83), with six early CDI recurrences (
CONCLUSIONS: While eradication of C. difficile is not required for clinical cure of rCDI by FMT, it is associated with reduced prevalence of early CDI recurrence, as are the full completion of pre-FMT vancomycin (at least 10 days) and avoiding post-FMT antibiotics.}, } @article {pmid39659943, year = {2024}, author = {Zhao, W and Chen, Y and Xiao, J and Tang, Z and Wang, L and Ren, Y and Chen, Y}, title = {Updated outcomes and exploratory analysis of RENMIN-215: tislelizumab plus fruquintinib and fecal microbiota transplantation in refractory microsatellite stable metastatic colorectal cancer.}, journal = {American journal of cancer research}, volume = {14}, number = {11}, pages = {5351-5364}, pmid = {39659943}, issn = {2156-6976}, abstract = {Primary analysis of the open-label, single-arm, phase II RENMIN-215 trial (primary data cutoff date: July 10, 2023) showed promising efficacy and tolerable safety with tislelizumab plus fruquintinib and fecal microbiota transplantation (FMT) in patients with refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Here, we reported updated survival and safety results with a median follow-up of 34.0 months (data cut-off May 20, 2024), as well as patient-reported outcomes and laboratory analysis. Twenty patients with MSS mCRC resistant or refractory to at least second-line therapy were enrolled and received tislelizumab plus fruquintinib and FMT. The primary endpoint was progression-free survival. Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate, safety, health-related quality of life questionnaire and exploratory laboratory tests. In addition, 94 mCRC patients who received third-line or above immunotherapy in real world were screened for propensity score matching (PSM) analysis to compare efficacy. Our results showed that the median OS was 13.7 months (95% CI, 9.3-17.7), and the ORR was 20.0% (95% CI, 5.7-43.7). After PSM, the median OS benefit of the study regimen remained statistically significant (HR = 0.26; 95% CI, 0.07-0.95; P = 0.042). Patients with primary tumor surgery had better clinical outcomes. No new safety concerns were detected. Seven (35.0%) patients had one or more grade 3 treatment-related adverse events. The majority of patients had improved or stable global health status (GHS). Median time to deterioration for GHS was 7.7 months. Peripheral blood lymphocyte analysis showed that increased gamma-delta 2 T cells were positively associated with improved response and survival. To conclude, the updated results provide further evidence of sustained antitumor activity of tislelizumab plus fruquintinib and FMT in heavily pretreated MSS mCRC patients with a consistent safety profile.}, } @article {pmid39659426, year = {2024}, author = {Abildinova, GZ and Benberin, VV and Vochshenkova, TA and Afshar, A and Mussin, NM and Kaliyev, AA and Zhussupova, Z and Tamadon, A}, title = {The gut-brain-metabolic axis: exploring the role of microbiota in insulin resistance and cognitive function.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1463958}, pmid = {39659426}, issn = {1664-302X}, abstract = {The gut-brain-metabolic axis has emerged as a critical area of research, highlighting the intricate connections between the gut microbiome, metabolic processes, and cognitive function. This review article delves into the complex interplay between these interconnected systems, exploring their role in the development of insulin resistance and cognitive decline. The article emphasizes the pivotal influence of the gut microbiota on central nervous system (CNS) function, demonstrating how microbial colonization can program the hypothalamic-pituitary-adrenal (HPA) axis for stress response in mice. It further elucidates the mechanisms by which gut microbial carbohydrate metabolism contributes to insulin resistance, a key factor in the pathogenesis of metabolic disorders and cognitive impairment. Notably, the review highlights the therapeutic potential of targeting the gut-brain-metabolic axis through various interventions, such as dietary modifications, probiotics, prebiotics, and fecal microbiota transplantation (FMT). These approaches have shown promising results in improving insulin sensitivity and cognitive function in both animal models and human studies. The article also emphasizes the need for further research to elucidate the specific microbial species and metabolites involved in modulating the gut-brain axis, as well as the long-term effects and safety of these therapeutic interventions. Advances in metagenomics, metabolomics, and bioinformatics are expected to provide deeper insights into the complex interactions within the gut microbiota and their impact on host health. Overall, this comprehensive review underscores the significance of the gut-brain-metabolic axis in the pathogenesis and treatment of metabolic and cognitive disorders, offering a promising avenue for the development of novel therapeutic strategies targeting this intricate system.}, } @article {pmid39658705, year = {2024}, author = {Wang, Z and Wang, Z and Lu, T and Yuan, G and Chen, W and Jin, J and Jiang, X and Yan, W and Yuan, K and Zou, G and Bao, Y and Shi, J and Liu, X and Wei, H and Han, Y and Lu, L}, title = {Gut microbiota regulate insomnia-like behaviors via gut-brain metabolic axis.}, journal = {Molecular psychiatry}, volume = {}, number = {}, pages = {}, pmid = {39658705}, issn = {1476-5578}, support = {82288101//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Sleep interacts reciprocally with the gut microbiota. However, mechanisms of the gut microbe-brain metabolic axis that are responsible for sleep behavior have remained largely unknown. Here, we showed that the absence of the gut microbiota can alter sleep behavior. Sleep deprivation reduced butyrate levels in fecal content and the hypothalamus in specific pathogen-free mice but not in germ-free mice. The microbial metabolite butyrate can promote sleep by modulating orexin neuronal activity in the lateral hypothalamic area in mice. Insomnia patients had lower serum butyrate levels and a deficiency in butyrate-producing species within the gut microbiota. Transplantation of the gut microbiota from insomnia patients to germ-free mice conferred insomnia-like behaviors, accompanied by a decrease in serum butyrate levels. The oral administration of butyrate rescued sleep disturbances in recipient mice. Overall, these findings reveal the causal role of microbial metabolic pathways in modulating insomnia-like behaviors, suggesting potential therapeutic strategies for treating sleep disorders.}, } @article {pmid39658176, year = {2025}, author = {Guo, B and Zhang, W and Zhang, J and Zou, J and Dong, N and Liu, B}, title = {Euglena gracilis polysaccharide modulated gut dysbiosis of obese individuals via acetic acid in an in vitro fermentation model.}, journal = {Food research international (Ottawa, Ont.)}, volume = {199}, number = {}, pages = {115385}, doi = {10.1016/j.foodres.2024.115385}, pmid = {39658176}, issn = {1873-7145}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Dysbiosis ; *Fermentation ; *Acetic Acid/metabolism ; Humans ; *Obesity/metabolism/microbiology ; *Polysaccharides/pharmacology/metabolism ; *Euglena gracilis/metabolism ; Prebiotics ; Male ; Feces/microbiology ; Adult ; Bacteria/metabolism/classification/drug effects ; Lipid Metabolism/drug effects ; Female ; }, abstract = {Gut dysbiosis is a characteristic feature of obesity and targeting gut microbiota presents a promising approach to attenuate obesity. Euglena gracilis polysaccharide (EGP) has emerged as a potential prebiotic capable of promoting health-beneficial bacteria. However, its effects on the gut dysbiosis of obese individuals remain unclear. This study investigated the impacts of EGP on gut microbiota from both non-obese and obese individuals using an in vitro fermentation model. Results showed that EGP significantly altered the gut microbiota composition and metabolism. Specifically, EGP improved the relative abundance of Paeniclostridium, Clostridium_sensu_stricto_1 and Paraclostridium of the non-obese individuals and Providencia, Enterococcus and Bacteroides of the obese individuals. Metabolomics results showed EGP significantly altered the lipid metabolism especially in the obese group with enriched bile secretion and cholesterol metabolism pathways. Noting that acetic acid was significantly increased in both groups, these acetic acid favorable microbiota from non-obese individuals was collected with acetic acid supplementation. Transplantation of these acetic acid-induced microbiota (AAiM) notably improved the richness and diversity of fecal microbiota of the obese individuals, enhancing the growth of probiotics like Bacteroides and Bifidobacterium. Consequently, AAiM significantly restructured macronutrients (including amino acids, carbohydrates and lipids) metabolism of the gut microbiota from obese individuals. Altogether, this study underscores the potential of EGP and acetic acid favorable microbiota in manipulating obesity-associated gut dysbiosis via acetic acid production.}, } @article {pmid39656490, year = {2024}, author = {Balakrishnan, R and Kang, SI and Lee, JY and Rho, YK and Kim, BK and Choi, DK}, title = {Gut Microbiota-Immune System Interactions in Health and Neurodegenerative Diseases: Insights into Molecular Mechanisms and Therapeutic Applications.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2024.1362}, pmid = {39656490}, issn = {2152-5250}, abstract = {The human body contains approximately 100 trillion microorganisms, predominantly within the gastrointestinal tract, collectively called the gut microbiota. Investigations have revealed the bidirectional communication between the gut microbiota and the brain, characterized as the "microbiota-gut-brain axis." This axis represents an important regulator of brain development and function, immune system development, and nutrient metabolism, making it a target for efforts to alleviate the development and progression of neurodegenerative diseases (NDDs). Despite extensive biomedical and clinical research, our understanding of the causes, optimal treatment, and progression of NDDs remains limited. This paper aims to summarize the available knowledge on the role played by gut microbiota and how it is connected to the progression of neurodegenerative conditions; in particular, the relationship between the microbiota and gut-brain communications and the gut microbiota and neuro-immune conditions is reviewed. We discuss how and why the gut immune system communicates with the brain and how this communication impacts neurodegeneration. Next, we examine the alterations in the gut microbiota, immune response, and brain changes associated with gut dysbiosis. Finally, we highlight the preclinical and clinical evidence for probiotics, prebiotics, fecal microbiota transplantation, dietary supplements, natural drugs, and exercise intervention as potential therapeutic approaches that could lead to a new treatment paradigm for NDDs.}, } @article {pmid39653685, year = {2024}, author = {Li, X and Zheng, P and Zou, Y and Guan, L and Li, N and Liu, J and Lu, N and Zhu, Y and He, C}, title = {Dietary inulin ameliorates obesity-induced severe acute pancreatitis via gut-pancreas axis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2436949}, pmid = {39653685}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Obesity/metabolism ; Mice ; *Inulin/pharmacology/administration & dosage ; *Diet, High-Fat/adverse effects ; *Mice, Inbred C57BL ; Male ; *Pancreas/pathology/metabolism/drug effects ; *Pancreatitis/metabolism ; Dysbiosis/microbiology ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Bacteria/classification/isolation & purification/metabolism/genetics ; }, abstract = {Obesity is a definitive factor of severity and mortality of acute pancreatitis (AP), and gut microbiota dysbiosis is involved in its pathogenesis. However, the effect of gut microbiota modulation by dietary components on high fat diet (HFD)-induced severe AP remains unclear. Here, we found that the inulin, a soluble dietary fiber, mitigated pancreatic injury and systematic inflammation in mice fed HFD, which was dependent on gut microbiota as this protective effect was attenuated in germ-free mice. Inulin treatment suppressed the overgrowth of pathogenic bacteria Escherichia Shigella, Enterococcus, Klebsiella, while increased the abundance of probiotics Akkermansia. Fecal microbiota transplantation from inulin-treated mice to recipient mice reduced pancreatic damage and remodeled intestinal homeostasis. Additionally, inulin increased fecal short chain fatty acids (SCFAs), strengthened gut barrier and restored Paneth cells. The beneficial effect of inulin on improving pancreatic damage and leaky gut was diminished after the suppression of SCFAs. Notably, SCFAs administration, especially butyrate, to HFD mice blocked pancreatic and intestinal injury with the inhibition of histone deacetylase 3 (HDAC3), and pharmacological HDAC3 inhibition mimicked the ameliorative effect of SCFAs. Mechanically, butyrate modulated macrophage M1/M2 polarization balance by suppressing HDAC3 and subsequent acetylation of histone H3K27. Collectively, our data offer new insights into the gut microbiota-pancreas axis that may be leveraged to augment the potential supplementation of prebiotic inulin in the management of obesity associated severe AP.}, } @article {pmid39653155, year = {2024}, author = {Zhao, Y and Sun, S and Liu, J and Zheng, M and Liu, M and Liu, J and Liu, H}, title = {Investigation of the protective mechanism of paeoniflorin against hyperlipidemia by an integrated metabolomics and gut microbiota strategy.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {109831}, doi = {10.1016/j.jnutbio.2024.109831}, pmid = {39653155}, issn = {1873-4847}, abstract = {The prevalence of hyperlipidemia is gradually increasing globally, posing a serious threat to public health. Previous studies have shown that paeoniflorin (PF) effectively improved abnormal lipid metabolism in atherosclerotic mice. However, the anti-hyperlipidemia effect and potential mechanism of paeoniflorin remain unclear. The gut microbiota (GM) is closely related to hyperlipidemia. This study was aimed to investigate effects of PF on improving the health of high-fat diet (HFD)-induced hyperlipidemic mice by modulating GM. A hyperlipidemic mouse model was established using an HFD, and the hypolipidemic effect of PF was detected in vivo. Besides16S ribosomal RNA sequencing and SCFAs metabolic analysis were performed to explore the lipid-lowering mechanism of PF. Importantly, fecal microbiota transplantation (FMT) experiments were conducted to verify the lipid-lowering mechanism of PF. The results showed that PF significantly inhibited the development of hyperlipidemia, reduced serum lipid and inflammatory cytokine levels, and improved liver steatosis. In addition, 16S rRNA sequencing revealed that PF treatment significantly increased the relative abundance of Lactobacillus, Coprococcus, Blautia, Roseburia, and Bacteroides while reducing the relative abundance of Prevotella. Meanwhile, the results of targeted metabolomics indicate that PF therapy can effectively restore butyric acid and propionic acid levels in the intestine. The FMT experiments further demonstrated that PF improved hyperlipidemia by regulating GM and its metabolites. The above results provide a valuable theoretical basis for the development and application of PF as a functional food for hyperlipidemia.}, } @article {pmid39652283, year = {2024}, author = {Lou, L and Zhou, L and Wang, Y}, title = {Gut Microbiota: A Modulator and Therapeutic Target for Chronic Pain.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {39652283}, issn = {1559-1182}, abstract = {Chronic pain is a prevalent condition, impacting nearly one-fifth of the global population. Despite the availability of various clinical treatments, each comes with inherent limitations, and few offer a complete cure, resulting in a significant social and economic burden. Therefore, it is important to determine the pathogenesis and causes of chronic pain. Numerous studies have shown a close link between the intestinal microflora and chronic pain. The gut microbiota can exert their effects on chronic pain through both central and peripheral mechanisms and is able to communicate with the brain through its own components or metabolites. They also can regulate chronic pain by affecting pro- and anti-inflammatory cells. This review is aimed at reviewing the connection between gut flora and different types of chronic pain, including visceral pain, neuropathic pain, inflammatory pain, musculoskeletal pain, migraine, and chronic cancer pain; exploring the central and peripheral mechanisms of the influence of gut flora on chronic pain; and attempting to provide novel treatment options for chronic pain, that is, the gut microbiota can be regulated by probiotics, fecal microbial transplantation, and natural products to treat chronic pain. By examining the intricate relationship between gut flora and chronic pain, the review sought to pave the way for new treatment strategies that target the gut microbiota, offering hope for more effective pain management.}, } @article {pmid39651062, year = {2024}, author = {Kaundal, S and Patil, AN and Ks, L and Sharma, V and Arora, A and Singh, C and Jandial, A and Jain, A and Prakash, G and Khadwal, A and Malhotra, P and Lad, DP}, title = {A role for diet and gut microbiota metabolites in autologous hematopoietic cell transplant recipients.}, journal = {Blood cell therapy}, volume = {7}, number = {4}, pages = {101-105}, pmid = {39651062}, issn = {2432-7026}, abstract = {INTRODUCTION: The gut microbiome has an established role in allogeneic hematopoietic cell transplantation (allo-HCT), but not in an auto-HCT setting. We have hypothesized that fecal short-chain fatty acids (SCFA) and urinary 3-indoxyl sulfate (3-IS), which are metabolites derived from the action of the gut microbiome on dietary fiber, play a role in auto-HCT outcomes.

METHODS: This was a single-center prospective study involving auto-HCT recipients. Baseline patient and disease details, diet diaries, and antibiotic exposure were recorded in consenting patients. Serial (pre-HCT, week two, and week four post-HCT) SCFA and urine 3-IS levels were measured using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). HCT outcomes were correlated with these metabolites.

RESULTS: Thirty patients (myeloma, n=13; lymphoma, n=17) were analyzed. The levels of urinary 3-IS, fecal acetate, propionate, and butyrate were found to be decreased at week two and were recovered by week four post-HCT. Those with low median nadir fecal butyrate levels at week two also had significantly lower pre-HCT and week four butyrate levels. Recipients with low butyrate levels had more grade ≥2 mucositis (80% vs. 33%, p=0.01) and low fiber intake (10.4 g vs. 13.6 g, p=0.04). They also had more carbapenem exposure (93% vs. 47%, p=0.005) and prolonged antibiotics (11 days vs. 8 days, p=0.008). There were no differences in the time to neutrophil or platelet engraftment, mortality, or disease response.

CONCLUSION: Low pre-HCT fecal butyrate levels tend to persist post-HCT and they are associated with mucositis, dietary fiber intake, and antibiotic exposure. The gut microbiome and its modulation may play a role in auto-HCT settings.}, } @article {pmid39651029, year = {2024}, author = {Suresh, SB and Malireddi, A and Abera, M and Noor, K and Ansar, M and Boddeti, S and Nath, TS}, title = {Gut Microbiome and Its Role in Parkinson's Disease.}, journal = {Cureus}, volume = {16}, number = {11}, pages = {e73150}, pmid = {39651029}, issn = {2168-8184}, abstract = {Parkinson's disease (PD) afflicted more than 8.5 million people globally in 2019, as the prevalence of the condition more than doubled during the preceding 25 years. Both non-motor symptoms, such as mood disorders and cognitive impairment, and motor symptoms, such as tremors and rigidity, are indicative of this progressive neurodegenerative disease. Recent data indicates a significant role for the gut microbiome in PD pathogenesis and progression, emphasizing the microbiota-gut-brain axis. In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement, this systematic review summarizes our current knowledge about the function of the gut microbiome in PD, highlighting recurrent microbial alterations and assessing microbiome-based treatment strategies. The review revealed several consistent patterns in the gut microbiota of PD patients, including reduced microbial diversity and specific taxonomic alterations, including a drop in Firmicutes abundance and an increase in Proteobacteria abundance. Functional changes in the gut microbiome, such as altered short-chain fatty acid (SCFA) production and tryptophan metabolism, were also noted. These microbial changes were observed even in early-stage and drug-naïve PD patients, suggesting they are not merely a consequence of disease progression or medication use. The review highlighted potential mechanisms linking gut microbiome alterations to PD, including increased intestinal permeability, neuroinflammation, and modulation of alpha-synuclein aggregation. Probiotics, prebiotics, and fecal microbiota transplantation are a few interventions that try to modify the gut microbiome and might be possible to halt the advancement of PD and enhance patients' quality of life with the condition. Future research should focus on establishing causality through large-scale longitudinal studies, standardizing microbiome analysis methods, and exploring personalized microbiome-based therapies.}, } @article {pmid39650985, year = {2024}, author = {Ina, EA and Ziton, S and Dourvetakis, K and Corallo, JP}, title = {Loop Ileostomy With Colonic Lavage: Case Report of an Alternative to Total Colectomy in the Setting of Fulminant Clostridium difficile Colitis.}, journal = {Cureus}, volume = {16}, number = {11}, pages = {e73141}, pmid = {39650985}, issn = {2168-8184}, abstract = {Fulminant Clostridium difficile colitis is a severe and potentially life-threatening form of Clostridium difficile-associated bacterial disease leading to inflammation and damage to the colon. Complications such as toxic megacolon, sepsis, and multi-organ failure commonly occur in individuals with compromised immune systems and recent antibiotic use. Management of Clostridium difficile colitis involves optimization of fluid and electrolyte balance, and elimination of bacteria commonly by administering vancomycin or fidaxomicin. In cases where pharmacological management has been ineffective, fecal microbiota transplantation and surgical intervention demonstrated success. Historically, surgical intervention has involved a total abdominal colectomy with end ileostomy; however, other surgical options have shown increasing benefits with preservation of the colon. This case report aims to provide an example of an alternative management strategy for fulminant Clostridium difficile infections, via the use of a loop ileostomy and colonic lavage. The combination of loop ileostomy and colonic lavage promotes bowel rest, removes toxins, and promotes healing while decreasing inflammation. As with all management modalities, it is essential to recognize the associated complications. The potential benefits should be carefully weighed against the risks on a case-by-case basis with the help of a multidisciplinary team as illustrated through this case report. Overall, early recognition and treatment of fulminant Clostridium difficile colitis using loop ileostomy and colonic lavage prevents further disease progression and improves patient outcomes.}, } @article {pmid39649613, year = {2024}, author = {Moreau, GB and Young, M and Behm, B and Tanyüksel, M and Ramakrishnan, G and Petri, WA}, title = {FMT Restores Colonic Protein Biosynthesis and Cell Proliferation in Patients with Recurrent Clostridioides difficile Disease.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.11.28.24318101}, pmid = {39649613}, abstract = {Recurrent C. difficile infection (CDI) is a major health threat with significant mortality and financial costs. Fecal Microbiota Transplantation (FMT) is an effective therapy, however the mechanisms by which it acts, particularly on the host, are poorly understood. Here we enrolled a prospective cohort of human patients with recurrent CDI (n=16) undergoing FMT therapy. Colonic biopsies were collected and bulk RNA sequencing was performed to compare changes in host gene expression pre- and two months post-FMT. Transcriptional profiles were significantly altered after FMT therapy, with many differentially expressed genes (∼15% of annotated genes detected). Enrichment analysis determined that these changes were reflective of increased protein production post-FMT, with enrichment of pathways such as Ribosome Biogenesis, Protein Processing, and signaling pathways (Myc, mTORc1, E2F) associated with cell proliferation and protein biosynthesis. Histology of H&E-stained biopsies identified a significant increase in colonic crypt length post-FMT, suggesting that this treatment promotes cell proliferation. Crypt length was significantly correlated with enriched Myc and mTOR signaling pathways as well as genes associated with polyamine biosynthesis, providing a potential mechanism through which this may occur. Finally, signaling pathways upstream of Myc and mTOR, notably IL-33 Signaling and EGFR ligands, were significantly upregulated, suggesting that FMT may utilize these signals to promote cell proliferation and restoration of the intestine.}, } @article {pmid39647752, year = {2024}, author = {Li, K and Ran, X and Han, J and Ding, H and Wang, X and Li, Y and Guo, W and Li, X and Guo, W and Fu, S and Bi, J}, title = {Astragalus polysaccharide alleviates mastitis disrupted by Staphylococcus aureus infection by regulating gut microbiota and SCFAs metabolism.}, journal = {International journal of biological macromolecules}, volume = {286}, number = {}, pages = {138422}, doi = {10.1016/j.ijbiomac.2024.138422}, pmid = {39647752}, issn = {1879-0003}, abstract = {Polysaccharides, key bioactive compounds derived from Chinese herbs, are increasingly recognized for their therapeutic potential in modulating gut microbiota to treat various diseases. However, their efficacy in alleviating mammary inflammation and oxidative stress and protecting the blood-milk barrier (BMB) compromised by Staphylococcus aureus (S. au) infection remains uncertain. As evidence for the gut-mammary axis grows, identifying natural prebiotic components that affect this axis is crucial. This study reveals that Astragalus polysaccharide (APS), the primary active constituent of Astragalus, effectively mitigates S. au infection in murine mammary glands, suppresses inflammatory responses, reduces oxidative stress, and restores BMB integrity. The involvement of APS in modulating gut microbiota was substantiated through gut microbial depletion experiments and fecal microbiota transplantation (FMT). Notably, APS uniquely enriched Ruminococcus bromii (R. bromii) in the gut, facilitating the metabolism of short-chain fatty acids (SCFAs), particularly acetate and butyrate, which are pivotal to APS's protective effects. Collectively, these results propose a novel therapeutic approach for the treatment and prevention of S. au-induced mastitis, leveraging APS and R. bromii as prebiotics and probiotics, respectively.}, } @article {pmid39647571, year = {2024}, author = {Sharma, A and Kapur, S and Kancharla, P and Yang, T}, title = {Sex Differences in Gut Microbiota, Hypertension, and Cardiovascular Risk.}, journal = {European journal of pharmacology}, volume = {}, number = {}, pages = {177183}, doi = {10.1016/j.ejphar.2024.177183}, pmid = {39647571}, issn = {1879-0712}, abstract = {The intricate ecosystem of the gut microbiome exhibits sex-specific differences, influencing the susceptibility to cardiovascular diseases (CVD). Imbalance within the gut microbiome compromises the gut barrier, activates inflammatory pathways, and alters the production of metabolites, all of which initiate chronic diseases including CVD. In particular, the interplay between lifestyle choices, hormonal changes, and metabolic byproducts uniquely affects sex-specific gut microbiomes, potentially shaping the risk profiles for hypertension and CVD differently in men and women. Understanding the gut microbiome's role in CVD risk offers informative reasoning behind the importance of developing tailored preventative strategies based on sex-specific differences in CVD risk. Furthermore, insight into the differential impact of social determinants and biological factors on CVD susceptibility emphasizes the necessity for more nuanced approaches. This review also outlines specific dietary interventions that may enhance gut microbiome health, offering a glimpse into potential therapeutic avenues for reducing CVD risk that require greater awareness. Imbalance in natural gut microbiomes may explain etiologies of chronic diseases; we advocate for future application to alter the gut microbiome as possible treatment of the aforementioned diseases. This review mentions the idea of altering the gut microbiome through interventions such as fecal microbiota transplantation (FMT), a major application of microbiome-based therapy that is first-line for Clostridium difficile infections and patient-specific probiotics highlights more innovative approaches to hypertension and CVD prevention. Through increased analysis of gut microbiota compositions along with patient-centric probiotics and microbiome transfers, this review advocates for future preventative strategies for hypertension.}, } @article {pmid39647535, year = {2024}, author = {Casañas-Martínez, M and Barbero-Herranz, R and Alegre-González, D and Mosquera-Lozano, JD and Campo, RD and , }, title = {Fecal Microbiota Transplantation in a Long-Standing Auto-Brewery Syndrome with Complex Symptomatology.}, journal = {Journal of hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhep.2024.12.005}, pmid = {39647535}, issn = {1600-0641}, } @article {pmid39645284, year = {2024}, author = {Dean, NJ and d'Arienzo, PD and Ibraheim, H and Lee, KA and Olsson-Brown, AC and Pinato, DJ and Powell, N}, title = {The role of the gut microbiome in regulating the response to immune checkpoint inhibitor therapy.}, journal = {Best practice & research. Clinical gastroenterology}, volume = {72}, number = {}, pages = {101944}, doi = {10.1016/j.bpg.2024.101944}, pmid = {39645284}, issn = {1532-1916}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/physiology ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; *Neoplasms/drug therapy/microbiology/immunology ; Immunotherapy/methods ; Treatment Outcome ; Anti-Bacterial Agents/therapeutic use/pharmacology ; }, abstract = {Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy, yet the proportion of patients who achieve long-term disease control remain suboptimal. Over the past decade, the gut microbiome has been shown to influence immune-mediated tumour suppression as well as responses to ICI therapies. Compositional differences in gut microbiome may account for the differences in outcomes from immune checkpoint blockade. Identifying microbiota species associated with favourable/unfavourable outcomes and modelling their dynamics throughout the course of ICI treatment could help develop predictive biomarkers of immunotherapy response, and manipulating the gut microbiome represent a novel approach to enhancing ICI effectiveness. Clinically, this raises the prospect of using gut microbiome-based therapies to overcome primary resistance to ICIs, mitigate the effects of microbiome-altering drugs such as antibiotics or proton pump inhibitors, and improve overall survival in patients across numerous different cancer types.}, } @article {pmid39645282, year = {2024}, author = {Józefczuk, P and Biliński, J and Minkowska, A and Łaguna, P}, title = {Gut microbiome in children undergoing hematopoietic stem cell transplantation.}, journal = {Best practice & research. Clinical gastroenterology}, volume = {72}, number = {}, pages = {101955}, doi = {10.1016/j.bpg.2024.101955}, pmid = {39645282}, issn = {1532-1916}, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Gastrointestinal Microbiome/physiology ; Child ; Animals ; }, abstract = {Hematopoietic stem cell transplantation (HSCT) is used in children as a treatment for various cancers, e.g. acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or other diseases, e.g. severe congenital immunodeficiency, metabolic disorders, hence the patient population is quite diverse. There is an increasing interest on the role of the microbiome in peri-transplant period. In this review, concepts of HSCT with the focus on the importance of microbiome composition, its changes during treatment and possible microbiota oriented interventions will be discussed. This paper analyzes data in pediatric population, but in view of interesting results and absence of analogous data for pediatric patients, it also looks at studies performed on adult population and pre-clinical trials on animals discussing possible translation to children.}, } @article {pmid39645278, year = {2024}, author = {Garcia-Mateo, S and Rondinella, D and Ponziani, FR and Miele, L and Gasbarrini, A and Cammarota, G and Lanas, Á and Gomollón, F}, title = {Gut microbiome and metabolic dysfunction-associated steatotic liver disease: Pathogenic role and potential for therapeutics.}, journal = {Best practice & research. Clinical gastroenterology}, volume = {72}, number = {}, pages = {101924}, doi = {10.1016/j.bpg.2024.101924}, pmid = {39645278}, issn = {1532-1916}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; *Prebiotics/administration & dosage ; Non-alcoholic Fatty Liver Disease/microbiology/therapy/metabolism ; Dysbiosis ; Diet, Mediterranean ; }, abstract = {Gut microbiota plays key functions in the human body, and its alteration is associated with several human disorders. Moreover, its manipulation is being investigated as a potential therapeutic strategy. In this narrative review we will dissect the involvement of the gut microbiota and of the gut-liver axis on metabolic dysfunction-associated steatotic liver disease (MASLD). Additionally, we will review the effects of lifestyle interventions commonly used for MASLD (i.e. Mediterranean diet and physical exercise) on gut microbiome, to understand if their beneficial effect can be microbially mediated. Finally, we will discuss the role and the available evidence of therapeutic microbiome modulators, including prebiotics, probiotics, symbiotics, and fecal microbiota transplantation (FMT), in the management of MASLD.}, } @article {pmid39643421, year = {2025}, author = {Zhang, S and Zhou, R and Xie, X and Xiong, S and Li, L and Li, Y}, title = {Polysaccharides from Lycium barbarum, yam, and sunflower ameliorate colitis in a structure and intrinsic flora-dependent manner.}, journal = {Carbohydrate polymers}, volume = {349}, number = {Pt A}, pages = {122905}, doi = {10.1016/j.carbpol.2024.122905}, pmid = {39643421}, issn = {1879-1344}, mesh = {Animals ; *Dioscorea/chemistry ; Mice ; *Mice, Inbred C57BL ; *Gastrointestinal Microbiome/drug effects ; *Colitis/drug therapy/chemically induced ; *Helianthus/chemistry ; Female ; *Polysaccharides/pharmacology/chemistry ; Lycium/chemistry ; Mice, Inbred ICR ; Disease Models, Animal ; Cytokines/metabolism ; Drugs, Chinese Herbal/pharmacology/chemistry ; }, abstract = {Polysaccharides have been suggested to ameliorate metabolic diseases. However, their differential colitis-mitigating effects in mouse models with different colony structures remain poorly understood. Therefore, this study investigated the effects of polysaccharides from Lycium barbarum (LBP), sunflower (SP), and yam (YP) on colitis in C57BL/6 J (B6) mice born via vaginal delivery (VD) and in both caesarean section (CS)- and VD-born Institute of Cancer Research (ICR) mice. LBP was mainly composed of glucose (30.2 %), galactose (27.5 %), and arabinose (26.9 %). The main components of SP and YP were galacturonic acid (75.8 %) and glucose (98.1 %), respectively. Interestingly, LBP effectively alleviated body weight loss, reduced inflammatory cytokine levels, and restored intestinal barrier function in all three mouse models. Moreover, LBP decreased the abundance of norank_f__norank_o__Clostridia_UCG-014, Coriobacteriaceae_UCG-002, and norank_f_Eubacterium_coprostanoligenes_group in B6 mice, and the abundance of these genera positively correlated with pro-inflammatory cytokine levels. LBP increased the abundance of Lactobacillus, which was positively correlated with the levels of the protective factor, IL-10, in CS-born ICR mice. Collectively, our study suggests the potential application of LBP in the treatment of ulcerative colitis. We also provide an alternative method for restoring intestinal homeostasis in CS-born offspring.}, } @article {pmid39643403, year = {2025}, author = {Zhang, Y and Ji, W and Qin, H and Chen, Z and Zhou, Y and Zhou, Z and Wang, J and Wang, K}, title = {Astragalus polysaccharides alleviate DSS-induced ulcerative colitis in mice by restoring SCFA production and regulating Th17/Treg cell homeostasis in a microbiota-dependent manner.}, journal = {Carbohydrate polymers}, volume = {349}, number = {Pt A}, pages = {122829}, doi = {10.1016/j.carbpol.2024.122829}, pmid = {39643403}, issn = {1879-1344}, mesh = {Animals ; *Colitis, Ulcerative/drug therapy/chemically induced/immunology ; *Th17 Cells/drug effects/immunology ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Dextran Sulfate ; *Polysaccharides/pharmacology/chemistry ; *T-Lymphocytes, Regulatory/drug effects/immunology/metabolism ; *Mice, Inbred C57BL ; Homeostasis/drug effects ; Fatty Acids, Volatile/metabolism ; Male ; Astragalus Plant/chemistry ; Astragalus propinquus/chemistry ; Fecal Microbiota Transplantation ; }, abstract = {Natural polysaccharides from Astragalus membranaceus have been shown to relieve ulcerative colitis (UC). However, the mechanism and causal relationship between the gut microbiota and Astragalus polysaccharides (APS) treatment of UC are unclear. The results of the present study showed that APS ameliorated colonic injury and the disruption of the gut microbiota and restored intestinal immune homeostasis in mice with DSS-induced colitis. Meanwhile, we found that APS treatment was ineffective in antibiotic-treated colitis mice but was effective when FMT (Fecal microbiota transplantation) was performed on UC mice using APS-treated mice as donors. APS increased the proportion of relevant microbiota that produce SCFAs and both direct administration of APS and administration of APS-adjusted gut microbiota significantly promoted the production of SCFAs in colitis mice. We demonstrated that APS dually inhibited NF-κB activation via the TLR4 and HDAC3 pathways and improved the balance in Th17/Treg cells in UC mice. In conclusion, our study revealed that APS is a promising prebiotic agent for the maintenance of intestinal health and demonstrated that APS may ameliorate colitis in a gut microbiota-dependent manner.}, } @article {pmid39640634, year = {2024}, author = {Nezhadi, J and Fadaee, M and Ahmadi, S and Kafil, HS}, title = {Microbiota transplantation.}, journal = {Heliyon}, volume = {10}, number = {20}, pages = {e39047}, pmid = {39640634}, issn = {2405-8440}, abstract = {Microbiota refers to a collection of living microorganisms, including bacteria, yeasts, and viruses, that coexist in various sites of the human body. Microbiota can perform multiple functions in the body, which have an essential effect on human health and homeostasis. For example, the microbiota can digest polysaccharides, produce vitamins, modulate the immune system, and protect the body against pathogens. Various factors can occasionally alter the microbiota population in the human body, a condition known as dysbiosis. Dysbiosis can disrupt the homeostasis of a person's body and cause disease. Recent years have witnessed efforts to restore the microbiota population of an individual's body to its original state and eradicate dysbiosis through microbiota transplantation. The noteworthy point is that different methods such as fecal microbiota transplantation, vaginal microbiota transplantation (VMT), skin microbiota transplantation (SMT), oral microbiota transplantation (OMT), washed microbiota transplantation (WMT), and sinonasal microbiota transplantation (SiMT) are used for microbiota transplantation (MT). According to the results of studies and the usefulness of MT in improving a person's health, the purpose of this study is to investigate different methods of MT to eliminate dysbiosis.}, } @article {pmid39640340, year = {2024}, author = {Ma, BDY and Chan, TYH and Lo, BWY}, title = {Unveiling the hidden culprit: How the brain-gut axis fuels neuroinflammation in ischemic stroke.}, journal = {Surgical neurology international}, volume = {15}, number = {}, pages = {394}, pmid = {39640340}, issn = {2229-5097}, abstract = {BACKGROUND: The brain-gut axis represents a bidirectional communication network between the gut microbiome and the central nervous system that plays an important role in homeostasis. Compelling evidence now confirms that ischemic stroke disrupts this delicate balance by inducing gut dysbiosis.

METHODS: A comprehensive literature search was performed in PubMed, Web of Science, and Google Scholar for articles published between January 2000 and January 2023 using relevant keywords. Studies were limited to English and included original studies, literature, and systematic reviewers from peer-reviewed journals which discussed gut microbiota composition in models/subjects with ischemic stroke or assessed stroke impact on gut microbiota. Comments, meeting abstracts, and case reports were excluded. From the 80 relevant articles, we summarized key findings related to gut microbiota changes after stroke and their association with stroke outcomes.

RESULTS: Emerging preclinical evidence underscores the pivotal role of the gut microbiome in glial cell development and function. Germ-free models exhibit compromised microglial activation and impaired cellular debris clearance, exacerbating tissue damage following ischemic stroke. Targeted interventions, including prebiotics, probiotics, and fecal microbiota transplantation, have demonstrated efficacy in rescuing glial phenotypes in preclinical stroke models. Beyond its local effects, the gut microbiome significantly influences systemic immunity. Ischemic stroke polarizes pro-inflammatory phenotypes of neutrophils and T cells, amplifying neurovascular inflammation. Microbiota manipulation modulates leukocyte trafficking and metabolic signaling, offering potential avenues to mitigate infarct pathology.

CONCLUSION: Our review demonstrates that in preclinical stroke models, modulating the lipopolysaccharide, short-chain fatty acid, and trimethylamine N-oxide pathways through the gut-brain axis reduces infarct sizes and edema and improves functional recovery after ischemic stroke. Further exploration of this important axis may unveil additional adjunctive stroke therapies by elucidating the complex interplay between the microbiome and the brain. Rigorously controlled clinical studies are now warranted to translate these promising preclinical findings and investigate whether manipulating the microbiome-brain relationship can help improve outcomes for stroke patients. Overall, continued research on the gut-brain axis holds exciting possibilities for developing novel treatment strategies that may enhance recovery after stroke.}, } @article {pmid39640265, year = {2024}, author = {Wang, H and Deng, F and Luo, M and Wang, X}, title = {Case report: Fecal microbiota transplant for Clostridium difficile infection in a pregnant patient with acute severe ulcerative colitis.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1417003}, pmid = {39640265}, issn = {1664-3224}, mesh = {Humans ; Female ; *Fecal Microbiota Transplantation ; Pregnancy ; *Colitis, Ulcerative/therapy/immunology/microbiology ; Adult ; *Clostridium Infections/therapy/immunology ; Clostridioides difficile ; Gastrointestinal Microbiome ; Pregnancy Complications, Infectious/therapy/microbiology ; Treatment Outcome ; Acute Disease ; Severity of Illness Index ; }, abstract = {Ulcerative colitis (UC) is a chronic colonic mucosal inflammation characterized by reduced gut microbial diversity. Patients with UC at pregnancy are prone to suffer from severe disease progression due to the changes of hormone and immune regulation. Fecal microbiota transplant (FMT) is a promising therapy for UC and recurrent Clostridium difficile infection (CDI). However, acute severe ulcerative colitis (ASUC) treatment especially in patients at pregnancy is clinically challenging. Herein, we report a 34-year-old pregnant woman who manifested with numerous bloody stools and markedly elevated serological inflammatory indicators and was diagnosed with ASUC and concurrent CDI. The use of intravenous injection steroids and anti-TNF-α therapy failed to improve her condition. Frozen encapsulated FMT therapy was finally performed to this patient with clearly improved symptoms and indications of safe delivery without UC flares or complications, and markedly increased diversity of the gut microbiota was also shown in this patient after FMT. This report firstly describes FMT as a safe salvage therapy for a pregnant patient with CDI and ASUC refractory to intravenous steroids and anti-TNF therapy.}, } @article {pmid39638178, year = {2024}, author = {Gong, JZ and Huang, JJ and Pan, M and Jin, QW and Fan, YM and Shi, WQ and Huang, SY}, title = {Cathepsin L of Fasciola hepatica meliorates colitis by altering the gut microbiome and inflammatory macrophages.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {138270}, doi = {10.1016/j.ijbiomac.2024.138270}, pmid = {39638178}, issn = {1879-0003}, abstract = {Helminths can relieve the development of autoimmune diseases and inflammatory diseases, by inducing anti-inflammatory innate immune responses. Here, we report that CL7, a Cathepsin L protein secreted by Fasciola hepatica, inhibited the activation of the NF-κB and MAPK signaling resulting in reduced secretion of inflammatory mediators in macrophages. Furthermore，we found that CL7 could prevent dextran sulfate sodium (DSS) induced ulcerative colitis (UC). CL7 and ESP administration restored DSS-induced body weight loss, colon shortening, and injury, significantly decreased the disease activity index (DAI) and alleviated colonic epithelial injury. CL7 noticeably suppressed the DSS-triggered M1 polarization upregulation and inhibited IL-17 and other inflammatory mediator production in UC mice. Additionally, CL7 ameliorated DSS-induced microbiota dysbiosis. Results of Antibiotic treatment (ABX) and fecal microbial transplants (FMT) suggested that the gut microbiota played an important role in CL7 treating UC. These findings propose that CL7 could be a promising strategy for UC therapy.}, } @article {pmid39635024, year = {2024}, author = {Skladany, L and Kubanek, N and Adamcova Selcanova, S and Zilincanova, D and Havaj, D and Sulejova, K and Soltys, K and Messingerova, L and Lichvar, M and Laffers, L and Zilincan, M and Honsova, E and Liptak, P and Banovcin, P and Bures, J and Koller, T and Golubnitschaja, O and Arab, JP}, title = {3PM-guided innovation in treatments of severe alcohol-associated hepatitis utilizing fecal microbiota transplantation.}, journal = {The EPMA journal}, volume = {15}, number = {4}, pages = {677-692}, pmid = {39635024}, issn = {1878-5077}, abstract = {RATIONALE: Severe alcohol-associated hepatitis (SAH) is the most critical, acute, inflammatory phenotype within the alcohol-associated liver disease (ALD) spectrum, characterized by high 30- and 90-day mortality. Since several decades, corticosteroids (CS) are the only approved pharmacotherapy offering highly limited survival benefits. Contextually, there is an evident demand for 3PM innovation in the area meeting patients' needs and improving individual outcomes. Fecal microbiota transplantation (FMT) has emerged as one of the new potential therapeutic options. In this study, we aimed to address the crucial 3PM domains in order to assess (i) the impact of FMT on mortality in SAH patients beyond CS, (ii) to identify factors associated with the outcome to be improved (iii) the prediction of futility, (iv) prevention of suboptimal individual outcomes linked to increased mortality, and (v) personalized allocation of therapy.

METHODS: We conducted a prospective study (NCT04758806) in adult patients with SAH who were non-responders (NR) to or non-eligible (NE) for CS between January 2018 and August 2022. The intervention consisted of five 100 ml of FMT, prepared from 30 g stool from an unrelated healthy donor and frozen at - 80 °C, administered daily to the upper gastrointestinal (GI) tract. We evaluated the impact of FMT on 30- and 90-day mortality which we compared to the control group selected by the propensity score matching and treated by the standard of care; the control group was derived from the RH7 registry of patients hospitalized at the liver unit (NCT04767945). We have also scrutinized the FMT outcome against established and potential prognostic factors for SAH - such as the model for end-stage liver disease (MELD), Maddrey Discriminant Function (MDF), acute-on-chronic liver failure (ACLF), Liver Frailty Index (LFI), hepatic venous-portal pressure gradient (HVPG) and Alcoholic Hepatitis Histologic Score (AHHS) - to see if the 3PM method assigns them a new dimension in predicting response to therapy, prevention of suboptimal individual outcomes, and personalized patient management.

RESULTS: We enrolled 44 patients with SAH (NR or NE) on an intention-to-treat basis; we analyzed 33 patients per protocol for associated factors (after an additional 11 being excluded for receiving less than 5 doses of FMT), and 31 patients by propensity score matching for corresponding individual outcomes, respectively. The mean age was 49.6 years, 11 patients (33.3%) were females. The median MELD score was 29, and ACLF of any degree had 27 patients (81.8%). FMT improved 30-day mortality (p = 0.0204) and non-significantly improved 90-day mortality (p = 0.4386). Univariate analysis identified MELD ≥ 30, MDF ≥ 90, and ACLF grade > 1 as significant predictors of 30-day mortality, (p = 0.031; p = 0.014; p = 0.034). Survival was not associated with baseline LFI, HVPG, or AHHS.

In the most difficult-to-treat sub-cohort of patients with SAH (i.e., NR/NE), FMT improved 30-day mortality. Factors associated with benefit included MELD ≤ 30, MDF ≤ 90, and ACLF < 2. These results support the potential of gut microbiome as a therapeutic target in the context of 3PM research and vice versa - to use 3PM methodology as the expedient unifying template for microbiome research. The results allow for immediate impact on the innovative concepts of (i) personalized phenotyping and stratification of the disease for the clinical research and practice, (ii) multilevel predictive diagnosis related to personalized/precise treatment allocation including evidence-based (ii) prevention of futile and sub-optimally effective therapy, as well as (iii) targeted prevention of poor individual outcomes in patients with SAH. Moreover, our results add to the existing evidence with the potential to generate new research along the SAH's pathogenetic pathways such as diverse individual susceptibility to alcohol toxicity, host-specific mitochondrial function and systemic inflammation, and the role of gut dysbiosis thereof.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-024-00381-5.}, } @article {pmid39633321, year = {2024}, author = {Farias, RM and Jiang, Y and Levy, EJ and Hwang, C and Wang, J and Burton, EM and Cohen, L and Ajami, N and Wargo, JA and Daniel, CR and McQuade, JL}, title = {Diet and Immune Effects Trial (DIET)- a randomized, double-blinded dietary intervention study in patients with melanoma receiving immunotherapy.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {1493}, pmid = {39633321}, issn = {1471-2407}, support = {R25 CA203650/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Melanoma/therapy/immunology/diet therapy ; Double-Blind Method ; *Gastrointestinal Microbiome/immunology ; Female ; Male ; Immunotherapy/methods ; Dietary Fiber/administration & dosage ; Adult ; Middle Aged ; Immune Checkpoint Inhibitors/therapeutic use ; Quality of Life ; Aged ; Diet ; Skin Neoplasms/diet therapy/immunology/therapy ; }, abstract = {BACKGROUND: Gut microbiome modulation is a promising strategy for enhancing the response to immune checkpoint blockade (ICB). Fecal microbiota transplant studies have shown positive signals of improved outcomes in both ICB-naïve and refractory melanoma patients; however, this strategy is challenging to scale. Diet is a key determinant of the gut microbiota, and we have previously shown that (a) habitual high dietary fiber intake is associated with an improved response to ICB and (b) fiber manipulation in mice impacts antitumor immunity. We recently demonstrated the feasibility of a controlled high-fiber dietary intervention (HFDI) conducted in melanoma survivors with excellent compliance and tolerance. Building on this, we are now conducting a phase II randomized trial of HFDI versus a healthy control diet in melanoma patients receiving ICB.

METHODS: This is a randomized, double-blind, fully controlled feeding study that will enroll 45 melanoma patients starting standard-of-care (SOC) ICB in three settings: adjuvant, neoadjuvant, and unresectable. Patients are randomized 2:1 to the HFDI (target fiber 50 g/day from whole foods) or healthy control diet (target fiber 20 g/day) stratified by BMI and cohort. All meals are prepared by the MD Anderson Bionutrition Core and are isocaloric and macronutrient-controlled. The intervention includes a 1-week equilibration period and then up to 11 weeks of diet intervention. Longitudinal blood, stool and tumor tissue (if available) are collected throughout the trial and at 12 weeks post intervention.

DISCUSSION: This DIET study is the first fully controlled feeding study among cancer patients who are actively receiving immunotherapy. The goal of the current study is to establish the effects of dietary intervention on the structure and function of the gut microbiome in patients with melanoma treated with SOC immunotherapies. The secondary endpoints include changes in systemic and tumor immunity, changes in the metabolic profile, quality of life, symptoms, disease response and immunotherapy toxicity.

TRIAL REGISTRATION: This protocol is registered with the U.S. National Institutes of Health trial registry, ClinicalTrials.gov, under the identifier NCT04645680. First posted 2020-11-27; last verified 2024-06.}, } @article {pmid39633000, year = {2024}, author = {Yang, D and Fu, S and Shi, Y}, title = {Gut microbiota modulation: a novel mechanism in arb-mediated hypertension treatment.}, journal = {Hypertension research : official journal of the Japanese Society of Hypertension}, volume = {}, number = {}, pages = {}, pmid = {39633000}, issn = {1348-4214}, } @article {pmid39631325, year = {2024}, author = {Zhang, Y and Liu, Q and Xie, H and Zhang, W and Lin, X and Zhang, H and Yu, H and Ma, Y and Zhang, C and Geng, H and Shi, N and Cui, L and Li, B and Li, YF}, title = {Fecal microbiota transplantation as an effective way in treating methylmercury-poisoned rats.}, journal = {The Science of the total environment}, volume = {957}, number = {}, pages = {177850}, doi = {10.1016/j.scitotenv.2024.177850}, pmid = {39631325}, issn = {1879-1026}, abstract = {Methylmercury (MeHg) can cause devastating neurotoxicity in animals and human beings. Gut microbiota dysbiosis has been found in MeHg-poisoned animals. Fecal microbiota transplantation (FMT) has been shown to improve clinical outcomes in a variety of diseases such as epilepsy, amyotrophic lateral sclerosis (ALS) and autism. The aim of this study was to investigate the effects of FMT on MeHg-poisoned rats. FMT treatment was applied to MeHg-poisoned rats for 14 days. The neurobehavior, weight changes, dopamine (DA), the total Hg and MeHg level were evaluated. Besides, the gut microbiota and metabolites change in feces were also checked. It was found that FMT helped weight gain, alleviated the neurological disorders, enhanced fecal mercury excretion and MeHg demethylation, reconstructed gut microbiome and promoted the production of gut-brain axis related-metabolites in MeHg-poisoned rats. This study elaborates on the therapeutic efficacy of FMT in treating of MeHg-poisoned rats, which sheds lights on the treatment of neurological diseases like Minamata Disease and even Parkinson's Disease.}, } @article {pmid39630000, year = {2024}, author = {Barbosa, IG and Miranda, AS and Berk, M and Teixeira, AL}, title = {The involvement of the microbiota-gut-brain axis in the pathophysiology of mood disorders and therapeutic implications.}, journal = {Expert review of neurotherapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1080/14737175.2024.2438646}, pmid = {39630000}, issn = {1744-8360}, abstract = {INTRODUCTION: There is a growing body of evidence implicating gut-brain axis dysfunction in the pathophysiology of mood disorders. Accordingly, gut microbiota has become a promising target for the development of biomarkers and novel therapeutics for bipolar and depressive disorders.

AREAS COVERED: We describe the observed changes in the gut microbiota of patients with mood disorders and discuss the available studies assessing microbiota-based strategies for their treatment.

EXPERT OPINION: Microbiota-targeted interventions, such as symbiotics, prebiotics, paraprobiotics, and fecal microbiota transplants seem to attenuate the severity of depressive symptoms. The available results must be seen as preliminary and need to be replicated and/or confirmed in larger and independent studies, also considering the pathophysiological and clinical heterogeneity of mood disorders.}, } @article {pmid39629909, year = {2024}, author = {Sin, HCL and Haifer, C}, title = {Faecal transplantation: the good, the bad and the ugly.}, journal = {Internal medicine journal}, volume = {}, number = {}, pages = {}, doi = {10.1111/imj.16559}, pmid = {39629909}, issn = {1445-5994}, abstract = {There continues to be significant interest from both clinicians and patients in using faecal transplantation, as the integral role of the gut microbiome is increasingly recognised in various disease conditions, both within and beyond the gut. This Clinical Perspectives article provides an overview of existing literature, factors limiting the use of faecal microbial transplantation in clinical practice and exciting new advancements on the horizon.}, } @article {pmid39628464, year = {2024}, author = {Hu, X and Wu, Q and Huang, L and Xu, J and He, X and Wu, L}, title = {Clinical efficacy of washed microbiota transplantation on metabolic syndrome and metabolic profile of donor outer membrane vesicles.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1465499}, pmid = {39628464}, issn = {2296-861X}, abstract = {OBJECT: To clarify the clinical efficacy of washed microbiota transplantation (WMT) for metabolic syndrome (MetS), and explore the differences in the metabolic profile of bacterial outer membrane vesicles (OMVs) in donor fecal bacteria suspension received by MetS patients with good and poor outcomes, and to construct a predictive model for the efficacy of WMT for MetS using differential metabolites.

METHODS: Medical data 65 MetS patients who had completed at least 2 courses of WMT from 2017.05 to 2023.07 were collected. Fecal bacteria suspension of WMT donors were collected, and the clinical data of MetS patients treated with WMT during this period were collected as well. The changes of BMI, blood glucose, blood lipids, blood pressure and other indicators before and after WMT were compared. OMVs were isolated from donor fecal bacteria suspension and off-target metabolomic sequencing was performed by Liquid Chromatograph Mass Spectrometer (LC-MS).

RESULTS: Compared with baseline, Body mass index (BMI), Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) of MetS patients showed significant decreases after the 1st (short-term) and 2nd (medium-term) courses, and fasting blood glucose (FBG) also showed significant decreases after the 1st session. There was a significant difference between the Marked Response OMVs and the Moderate Response OMVs. It was showed that 960 metabolites were significantly up-regulated in Marked Response OMVs and 439 metabolites that were significantly down-regulated. The ROC model suggested that 9-carboxymethoxymethylguanine, AUC = 0.8127, 95% CI [0.6885, 0.9369], was the most potent metabolite predicting the most available metabolite for efficacy.

CONCLUSION: WMT had significant short-term and medium-term clinical efficacy in MetS. There were differences in the structure of metabolites between Marked Response OMVs and Moderate Response OMVs. The level of 9-Carboxy methoxy methylguanine in Marked Response OMVs can be a good predictor of the efficacy of WMT in the treatment of MetS.}, } @article {pmid39624719, year = {2024}, author = {Xiang, A and Chang, Y and Shi, L and Zhou, X}, title = {Mapping the relationship between alcohol use disorder and gut microbiota: a 20-year bibliometric study.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1457969}, pmid = {39624719}, issn = {1664-302X}, abstract = {BACKGROUND: Alcohol use disorder (AUD) is a psychiatric disorder that is widespread worldwide. Alcohol use is a significant contributor to the global burden of death, disability and disease. Modulation of the gut microbiota is a promising approach to improve the efficacy and minimize the adverse effects of colorectal cancer treatment. The relationship between the presence of microbes and AUD has been widely validated. However, few studies have examined this relationship using bibliometric methods. Therefore, this study analyzes the research hotspots and trends in human gut microbiology and AUD over the last two decades from a bibliometric perspective. This study aims at provide new directions for basic and clinical research in this field.

OBJECTIVE: A comprehensive discussion of the relationship between the current state of research and trends in AUD and intestinal flora.

METHODS: We collected publications from the Web of Science Core Collection database from 2003 to 2023 according to established inclusion criteria. We analyzed countries, institutions, authors, and research contributions using CiteSpace, VOSviewer, and Scimago Graphics to visualize research trends in the field.

RESULTS: A total of 2,102 publications were obtained, with a rapid increase in the number of publications since 2016. The United States and China are major contributors to the field and have established a network of partners in several countries. Five hundred ninety-five academic journals published articles on the topic. The author with the highest number of publications is Prof. Bernd Schnabl of the Department of Gastroenterology at the University of California, San Diego. In addition to "gut flora" and "AUD," high frequency words in the keyword co-occurrence network analysis included alcoholic liver disease, tryptophan metabolism, enterohepatic axis, and fecal microbial transplantation.

CONCLUSION: The results of this study provide a bibliometric analysis and visualization of key research areas in the gut microbiota and AUD over the past 20 years. The results suggest that the role of the gut microbiota in AUD and its potential mechanisms, especially therapeutic targets, should be closely monitored and could become a hot topic in the field.}, } @article {pmid39621384, year = {2024}, author = {Hoeg, A and Kuchma, N and Krane, A and Graiziger, C and Thomas, J and Kelly, CR and Khoruts, A}, title = {Oral Capsule FMT Combined With Bezlotoxumab Is a Successful Rescue Protocol Following Failure of FMT Alone in the Treatment of Recurrent C. difficile Infection.}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCG.0000000000002108}, pmid = {39621384}, issn = {1539-2031}, abstract = {GOALS: Evaluate the benefit of adding bezlotoxumab to repeat fecal microbiota transplantation (FMT) in patients with recurrent Clostridioides difficile infections after the failure of FMT alone.

BACKGROUND: The initial failure of FMT in breaking the cycle of recurrent Clostridium difficile(C. difficile) infections is associated with a greater risk of subsequent failure. Our previous analysis showed that FMT failure is associated with delayed repair of fecal microbiota at 1 week after administration. We hypothesized that increasing the symptom-free interval by adding bezlotoxumab would improve the outcomes of a second FMT.

STUDY: A new rescue protocol that combines FMT with bezlotoxumab for patients who previously failed FMT alone was implemented in 2 academic medical centers. The clinical outcomes of a new protocol were captured in a prospective registry. The results were compared in a retrospective analysis of clinical outcomes of prior experience with repeat FMT by itself. All FMT preparations were standardized for dose. Bezlotoxumab administration was synchronized temporally with the second FMT to maximize its duration of action.

RESULTS: Our historical cure rate of second FMT in treatment of recurrent C. difficile infection was 48% (15/31 patients). Addition of bezlotoxumab to the second FMT resulted in a cure rate of 89% (24/27 patients).

CONCLUSIONS: Addition of bezlotoxumab markedly improved the cure rate of the second FMT following initial FMT failure. The rationale for the protocol design highlights the importance of understanding the pharmacokinetics of both bezlotoxumab and FMT. Similar principles may apply to other live biotherapeutic products that are becoming available for prevention of C. difficile infection recurrence.}, } @article {pmid39619696, year = {2024}, author = {Kang, P and Bae, GS and Jeon, E and Choi, J and Hwang, EH and Kim, G and Baek, SH and Shim, K and An, YJ and Lim, KS and Kim, Y and Oh, T and Hong, JJ and Lee, WK and Kim, SH and Koo, BS}, title = {Comprehensive effects of fecal microbiota transplantation on cynomolgus macaques across various fecal conditions.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1458923}, pmid = {39619696}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) and probiotics therapies represent key clinical options, yet their complex effects on the host are not fully understood. We evaluated the comprehensive effects of FMT using diarrheal or normal feces, as well as probiotic therapies, on multiple anatomical sites in healthy cynomolgus macaques through colonoscopy and surgery. Our research revealed that FMT led to a partial microbiome transplantation without exhibiting the donor's fecal clinical characteristics. Notably, FMT increased insulin and C-peptide levels in each animal according time series, regardless of fecal conditions. Immunologically, a reduction in neutrophil-to-lymphocyte ratio were exclusively observed in femoral veins of FMT group. In blood chemistry analyses, reductions in aspartate aminotransferase, blood urea nitrogen, and creatinine were observed in the femoral veins, while elevated levels of alanine aminotransferase and calcium were exclusively detected in the portal veins. These changes were not observed in the probiotic group. Also, short chain fatty acids were significantly higher increase in portal veins rather than femoral veins. Transcriptome analysis of liver tissues showed that metabolic pathways were primarily affected by both FMT and probiotics therapies. In summary, FMT therapy significantly influenced metabolic, immunologic and transcriptomic responses in normal macaque models, regardless of fecal conditions. Also, these macaque models, which utilize surgery and colonoscopy, serve as a human-like preclinical platform for evaluating long-term effects and anatomically specific responses to gut-targeted interventions, without the need for animal sacrifice.}, } @article {pmid39619695, year = {2024}, author = {Han, X and Zhang, BW and Zeng, W and Ma, ML and Wang, KX and Yuan, BJ and Xu, DQ and Geng, JX and Fan, CY and Gao, ZK and Arshad, M and Gao, S and Zhao, L and Liu, SL and Mu, XQ}, title = {Suppressed oncogenic molecules involved in the treatment of colorectal cancer by fecal microbiota transplantation.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1451303}, pmid = {39619695}, issn = {1664-302X}, abstract = {Dysbiosis of the intestinal microbiota is prevalent among patients with colorectal cancer (CRC). This study aims to explore the anticancer roles of the fecal microbiota in inhibiting the progression of colorectal cancer and possible mechanisms. The intestinal microbial dysbiosis in CRC mice was significantly ameliorated by fecal microbiota transplantation (FMT), as indicated by the restored ACE index and Shannon index. The diameter and number of cancerous foci were significantly decreased in CRC mice treated with FMT, along with the restoration of the intestinal mucosal structure and the lessening of the gland arrangement disorder. Key factors in oxidative stress (TXN1, TXNRD1, and HIF-1α); cell cycle regulators (IGF-1, BIRC5, CDK8, HDAC2, EGFR, and CTSL); and a critical transcription factor of the innate immune signal pathway (IRF5) were among the repressed oncogenic targets engaged in the FMT treatment of CRC. Correlation analysis revealed that their expressions were positively correlated with uncultured_bacterium_o_Mollicutes_RF39, Rikenellaceae_RC9_gut_group, and negatively correlated with Bacillus, Marvinbryantia, Roseburia, Angelakisella, Enterorhabdus, Bacteroides, Muribaculum, and genera of uncultured_bacterium_f_Eggerthellaceae, uncultured_bacterium_f_Xanthobacteraceae, Prevotellaceae_UCG-001, uncultured_bacterium_f_Erysipelotrichaceae, uncul-tured_bacterium_f_Lachnospiraceae, uncultured_bacterium_f_Ruminococcaceae, Eubacterium_coprostanoligenes_group, Ruminococcaceae_UCG-005, and uncultured_bacterium_f_Peptococcaceae. This study provides more evidence for the application of FMT in the clinical treatment of CRC.}, } @article {pmid39619660, year = {2024}, author = {Xi, M and Ruan, Q and Zhong, S and Li, J and Qi, W and Xie, C and Wang, X and Abuduxiku, N and Ni, J}, title = {Periodontal bacteria influence systemic diseases through the gut microbiota.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1478362}, pmid = {39619660}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology ; Diabetes Mellitus/microbiology ; Alzheimer Disease/microbiology ; Bacteria/classification/genetics/pathogenicity ; Cardiovascular Diseases/microbiology ; Mouth/microbiology ; Animals ; }, abstract = {Many systemic diseases, including Alzheimer disease (AD), diabetes mellitus (DM) and cardiovascular disease, are associated with microbiota dysbiosis. The oral and intestinal microbiota are directly connected anatomically, and communicate with each other through the oral-gut microbiome axis to establish and maintain host microbial homeostasis. In addition to directly, periodontal bacteria may also be indirectly involved in the regulation of systemic health and disease through the disturbed gut. This paper provides evidence for the role of periodontal bacteria in systemic diseases via the oral-gut axis and the far-reaching implications of maintaining periodontal health in reducing the risk of many intestinal and parenteral diseases. This may provide insight into the underlying pathogenesis of many systemic diseases and the search for new preventive and therapeutic strategies.}, } @article {pmid39617896, year = {2024}, author = {Feng, R and Zhu, Q and Wang, A and Wang, H and Wang, J and Chen, P and Zhang, R and Liang, D and Teng, J and Ma, M and Ding, X and Wang, X}, title = {Effect of fecal microbiota transplantation on patients with sporadic amyotrophic lateral sclerosis: a randomized, double-blind, placebo-controlled trial.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {566}, pmid = {39617896}, issn = {1741-7015}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; *Fecal Microbiota Transplantation/methods ; Double-Blind Method ; Female ; Male ; Middle Aged ; Aged ; Gastrointestinal Microbiome/physiology ; Treatment Outcome ; Quality of Life ; Adult ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder marked by the progressive loss of motor neurons. Recent insights into ALS pathogenesis underscore the pivotal role of the gut microbiome, prompting an investigation into the potential therapeutic impact of fecal microbiota transplantation (FMT) on sporadic ALS patients.

METHODS: Conducted as a double-blind, placebo-controlled, parallel-group, randomized clinical trial, the study enrolled 27 participants from October 2022 to April 2023. The participants were followed up for 6 months from February 2023 to October 2023, during in-person visits at baseline, week 15, week 23, and week 35. The participants, evenly randomized, received either healthy donor FMT (FMT, n = 14) or a mixture of 0.9% saline and food coloring (E150c) as sham transplantation (placebo, n = 13). The primary outcome measured the change in the ALS Functional Rating Scale-Revised (ALSFRS-R) total score from baseline to week 35. Secondary outcomes included changes in gastrointestinal and respiratory functions, muscle strength, autonomic function, cognition, quality of life, intestinal microbiome composition, and plasm neurofilament light chain protein (NFL). Efficacy and safety outcomes were assessed in the intention-to-treat population.

RESULTS: A total of 27 randomized patients (47% women; mean age, 67.2 years), 24 participants completed the entire study. Notably, ALSFRS-R score changes exhibited no significant differences between FMT (6.1 [SD, 3.11]) and placebo (6.41[SD, 2.73]) groups from baseline to week 35. Secondary efficacy outcomes, encompassing respiratory function, muscle strength, autonomic function, cognition, quality of life, and plasm NFL, showed no significant differences. Nevertheless, the FMT group exhibited improvements in constipation, depression, and anxiety symptoms. FMT induced a shift in gut microbiome community composition, marked by increased abundance of Bifidobacterium, which persisted until week 15 (95% CI, 0.04 to 0.28; p = 0.01). Gastrointestinal adverse events were the primary manifestations of FMT-related side effects.

CONCLUSIONS: In this clinical trial involving 27 sporadic ALS patients, FMT did not significantly slow the decline in ALSFRS-R score. Larger multicenter trials are needed to confirm the efficacy of FMT in sporadic ALS patients and to explore the underlying biological mechanisms.

TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR 2200064504.}, } @article {pmid39617011, year = {2024}, author = {Berzack, S and Galor, A}, title = {Microbiome-based therapeutics for ocular diseases.}, journal = {Clinical & experimental optometry}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/08164622.2024.2422479}, pmid = {39617011}, issn = {1444-0938}, abstract = {The relationship between the gut microbiome and ocular health has garnered increasing attention within the scientific community. Recent research has focused on the gut-eye axis, examining whether imbalances within the gut microbiome can influence the development, progression and severity of ocular diseases, including dry eye disease, uveitis, and glaucoma. Dysbiosis within the gut microbiome is linked to immune dysregulation, chronic inflammation, and epithelial barrier dysfunction, all of which contribute to ocular pathology. This review synthesises current evidence on these associations, exploring how gut microbiome alterations drive disease mechanisms. Furthermore, it examines the therapeutic potential of microbiome-targeted interventions, including antibiotics, prebiotics, probiotics, and faecal microbiota transplantation, all of which aim to restore microbial balance and modulate immune responses. As the prevalence of these conditions continues to rise, a deeper understanding of the gut-eye axis may facilitate the development of novel, targeted therapies to address unmet needs in the management of ocular diseases.}, } @article {pmid39614243, year = {2024}, author = {Gan, G and Zhang, R and Zeng, Y and Lu, B and Luo, Y and Chen, S and Lei, H and Cai, Z and Huang, X}, title = {Fecal microbiota transplantation validates the importance of gut microbiota in an ApoE[-/-] mouse model of chronic apical periodontitis-induced atherosclerosis.}, journal = {BMC oral health}, volume = {24}, number = {1}, pages = {1455}, pmid = {39614243}, issn = {1472-6831}, support = {2022QNA073//Fujian Provincial Health Technology Project/ ; 2022GGA042//Fujian Provincial Health Technology Project/ ; 2023J01709//Fujian Province Natural Science Founding of China/ ; 81970926//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Atherosclerosis/microbiology/etiology ; *Gastrointestinal Microbiome ; Mice ; *Fecal Microbiota Transplantation ; *Periapical Periodontitis/microbiology/metabolism ; *Disease Models, Animal ; *Methylamines/blood/metabolism ; Apolipoproteins E ; Male ; Mice, Inbred C57BL ; Oxygenases/metabolism ; }, abstract = {BACKGROUND: Chronic apical periodontitis (CAP) has been linked to the development of atherosclerosis, although the underlying mechanisms remain unclear. This study aimed to investigate the role of gut microbiota disruption in CAP-induced atherosclerosis development, focusing on trimethylamine N-oxide (TMAO)-related metabolites.

METHODS: The study utilized fecal microbiota transplantation (FMT) to transfer gut microbiota from mice with CAP to healthy mice. Atherosclerosis development was assessed by analyzing lesions in the aortic arch and aortic root. Serum lipid and inflammatory factor levels were measured. Composition and diversity of gut microbiota were analyzed using targeted metabolomics, with a focus on the ratio of Firmicutes to Bacteroidetes. The expression of hepatic flavin-containing monooxygenase 3 (FMO3) and serum TMAO levels were also evaluated.

RESULTS: Mice receiving gut microbiota from CAP mice showed increased atherosclerotic lesions compared to controls, without significant differences in serum lipid or inflammatory factor levels. Alterations in gut microbiota composition were observed, characterized by an increase in the Firmicutes to Bacteroidetes ratio. Peptostreptococcaceae abundance positively correlated with atherosclerosis severity, while Odoribacteraceae showed a negative correlation. No significant differences were found in hepatic FMO3 expression or serum TMAO levels.

CONCLUSIONS: The study confirms the role of gut microbiota disruption in CAP-mediated atherosclerosis development, independent of serum lipid or TMAO levels. Alterations in gut microbiota composition, particularly increased Firmicutes to Bacteroidetes ratio and specific bacterial families, were associated with atherosclerosis severity. These findings highlight the intricate interplay between gut microbiota and cardiovascular health in the context of CAP.}, } @article {pmid39612216, year = {2024}, author = {Wang, T and Luo, Y and Kong, X and Fang, L and Zhu, L and Yu, B and Zheng, P and Huang, Z and Mao, X and Jie, Y and Luo, J and Yan, H and He, J}, title = {Multiomics comparative analysis of feces AMRGs of Duroc pigs and Tibetan and the effect of fecal microbiota transplantation on AMRGs upon antibiotic exposure.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0198324}, doi = {10.1128/spectrum.01983-24}, pmid = {39612216}, issn = {2165-0497}, abstract = {UNLABELLED: Fecal matter is recognized as both a reservoir and a transmission source for various antimicrobial resistance genes (AMRGs). However, the transcriptional activity of AMRGs in swine feces is not well understood. In addition, the effect of fecal microbiota transplantation (FMT) on the excretion of AMRGs has rarely been reported. Our study explored the diversity, abundance, transcriptional activity, and bacterial hosts of AMRGs in Tibetan and Duroc pig feces using metagenomic and metatranscriptomic sequencing technologies. We discovered a significantly higher genomic abundance of AMRGs in the feces of Duroc pigs compared to Tibetan pigs (P < 0.001), although the transcript levels did not show a significant difference. The results showed that the core composition of AMRGs in pig feces varied considerably, with the most transcriptionally active AMRGs being oqxB, tetQ, Bla1, dfrA1, and amrB. Furthermore, the Firmicutes phylum is the main host of AMRGs. By transplanting fecal flora from Tibetan and Duroc pigs into the intestines of Duroc Landrace Yorkshire (DLY) piglets after acute antibiotic exposure, we found that only Tibetan pig fecal flora significantly reduced AMRGs in the feces of DLY piglets (P < 0.05). The effectiveness of Tibetan pig fecal microorganisms in removing AMRGs from DLY pig feces was mainly influenced by microbial communities, especially the Bacteroidota phylum. These findings offer valuable insights for the prevention and control of AMRG pollution.

IMPORTANCE: To the best of our knowledge, this study represents the first comprehensive analysis of antimicrobial resistance gene (AMRGs) expression in the fecal microbiota of Tibetan and Duroc pigs, employing an integrated metagenomic and metatranscriptomic approach. Our findings indicate a higher risk of AMRGs transmission in the feces of Duroc pigs compared to Tibetan pigs. Given the escalating antimicrobial resistance crisis, novel therapeutic interventions are imperative to mitigate gut colonization by pathogens and AMRGs. In this regard, we investigated the impact of fecal microbiota from Tibetan and Duroc pig sources on AMRGs excretion in Duroc Landrace Yorkshire (DLY) piglets' feces following acute antibiotic exposure. Remarkably, only fecal microbiota sourced from Tibetan pigs exhibited a reduction in AMRGs excretion in DLY piglets' feces. This underscores the significance of evaluating the presence of AMRGs within donor fecal microbiota for effective AMRGs decolonization strategies.}, } @article {pmid39471905, year = {2025}, author = {Salia, S and Burke, FF and Hinks, ME and Randell, AM and Matheson, MA and Walling, SG and Swift-Gallant, A}, title = {Gut microbiota transfer from the preclinical maternal immune activation model of autism is sufficient to induce sex-specific alterations in immune response and behavioural outcomes.}, journal = {Brain, behavior, and immunity}, volume = {123}, number = {}, pages = {813-823}, doi = {10.1016/j.bbi.2024.10.030}, pmid = {39471905}, issn = {1090-2139}, mesh = {Animals ; *Gastrointestinal Microbiome/immunology ; Female ; Male ; Mice ; *Disease Models, Animal ; *Mice, Inbred C57BL ; *Autism Spectrum Disorder/immunology/microbiology ; *Behavior, Animal/physiology ; Pregnancy ; Fecal Microbiota Transplantation ; Autistic Disorder/immunology/microbiology ; Sex Characteristics ; Social Behavior ; Sex Factors ; Anxiety/immunology/microbiology ; Cytokines/metabolism ; }, abstract = {The gut microbiome plays a vital role in health and disease, including neurodevelopmental disorders like autism spectrum disorder (ASD). ASD affects 4:1 males-to-females, and sex differences are apparent in gut microbiota composition among ASD individuals and in animal models of this condition, such as the maternal immune activation (MIA) mouse model. However, few studies have included sex as a biological variable when assessing the role of gut microbiota in mediating ASD symptoms. Using the MIA model of ASD, we assessed whether gut microbiota contributes to the sex differences in the presentation of ASD-like behaviors. Gut microbiota transplantation from MIA or vehicle/control male and female mice into healthy, otherwise unmanipulated, 4-week-old C57Bl/6 mice was performed for 6 treatments over 12 days. Colonization with male, but not female, MIA microbiota was sufficient to reduce sociability, decrease microbiota diversity and increase neuroinflammation with more pronounced deficits in male recipients. Colonization with both male and female donor microbiota altered juvenile ultrasonic vocalizations and anxiety-like behavior in recipients of both sexes, and there was an accompanied change in the gut microbiota and serum cytokine IL-4 and IL-7 levels of all recipients of MIA gut microbiota. In addition to the increases in gut microbes associated with pathological states, the female donor microbiota profile also had increases in gut microbes with known neural protective effects (e.g., Lactobacillus and Rikenella). These results suggest that gut reactivity to environmental insults, such as in the MIA model, may play a role in shaping the sex disparity in ASD development.}, } @article {pmid39608831, year = {2024}, author = {Tang, JMF and Habib, F and Rahmdil, M and Apostolou, N}, title = {Autologous faecal microbiota transplantation via double barrel stoma to treat chronic diversion colitis.}, journal = {BMJ case reports}, volume = {17}, number = {11}, pages = {}, doi = {10.1136/bcr-2024-262806}, pmid = {39608831}, issn = {1757-790X}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Colitis/therapy/microbiology/surgery ; *Ileostomy ; Male ; Transplantation, Autologous ; Middle Aged ; Treatment Outcome ; Chronic Disease ; Female ; }, abstract = {Diversion colitis is a common phenomenon affecting patients after defunctioning ileostomy. We present a complex case of diversion colitis where the patient was deemed unsuitable for restorative surgery due to multiple areas of stricturing in a long defunctioned colonic segment. Despite initial treatments with rectally administered topical mesalazine, butyrate enemas and topical steroid therapy, the patient remained symptomatic with rectal bleeding and mucus discharge. Furthermore, the appearance of colitis could be appreciated on endoscopy and radiological investigations with changes in histology consistent with moderate-severe diversion colitis. This article describes our experience in the use of autologous faecal transplant administered via the efferent loop of a double-barrel ileostomy to successfully treat diversion colitis refractory to standard topical therapy.}, } @article {pmid39607612, year = {2024}, author = {Qasem, HH and El-Sayed, WM}, title = {The bacterial microbiome and cancer: development, diagnosis, treatment, and future directions.}, journal = {Clinical and experimental medicine}, volume = {25}, number = {1}, pages = {12}, pmid = {39607612}, issn = {1591-9528}, mesh = {Humans ; *Neoplasms/therapy/microbiology/diagnosis ; *Dysbiosis ; *Microbiota ; Bacteria/classification/genetics ; Probiotics/therapeutic use ; }, abstract = {The term "microbiome" refers to the collection of bacterial species that reside in the human body's tissues. Sometimes, it is used to refer to all microbial entities (bacteria, viruses, fungi, and others) which colonize the human body. It is now generally acknowledged that the microbiome plays a critical role in the host's physiological processes and general well-being. Changes in the structure and/or function of the microbiome (dysbiosis) are linked to the development of many diseases including cancer. The claim that because of their negatively charged membrane, cancer cells are more vulnerable to some bacteria than normal cells and that is how the link between these bacteria and cancer evolved has been refuted. Furthermore, the relationship between the microbiome and cancer is more evident in the emerging field of cancer immunotherapy. In this narrative review, we detailed the correlation between the presence/absence of specific bacterial species and the development, diagnosis, prognosis, and treatment of some types of cancer including colorectal, lung, breast, and prostate cancer. In addition, we discussed the mechanisms of microbiome-cancer interactions including genotoxin production, the role of free radicals, modification of signaling pathways in host cells, immune modulation, and modulation of drug metabolism by microbiome. Future directions and clinical application of microbiome in the early detection, prognosis, and treatment of cancer emphasizing on the role of fecal transplantation, probiotics, prebiotics, and microbiome biomarkers were also considered.}, } @article {pmid39606629, year = {2024}, author = {Zhang, Z and Yang, M and Zhou, T and Chen, Y and Zhou, X and Long, K}, title = {Emerging trends and hotspots in intestinal microbiota research in sepsis: bibliometric analysis.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1510463}, pmid = {39606629}, issn = {2296-858X}, abstract = {BACKGROUND: The association between the gut microbiota and sepsis has garnered attention in the field of intestinal research in sepsis. This study utilizes bibliometric methods to visualize and analyze the literature on gut microbiota research in sepsis from 2011 to 2024, providing a scientific foundation for research directions and key issues in this domain.

METHODS: Original articles and reviews of gut microbiota research in sepsis, which published in English between 2011 and 2024, were obtained from the Web of Science Core Collection on June 21, 2024. Python, VOSviewer, and CiteSpace software were used for the visual analysis of the retrieved data.

RESULTS: A total of 1,031 articles were analyzed, originating from 72 countries or regions, 1,614 research institutions, and 6,541 authors. The articles were published in 434 different journals, covering 89 different research fields. The number of publications and citations in this research area showed a significant growth trend from 2011 to 2024, with China, the United States, and the United Kingdom being the main research forces. Asada Leelahavanichkul from Thailand was identified as the most prolific author, making him the most authoritative expert in this field. "Nutrients" had the highest number of publications, while "Frontiers in Cellular and Infection Microbiology," "Frontiers in Immunology" and "the International Journal of Molecular Sciences" have shown increasing attention to this field in the past 2 years. Author keywords appearing more than 100 times included "gut microbiota (GM)," "sepsis" and "microbiota." Finally, this study identified "lipopolysaccharides (LPS)," "short-chain fatty acids (SCFAs)," "probiotics," "fecal microbiota transplantation (FMT)" and "gut-liver axis" as the research hotspots and potential frontier directions in this field.

CONCLUSION: This bibliometric study summarizes current important perspectives and offers comprehensive guidance between sepsis and intestinal microbiota, which may help researchers choose the most appropriate research directions.}, } @article {pmid39605286, year = {2024}, author = {Yerushalmy-Feler, A and Spencer, EA and Dolinger, MT and Suskind, DL and Mitrova, K and Hradsky, O and Conrad, MA and Kelsen, JR and Uhlig, HH and Tzivinikos, C and Ancona, S and Wlazlo, M and Hackl, L and Shouval, DS and Bramuzzo, M and Urlep, D and Olbjorn, C and D'Arcangelo, G and Pujol-Muncunill, G and Yogev, D and Kang, B and Gasparetto, M and Rungø, C and Kolho, KL and Hojsak, I and Norsa, L and Rinawi, F and Sansotta, N and Magen Rimon, R and Granot, M and Scarallo, L and Trindade, E and Velasco Rodríguez-Belvís, M and Turner, D and Cohen, S}, title = {Upadacitinib for Induction of Remission in Pediatric Ulcerative Colitis: An International Multi‑center Study.}, journal = {Journal of Crohn's & colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjae182}, pmid = {39605286}, issn = {1876-4479}, abstract = {BACKGROUND AND AIMS: Data on upadacitinib therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBD-U) are scarce. We aimed to evaluate the effectiveness and safety of upadacitinib as an induction therapy in pediatric UC or IBD-U.

METHODS: In this multicenter retrospective study, children treated with upadacitinib for induction of remission of active UC or IBD-U from 30 centers worldwide were enrolled. Demographic, clinical and laboratory data as well as adverse events (AEs) were recorded at week 8 post induction.

RESULTS: One hundred children were included (90 UC and 10 IBD-U, median age 15.6 [interquartile range 13.3-17.1] years). Ninety-eight were previously treated with biologic therapies, and 76 were treated with ≥2 biologics. At the end of the 8-week induction period, clinical response, clinical remission, and corticosteroid-free clinical remission (CFR) were observed in 84%, 62%, and 56% of the children, respectively. Normal C-reactive protein and fecal calprotectin (FC) <150 mcg/g were achieved in 75% and 50%, respectively. Combined CFR and FC remission was observed in 18/46 (39%) children with available data at 8 weeks. AEs were recorded in 37 children, including one serious AE of an appendiceal neuroendocrine tumor. The most frequent AEs were hyperlipidemia (n=13), acne (n=12), and infections (n=10, five of whom with herpes viruses).

CONCLUSION: Upadacitinib is an effective induction therapy for refractory pediatric UC and IBD-U. Efficacy should be weighed against the potential risks of AEs.}, } @article {pmid39605077, year = {2024}, author = {Zou, P and Bi, Y and Tong, Z and Wu, T and Li, Q and Wang, K and Fan, Y and Zhao, D and Wang, X and Shao, H and Huang, H and Ma, S and Qian, Y and Zhang, G and Liu, X and Jin, Q and Ru, Q and Qian, Z and Sun, W and Chen, Q and You, L and Wang, F and Zhang, X and Qiu, Z and Lin, Q and Lv, J and Zhang, Y and Geng, J and Mao, R and Liu, J and Zheng, Y and Ding, F and Wang, H and Gao, H}, title = {Comparisons of efficacy and safety of 400 or 800 ml bacterial count fecal microbiota transplantation in the treatment of recurrent hepatic encephalopathy: a multicenter prospective randomized controlled trial in China.}, journal = {Trials}, volume = {25}, number = {1}, pages = {799}, pmid = {39605077}, issn = {1745-6215}, mesh = {Humans ; *Hepatic Encephalopathy/therapy/microbiology ; Prospective Studies ; *Fecal Microbiota Transplantation/adverse effects ; China ; *Quality of Life ; Treatment Outcome ; *Recurrence ; Multicenter Studies as Topic ; Male ; Bacterial Load ; Randomized Controlled Trials as Topic ; Middle Aged ; Adult ; Female ; }, abstract = {BACKGROUND: Hepatic encephalopathy (HE) represents a critical complications of end-stage liver disease, serving as an independent predictor of mortality among patients with cirrhosis. Despite effective treatment with rifaximin, some patients with HE still progress to recurrent episodes, posing a significant therapeutic challenge. Recurrent HE is defined as experiencing two or more episodes within a 6-month period. Previous research has suggested that FMT may emerge as a promising treatment for recurrent HE. However, there remains a critical need to explore the optimal dosage. This trial aims to abscess the efficacy and safety of two FMT dosages: 800 ml or 400 ml total bacterial count, including mortality and quality of life.

METHODS: This multicenter, prospective, randomized controlled trial will enroll 100 eligible patients from 31 hospitals in China. Participants will be randomly assigned in a 1:1 ratio to either the high-dose group (800 ml total bacterial count) or the low-dose group (400 ml total bacterial count). The primary objective is to assess the efficacy and safety of both dosages on outcomes at 24 and 48 weeks, including mortality and quality of life.

DISCUSSION: If either or both dosages of FMT demonstrate safe and effective treatment of recurrent HE, leading to improve quality of life and survival at 24 and 48 weeks, this trial would address a significant gap in the management of recurrent HE, carrying innovative and clinically significant implications.

TRIAL REGISTRATION: NCT05669651 on ClinicalTrials.gov. Registered on 29 December 2022. CHiCTR2200067135 on China Registered Clinical Trial Registration Center. Registered on 27 December 2022.}, } @article {pmid39604726, year = {2024}, author = {Chen-Liaw, A and Aggarwala, V and Mogno, I and Haifer, C and Li, Z and Eggers, J and Helmus, D and Hart, A and Wehkamp, J and Lamousé-Smith, ESN and Kerby, RL and Rey, FE and Colombel, JF and Kamm, MA and Olle, B and Norman, JM and Menon, R and Watson, AR and Crossett, E and Terveer, EM and Keller, JJ and Borody, TJ and Grinspan, A and Paramsothy, S and Kaakoush, NO and Dubinsky, MC and Faith, JJ}, title = {Gut microbiota strain richness is species specific and affects engraftment.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {39604726}, issn = {1476-4687}, abstract = {Despite the fundamental role of bacterial strain variation in gut microbiota function[1-6], the number of unique strains of a species that can stably colonize the human intestine is still unknown for almost all species. Here we determine the strain richness (SR) of common gut species using thousands of sequenced bacterial isolates with paired metagenomes. We show that SR varies across species, is transferable by faecal microbiota transplantation, and is uniquely low in the gut compared with soil and lake environments. Active therapeutic administration of supraphysiologic numbers of strains per species increases recipient SR, which then converges back to the population average after dosing is ceased. Stratifying engraftment outcomes by high or low SR shows that SR predicts microbial addition or replacement in faecal transplants. Together, these results indicate that properties of the gut ecosystem govern the number of strains of each species colonizing the gut and thereby influence strain addition and replacement in faecal microbiota transplantation and defined live biotherapeutic products.}, } @article {pmid39604623, year = {2024}, author = {Procházková, N and Laursen, MF and La Barbera, G and Tsekitsidi, E and Jørgensen, MS and Rasmussen, MA and Raes, J and Licht, TR and Dragsted, LO and Roager, HM}, title = {Gut physiology and environment explain variations in human gut microbiome composition and metabolism.}, journal = {Nature microbiology}, volume = {9}, number = {12}, pages = {3210-3225}, pmid = {39604623}, issn = {2058-5276}, support = {NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Feces/microbiology ; Adult ; Hydrogen-Ion Concentration ; Male ; Female ; Bacteria/classification/metabolism/genetics/isolation & purification ; Gastrointestinal Transit/physiology ; Young Adult ; Middle Aged ; Diet ; Fermentation ; Gastrointestinal Tract/microbiology/metabolism ; Methane/metabolism ; Healthy Volunteers ; }, abstract = {The human gut microbiome is highly personal. However, the contribution of gut physiology and environment to variations in the gut microbiome remains understudied. Here we performed an observational trial using multi-omics to profile microbiome composition and metabolism in 61 healthy adults for 9 consecutive days. We assessed day-to-day changes in gut environmental factors and measured whole-gut and segmental intestinal transit time and pH using a wireless motility capsule in a subset of 50 individuals. We observed substantial daily fluctuations, with intra-individual variations in gut microbiome and metabolism associated with changes in stool moisture and faecal pH, and inter-individual variations accounted for by whole-gut and segmental transit times and pH. Metabolites derived from microbial carbohydrate fermentation correlated negatively with the gut passage time and pH, while proteolytic metabolites and breath methane showed a positive correlation. Finally, we identified associations between segmental transit time/pH and coffee-, diet-, host- and microbial-derived metabolites. Our work suggests that gut physiology and environment are key to understanding the individuality of the human gut microbial composition and metabolism.}, } @article {pmid39604327, year = {2024}, author = {Saeed, H and Díaz, LA and Gil-Gómez, A and Burton, J and Bajaj, J and Romero-Gomez, M and Arrese, M and Arab, JP and Khan, MQ}, title = {Microbiome-Centered Therapies for the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease.}, journal = {Clinical and molecular hepatology}, volume = {}, number = {}, pages = {}, doi = {10.3350/cmh.2024.0811}, pmid = {39604327}, issn = {2287-285X}, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant global health issue, affecting over 30% of the population worldwide due to the rising prevalence of metabolic risk factors such as obesity and type 2 diabetes mellitus (T2DM). This spectrum of liver disease ranges from isolated steatosis to more severe forms such as steatohepatitis, fibrosis, and cirrhosis. Recent studies highlight the role of gut microbiota in MASLD pathogenesis, showing that dysbiosis significantly impacts metabolic health and the progression of liver disease. This review critically evaluates current microbiome-centered therapies in MASLD management, including prebiotics, probiotics, synbiotics, fecal microbiota transplantation (FMT), and emerging therapies such as engineered bacteria and bacteriophage therapy. We explore the scientific rationale, clinical evidence, and potential mechanisms by which these interventions influence MASLD. The gut-liver axis is crucial in MASLD, with notable changes in microbiome composition linked to disease progression. For instance, specific microbial profiles and reduced alpha diversity are associated with MASLD severity. Therapeutic strategies targeting the microbiome could modulate disease progression by improving gut permeability, reducing endotoxin-producing bacteria, and altering bile acid metabolism. Although promising, these therapies require further research to fully understand their mechanisms and optimize their efficacy. This review integrates findings from clinical trials and experimental studies, providing a comprehensive overview of microbiome-centered therapies' potential in managing MASLD. Future research should focus on personalized strategies, utilizing microbiome features, blood metabolites, and customized dietary interventions to enhance the effectiveness of these therapies.}, } @article {pmid39269772, year = {2024}, author = {Rahal, Z and Liu, Y and Peng, F and Yang, S and Jamal, MA and Sharma, M and Moreno, H and Damania, AV and Wong, MC and Ross, MC and Sinjab, A and Zhou, T and Chen, M and Tarifa Reischle, I and Feng, J and Chukwuocha, C and Tang, E and Abaya, C and Lim, JK and Leung, CH and Lin, HY and Deboever, N and Lee, JJ and Sepesi, B and Gibbons, DL and Wargo, JA and Fujimoto, J and Wang, L and Petrosino, JF and Ajami, NJ and Jenq, RR and Moghaddam, SJ and Cascone, T and Hoffman, K and Kadara, H}, title = {Inflammation Mediated by Gut Microbiome Alterations Promotes Lung Cancer Development and an Immunosuppressed Tumor Microenvironment.}, journal = {Cancer immunology research}, volume = {12}, number = {12}, pages = {1736-1752}, doi = {10.1158/2326-6066.CIR-24-0469}, pmid = {39269772}, issn = {2326-6074}, support = {R01 CA205608/CA/NCI NIH HHS/United States ; R01 CA248731/CA/NCI NIH HHS/United States ; R01CA248731//National Cancer Institute (NCI)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/immunology ; *Tumor Microenvironment/immunology ; *Lung Neoplasms/immunology/microbiology/pathology ; Mice ; Humans ; *Inflammation/immunology ; Adenocarcinoma of Lung/immunology/microbiology/pathology ; Lipocalin-2/metabolism ; Mice, Inbred C57BL ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Mice, Knockout ; }, abstract = {Accumulating evidence indicates that the gut microbiome influences cancer progression and therapy. We recently showed that progressive changes in gut microbial diversity and composition are closely coupled with tobacco-associated lung adenocarcinoma in a human-relevant mouse model. Furthermore, we demonstrated that the loss of the antimicrobial protein Lcn2 in these mice exacerbates protumor inflammatory phenotypes while further reducing microbial diversity. Yet, how gut microbiome alterations impinge on lung adenocarcinoma development remains poorly understood. In this study, we investigated the role of gut microbiome changes in lung adenocarcinoma development using fecal microbiota transfer and delineated a pathway by which gut microbiome alterations incurred by loss of Lcn2 fostered the proliferation of proinflammatory bacteria of the genus Alistipes, triggering gut inflammation. This inflammation propagated systemically, exerting immunosuppression within the tumor microenvironment, augmenting tumor growth through an IL6-dependent mechanism and dampening response to immunotherapy. Corroborating our preclinical findings, we found that patients with lung adenocarcinoma with a higher relative abundance of Alistipes species in the gut showed diminished response to neoadjuvant immunotherapy. These insights reveal the role of microbiome-induced inflammation in lung adenocarcinoma and present new potential targets for interception and therapy.}, } @article {pmid39603188, year = {2024}, author = {Xie, C and Liang, Q and Cheng, J and Yuan, Y and Xie, L and Ji, J}, title = {Transplantation of fecal microbiota from low to high residual feed intake chickens: Impacts on RFI, microbial community and metabolites profiles.}, journal = {Poultry science}, volume = {104}, number = {1}, pages = {104567}, doi = {10.1016/j.psj.2024.104567}, pmid = {39603188}, issn = {1525-3171}, abstract = {Improving feed efficiency is vital to bolster profitability and sustainability in poultry production. Although several studies have established links between gut microbiota and feed efficiency, the direct effects remain unclear. In this study, two distinct lines of Huiyang bearded chickens, exhibiting significant differences in residual feed intake (RFI), were developed after 15 generations of selective breeding. Fecal microbiota transplantation (FMT) from low RFI (LRFI) chickens to high RFI (HRFI) chickens resulted in a reduction trend in RFI, decreasing from 5.65 to 4.49 in the HRFI recipient chickens (HFMT). Microbiota composition and functional profiles in LRFI and HFMT chickens formed a distinct cluster compared to HRFI chickens. Using 16S rDNA sequencing and RandomForest analysis, Slackia, Peptococcus, Blautia, and Dorea were identified as key microbial markers associated with feed efficiency. Additionally, untargeted metabolomics identified common differential metabolites between HFMT and LRFI vs. HRFI groups. Correlation analysis showed significant correlations between these microbial markers and differential metabolites. These findings provide a foundation for microbiome-based strategies to improve feed efficiency in poultry.}, } @article {pmid39600755, year = {2024}, author = {Castro-Vidal, ZA and Mathew, F and Ibrahim, AA and Shubhangi, F and Cherian, RR and Choi, HK and Begum, A and Ravula, HK and Giri, H}, title = {The Role of Gastrointestinal Dysbiosis and Fecal Transplantation in Various Neurocognitive Disorders.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e72451}, pmid = {39600755}, issn = {2168-8184}, abstract = {This review explores the critical role of the human microbiome in neurological and neurodegenerative disorders, focusing on gut-brain axis dysfunction caused by dysbiosis, an imbalance in gut bacteria. Dysbiosis has been linked to diseases such as Alzheimer's disease, Parkinson's disease (PD), multiple sclerosis (MS), and stroke. The gut microbiome influences the central nervous system (CNS) through signaling molecules, including short-chain fatty acids, neurotransmitters, and metabolites, impacting brain health and disease progression. Emerging therapies, such as fecal microbiota transplantation (FMT), have shown promise in restoring microbial balance and alleviating neurological symptoms, especially in Alzheimer's and PD. Additionally, nutritional interventions such as probiotics, prebiotics, and specialized diets are being investigated for their ability to modify gut microbiota and improve patient outcomes. This review highlights the therapeutic potential of gut microbiota modulation but emphasizes the need for further clinical trials to establish the safety and efficacy of these interventions in neurological and mental health disorders.}, } @article {pmid39600698, year = {2024}, author = {Liu, X and Li, B and Liang, L and Han, J and Mai, S and Liu, L}, title = {From microbes to medicine: harnessing the power of the microbiome in esophageal cancer.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1450927}, pmid = {39600698}, issn = {1664-3224}, mesh = {Humans ; *Esophageal Neoplasms/therapy/microbiology/immunology ; *Dysbiosis/therapy/microbiology ; *Gastrointestinal Microbiome/immunology ; Animals ; Probiotics/therapeutic use ; Microbiota/immunology ; }, abstract = {Esophageal cancer (EC) is a malignancy with a high incidence and poor prognosis, significantly influenced by dysbiosis in the esophageal, oral, and gut microbiota. This review provides an overview of the roles of microbiota dysbiosis in EC pathogenesis, emphasizing their impact on tumor progression, drug efficacy, biomarker discovery, and therapeutic interventions. Lifestyle factors like smoking, alcohol consumption, and betel nut use are major contributors to dysbiosis and EC development. Recent studies utilizing advanced sequencing have revealed complex interactions between microbiota dysbiosis and EC, with oral pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum promoting inflammation and suppressing immune responses, thereby driving carcinogenesis. Altered esophageal microbiota, characterized by reduced beneficial bacteria and increased pathogenic species, further exacerbate local inflammation and tumor growth. Gut microbiota dysbiosis also affects systemic immunity, influencing chemotherapy and immunotherapy efficacy, with certain bacteria enhancing or inhibiting treatment responses. Microbiota composition shows potential as a non-invasive biomarker for early detection, prognosis, and personalized therapy. Novel therapeutic strategies targeting the microbiota-such as probiotics, dietary modifications, and fecal microbiota transplantation-offer promising avenues to restore balance and improve treatment efficacy, potentially enhancing patient outcomes. Integrating microbiome-focused strategies into current therapeutic frameworks could improve EC management, reduce adverse effects, and enhance patient survival. These findings highlight the need for further research into microbiota-tumor interactions and microbial interventions to transform EC treatment and prevention, particularly in cases of late-stage diagnosis and poor treatment response.}, } @article {pmid39600557, year = {2024}, author = {Wohl, P and Krausova, A and Wohl, P and Fabian, O and Bajer, L and Brezina, J and Drastich, P and Hlavaty, M and Novotna, P and Kahle, M and Spicak, J and Gregor, M}, title = {Limited validity of Mayo endoscopic subscore in ulcerative colitis with concomitant primary sclerosing cholangitis.}, journal = {World journal of gastrointestinal endoscopy}, volume = {16}, number = {11}, pages = {607-616}, pmid = {39600557}, issn = {1948-5190}, abstract = {BACKGROUND: Ulcerative colitis (UC) with concomitant primary sclerosing cholangitis (PSC) represents a distinct disease entity (PSC-UC). Mayo endoscopic subscore (MES) is a standard tool for assessing disease activity in UC but its relevance in PSC-UC remains unclear.

AIM: To assess the accuracy of MES in UC and PSC-UC patients, we performed histological scoring using Nancy histological index (NHI).

METHODS: MES was assessed in 30 PSC-UC and 29 UC adult patients during endoscopy. NHI and inflammation were evaluated in biopsies from the cecum, rectum, and terminal ileum. In addition, perinuclear anti-neutrophil cytoplasmic antibodies, fecal calprotectin, body mass index, and other relevant clinical characteristics were collected.

RESULTS: The median MES and NHI were similar for UC patients (MES grade 2 and NHI grade 2 in the rectum) but were different for PSC-UC patients (MES grade 0 and NHI grade 2 in the cecum). There was a correlation between MES and NHI for UC patients (Spearman's r = 0.40, P = 0.029) but not for PSC-UC patients. Histopathological examination revealed persistent microscopic inflammation in 88% of PSC-UC patients with MES grade 0 (46% of all PSC-UC patients). Moreover, MES overestimated the severity of active inflammation in an additional 11% of PSC-UC patients.

CONCLUSION: MES insufficiently identifies microscopic inflammation in PSC-UC. This indicates that histological evaluation should become a routine procedure of the diagnostic and grading system in both PSC-UC and PSC.}, } @article {pmid39599742, year = {2024}, author = {Al-Habsi, N and Al-Khalili, M and Haque, SA and Elias, M and Olqi, NA and Al Uraimi, T}, title = {Health Benefits of Prebiotics, Probiotics, Synbiotics, and Postbiotics.}, journal = {Nutrients}, volume = {16}, number = {22}, pages = {}, pmid = {39599742}, issn = {2072-6643}, support = {(SR/AGR/Food/23/01)//His Majesty Trust Funds/ ; }, mesh = {Humans ; *Prebiotics/administration & dosage ; *Probiotics/administration & dosage ; *Synbiotics/administration & dosage ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Functional Food ; }, abstract = {The trillions of microbes that constitute the human gut microbiome play a crucial role in digestive health, immune response regulation, and psychological wellness. Maintaining gut microbiota is essential as metabolic diseases are associated with it. Functional food ingredients potentially improving gut health include prebiotics, probiotics, synbiotics, and postbiotics (PPSPs). While probiotics are living bacteria that provide health advantages when ingested sufficiently, prebiotics are non-digestible carbohydrates that support good gut bacteria. Synbiotics work together to improve immunity and intestinal health by combining probiotics and prebiotics. Postbiotics have also demonstrated numerous health advantages, such as bioactive molecules created during probiotic fermentation. According to a recent study, PPSPs can regulate the synthesis of metabolites, improve the integrity of the intestinal barrier, and change the gut microbiota composition to control metabolic illnesses. Additionally, the use of fecal microbiota transplantation (FMT) highlights the potential for restoring gut health through microbiota modulation, reinforcing the benefits of PPSPs in enhancing overall well-being. Research has shown that PPSPs provide several health benefits, such as improved immunological function, alleviation of symptoms associated with irritable bowel disease (IBD), decreased severity of allergies, and antibacterial and anti-inflammatory effects. Despite encouraging results, many unanswered questions remain about the scope of PPSPs' health advantages. Extensive research is required to fully realize the potential of these functional food components in enhancing human health and well-being. Effective therapeutic and prophylactic measures require further investigation into the roles of PPSPs, specifically their immune-system-modulating, cholesterol-lowering, antioxidant, and anti-inflammatory characteristics.}, } @article {pmid39598283, year = {2024}, author = {Mederle, AL and Dima, M and Stoicescu, ER and Căpăstraru, BF and Levai, CM and Hațegan, OA and Maghiari, AL}, title = {Impact of Gut Microbiome Interventions on Glucose and Lipid Metabolism in Metabolic Diseases: A Systematic Review and Meta-Analysis.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {11}, pages = {}, pmid = {39598283}, issn = {2075-1729}, abstract = {BACKGROUND: The gut microbiome is increasingly recognized as a key player in metabolic health, influencing glucose and lipid metabolism through various mechanisms. However, the efficacy of gut microbiota-targeted interventions, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and diet-based treatments, remains unclear for specific metabolic outcomes. In this study, the aim was to evaluate the impact of these interventions on the glucose and lipid parameters in individuals with metabolic diseases such as diabetes mellitus (DM), obesity, and metabolic syndrome.

METHODS: This systematic review and meta-analysis included 41 randomized controlled trials that investigated the effects of gut microbiota-targeted treatments on metabolic parameters such as fasting glucose, glycated hemoglobin (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. A comprehensive search was conducted using databases like PubMed, Google Scholar, and Scopus, focusing on interventions targeting the gut microbiota. A meta-analysis was performed using random-effects models, with effect sizes calculated for each outcome. Risk of bias was assessed using the Cochrane Risk of Bias tool.

RESULTS: Gut microbiota-targeted interventions significantly reduced fasting glucose, HbA1c, HOMA-IR, total cholesterol, LDL-C, and triglycerides, with moderate heterogeneity observed across studies. The interventions also led to modest increases in HDL-C levels. Probiotic and synbiotic interventions showed the most consistent benefits in improving both glucose and lipid profiles, while FMT yielded mixed results. Short-term interventions showed rapid microbial shifts but less pronounced metabolic improvements, whereas longer-term interventions had more substantial metabolic benefits.

CONCLUSIONS: In this study, it is demonstrated that gut microbiota-targeted interventions can improve key metabolic outcomes, offering a potential therapeutic strategy for managing metabolic diseases. However, the effectiveness of these interventions varies depending on the type, duration, and population characteristics, highlighting the need for further long-term studies to assess the sustained effects of microbiota modulation on metabolic health.}, } @article {pmid39597729, year = {2024}, author = {Alexandrescu, L and Suceveanu, AP and Stanigut, AM and Tofolean, DE and Axelerad, AD and Iordache, IE and Herlo, A and Nelson Twakor, A and Nicoara, AD and Tocia, C and Dumitru, A and Dumitru, E and Condur, LM and Aftenie, CF and Tofolean, IT}, title = {Intestinal Insights: The Gut Microbiome's Role in Atherosclerotic Disease: A Narrative Review.}, journal = {Microorganisms}, volume = {12}, number = {11}, pages = {}, pmid = {39597729}, issn = {2076-2607}, abstract = {Recent advances have highlighted the gut microbiota as a significant contributor to the development and progression of atherosclerosis, which is an inflammatory cardiovascular disease (CVD) characterized by plaque buildup within arterial walls. The gut microbiota, consisting of a diverse collection of microorganisms, impacts the host's metabolism, immune responses, and lipid processing, all of which contribute to atherosclerosis. This review explores the complex mechanisms through which gut dysbiosis promotes atherogenesis. We emphasize the potential of integrating microbiota modulation with traditional cardiovascular care, offering a holistic approach to managing atherosclerosis. Important pathways involve the translocation of inflammatory microbial components, modulation of lipid metabolism through metabolites such as trimethylamine-N-oxide (TMAO), and the production of short-chain fatty acids (SCFAs) that influence vascular health. Studies reveal distinct microbial profiles in atherosclerosis patients, with increased pathogenic bacteria (Megamonas, Veillonella, Streptococcus) and reduced anti-inflammatory genera (Bifidobacterium, Roseburia), highlighting the potential of these profiles as biomarkers and therapeutic targets. Probiotics are live microorganisms that have health benefits on the host. Prebiotics are non-digestible dietary fibers that stimulate the growth and activity of beneficial gut bacteria. Interventions targeting microbiota, such as probiotics, prebiotics, dietary modifications, and faecal microbiota transplantation (FMT), present effective approaches for restoring microbial equilibrium and justifying cardiovascular risk. Future research should focus on longitudinal, multi-omics studies to clarify causal links and refine therapeutic applications.}, } @article {pmid39597606, year = {2024}, author = {Qiao, Y and Feng, Q and Wang, Q and Zhao, Q and Zhu, S and Zhao, F and Wang, Z and Zhang, R and Wang, J and Yu, Y and Han, H and Dong, H}, title = {Alteration in the Gut Microbiota of Chickens Resistant to Eimeria tenella Infection.}, journal = {Microorganisms}, volume = {12}, number = {11}, pages = {}, pmid = {39597606}, issn = {2076-2607}, support = {Grant No. 2023YFD18024//National Key Research and Development Program of China/ ; XZ202401ZY0052//Key Research and Development of Science and Technology Plan in Tibet Autonomous Region/ ; Grant No. 32373038//National Natural Science Foundation of China/ ; NPRC-2019-194-30//National Parasitic Resources Center/ ; }, abstract = {Avian coccidiosis, caused by several species of Eimeria, is a widespread and economically important poultry disease that inflicts severe losses in the poultry industry. Understanding the interplay between Eimeria and gut microbiota is critical for controlling coccidiosis and developing innovative treatments to ensure good poultry health. In the present study, chickens were immunized six times with a low dose of Eimeria tenella, resulting in complete immunity against Eimeria infection. The results of fecal microbiota transplantation showed that the gut microbiota of immunized chickens induced a certain degree of resistance to coccidial infection. To investigate the types of intestinal microbiota involved in the development of resistance to Eimeria, the intestinal contents and fecal samples from both immunized and unimmunized groups were collected for 16S rRNA gene sequencing. The results showed that, at the genus level, the abundance of the Eubacterium coprostanoligenes group, Erysipelatoclostridium, Shuttleworthia, and Colidextribacter was significantly increased in the intestinal content of immunized chickens, whereas the abundance of Eisenbergiella was significantly decreased. In fecal samples, the abundance of Clostridiaceae and Muribaculaceae significantly increased, whereas that of Bacillales significantly decreased. These findings will help to elucidate the interactions between E. tenella and the gut microbiota of chickens, providing a basis for isolating E. tenella-resistant strains from the gut microbiome and developing new vaccines against coccidiosis.}, } @article {pmid39597084, year = {2024}, author = {Ko, Y and Alaedin, S and Fernando, D and Zhou, J and Ho, V}, title = {A Review of Fecal Microbiota Transplantation in Children-Exploring Its Role in the Treatment of Inflammatory Bowel Diseases.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {11}, pages = {}, pmid = {39597084}, issn = {1648-9144}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Child ; *Inflammatory Bowel Diseases/therapy/microbiology ; Gastrointestinal Microbiome ; Treatment Outcome ; }, abstract = {Background and Objectives: There is an increasing use of fecal matter transplantation (FMT) worldwide as research into the impact of the gut microbiome in various disease states is growing. FMT is the transfer of stool from a healthy human donor to a patient for the purpose of restoring intestinal dysbiosis. This review will assess the efficacy and safety of FMT in the treatment of pediatric inflammatory bowel diseases (IBDs) and explore the future directions of the use of FMT in children. Materials and Methods: A systematic review was performed where a literature search of publications published prior to 15 September 2023 was performed. Efficacy outcomes and safety data as well as microbiome analysis were reviewed from the studies where applicable. Results: Nine studies on UC and two studies on CD satisfied eligibility criteria and individually analysed. Most of the studies provided microbiome analyses. Conclusions: FMT is a safe treatment for paediatric IBD, and is shown to be effective in inducing clinical response by some studies. However the lack of randomized controlled trials limited the results of our study.}, } @article {pmid39596154, year = {2024}, author = {Sevcikova, A and Martiniakova, M and Omelka, R and Stevurkova, V and Ciernikova, S}, title = {The Link Between the Gut Microbiome and Bone Metastasis.}, journal = {International journal of molecular sciences}, volume = {25}, number = {22}, pages = {}, pmid = {39596154}, issn = {1422-0067}, support = {2/0069/22//Scientific Grant Agency of the Ministry of Education, Research, Development, and Youth of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; 1/0071/24//Scientific Grant Agency of the Ministry of Education, Research, Development, and Youth of the Slovak Republic and Slovak Academy of Sciences/ ; KEGA 034UKF-4/2022//Ministry of Education, Research, Development, and Youth of the Slovak Republic/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Bone Neoplasms/secondary/microbiology ; Animals ; Dysbiosis/microbiology ; Probiotics ; }, abstract = {The gut microbiome is essential for regulating host metabolism, defending against pathogens, and shaping the host's immune system. Mounting evidence highlights that disruption in gut microbial communities significantly impacts cancer development and treatment. Moreover, tumor-associated microbiota, along with its metabolites and toxins, may contribute to cancer progression by promoting epithelial-to-mesenchymal transition, angiogenesis, and metastatic spread to distant organs. Bones, in particular, are common sites for metastasis due to a rich supply of growth and neovascularization factors and extensive blood flow, especially affecting patients with thyroid, prostate, breast, lung, and kidney cancers, where bone metastases severely reduce the quality of life. While the involvement of the gut microbiome in bone metastasis formation is still being explored, proposed mechanisms suggest that intestinal dysbiosis may alter the bone microenvironment via the gut-immune-bone axis, fostering a premetastatic niche and immunosuppressive milieu suitable for cancer cell colonization. Disruption in the delicate balance of bone modeling and remodeling may further create a favorable environment for metastatic growth. This review focuses on the link between beneficial or dysbiotic microbiome composition and bone homeostasis, as well as the role of the microbiome in bone metastasis development. It also provides an overview of clinical trials evaluating the impact of gut microbial community structure on bone parameters across various conditions or health-related issues. Dietary interventions and microbiota modulation via probiotics, prebiotics, and fecal microbiota transplantation help support bone health and might offer promising strategies for addressing bone-related complications in cancer.}, } @article {pmid39595097, year = {2024}, author = {López-Tenorio, II and Aguilar-Villegas, ÓR and Espinoza-Palacios, Y and Segura-Real, L and Peña-Aparicio, B and Amedei, A and Aguirre-García, MM}, title = {Primary Prevention Strategy for Non-Communicable Diseases (NCDs) and Their Risk Factors: The Role of Intestinal Microbiota.}, journal = {Biomedicines}, volume = {12}, number = {11}, pages = {}, pmid = {39595097}, issn = {2227-9059}, support = {CF 2023-2024 -734//Consejo Nacional de Humanidades, Ciencias y Tecnologías/ ; IN21222//Universidad Nacional Autónoma de México/ ; }, abstract = {Non-communicable diseases (NCDs) are the leading cause of morbidity and mortality worldwide. These conditions have numerous health consequences and significantly impact patients' lifestyles. Effective long-term treatment is essential since NCDs are irreversible. Therefore, primary healthcare must be both exclusive and of the highest quality, ensuring comprehensive care. The primary goal should be to improve quality of life with a focus on patients, families, and communities, as most of these diseases can be prevented and controlled, although not cured. Several factors have been linked to individual health, including social, cultural, and economic aspects, lifestyle, and certain environmental factors, including work, that can have positive or negative effects. More of these variables may contribute to the onset of NCDs, which are defined by their chronic nature, propensity for prolongation, and generally slow rate of progression. Examples of NCDs include hypertension, type 2 diabetes (T2D), dyslipidemia, and fatty liver disease linked to metabolic dysfunction. The onset of these diseases has been associated with an imbalance in certain microbial niches, such as the gut, which hosts billions of microorganisms performing multiple metabolic functions, such as the production of metabolites like bile acids (BAs), short-chain fatty acids (SCFAs), and trimethylamine N-oxide (TMAO). Therefore, lifestyle changes and personal habits can significantly impact the gut microbiota (GM), potentially preventing chronic diseases associated with metabolism. NCDs are highly prevalent worldwide, prompting increased attention to strategies for modifying the intestinal microbiota (IM). Approaches such as probiotics, prebiotics, synbiotics, and fecal transplantation (FMT) have demonstrated improvements in the quality of life for individuals with these conditions. Additionally, lifestyle changes and the adoption of healthy habits can significantly impact IM and may help prevent chronic diseases related to metabolism. Therefore, the main aim of this review is to analyze and understand the importance of microbiota intervention in the prevention of non-communicable diseases. R3:A1.}, } @article {pmid39594528, year = {2024}, author = {Scarpellini, E and Scarcella, M and Tack, JF and Scarlata, GGM and Zanetti, M and Abenavoli, L}, title = {Gut Microbiota and Metabolic Dysfunction-Associated Steatotic Liver Disease.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {13}, number = {11}, pages = {}, doi = {10.3390/antiox13111386}, pmid = {39594528}, issn = {2076-3921}, abstract = {Background: The gut microbiota constitutes a complex microorganism community that harbors bacteria, viruses, fungi, protozoa, and archaea. The human gut bacterial microbiota has been extensively proven to participate in human metabolism, immunity, and nutrient absorption. Its imbalance, namely "dysbiosis", has been linked to disordered metabolism. Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the features of deranged human metabolism and is the leading cause of liver cirrhosis and hepatocellular carcinoma. Thus, there is a pathophysiological link between gut dysbiosis and MASLD. Aims and Methods: We aimed to review the literature data on the composition of the human bacterial gut microbiota and its dysbiosis in MASLD and describe the concept of the "gut-liver axis". Moreover, we reviewed the approaches for gut microbiota modulation in MASLD treatment. Results: There is consolidated evidence of particular gut dysbiosis associated with MASLD and its stages. The model explaining the relationship between gut microbiota and the liver has a bidirectional organization, explaining the physiopathology of MASLD. Oxidative stress is one of the keystones in the pathophysiology of MASLD and fibrosis generation. There is promising and consolidated evidence for the efficacy of pre- and probiotics in reversing gut dysbiosis in MASLD patients, with therapeutic effects. Few yet encouraging data on fecal microbiota transplantation (FMT) in MASLD are available in the literature. Conclusions: The gut dysbiosis characteristic of MASLD is a key target in its reversal and treatment via diet, pre/probiotics, and FMT treatment. Oxidative stress modulation remains a promising target for MASLD treatment, prevention, and reversal.}, } @article {pmid39593402, year = {2024}, author = {Tian, B and Pan, Y and Zhang, X and Wu, Y and Luo, X and Yang, K}, title = {Etiolated-green tea attenuates colonic barrier dysfunction and inflammation in high-fat diet-induced mice by modulating gut microbiota.}, journal = {Food research international (Ottawa, Ont.)}, volume = {197}, number = {Pt 1}, pages = {115192}, doi = {10.1016/j.foodres.2024.115192}, pmid = {39593402}, issn = {1873-7145}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Diet, High-Fat/adverse effects ; *Tea/chemistry ; Mice ; Male ; *Colon/microbiology/metabolism/drug effects ; *Mice, Inbred C57BL ; *Inflammation ; Fatty Acids, Volatile/metabolism ; Dysbiosis ; Obesity/metabolism ; NF-kappa B/metabolism ; Intestinal Mucosa/metabolism/drug effects ; Fecal Microbiota Transplantation ; Toll-Like Receptor 4/metabolism ; Signal Transduction/drug effects ; Receptors, G-Protein-Coupled/metabolism ; Tight Junctions/drug effects/metabolism ; }, abstract = {Colonic barrier dysfunction and inflammation arising from dysbiosis gut microbiota (GM) are strongly associated with a high-fat diet (HFD). Yellow leaf green tea (YLGT), a novel variety of etiolated-green tea, improving the intestinal barrier and inflammation is related to the regulation of GM disorders. To explore the ameliorative mechanism of YLGT, mice were fed an HFD with or without YLGT at doses of 150, 300, and 450 mg kg[-1] for 12 weeks. YLGT rectified the GM imbalance, enriched short-chain fatty acid (SCFA)-producing bacteria and gut SCFA contents, activated G protein-coupled receptors, inhibited TLR4/NF-κB signaling pathway, strengthened the tight junction, and repaired the damaged intestinal barrier. The fecal microbiota transplantation experiment further confirmed that the GM was a key element in the anti-obesity and anti-intestinal inflammation effect of YLGT. YLGT has great promise in attenuating obesity-induced intestinal dysfunction. This research provides novel insights into the new mechanism of YLGT on HFD-induced obesity.}, } @article {pmid39592752, year = {2024}, author = {Chatthanathon, P and Leelahavanichkul, A and Cheibchalard, T and Wilantho, A and Hirankarn, N and Somboonna, N}, title = {Author Correction: Comparative time-series analyses of gut microbiome profiles in genetically and chemically induced lupus-prone mice and the impacts of fecal transplantation.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {29391}, doi = {10.1038/s41598-024-79960-5}, pmid = {39592752}, issn = {2045-2322}, } @article {pmid39592644, year = {2024}, author = {Hunthai, S and Usawachintachit, M and Taweevisit, M and Srisa-Art, M and Anegkamol, W and Tosukhowong, P and Rattanachaisit, P and Chuaypen, N and Dissayabutra, T}, title = {Publisher Correction: Unraveling the role of gut microbiota by fecal microbiota transplantation in rat model of kidney stone disease.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {29360}, doi = {10.1038/s41598-024-78864-8}, pmid = {39592644}, issn = {2045-2322}, } @article {pmid39592438, year = {2024}, author = {Zhang, S and Wen, H and Chen, Y and Ning, J and Hu, D and Dong, Y and Yao, C and Yuan, B and Yang, S}, title = {Crosstalk between gut microbiota and tumor: tumors could cause gut dysbiosis and metabolic imbalance.}, journal = {Molecular oncology}, volume = {}, number = {}, pages = {}, doi = {10.1002/1878-0261.13763}, pmid = {39592438}, issn = {1878-0261}, support = {82303747//National Natural Science Foundation of China/ ; 2020GXLH-Y-010//Key Research and Development Projects of Shaanxi Province/ ; 2022JM-509//Natural Science Basic Research Program of Shaanxi Province/ ; }, abstract = {Gut microbiota has a proven link with the development and treatment of cancer. However, the causality between gut microbiota and cancer development is still unknown and deserves exploration. In this study, we aimed to explore the alterations in gut microbiota in murine tumor models and the crosstalk between the tumor and the gut microbiota. The subcutaneous and intravenous murine tumor models using both the colorectal cancer cell line MC38 and lung cancer cell line LLC were constructed. Then fecal samples before and after tumor inoculation were collected for whole metagenomics sequencing. Both subcutaneous and metastatic tumors markedly elevated the α-diversity of the gut microbiota. Relative abundance of Ligilactobacillus and Lactobacillus was reduced after subcutaneously inoculating tumor cells, whereas Bacteroides and Duncaniella were reduced in metastatic tumors, regardless of tumor type. At the species level, Lachnospiraceae bacterium was enriched after both subcutaneous and intravenous tumors inoculation, whereas levels of Muribaculaceae bacterium Isolate-110 (HZI), Ligilactobacillus murinus and Bacteroides acidifaciens reduced. Metabolic function analysis showed that the reductive pentose phosphate cycle, urea cycle, ketone body biosynthesis, ectoine biosynthesis, C4-dicarboxylic acid cycle, isoleucine biosynthesis, inosine 5'-monophosphate (IMP), and uridine 5'-monophosphate (UMP) biosynthesis were elevated after tumor inoculation, whereas the cofactor and vitamin biosynthesis were deficient. Principal coordinates analysis (PCoA) showed that subcutaneous and metastatic tumors partially shared the same effect patterns on gut microbiota. Furthermore, fecal microbiota transplantation revealed that this altered microbiota could influence tumor growth. Taken together, this study demonstrated that both colorectal cancer (MC38) and non-colorectal cancer (LLC) can cause gut dysbiosis and metabolic imbalance, regardless of tumor type and process of tumor inoculation, and this dysbiosis influenced the tumor growth. This research gives novel insights into the crosstalk between tumors and the gut microbiota.}, } @article {pmid39591377, year = {2024}, author = {Tafader, A and Bajaj, JS}, title = {Present and future of fecal microbiome transplantation in cirrhosis.}, journal = {Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society}, volume = {}, number = {}, pages = {}, doi = {10.1097/LVT.0000000000000542}, pmid = {39591377}, issn = {1527-6473}, abstract = {Over the last few decades, there have been tremendous advances in our understanding of the role of the gut microbiome in cirrhosis and the clinical sequelae that follows. Progressive dysbiosis and immune dysregulation occurs in patients with cirrhosis. In fact, alterations in the gut microbiome occur long before a diagnosis of cirrhosis is made. Understandably, our attention has recently been diverted towards potential modulators of the gut microbiome and the gut-liver axis as targets for treatment. The goal of this review is to highlight the utility of manipulating the gut microbiome with a focus on fecal microbiome transplantation (FMT) in patients with cirrhosis. In addition, we will provide an overview of disease-specific microbial alterations and the resultant impact this has on cirrhosis-related complications.}, } @article {pmid39590350, year = {2024}, author = {Chen, Z and Liao, Y and Chai, S and Yang, Y and Ga, Q and Ge, R and Wang, S and Liu, S}, title = {Modification of Intestinal Flora Can Improve Host Metabolism and Alleviate the Damage Caused by Chronic Hypoxia.}, journal = {Current issues in molecular biology}, volume = {46}, number = {11}, pages = {12733-12745}, pmid = {39590350}, issn = {1467-3045}, support = {[2130122.1779.36]//Qinghai Province Cattle Industry Science and Technology Innovation Platform under Grant/ ; }, abstract = {Prolonged exposure to hypoxic conditions can lead to reduced appetite, stunted growth, systemic inflammation, and pulmonary hypertension. Previous studies have indicated a correlation between gut dysbiosis and the development of hypoxia-related hazards. We designed an experiment to investigate the effect of microbiota on mitigating hypoxic damage. Gut microbiota from high-altitude-adapted species (Ochotona curzoniae) were transplanted into Sprague Dawley (SD) rats, which were then housed in a simulated 6000 m altitude environment for 30 days. After the experiment, we conducted analyses on average daily weight gain (ADG), feed conversion ratio (FCR), mean pulmonary artery pressure (mPAP), gut flora, and fecal metabolism. The results demonstrated that the ADG in the transplantation group (2.98 ± 0.17 g) was significantly higher than in the control groups (2.68 ± 0.19 g and 2.26 ± 0.13 g) (p < 0.05). The FCR was reduced in the transplantation group (6.30 ± 0.33 g) compared to the control groups (8.20 ± 1.15 g and 8.83 ± 0.45 g) (p < 0.05). The mPAP was decreased in the transplantation group (38.1 ± 1.13 mmHg) compared to the control groups (43.4 ± 1.30 mmHg and 43.5 ± 1.22 mmHg) (p < 0.05). Multi-omics analysis revealed that Lachnospiraceae, Desulfovibrionaceae, and specific amino acid metabolic pathways play crucial roles in hypoxia and are associated with both inflammation and nutritional metabolism. This study proposes a novel approach to the treatment of hypoxic pulmonary hypertension and holds potential significance for improving high-altitude developmental potential.}, } @article {pmid39589553, year = {2025}, author = {Kellogg, TD and Ceglia, S and Mortzfeld, BM and Tanna, TM and Zeamer, AL and Mancini, MR and Foley, SE and Ward, DV and Bhattarai, SK and McCormick, BA and Reboldi, A and Bucci, V}, title = {Succinate-producing microbiota drives tuft cell hyperplasia to protect against Clostridioides difficile.}, journal = {The Journal of experimental medicine}, volume = {222}, number = {1}, pages = {}, doi = {10.1084/jem.20232055}, pmid = {39589553}, issn = {1540-9538}, support = {PRMP W81XWH2020013//Congressionally Directed Medical Research Programs/ ; /GATES/Bill & Melinda Gates Foundation/United States ; U01AI172987/NH/NIH HHS/United States ; //Kenneth Rainin Foundation/ ; //American Association of Immunologists/ ; //Charles A. King Trust/ ; }, mesh = {Animals ; *Clostridioides difficile ; Mice ; *Succinic Acid/metabolism ; *Hyperplasia ; *Gastrointestinal Microbiome ; *Clostridium Infections/microbiology/metabolism ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/pharmacology ; Colon/microbiology/pathology/metabolism ; Mice, Knockout ; Cytokines/metabolism ; Tuft Cells ; }, abstract = {The role of microbes and their metabolites in modulating tuft cell (TC) dynamics in the large intestine and the relevance of this pathway to infections is unknown. Here, we uncover that microbiome-driven colonic TC hyperplasia protects against Clostridioides difficile infection. Using selective antibiotics, we demonstrate increased type 2 cytokines and TC hyperplasia in the colon but not in the ileum. We demonstrate the causal role of the microbiome in modulating this phenotype using fecal matter transplantation and administration of consortia of succinate-producing bacteria. Administration of succinate production-deficient microbes shows a reduced response in a Pou2f3-dependent manner despite similar intestinal colonization. Finally, antibiotic-treated mice prophylactically administered with succinate-producing bacteria show increased protection against C. difficile-induced morbidity and mortality. This effect is nullified in Pou2f3-/- mice, confirming that the protection occurs via the TC pathway. We propose that activation of TCs by the microbiota in the colon is a mechanism evolved by the host to counterbalance microbiome-derived cues that facilitate invasion by pathogens.}, } @article {pmid39589476, year = {2024}, author = {Ma, G and Chen, Z and Li, Z and Xiao, X}, title = {Unveiling the neonatal gut microbiota: exploring the influence of delivery mode on early microbial colonization and intervention strategies.}, journal = {Archives of gynecology and obstetrics}, volume = {}, number = {}, pages = {}, pmid = {39589476}, issn = {1432-0711}, support = {No. 81771664//National Natural Science Foundation of China/ ; }, abstract = {Recent research has emphasized the critical importance of establishing the neonatal gut microbiota for overall health and immune system development, prompting deeper studies about the early formation of neonatal gut microbiota and its influencing factors. Various factors, including maternal and environmental factors, affect the early formation of neonatal gut microbiota, in which delivery mode has been considered as one of the most crucial influencing factors. In recent years, the increasing trend of cesarean section during childbirth has become a serious challenge for global public health. This review thoroughly analyzes the effects of vaginal delivery and cesarean section on the establishment of neonatal gut microbiota and the potential long-term impacts. In addition, we analyze and discuss interventions such as probiotics, prebiotics, vaginal seeding, fecal microbiota transplantation, and breastfeeding to address the colonization defects of the neonatal gut microbiota caused by cesarean section, aiming to provide theoretical basis for the prevention and treatment of colonization defects and related diseases in infants caused by cesarean section in clinical practice and to provide a theoretical foundation for optimizing the development of neonatal gut microbiota.}, } @article {pmid39589434, year = {2024}, author = {Liu, L and Zhu, JW and Wu, JL and Li, MZ and Lu, ML and Yu, Y and Pan, L}, title = {Insomnia and intestinal microbiota: a narrative review.}, journal = {Sleep & breathing = Schlaf & Atmung}, volume = {29}, number = {1}, pages = {10}, pmid = {39589434}, issn = {1522-1709}, support = {No. ZR2021MH360//Natural Science Foundation of Shandong Province/ ; No. 82370092//National Natural Science Foundation of China/ ; No. 2023SHFZ033//Science and Technology Innovation Project of Binzhou Social Development/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Sleep Initiation and Maintenance Disorders/therapy/physiopathology/microbiology ; Fecal Microbiota Transplantation ; Brain-Gut Axis/physiology ; Probiotics/therapeutic use ; }, abstract = {PURPOSE: The intestinal microbiota and insomnia interact through the microbiota-gut-brain axis. The purpose of this review is to summarize and analyze the changes of intestinal microbiota in insomnia, the interaction mechanisms between intestinal microbiota and insomnia and the treatment methods based on the role of microbiota regulation in insomnia, in order to reveal the feasibility of artificial intervention of intestinal microbiota to improve insomnia.

METHODS: Pubmed/ Embase were searched through March 2024 to explore the relevant studies, which included the gut microbiota characteristics of insomnia patients, the mechanisms of interaction between insomnia and gut microbiota, and the relationship between gut microbiota and insomnia treatment.

RESULTS: Numerous studies implicated insomnia could induce intestinal microbiota disorder by activating the immune response, the hypothalamic-pituitary-adrenal axis, the neuroendocrine system, and affecting bacterial metabolites, resulting in intestinal ecological imbalance, intestinal barrier destruction and increased permeability. The intestinal microbiota exerted an influence on the central nervous system through its interactions with intestinal neurons, releasing neurotransmitters and inflammatory factors, which in turn, can exacerbate symptoms of insomnia. Artificial interventions of gut microbiota included probiotics, traditional Chinese medicine, fecal microbiota transplantation, diet and exercise, whose main pathway of action is to improve sleep by affecting the release of neurotransmitters and gut microbial metabolites.

CONCLUSION: There is an interaction between insomnia and gut microbiota, and it is feasible to diagnose and treat insomnia by focusing on changes in the gut microbiota of patients with insomnia. Large cross-sectional studies and fecal transplant microbiota studies are still needed in the future to validate its safety and efficacy.}, } @article {pmid39588934, year = {2024}, author = {Gil-Gómez, A and Muñoz-Hernández, R and Martínez, F and Jiménez, F and Romero-Gómez, M}, title = {Hepatic encephalopathy: experimental drugs in development and therapeutic potential.}, journal = {Expert opinion on investigational drugs}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/13543784.2024.2434053}, pmid = {39588934}, issn = {1744-7658}, abstract = {INTRODUCTION: Hepatic encephalopathy (HE) presents a complex pathophysiology, creating multiple potential treatment avenues. This review covers current and emerging treatments for HE.

AREAS COVERED: Standard therapies, including non-absorbable disaccharides and rifaximin, are widely used but show inconsistent efficacy. Alternatives such as polyethylene glycol and L-ornithine L-aspartate have been effective in certain cases. Advancements in understanding HE reveal a growing need for personalized treatments. Novel approaches targeting immune modulation and neuroinflammation are under investigation, though clinical translation is slow. Nutritional interventions and fecal microbiota transplantation show potential but lack robust evidence. Innovative therapies like gene and cell therapies, as well as extracellular vesicles from mesenchymal stem cells, present promising avenues for liver disease treatment, potentially benefiting HE.

EXPERT OPINION: A key challenge in HE research is the design of randomized clinical trials, which often suffer from small sample sizes, heterogeneity in patient population, and inconsistent blinding. Additionally, the multifactorial nature of HE, together with a high spontaneous response rate, complicates efforts to isolate treatment effects. Despite current limitations, ongoing research and technological advances hold promise for more effective and individualized HE treatments in the future.}, } @article {pmid39588716, year = {2024}, author = {Tiwari, A and Ika Krisnawati, D and Susilowati, E and Mutalik, C and Kuo, TR}, title = {Next-Generation Probiotics and Chronic Diseases: A Review of Current Research and Future Directions.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c08702}, pmid = {39588716}, issn = {1520-5118}, abstract = {The burgeoning field of microbiome research has profoundly reshaped our comprehension of human health, particularly highlighting the potential of probiotics and fecal microbiota transplantation (FMT) as therapeutic interventions. While the benefits of traditional probiotics are well-recognized, the efficacy and mechanisms remain ambiguous, and FMT's long-term effects are still being investigated. Recent advancements in high-throughput sequencing have identified gut microbes with significant health benefits, paving the way for next-generation probiotics (NGPs). These NGPs, engineered through synthetic biology and bioinformatics, are designed to address specific disease states with enhanced stability and viability. This review synthesizes current research on NGP stability, challenges in delivery, and their applications in preventing and treating chronic diseases such as diabetes, obesity, and cardiovascular diseases. We explore the physiological characteristics, safety profiles, and mechanisms of action of various NGP strains while also addressing the challenges and opportunities presented by their integration into clinical practice. The potential of NGPs to revolutionize microbiome-based therapies and improve clinical outcomes is immense, underscoring the need for further research to optimize their efficacy and ensure their safety.}, } @article {pmid39588509, year = {2024}, author = {Zhang, A and Chen, S and Zhu, Y and Wu, M and Lu, B and Zhou, X and Zhu, Y and Xu, X and Liu, H and Zhu, F and Lin, R}, title = {Intestinal microbiome changes and mechanisms of maintenance hemodialysis patients with constipation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1495364}, pmid = {39588509}, issn = {2235-2988}, mesh = {Humans ; *Constipation/microbiology ; *Gastrointestinal Microbiome ; *Renal Dialysis ; *Feces/microbiology ; Male ; *RNA, Ribosomal, 16S/genetics ; Middle Aged ; Female ; *Bacteria/classification/isolation & purification/genetics ; Aged ; Adult ; }, abstract = {BACKGROUND: Constipation is a common symptom in maintenance hemodialysis patients and greatly affects the quality of survival of hemodialysis patients. Fecal microbiota transplantation and probiotics are feasible treatments for functional constipation, but there is still a gap in the research on the characteristics of gut flora in patients with maintenance hemodialysis combined with constipation. The aim of this study is to clarify the characteristics of the intestinal flora and its changes in maintenance hemodialysis patients with constipation.

METHODS: Fecal samples were collected from 45 participants, containing 15 in the maintenance hemodialysis constipation group,15 in the maintenance hemodialysis non-constipation group and 15 in the healthy control group. These samples were analyzed using 16S rRNA gene sequencing. The feature of the intestinal microbiome of maintenance hemodialysis constipation group and the microbiome differences among the three groups were elucidated by species annotation analysis, α-diversity analysis, β-diversity analysis, species difference analysis, and predictive functional analysis.

RESULTS: The alpha diversity analysis indicated that maintenance hemodialysis constipation group was less diverse and homogeneous than maintenance hemodialysis non-constipation group and healthy control group. At the genus level, the top ten dominant genera in maintenance hemodialysis constipation group patients were Enterococcus, Escherichia-Shigella, Bacteroides, Streptococcus, Bifidobacterium, Ruminococcus_gnavus_group, Lachnospiraceae_unclassified, Faecalibacterium, Akkermansia and UCG-002. Compared with non-constipation group, the Enterococcus, Rhizobiales_unclassified, Filomicrobium, Eggerthella, Allobaculum, Prevotella_7, Gordonibacter, Mitochondria_unclassified, Lachnoanaerobaculum were significantly higher in constipation group (p<0.05). Compared with non-constipation group, the Kineothrix, Rhodopirellula, Weissella were significantly lower in constipation group (p<0.05). The predictive functional analysis revealed that compared with non-constipation group, constipation group was significantly enriched in pathways associated with pyruate metabolism, flavonoid biosynthesis.

CONCLUSIONS: This study describes for the first time the intestinal microbiome characteristics of maintenance hemodialysis patients with constipation. The results of this study suggest that there is a difference in the intestinal flora between maintenance hemodialysis patients with constipation and maintenance hemodialysis patients without constipation.}, } @article {pmid39588438, year = {2024}, author = {Dandamudi, BJ and Dimaano, KAM and Shah, N and AlQassab, O and Al-Sulaitti, Z and Nelakuditi, B and Mohammed, L}, title = {Neurodegenerative Disorders and the Gut-Microbiome-Brain Axis: A Literature Review.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e72427}, pmid = {39588438}, issn = {2168-8184}, abstract = {Neurodegenerative diseases are severe, age-related conditions with complex etiologies that result in significant morbidity and mortality. The gut microbiome, a dynamic symbiotic environment comprising commensal organisms, represents the largest reservoir of these organisms within the human body. It produces short-chain fatty acids, endogenous signals, and neuroactive compounds, which can modulate neuronal function, plasticity, and behavior. Emerging evidence suggests that the gut microbiome plays a pivotal role in neurodevelopment, aging, and brain diseases, including Alzheimer's disease, Parkinson's disease, and stroke. Communication between the gut and brain occurs through a bidirectional channel known as the gut-microbiome-brain axis, which is being explored for therapeutic potential in neurodegenerative disorders. This literature review was conducted through a comprehensive search of five electronic databases - PubMed, Scopus, Ovid Medline, Cochrane Review, and Google Scholar - from inception to June 2024, focusing on English-language studies. Keywords included "gut-brain axis", "microbiome dysbiosis", "neurodegeneration", and disorder-specific terms such as "Alzheimer's disease" and "Parkinson's disease", paired with "gut microbiome". The review examines current knowledge on the relationship between gut microbiota and neurodegenerative disorders, emphasizing potential mechanisms and therapeutic options. Results indicate that gut dysbiosis, characterized by microbial imbalance, is intricately associated with neurodegenerative disease pathogenesis by influencing immune responses, increasing blood-brain barrier permeability, and generating neurotoxic metabolites. Therapeutic approaches targeting the gut microbiome, including probiotics, prebiotics, and fecal microbiota transplantation, show promise in restoring microbial balance and slowing disease progression. However, further research is essential to validate these findings and develop effective clinical interventions.}, } @article {pmid39587707, year = {2024}, author = {Ilozumba, MN and Lin, T and Hardikar, S and Byrd, DA and Round, JL and Stephens, WZ and Holowatyj, AN and Warby, CA and Damerell, V and Li, CI and Figueiredo, JC and Toriola, AT and Shibata, D and Fillmore, GC and Pickron, B and Siegel, EM and Kahlert, C and Florou, V and Gigic, B and Ose, J and Ulrich, CM}, title = {Fusobacterium nucleatum Abundance is Associated with Cachexia in Colorectal Cancer Patients: The ColoCare Study.}, journal = {Cancer medicine}, volume = {13}, number = {22}, pages = {e70431}, pmid = {39587707}, issn = {2045-7634}, support = {//the German Ministry of Education and Research project PerMiCCion (01KD2101D)/ ; //German Cancer Research Center/ ; //the German Consortium of Translational Cancer Research, (DKTK)/ ; R01 CA189184/CA/NCI NIH HHS/United States ; R01 CA207371/CA/NCI NIH HHS/United States ; R01 CA211705/CA/NCI NIH HHS/United States ; R01 CA254108/CA/NCI NIH HHS/United States ; U01 CA206110/CA/NCI NIH HHS/United States ; //University of Utah Immunology, Inflammation, and Infectious Disease Initiative/ ; //Huntsman Cancer Foundation/ ; //Stiftung LebensBlicke, Matthias Lackas Stiftung, Claussen-Simon Stiftung/ ; //the Rahel-Goitein-Straus-Program, Medical Faculty Heidelberg University/ ; //ERA-NET (European Research Area Network) on Translational Cancer Research (TRANSCAN) project/ ; //Cancer Control and Population Health Sciences (CCPS) at the University of Utah/ ; }, mesh = {Humans ; *Colorectal Neoplasms/complications/microbiology ; Male ; *Cachexia/etiology/microbiology ; *Fusobacterium nucleatum/isolation & purification ; Female ; Aged ; Middle Aged ; *Feces/microbiology ; Fusobacterium Infections/complications/microbiology ; Neoplasm Staging ; Risk Factors ; }, abstract = {BACKGROUND: Cachexia accounts for about 20% of all cancer-related deaths and indicates poor prognosis. The impact of Fusobacterium nucleatum (Fn), a microbial risk factor for colorectal cancer (CRC), on the development of cachexia in CRC has not been established.

METHODS: We evaluated the association between Fn abundance in pre-surgical stool samples and onset of cachexia at 6 months post-surgery in n = 87 patients with stages I-III CRC in the ColoCare Study.

RESULTS: High fecal Fn abundance compared to negative/low fecal Fn abundance was associated with 4-fold increased risk of cachexia onset at 6 months post-surgery (OR = 4.82, 95% CI = 1.15, 20.10, p = 0.03).

CONCLUSION: Our findings suggest that high fecal Fn abundance was associated with an increased risk of cachexia at 6 months post-surgery in CRC patients. This is the first study to link Fn abundance with cachexia in CRC patients, offering novel insights into biological mechanisms and potential management of cancer cachexia. Due to the small sample size, our results should be interpreted with caution. Future studies with larger sample sizes are needed to validate these findings.}, } @article {pmid39587339, year = {2024}, author = {Castells-Nobau, A and Puig, I and Motger-Albertí, A and de la Vega-Correa, L and Rosell-Díaz, M and Arnoriaga-Rodríguez, M and Escrichs, A and Garre-Olmo, J and Puig, J and Ramos, R and Ramió-Torrentà, L and Pérez-Brocal, V and Moya, A and Pamplona, R and Jové, M and Sol, J and Martin-Garcia, E and Martinez-Garcia, M and Deco, G and Maldonado, R and Fernández-Real, JM and Mayneris-Perxachs, J}, title = {Microviridae bacteriophages influence behavioural hallmarks of food addiction via tryptophan and tyrosine signalling pathways.}, journal = {Nature metabolism}, volume = {6}, number = {11}, pages = {2157-2186}, pmid = {39587339}, issn = {2522-5812}, support = {PI15/01934//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; CD20/00051//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; RD16/0017/0020//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; PI20/01090//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; CP18/00009//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; PI23/00575//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; SLT017_20_000164//Generalitat de Catalunya (Government of Catalonia)/ ; 2021SGR00990//Generalitat de Catalunya (Government of Catalonia)/ ; 2017 SGR-669//Generalitat de Catalunya (Government of Catalonia)/ ; SLT002/16/00250//Government of Catalonia | Departament de Salut, Generalitat de Catalunya/ ; LCF/PR/HR22/52420017//"la Caixa" Foundation (Caixa Foundation)/ ; PNSD- 2019I006//Ministerio de Sanidad, Servicios Sociales e Igualdad (Ministry of Health, Social Services and Equality)/ ; PNSD- 2021I076//Ministerio de Sanidad, Servicios Sociales e Igualdad (Ministry of Health, Social Services and Equality)/ ; }, mesh = {*Tryptophan/metabolism ; Animals ; Mice ; Humans ; *Bacteriophages/physiology ; *Signal Transduction ; *Gastrointestinal Microbiome ; *Tyrosine/metabolism ; *Food Addiction ; Male ; Female ; }, abstract = {Food addiction contributes to the obesity pandemic, but the connection between how the gut microbiome is linked to food addiction remains largely unclear. Here we show that Microviridae bacteriophages, particularly Gokushovirus WZ-2015a, are associated with food addiction and obesity across multiple human cohorts. Further analyses reveal that food addiction and Gokushovirus are linked to serotonin and dopamine metabolism. Mice receiving faecal microbiota and viral transplantation from human donors with the highest Gokushovirus load exhibit increased food addiction along with changes in tryptophan, serotonin and dopamine metabolism in different regions of the brain, together with alterations in dopamine receptors. Mechanistically, targeted tryptophan analysis shows lower anthranilic acid (AA) concentrations associated with Gokushovirus. AA supplementation in mice decreases food addiction and alters pathways related to the cycle of neurotransmitter synthesis release. In Drosophila, AA regulates feeding behaviour and addiction-like ethanol preference. In summary, this study proposes that bacteriophages in the gut microbiome contribute to regulating food addiction by modulating tryptophan and tyrosine metabolism.}, } @article {pmid39586550, year = {2024}, author = {Novelle, MG and Naranjo, B and López-Cánovas, JL and Díaz-Ruiz, A}, title = {Fecal Microbiota Transplantation, a tool to transfer healthy longevity.}, journal = {Ageing research reviews}, volume = {}, number = {}, pages = {102585}, doi = {10.1016/j.arr.2024.102585}, pmid = {39586550}, issn = {1872-9649}, abstract = {The complex gut microbiome influences host aging and plays an important role in the manifestation of age-related diseases. Restoring a healthy gut microbiome via Fecal Microbiota Transplantation (FMT) is receiving extensive consideration to therapeutically transfer healthy longevity. Herein, we comprehensively review the benefits of gut microbial rejuvenation - via FMT - to promote healthy aging, with few studies documenting life length properties. This review explores how preconditioning donors via standard - lifestyle and pharmacological - antiaging interventions reshape gut microbiome, with the resulting benefits being also FMT-transferable. Finally, we expose the current clinical uses of FMT in the context of aging therapy and address FMT challenges - regulatory landscape, protocol standardization, and health risks - that require refinement to effectively utilize microbiome interventions in the elderly.}, } @article {pmid39586125, year = {2024}, author = {Ye, H and Wang, H and Han, B and Chen, K and Wang, X and Ma, F and Cheng, L and Zheng, S and Zhao, X and Zhu, J and Li, J and Hong, M}, title = {Guizhi Shaoyao Zhimu decoction inhibits neutrophil extracellular traps formation to relieve rheumatoid arthritis via gut microbial outer membrane vesicles.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {136}, number = {}, pages = {156254}, doi = {10.1016/j.phymed.2024.156254}, pmid = {39586125}, issn = {1618-095X}, abstract = {BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease with a high disability rate. Accumulating studies suggest that neutrophil extracellular traps (NETs) play a crucial role in the pathogenesis of RA and targeting NETs has emerged as a potential therapeutic strategy for RA. As a traditional Chinese medicine, Guizhi-Shaoyao-Zhimu Decoction (GSZD) has exhibited good efficacy in the treatment of rheumatoid arthritis (RA), while the underly mechanism especially the possibility that GSZD alter NETs formation to relieve RA remains unknown.

PURPOSE: Our study aimed to investigate relationship between GSZD and NETs in RA treatment and revealed underlying mechanism.

METHODS: We constructed collagen-induced arthritis (CIA) model and treated CIA mice with GZSY to validate therapeutic effects of GSZD and examine whether GZSD could inhibit NETs formation in RA. And 16S rRNA sequencing and Fecal microbiota transplantation (FMT) experiment were performed to determine whether GSZD could reduce NETs formation to alleviate RA in gut microbiota-associated manner and identify crucial bacterium in response to GSZD administration. CIA mice treated with effective bacteria and its outer membrane vesicles (OMVs) with oral administration to investigate protective effect against RA and NETs regulative efficiency. We utilized small interfering RNA in vivo and vitro to silence gene mediating effect of GZSD-gut microbiota-NETs.

RESULTS: GSZD could inhibit NETs formation and relive arthritis in CIA mice. Additionally, GSZD alter gut microbiota composition and significantly increase intestinal Parabacteroides goldsteinii (P.goldsteinii) abundance. Mechanistically, P.goldsteinii enriched by GSZD secreted outer membrane vesicles (OMVs) to translocate into joints and activate Cav-1-Nrf2 axis, leading to reduced NETs formation and alleviate arthritis. In clinical, the abundance of P.goldsteinii exhibited negative correlation with NETs indexes and RA disease activities.

CONCLUSION: Our findings suggest that GSZD inhibits NETs formation to relieve RA in P.goldsteinii-Cav-1-Nrf2 associated manner, which could provide new sight of the prevention and treatment of RA.}, } @article {pmid39583974, year = {2024}, author = {Naito, Y and Takagi, T}, title = {Role of gut microbiota in inflammatory bowel disease pathogenesis.}, journal = {Journal of clinical biochemistry and nutrition}, volume = {75}, number = {3}, pages = {175-177}, pmid = {39583974}, issn = {0912-0009}, abstract = {The role of the gut microbiota, especially bacterial flora, in the pathogenesis of inflammatory bowel disease (IBD) is becoming clearer. Advances in gut microbiota analysis and the use of gnotobiotics models have underscored the importance of gut bacteria and their metabolites in the progression of IBD. Fecal microbiota transplantation has shown promise in clinical trials for ulcerative colitis started as Advanced Medical Care B in Japan, raising expectations for its outcomes. This review explores the gut microbiota's role in IBD, encompassing both current knowledge and future prospects.}, } @article {pmid39582897, year = {2024}, author = {Wang, Z and Wu, X and Wang, Y and Wen, Q and Cui, B and Zhang, F}, title = {Colonic transendoscopic enteral tubing is revolutionizing intestinal therapeutics, diagnosis, and microbiome research.}, journal = {Therapeutic advances in gastroenterology}, volume = {17}, number = {}, pages = {17562848241301574}, pmid = {39582897}, issn = {1756-283X}, abstract = {The intestine, as a crucial organ of the human body, has remained enigmatic despite the remarkable advancements in modern medical technology. Over the past decades, the invention of endoscopic technology has made the noninvasive intervention of the intestine a reality, expanding diagnostic and therapeutic options for diseases. However, due to the single-treatment feature of endoscopic procedures, continuous or repeated medication administration, sampling, and decompression drainage within the intestine have yet to be fulfilled. These limitations persisted until the invention of colonic transendoscopic enteral tubing (TET) in 2014, which realized repeated fecal microbiota transplantation, medication administration, and decompression drainage for the treatment of colon perforation and intestinal obstruction, as well as in situ dynamic sampling. These breakthroughs have not gone unnoticed, gaining global attention and recommendations from guidelines and consensuses. TET has emerged as a novel microbial research tool that offers new paradigms for human microbiome research. This review aims to update the research progress based on TET.}, } @article {pmid39581510, year = {2024}, author = {Zhang, X and Klöhn, M and Ouwerkerk-Mahadevan, S and Jagst, M and Vereyken, L and Verboven, P and Goovaerts, Q and Todt, D and Jonckers, THM and Coelmont, L and Fletcher, H and Das, K and Samby, K and Neyts, J and Steinmann, E and Koul, A and Kaptein, SJF}, title = {A pan-genotypic hepatitis E virus replication inhibitor with high potency in a rat infection model.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2024.10.043}, pmid = {39581510}, issn = {1528-0012}, abstract = {BACKGROUND & AIMS: Hepatitis E virus (HEV) constitutes a substantial public health burden with ∼20 million human infections annually, including 3.3 million symptomatic cases. Appropriate treatment options for, in particular, HEV-infected immunocompromised patients and pregnant women are lacking, underscoring the urgent need for potent and safe antiviral drugs.

METHODS: HEV subgenomic replicon systems were used to screen a small library of pre-selected nucleoside analogues, originally developed in a hepatitis C virus (HCV) antiviral program. Antiviral activity of the selected hit on HEV infection was evaluated in a variety of cell culture systems; the efficacy of the compound was assessed in the athymic nude rat HEV infection model.

RESULTS: Compound JNJ-9117 exerts pan-genotype antiviral activity against HEV in different cell types as well as in primary human hepatocytes. A high level of conservation is observed between three crucial motifs in the catalytic domain of the HCV and HEV polymerases. This suggests a mechanism of action that is identical to that of the molecule against HCV, whereby the 5'-triphosphate of JNJ-9117 acts as a chain terminator during viral RNA synthesis. JNJ-9117 has a favorable pharmacokinetic and safety profile in rats and results in a pronounced antiviral effect in a chronic rat HEV infection model, both in a prophylactic and therapeutic setting. The combination of JNJ-9117 and ribavirin (each at an intentionally selected suboptimal/inactive dose) was in infected rats highly effective in lowering viral RNA load in liver and feces to (almost) undetectable levels.

CONCLUSIONS: JNJ-9117 has a profile that holds promise for the treatment of life-threatening HEV infections in humans. Phase 1 studies with JNJ-9117 have been initiated in healthy human volunteers.}, } @article {pmid39581509, year = {2024}, author = {Chen, S and Wen, Q and Zhang, F}, title = {An Unusual Cause of Diarrhea and Hematochezia.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2024.11.007}, pmid = {39581509}, issn = {1528-0012}, } @article {pmid39580105, year = {2024}, author = {Fülöpová, N and Brückner, K and Muselík, J and Pavloková, S and Franc, A}, title = {Development and evaluation of innovative enteric-coated capsules for colon-specific delivery of hydrophilic biomaterials.}, journal = {International journal of pharmaceutics}, volume = {}, number = {}, pages = {124991}, doi = {10.1016/j.ijpharm.2024.124991}, pmid = {39580105}, issn = {1873-3476}, abstract = {OBJECTIVE: This research aims to design and evaluate an enteric-coated hard capsule dosage form for targeted delivery of biological materials, such as FMT (fecal microbiota transplant) or live microbes, to the distal parts of the GIT. The capsules are designed to be internally protected against destruction by hydrophilic filling during passage through the digestive tract.

METHODS: Hard gelatin capsules and DRcaps[TM]capsules based on HPMC and gellan were used to encapsulate a hydrophilic body temperature-liquefying gelatin hydrogel with caffeine or insoluble iron oxide mixture. Different combinations of polymers were tested for the internal (ethylcellulose, Eudragit® E, and polyvinyl acetate) and external (Eudragit® S, Acryl-EZE®, and cellacefate) coating. The external protects against the acidic gastric environment, while the internal protects against the liquid hydrophilic filling during passage. Coated capsules were evaluated using standard disintegration and modified dissolution methods for delayed-release dosage forms.

RESULTS: Combining suitable internal (ethylcellulose 1.0 %) and external (Eudragit® S 20.0 %) coating of DRcaps[TM] capsules with the wiping and immersion method achieved colonic release times. While most coated capsules met the pharmaceutical requirements for delayed release, one combination stood out. Colonic times were indicated by the dissolution of soluble caffeine (during 120-720 min) measured by the dissolution method, and capsule rupture was indicated by the release of insoluble iron oxide (after 480 min) measured by the disintegration method. This promising result demonstrates the composition's suitability and potential to protect the content until it's released, inspiring hope for the future of colon-targeted delivery systems and its potential for the pharmaceutical and biomedical fields.

CONCLUSION: Innovative and easy capsule coatings offer significant potential for targeted drugs, especially FMT water suspension, to the GIT, preferably the colon. The administration method is robust and not considerably affected by the quantity of internal or external coatings. It can be performed in regular laboratories without specialized individual and personalized treatment equipment, making it a practical and feasible method for drug delivery.}, } @article {pmid39579562, year = {2024}, author = {Yang, Y and Wu, R and Qian, C and Wu, D and Ou, J}, title = {Mume fructus alters the abundance of intestinal microbiota and alleviates damaged intestinal barrier and inflammation in rats with DSS induced colitis.}, journal = {Molecular immunology}, volume = {176}, number = {}, pages = {60-72}, doi = {10.1016/j.molimm.2024.11.008}, pmid = {39579562}, issn = {1872-9142}, abstract = {The gut microbiota plays a crucial role in the development of colitis by influencing the immune response and inflammation in the colon. Previous research has shown that Mume Fructus, a traditional Chinese medicine, can alleviate colitis by reducing the activity of inflammatory pathways. However, the specific connection between Mume Fructus-treated colitis and regulation of gut flora remains unclear, prompting further investigation. This research aims to delve deeper into the possible impact of the gut microbiota in colitis when treated with the aqueous decoction of Mume Fructus (MF). The effects of MF on rats with DSS-induced colitis were assessed through examination of pathological indicators, intestinal barrier proteins, and analysis of 16S rDNA sequencing to investigate its impact on the gut microbiota. In addition, the colon contents of rats after the administration of MF were transplanted into rats with colitis, and the effect of MF on intestinal flora was verified, and "beneficial bacteria" were identified by 16S rDNA sequencing and Spearman's correlation analysis. In summary, our findings suggest that MF has the potential to ameliorate symptoms of colitis through modulation of intestinal microbiota and restoration of intestinal barrier function.}, } @article {pmid39574673, year = {2024}, author = {Wolfe, TM and Jo, J and Pinkham, NV and Garey, KW and Walk, ST}, title = {Microbiome impact of ibezapolstat and other Clostridioides difficile infection relevant antibiotics using humanized mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.11.06.622322}, pmid = {39574673}, issn = {2692-8205}, abstract = {BACKGROUND: Ibezapolstat (IBZ) is a competitive inhibitor of the bacterial Pol IIIC enzyme in clinical development for treatment of Clostridioides difficile infection (CDI). Previous studies demonstrated IBZ carries a favorable microbiome diversity profile compared to vancomycin (VAN). However, head-to-head comparisons with other CDI antibiotics have not been done. The purpose of this study was to compare microbiome changes associated with IBZ to other clinically used CDI antibiotics.

METHODS: Groups of germ-free (GF) mice received a fecal microbiota transplant from one of two healthy human donors and were subsequently exposed to either IBZ, VAN, fidaxomicin (FDX), metronidazole (MET), or no antibiotic (control). 16S rRNA encoding gene sequencing of temporally collected stool samples was used to compare gut microbiome perturbation between treatment and no-drug control groups.

RESULTS: Among the tested antibiotics, the most significant change in microbiome diversity was observed in MET-treated mice. Each antibiotic had a unique effect, but changes in alpha and beta diversity following FDX- and IBZ-treated groups were less pronounced compared to those observed in VAN-or MET-treated groups. By the end of therapy, both IBZ and FDZ increased the relative abundance of Bacteroidota (phylum), with IBZ additionally increasing the relative abundance of Actinomycetota (phylum).

CONCLUSION: In microbiome-humanized mice, IBZ and FDX had smaller effects on gut microbiome diversity compared to VAN and MET. Notable differences were observed between the microbiome of IBZ- and FDX-treated groups, which may allow for differentiation of these two antibiotics in future studies.}, } @article {pmid39574251, year = {2024}, author = {Shen, CL and Deshmukh, H and Santos, JM and Elmassry, MM and Presto, P and Driver, Z and Bhakta, V and Yakhnitsa, V and Kiritoshi, T and Ji, G and Lovett, J and Hamood, A and Neugebauer, V}, title = {Fecal Microbiota Transplantation Modulates Gut Microbiome Composition and Glial Signaling in Brain and Colon of Rats with Neuropathic Pain: Evidence for Microbiota-Gut-Brain Axis.}, journal = {The Journal of frailty & aging}, volume = {13}, number = {4}, pages = {319-330}, doi = {10.14283/jfa.2024.65}, pmid = {39574251}, issn = {2260-1341}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Fecal Microbiota Transplantation ; *Neuralgia/therapy/microbiology/metabolism ; Rats ; Male ; *Brain-Gut Axis/physiology ; Neuroglia/metabolism ; Colon/microbiology ; Brain/metabolism ; Rats, Sprague-Dawley ; Disease Models, Animal ; Signal Transduction ; }, abstract = {Despite evidence linking the gut microbiome to neuropathic pain (NP), it is not known if altering gut microbiota can alleviate NP via the microbiome-gut-brain axis. This study examined if healthy gut microbiota of sham male rats (Sham+V) and dysbiotic gut microbiota of NP rats (spinal nerve ligation: NP, SNL+V) can be disrupted and restored, respectively, via fecal microbiota transplant (FMT) from the opposite group [Sham+(SNL-FMT) and SNL+(Sham-FMT), respectively]. All groups received FMT daily for two weeks, followed by three weeks without FMT. SNL rats showed higher mechanical hypersensitivity [SNL+V vs. Sham+V] throughout the study. After two weeks, the FMT of healthy gut microbiota decreased mechanical hypersensitivity in SNL rats [SNL+(Sham-FMT) vs. SNL+V]. A temporal shift in microbiome profiles after 2-week FMT treatment was observed in Sham+(SNL-FMT) and SNL+(Sham-FMT) groups, while the microbiome profile shifted back a certain extent after FMT ceased. At the end of study, the Sham+(SNL-FMT) group acquired low abundance of UCG-001, Odoribacter, and Peptococcaceae, and high abundance of UBA1819 and Victivallis. The SNL+(Sham-FMT) group maintained high abundance of Butyricimonas and Escherichia-Shigella. The SNL+(Sham-FMT) group had altered glial and macrophage activation/inflammation markers in the brain/colon than the SNL+V group. Relative to the SNL+V group, the SNL+(Sham-FMT) group had significantly lower gene expressions of GFAP (hypothalamus), IBA-1 (colon), and NF-κB (amygdala/colon), but higher gene expressions of complex I (amygdala/hypothalamus) and claudin-3 (amygdala/hypothalamus/colon). In conclusion, FMT containing healthy microbiota given to SNL rats attenuates mechanical hypersensitivity, modulates microbiota composition, and mitigates downstream glial activation/inflammation markers in a NP model.}, } @article {pmid39571844, year = {2024}, author = {Yu, L and Lin, F and Yu, Y and Deng, X and Shi, X and Lu, X and Lu, Y and Wang, D}, title = {Rehmannia glutinosa polysaccharides enhance intestinal immunity of mice through regulating the microbiota.}, journal = {International journal of biological macromolecules}, volume = {283}, number = {Pt 3}, pages = {137878}, doi = {10.1016/j.ijbiomac.2024.137878}, pmid = {39571844}, issn = {1879-0003}, abstract = {The Rehmannia glutinosa polysaccharides (RGP) have various benefits such as enhancing immune cell activity, decreasing oxidative stress and delaying or inhibiting tumor occurrence. Although much research has been directed at understanding the role of RGP, its influence on gut immunity is largely understudied. Here, we aimed to dissect the immune-regulating effects of RGP in the mice intestines. In vivo experiments involving the oral administration of RGP to mice at dosages of 100, 200, and 400 mg/kg over seven consecutive days revealed that RGP therapy significantly increased the percentages of CD3[+] T lymphocytes and CD19[+] B lymphocytes in intestines and improved the integrity of the mucosal barrier. Moreover, RGP modified the gut microbiota composition by enhancing the abundance of beneficial bacteria like Lactobacillus and Akkermansia. Fecal microbiota transplantation (FMT) experiments further revealed that RGP modulated the host's intestinal immunological function by altering the gut microbiota composition. These findings indicate that RGP may control the immunological function of the intestines.}, } @article {pmid39571733, year = {2024}, author = {Yu, J and Feng, L and Luo, Z and Yang, J and Zhang, Q and Liu, C and Liang, D and Xie, Y and Li, H and Gong, J and He, Z and Lan, P}, title = {Interleukin-10 deficiency suppresses colorectal cancer metastasis by enriching gut Parabacteroides distasonis.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2024.11.024}, pmid = {39571733}, issn = {2090-1224}, abstract = {INTRODUCTION: The intricate interplay of interleukin-10 (IL-10) and gut microbiota influences tumor development and progression, yet the impacts on colorectal cancer (CRC) metastasis remain incompletely understood.

METHODS: The impact of Il10 deficiency on CRC metastasis was first evaluated in CRC metastasis tumor samples and mouse model. Antibiotic sterilization and fecal microbiota transplantation (FMT) experiment were used to assess the role of gut microbiota in IL-10 mediated CRC metastasis, and full-length 16S rDNA sequencing analysis further identified the potential target bacteria influencing CRC metastasis. The inhibitory effect of Parabacteroides distasonis (P. distasonis) on CRC metastasis was evaluated by oral administration in mice. Key metabolites involved in P. distasonis inhibition of CRC metastasis was identified by widely-targeted metabolome analysis and validated both in vivo and in vitro. The underlying mechanisms of P-hydroxyphenyl acetic acid (4-HPAA) inhibiting CRC metastasis was investigated via RNA-sequencing and validated in cellular experiments.

RESULTS: We revealed that serum IL-10 levels were markedly elevated in metastatic CRC patients compared to non-metastatic cases. In parallel, Il10-deficiency (Il10[-/]) in mice resulted in decreased CRC metastasis in a gut microbiota-dependent manner. Mechanistically, Il10[-/-] mice reshaped gut microbiota composition, notably enriching P. distasonis. The enriched P. distasonis produced 4-HPAA, which activated the aryl hydrocarbon receptor (AHR) and subsequently inhibited the expression of VEGFA, a typical oncogene, thereby sequentially suppressing CRC metastasis. Importantly, engineered bacteria capable of producing 4-HPAA effectively hindered CRC metastasis. Furthermore, AHR depletion significantly disrupted the 4-HPAA-induced reduction in CRC cell migration and the inhibition of metastasis in both in vitro and in vivo lung metastasis mouse models.

CONCLUSIONS: These findings demonstrate the significance of IL-10 deficiency in suppressing CRC metastasis through the 4-HPPA-AHR-VEGFA axis mediated by gut P. distasonis, suggesting that P. distasonis or 4-HPAA supplementation could offer a promising therapeutic strategy for CRC metastasis prevention.}, } @article {pmid39571265, year = {2024}, author = {Mansouri, P and Mansouri, P and Behmard, E and Najafipour, S and Kouhpayeh, A and Farjadfar, A}, title = {Novel targets for mucosal healing in inflammatory bowel disease therapy.}, journal = {International immunopharmacology}, volume = {144}, number = {}, pages = {113544}, doi = {10.1016/j.intimp.2024.113544}, pmid = {39571265}, issn = {1878-1705}, abstract = {Inflammatory bowel disease (IBD) is a chronic condition affecting the gastrointestinal tract, primarily manifesting as ulcerative colitis (UC) or Crohn's disease (CD). Both inflammation and disruption of the intestinal epithelial barrier are key factors in IBD pathogenesis. Substantial evidence has revealed a significant association between aberrant immune responses and impairment of the intestinal epithelial barrier in IBD pathogenesis. The components of the intestinal epithelium, particularly goblet cells and Paneth cells, are crucial to gut homeostasis, as they secrete mucin, antimicrobial peptides (AMPs), and cytokines. Furthermore, impairment of epithelial integrity, which is regulated by tight junctions, is a hallmark of IBD pathology. While common treatments for IBD, such as anti-inflammatory drugs, target various signaling pathways with varying efficacies, therapeutic approaches focused on mucosal and epithelial barrier healing have been largely neglected. Moreover, high costs, side effects, and insufficient or inconsistent therapeutic outcomes remain major drawbacks of conventional anti-IBD drugs. Recent studies on epithelial barrier regeneration and permeability reduction have introduced promising therapeutic targets, including farnesoid X receptor (FXR), urokinase-type plasminogen activator (uPA)-urokinase-type plasminogen activator receptor (uPAR) interaction, fecal microbiota transplantation (FMT), and insulin receptor (INSR). Notably, the simultaneous targeting of intestinal inflammation and promotion of epithelial barrier healing shows promise for efficient IBD treatment. Future research should explore targeted therapies and combination treatments, including natural remedies, microbiota colonization, stem cell approaches, and computer-aided drug design. It is also crucial to focus on accurate prognosis and developing a thorough understanding of IBD development mechanisms.}, } @article {pmid39570086, year = {2024}, author = {Justice, J and Kankaria, RA and Johnson, DB}, title = {Immune checkpoint inhibition of metastatic melanoma: achieving high efficacy in the face of high toxicity.}, journal = {Expert review of clinical pharmacology}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/17512433.2024.2431513}, pmid = {39570086}, issn = {1751-2441}, abstract = {INTRODUCTION: Immune checkpoint inhibitors (ICIs) have advanced the treatment of metastatic melanoma by blocking immune system down-regulators enhancing T-cell-mediated anti-tumor responses. However, many ICIs induce immune-related adverse effects (irAEs) that can impact many organ systems.

AREAS COVERED: Strategies used to manage irAEs include corticosteroids, anti-tumor necrosis factor alpha (TNF-α) agents, other biological therapies, fecal microbiota transplantation (FMT), and emerging regimens. In this review, we describe current evidence for the efficacy of ICIs, acute and chronic immune toxicities, and strategies to manage toxicities for patients treated with ICIs.

EXPERT OPINION: IrAE management will likely evolve by developing more tailored approaches to prevent toxicities, improving non-steroidal management strategies and tailoring the dose of steroids, and identifying biomarkers of severe toxicities.}, } @article {pmid39569890, year = {2024}, author = {Jang, S and Yu, J and Park, S and Lim, H and Koh, H and Park, YR}, title = {Development of Time-Aggregated Machine Learning Model for Relapse Prediction in Pediatric Crohn's Disease.}, journal = {Clinical and translational gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ctg.0000000000000794}, pmid = {39569890}, issn = {2155-384X}, support = {//Ministry of Health and Welfare/ ; }, abstract = {INTRODUCTION: Pediatric Crohn's disease (CD) easily progresses to an active disease compared to adult CD, making it important to predict and minimize CD relapses. However, prediction of relapse at various time points (TPs) during pediatric CD remains understudied. We aimed to develop a real-time aggregated model to predict pediatric CD relapse in different TPs and time windows (TWs).

METHODS: This retrospective study was conducted on children diagnosed with CD between 2015 and 2022 at Severance Hospital. Laboratory test results and demographic data were collected starting at 3 months after diagnosis, and cohorts were formed using data from six different TPs at 1-month intervals. Relapse-defined as a pediatric CD activity index ≥30 points-was predicted, and TWs were 3-7 months with 1-month intervals. The feature importance of the variables in each setting was determined.

RESULTS: Data from 180 patients were used to construct cohorts corresponding to the TPs. We identified the optimal TP and TW to reliably predict pediatric CD relapse with an area under the receiver operating characteristic curve score of 0.89 when predicting with a 3-month TW at a 3-month TP. Variables such as C-reactive protein levels and lymphocyte fraction were found to be important factors.

DISCUSSION: We developed a time-aggregated model to predict pediatric CD relapse in multiple TPs and TWs. This model identified important variables that predicted relapse in pediatric CD to support real-time clinical decision making.}, } @article {pmid39568727, year = {2024}, author = {Alam, M and Abbas, K and Mustafa, M and Usmani, N and Habib, S}, title = {Microbiome-based therapies for Parkinson's disease.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1496616}, pmid = {39568727}, issn = {2296-861X}, abstract = {The human gut microbiome dysbiosis plays an important role in the pathogenesis of Parkinson's disease (PD). The bidirectional relationship between the enteric nervous system (ENS) and central nervous system (CNS) under the mediation of the gut-brain axis control the gastrointestinal functioning. This review article discusses key mechanisms by which modifications in the composition and function of the gut microbiota (GM) influence PD progression and motor control loss. Increased intestinal permeability, chronic inflammation, oxidative stress, α-synuclein aggregation, and neurotransmitter imbalances are some key factors that govern gastrointestinal pathology and PD progression. The bacterial taxa of the gut associated with PD development are discussed with emphasis on the enteric nervous system (ENS), as well as the impact of gut bacteria on dopamine production and levodopa metabolism. The pathophysiology and course of the disease are associated with several inflammatory markers, including TNF-α, IL-1β, and IL-6. Emerging therapeutic strategies targeting the gut microbiome include probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT). The article explored how dietary changes may affect the gut microbiota (GM) and the ways that can affect Parkinson's disease (PD), with a focus on nutrition-based, Mediterranean, and ketogenic diets. This comprehensive review synthesizes current evidence on the role of the gut microbiome in PD pathogenesis and explores its potential as a therapeutic target. Understanding these complex interactions may assist in the development of novel diagnostic tools and treatment options for this neurodegenerative disorder.}, } @article {pmid39567117, year = {2025}, author = {Lu, X and Jing, Y and Zhang, N and Chen, L and Tai, J and Cao, Y}, title = {Structural characterization and anti-obesity effect of a novel water-soluble galactomannan isolated from Eurotium cristatum.}, journal = {Carbohydrate polymers}, volume = {348}, number = {Pt B}, pages = {122870}, doi = {10.1016/j.carbpol.2024.122870}, pmid = {39567117}, issn = {1879-1344}, mesh = {Animals ; *Galactose/analogs & derivatives ; *Mannans/chemistry/pharmacology/isolation & purification ; Mice ; *Anti-Obesity Agents/pharmacology/chemistry/isolation & purification ; *Obesity/drug therapy ; Male ; *Diet, High-Fat ; *Eurotium/chemistry ; *Solubility ; Gastrointestinal Microbiome/drug effects ; Water/chemistry ; Mice, Inbred C57BL ; }, abstract = {Obesity is a serious public health challenge worldwide, the present study is aimed to investigate the structural characteristic and anti-obesity effect of a water-soluble galactomannan (PEC) extracted from Eurotium cristatum (E. cristatum). Detailed analysis of the PEC structure showed a weight-average molecular weight of 32,305 Da and a composition of mainly mannose, galactose and small amounts of glucose. Nuclear magnetic resonance spectroscopy combined with methylation analysis indicated that the main chain of PEC is →5)-β-D-Galf-(1 → 6)-α-D-Manp-(1 → glycosidic bond, and the branched chain →2)-α-D-Manp-(1 → through →2,6)-α-D-Manp-(1 → is connected to the main chain by an O-2 bond. Furthermore, PEC was found to ameliorate body weight gain, metabolic disorders, and to modulate the gut microbiota in HFD-fed mice. Fecal microbiota transplantation trial confirmed that PEC prevented obesity development and metabolic disorders by reversing gut dysbiosis in HFD-fed mice. This is the first report of the isolation of PEC from E. cristatum, and the findings suggested that PEC exerted its antiobesity and related beneficial effects by regulating the gut microbiota. In conclusion, as a polysaccharide, PEC could reduce obesity by modulating the gut microbiota and has potential been a prophylactic agent for obesity and related metabolic diseases.}, } @article {pmid39566790, year = {2024}, author = {Liu, Z and Wang, M and Li, J and Liang, Y and Jiang, K and Hu, Y and Gong, W and Guo, X and Guo, Q and Zhu, B}, title = {Hizikia fusiforme polysaccharides synergized with fecal microbiota transplantation to alleviate gut microbiota dysbiosis and intestinal inflammation.}, journal = {International journal of biological macromolecules}, volume = {283}, number = {Pt 4}, pages = {137851}, doi = {10.1016/j.ijbiomac.2024.137851}, pmid = {39566790}, issn = {1879-0003}, abstract = {Ulcerative colitis (UC) is closely associated with disruptions in gut microbiota. Restoring balance to gut microbiota and reducing intestinal inflammation has become a promising therapeutic approach for UC. However, challenges remain, including limited efficacy in some treatments. This study explores the synergistic effects and underlying mechanisms of Hizikia fusiforme polysaccharides (HFP) combined with fecal microbiota transplantation (FMT) to improve UC symptoms. Seven-week-old C57/BL6J mice were induced with UC using dextran sodium sulfate (DSS). Supplementation with either FMT alone or in combination with HFP effectively alleviated UC symptoms, reduced colonic inflammation, and corrected gut microbiota imbalance. Notably, HFP combined with FMT yielded showed better effects in ameliorating DSS-induced UC in mice than did FMT alone. Enrichment of probiotics, such as Bifidobacterium, and upregulation of beneficial metabolites, such as betaine, were identified as potential mechanisms for the enhanced effects of HFP combined with FMT against DSS-induced UC. These findings suggest that the combination of Hizikia fusiforme polysaccharides with FMT has potential applications in rectifying dysbiosis and ameliorating inflammatory bowel diseases.}, } @article {pmid39564459, year = {2024}, author = {Zhao, J and Liu, J and Feng, J and Liu, X and Hu, Q}, title = {The gut microbiota-brain connection: insights into major depressive disorder and bipolar disorder.}, journal = {Frontiers in psychiatry}, volume = {15}, number = {}, pages = {1421490}, pmid = {39564459}, issn = {1664-0640}, abstract = {Major depressive disorder (MDD) and bipolar disorder (BD) are two of the most prevalent mood disorders that seriously jeopardize both physical and mental health. The current diagnosis of MDD and BD relies primarily on clinical symptoms. However, correctly differentiating between MDD and BD during depressive episode states remains a substantial clinical challenge. The human gut hosts a large and diverse microbiota, which plays a pivotal role in various physiological processes. Emerging evidence suggests that the gut microbiota (GM) exerts beneficial effects on mental health disorders, including MDD, BD, and schizophrenia, through the microbe-gut-brain axis (MGBA). In recent years, the relationship between GM and mood disorders has garnered considerable attention, leading to intensive research in this area. The MGBA is a bidirectional communication system between the gut and the brain. Growing evidence indicates that the brain can influence the GM, which in turn may modulate the brain through this axis. This review aims to explore the changes in the GM of patients with MDD and BD and evaluate the effects of different treatments on their GM, including medication, probiotic, prebiotic and synbiotic interventions, and fecal microbiota transplantation (FMT). By doing so, we seek to identify potential disease-specific biomarkers, improve differential diagnosis, and offer novel therapeutic avenues for these disorders.}, } @article {pmid39562050, year = {2024}, author = {Li, N and Li, Y and Huang, Z and Cao, Z and Cao, C and Gao, X and Zuo, T}, title = {Faecal phageome transplantation alleviates intermittent intestinal inflammation in IBD and the timing of transplantation matters: a preclinical proof-of-concept study in mice.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2024-333598}, pmid = {39562050}, issn = {1468-3288}, } @article {pmid39557804, year = {2024}, author = {Lee, JY and Kim, Y and Kim, J and Kim, JK}, title = {Fecal Microbiota Transplantation: Indications, Methods, and Challenges.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {}, number = {}, pages = {}, pmid = {39557804}, issn = {1976-3794}, support = {RS-2024-00340833//National Research Foundation of Korea/ ; }, abstract = {Over the past two decades, as the importance of gut microbiota to human health has become widely known, attempts have been made to treat diseases by correcting dysbiosis of gut microbiota through fecal microbiota transplantation (FMT). Apart from current knowledge of gut microbiota, FMT to treat disease has a long history, from the treatment of food poisoning in the fourth century to the treatment of Clostridioides difficile infections in the twentieth century. In 2013, FMT was recognized as a standard treatment for recurrent C. difficile because it consistently showed high efficacy. Though recurrent C. difficile is the only disease internationally recognized for FMT efficacy, FMT has been tested for other diseases and shown some promising preliminary results. Different FMT methods have been developed using various formulations and administration routes. Despite advances in FMT, some issues remain to be resolved, such as donor screening, manufacturing protocols, and unknown components in the fecal microbiota. In this review, we discuss the mechanisms, clinical indications, methods, and challenges of current FMT. We also discuss the development of alternative therapies to overcome the challenges of FMT.}, } @article {pmid39555931, year = {2024}, author = {Wang, J and Xiang, J-H and Peng, X-Y and Liu, M and Sun, L-J and Zhang, M and Zhang, L-Y and Chen, Z-B and Tang, Z-Q and Cheng, L}, title = {Characteristic alterations of gut microbiota and serum metabolites in patients with chronic tinnitus: a multi-omics analysis.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0187824}, doi = {10.1128/spectrum.01878-24}, pmid = {39555931}, issn = {2165-0497}, abstract = {Chronic tinnitus is a central nervous system disorder. Currently, the effects of gut microbiota on tinnitus remain unexplored. To explore the connection between gut microbiota and tinnitus, we conducted 16S rRNA sequencing of fecal microbiota and serum metabolomic analysis in a cohort of 70 patients with tinnitus and 30 healthy volunteers. We used the weighted gene co-expression network method to analyze the relationship between the gut microbiota and the serum metabolites. The random forest technique was utilized to select metabolites and gut taxa to construct predictive models. A pronounced gut dysbiosis in the tinnitus group, characterized by reduced bacterial diversity, an increased Firmicutes/Bacteroidetes ratio, and some opportunistic bacteria including Aeromonas and Acinetobacter were enriched. In contrast, some beneficial gut probiotics decreased, including Lactobacillales and Lactobacillaceae. In serum metabolomic analysis, serum metabolic disturbances in tinnitus patients and these differential metabolites were enriched in pathways of neuroinflammation, neurotransmitter activity, and synaptic function. The predictive models exhibited great diagnostic performance, achieving 0.94 (95% CI: 0.85-0.98) and 0.96 (95% CI: 0.86-0.99) in the test set. Our study suggests that changes in gut microbiota could potentially influence the occurrence and chronicity of tinnitus, and exert regulatory effects through changes in serum metabolites. Overall, this research provides new perceptions into the potential role of gut microbiota and serum metabolite in the pathogenesis of tinnitus, and proposes the "gut-brain-ear" concept as a pathomechanism underlying tinnitus, with significant clinical diagnostic implications and therapeutic potential.IMPORTANCETinnitus affects millions of people worldwide. Severe cases may lead to sleep disorders, anxiety, and depression, subsequently impacting patients' lives and increasing societal healthcare expenditures. However, tinnitus mechanisms are poorly understood, and effective therapeutic interventions are currently lacking. We discovered the gut microbiota and serum metabolomics changes in patients with tinnitus, and provided the potential pathological mechanisms of dysregulated gut flora in chronic tinnitus. We proposed the innovative concept of the "gut-brain-ear axis," which underscores the exploration of gut microbiota impact on susceptibility to chronic tinnitus through serum metabolic profile modulation. We also reveal novel biomarkers associated with chronic tinnitus, offering a new conceptual framework for further investigations into the susceptibility of patients, potential treatment targets for tinnitus, and assessing patient prognosis. Subsequently, gut microbiota and serum metabolites can be used as molecular markers to assess the susceptibility and prognosis of tinnitus.Furthermore, fecal transplantation may be used to treat tinnitus.}, } @article {pmid39555739, year = {2024}, author = {Liu, X and Kang, W and Li, J and Li, X and Yang, P and Shi, M and Wang, Z and Wang, Y and Medina, ADPA and Liu, D and Zhu, F and Shen, H and Huang, K and Chen, X and Liu, Y}, title = {Melatonin Ameliorates Cadmium-Induced Liver Fibrosis Via Modulating Gut Microbiota and Bile Acid Metabolism.}, journal = {Journal of pineal research}, volume = {76}, number = {8}, pages = {e70005}, doi = {10.1111/jpi.70005}, pmid = {39555739}, issn = {1600-079X}, support = {//This study was funded by the National Natural Science Foundation of China (32102741) and Fundamental Research Funds for the Central Universities (Grant No. KJYQ2024010; KYT2023004)./ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Bile Acids and Salts/metabolism ; *Melatonin/pharmacology ; Mice ; *Liver Cirrhosis/metabolism/chemically induced/pathology ; Male ; *Cadmium/toxicity ; Mice, Knockout ; Mice, Inbred C57BL ; Receptors, Cytoplasmic and Nuclear/metabolism ; }, abstract = {Cadmium (Cd) is a widespread environmental contaminant with high toxicity to human health. Melatonin has been shown to improve Cd-induced liver damage. However, its mechanism has not yet been elucidated. In this study, we aimed to investigate the effects of melatonin on Cd-induced liver damage and fibrosis. A combination of 16S rRNA gene sequencing and mass spectrometry-based metabolomics was adopted to investigate changes in the gut microbiome and its metabolites on the regulation of melatonin in Cd-induced liver injury and fibrosis of mice. Further, nonabsorbable antibiotics, a fecal microbiota transplantation (FMT) program and intestine-specific farnesoid X receptor (FXR) knockout mice were employed to explore the mechanism of melatonin (MT) on liver injury and fibrosis in Cd treated mice. MT significantly improved hepatic inflammation, bile duct hyperplasia, liver damage, and liver fibrosis, with a notable decrease in liver bile acid levels in Cd-exposed mice. MT treatment remodeled the gut microbiota, improved gut barrier function, and reduced the production of gut-derived lipopolysaccharide (LPS). MT significantly decreased the intestinal tauro-β-muricholic acid levels, which are known as FXR antagonists. Notably, MT prominently activated the intestinal FXR signaling, subsequently inhibiting liver bile acid synthesis and decreasing hepatic inflammation in Cd-exposed mice. However, MT could not ameliorate Cd-induced liver damage and fibrosis in Abx-treated mice. Conversely, MT still exerted a protective effect on Cd-induced liver damage and fibrosis in FMT mice. Interestingly, MT failed to reverse liver damage and fibrosis in Cd-exposed intestinal epithelial cell-specific FXR gene knockout mice, indicating that intestinal FXR signaling mediated the protective effect of MT treatment. MT improves Cd-induced liver damage and fibrosis through reshaping the intestinal flora, activating the intestinal FXR-mediated suppression of liver bile acid synthesis and reducing LPS leakage in mice.}, } @article {pmid39552646, year = {2024}, author = {Dong, X and Su, Y and Luo, Z and Li, C and Gao, J and Han, X and Yao, S and Wu, W and Tian, L and Bai, Y and Wang, G and Ren, W}, title = {Fecal microbiota transplantation alleviates cognitive impairment by improving gut microbiome composition and barrier function in male rats of traumatic brain injury following gas explosion.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1485936}, pmid = {39552646}, issn = {1664-302X}, abstract = {BACKGROUND: Dysbiosis of gut microbiota (GM) is intricately linked with cognitive impairment and the incidence of traumatic brain injury (TBI) in both animal models and human subjects. However, there is limited understanding of the impact and mechanisms of fecal microbiota transplantation (FMT) on brain and gut barrier function in the treatment of TBI induced by gas explosion (GE).

METHODS: We have employed FMT technology to establish models of gut microbiota dysbiosis in male rats, and subsequently conducted non-targeted metabolomics and microbiota diversity analysis to explore the bacteria with potential functional roles.

RESULTS: Hematoxylin-eosin and transmission electron microscopy revealed that GE induced significant pathological damage and inflammation responses, as well as varying degrees of mitochondrial impairment in neuronal cells in the brains of rats, which was associated with cognitive decline. Furthermore, GE markedly elevated the levels of regulatory T cell (Tregs)-related factors interleukin-10, programmed death 1, and fork head box protein P3 in the brains of rats. Similar changes in these indicators were also observed in the colon; however, these alterations were reversed upon transfer of normal flora into the GE-exposed rats. Combined microbiome and metabolome analysis indicated up-regulation of Clostridium_T and Allobaculum, along with activation of fatty acid biosynthesis after FMT. Correlation network analysis indirectly suggested a causal relationship between FMT and alleviation of GE-induced TBI. FMT improved intestinal structure and up-regulated expression of tight junction proteins Claudin-1, Occludin, and ZO-1, potentially contributing to its protective effects on both brain and gut.

CONCLUSION: Transplantation of gut microbiota from healthy rats significantly enhanced cognitive function in male rats with traumatic brain injury caused by a gas explosion, through the modulation of gut microbiome composition and the improvement of both gut and brain barrier integrity via the gut-brain axis. These findings may offer a scientific foundation for potential clinical interventions targeting gas explosion-induced TBI using FMT.}, } @article {pmid39548908, year = {2024}, author = {Gopal, RK and Ganesh, PS and Pathoor, NN}, title = {Synergistic Interplay of Diet, Gut Microbiota, and Insulin Resistance: Unraveling the Molecular Nexus.}, journal = {Molecular nutrition & food research}, volume = {}, number = {}, pages = {e2400677}, doi = {10.1002/mnfr.202400677}, pmid = {39548908}, issn = {1613-4133}, abstract = {This comprehensive review explores the intricate relationship between gut microbiota, diet, and insulin resistance, emphasizing the novel roles of diet-induced microbial changes in influencing metabolic health. It highlights how diet significantly influences gut microbiota composition, with different dietary patterns fostering diverse microbial communities. These diet-induced changes in the microbiome impact human metabolism by affecting inflammation, energy balance, and insulin sensitivity, particularly through microbial metabolites like short-chain fatty acids (SCFAs). Focusing the key mediators like endotoxemia and systemic inflammation, and introduces personalized microbiome-based therapeutic strategies, it also investigates the effects of dietary components-fiber, polyphenols, and lipids-on microbiota and insulin sensitivity, along with the roles of protein intake and amino acid metabolism. The study compares the effects of Western and Mediterranean diets on the microbiota-insulin resistance axis. Therapeutic implications, including probiotics, fecal microbiota transplantation (FMT), and personalized diets, are discussed. Key findings reveal that high-fat diets, especially those rich in saturated fats, contribute to dysbiosis and increased intestinal permeability, while high-fiber diets promote beneficial bacteria and SCFAs. The review underscores the future potential of food and microbiota interventions for preventing or managing insulin resistance.}, } @article {pmid39548468, year = {2024}, author = {Song, Q and Gao, Y and Liu, K and Tang, Y and Man, Y and Wu, H}, title = {Gut microbial and metabolomics profiles reveal the potential mechanism of fecal microbiota transplantation in modulating the progression of colitis-associated colorectal cancer in mice.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {1028}, pmid = {39548468}, issn = {1479-5876}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Metabolomics ; Humans ; *Disease Progression ; *Colitis-Associated Neoplasms/microbiology/pathology/metabolism ; Mice, Inbred C57BL ; Male ; Colorectal Neoplasms/microbiology/pathology/metabolism ; Dextran Sulfate ; Metabolome ; Mice ; Female ; Azoxymethane ; Wnt Signaling Pathway ; Feces/microbiology ; }, abstract = {PURPOSE: Intestinal flora promotes the pathogenesis of colorectal cancer (CRC) through microorganisms and their metabolites. This study aimed to investigate the composition of intestinal flora in different stages of CRC progression and the effect of fecal microbiota transplantation (FMT) on CRC mice.

METHODS: The fecal microbiome from healthy volunteers (HC), colorectal adenoma (CRA), inflammatory bowel disease (IBD), and CRC patients were analyzed by 16s rRNA gene sequencing. In an azoxymethane (AOM)/dextran-sulfate-sodium (DSS)-induced CRC mouse, the effect of FMT from HC, CRA, CRC, and IBD patients on CRC mice was assessed by histological analysis. Expression of inflammation- EMT-associated proteins and Wnt/β-catenin pathway were assessed using qRT-PCR and western blot. The ratio of the fecal microorganisms and metabolomics alteration after FMT were also assessed.

RESULT: Prevotella, Faecalibacterium, Phascolarctobacterium, Veillonella, Alistipes, Fusobacterium, Oscillibacter, Blautia, and Ruminococcus abundance was different among HC, IBD, CRC, and CRA patients. HC-FMT alleviated disease progression and inflammatory response in CRC mice, inhibited splenic T help (Th)1 and Th17 cell numbers, and suppressed the EMT and Wnt/β-catenin pathways in tumor tissues of CRC mice. IBD-FMT, CRA-FMT, and CRC-FMT played deleterious roles; the CRC-FMT mice exhibited the most malignant phenotype. Compared with the non-FMT CRC mice, Muribaculaceae abundance was lower after FMT, especially lowest in the IBD-FMT group; while Lactobacillus abundance was higher after FMT and especially high in HC-FMT. Akkermansia and Ileibacterium abundance increased after FMT-HC compared to other groups. Metabolite correlation analysis revealed that Muribaculaceae abundance was significantly correlated with metabolites such as Betaine, LysoPC, and Soyasaponin III. Lactobacillus abundance was positively correlated with Taurocholic acid 3-sulfate, and Ileibacterium abundance was positively correlated with Linoleoyl ethanolamide.

CONCLUSION: The different intestinal microbiota communities of HC, IBD, CRA, and CRC patients may be attributed to the different modulation effects of FMT on CRC mice. CRC-FMT promoted, while HC-FMT inhibited the progress of CRC. Increased linoleoyl ethanolamide levels and abundance of Muribaculaceae, Akkermansia, and Ileibacterium and reduced Fusobacterium might participate in inhibiting CRC initiation and development. This study demonstrated that FMT intervention could restore the intestinal microbiota and metabolomics of CRC mice, suggesting FMT as a potential strategy for CRC therapy.}, } @article {pmid39548040, year = {2024}, author = {Wang, J and Yang, R and Zhong, H and Liu, YJ}, title = {Fecal microbiota transplants in pediatric autism: opportunities and challenges.}, journal = {World journal of pediatrics : WJP}, volume = {}, number = {}, pages = {}, pmid = {39548040}, issn = {1867-0687}, support = {82070823//National Natural Science Foundation of China/ ; }, } @article {pmid39547534, year = {2024}, author = {Birch, CR and Paaske, SE and Jensen, MB and Baunwall, SMD and Ehlers, LH and Hvas, CL}, title = {Cost-effectiveness of faecal microbiota transplantation compared with vancomycin monotherapy for early Clostridioides difficile infection: economic evaluation alongside a randomised controlled trial.}, journal = {The Journal of hospital infection}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhin.2024.11.003}, pmid = {39547534}, issn = {1532-2939}, abstract = {For Clostridioides difficile infection (CDI), faecal microbiota transplantation (FMT) is currently recommended for patients with three or more CDI episodes. A recent randomised controlled trial (RCT) show that FMT may be considered early, defined as intervention during the first or second CDI episode. Compared with standard care for first or second CDI, patients randomised to FMT had €1,645 lower hospital costs over 26 weeks owing to fewer admissions and hospital contacts and less medication use.}, } @article {pmid39547500, year = {2024}, author = {Huang, ZB and Zhang, GP and Lu, CX and Gong, C and Gao, X and Lin, Y and Su, P and Xu, W and Lin, Y and Lin, N and Wu, X and Chen, X and Zheng, T and Zheng, X}, title = {Gut microbiota-derived 3-indoleacetic acid confers a protection against sepsis-associated encephalopathy through microglial aryl hydrocarbon receptors.}, journal = {Experimental neurology}, volume = {384}, number = {}, pages = {115055}, doi = {10.1016/j.expneurol.2024.115055}, pmid = {39547500}, issn = {1090-2430}, abstract = {BACKGROUND: The gut microbiota significantly contributes to the pathogenesis of central nervous system disorders. Among the bioactive molecules produced by the gut microbiota, 3-indoleacetic acid (IAA) has been shown to attenuate oxidative stress and inflammatory responses. This experiment aimed to determine the impacts of IAA on sepsis-associated encephalopathy (SAE) and the underlying mechanisms.

METHODS: A total of 34 septic patients and 24 healthy controls were included in the analysis of the clinical correlation between fecal IAA and septic encephalopathy. Fecal microbiota transplantation was used to verify the role of the gut microbiota and its metabolites in SAE. Male C57BL/6 mice aged six to eight weeks, pre-treated with IAA via oral gavage, were subjected to the cecal ligation and puncture (CLP) procedures. This treatment was administered either in combination with an aryl hydrocarbon receptor (AhR) antagonist, CH223191, or a CSF1R inhibitor, PLX3397, to eliminate microglia. Both immunofluorescence staining and enzyme-linked immunosorbent assays were used to evaluate microglia activation and inflammatory cytokine secretion. Behavioral assessments were conducted to quantify neurological deficits.

RESULTS: A decreased fecal level of IAA was observed in the patients with sepsis-associated delirium (SAD), a manifestation of SAE. A reduced IAA level was significantly associated with worsen clinical outcomes. Fecal microbiota transplantation from the SAD patients induced an SAE-like phenotype in mice, but supplementing exogenous IAA improved the SAE-like phenotype, mediated by microglia. IAA effectively binded with the aryl hydrocarbon receptor (AhR). Furthermore, IAA increased the nuclear activity of AhR in the lipopolysaccharide (LPS)-treated microglial cells, leading to reduced secretion of inflammatory cytokines. The AhR inhibitor CH223191 counteracted the protective effect of IAA against SAE in mice.

CONCLUSIONS: Gut microbiota-derived IAA confers a protection against SAE by activating AhR in microglia, improving neuronal and cognitive impairments. Thus, IAA holds the promise as a potential therapeutic agent for managing SAE.}, } @article {pmid39547012, year = {2024}, author = {Wang, J and Hou, Y and Mu, L and Yang, M and Ai, X}, title = {Gut microbiota contributes to the intestinal and extraintestinal immune homeostasis by balancing Th17/Treg cells.}, journal = {International immunopharmacology}, volume = {143}, number = {Pt 3}, pages = {113570}, doi = {10.1016/j.intimp.2024.113570}, pmid = {39547012}, issn = {1878-1705}, abstract = {Gut microbiota is generally considered to play an important role in host health due to its extensive immunomodulatory activities. Th17 and Treg cells are two important CD4+ T cell subsets involved in immune regulation, and their imbalance is closely tied to many immune diseases. Recently, abundant researches have highlighted the importance of gut microbiota in supporting intestinal and extraintestinal immunity through the balance of Th17 and Treg cells. Here, we presented a comprehensive review of these findings. This review first provided an overview of gut microbiota, along with Th17/Treg cell differentiation and cytokine production. Subsequently, the review summarized the regulatory effects of gut microbiota (in terms of species, components, and metabolites) on the Th17/Treg cell balance in the local intestines and extraintestinal organs, such as lung, liver, brain, kidney, and bone. Specifically, the Th17 and Treg cells that can be modulated by gut microbiota originate not only from the gut and extraintestinal organs, but also from peripheral blood and spleen. Then, the microbial therapeutics, including probiotics, prebiotics, postbiotics, and fecal microbiota transplantation (FMT), were also reviewed because of their therapeutic potentials in addressing intestinal and extraintestinal diseases via the Th17/Treg axis. Finally, the review discussed the clinical applications and future study prospects of microbial therapeutics by targeting the Th17/Treg cell balance. In conclusion, this review focused on elucidating the regulatory effects of gut microbiota in balancing Th17/Treg cells to maintain intestinal and extraintestinal immune homeostasis, contributing to the further development and promotion of microbial therapeutics.}, } @article {pmid39546851, year = {2024}, author = {Peña-Ocaña, BA and Silva-Flores, M and Shotaro, T and García-Gálvez, L and Hernández-Esquivel, L and Robledo-Cadena, DX and Barrera-Oviedo, D and Pérez-Torres, I and Tostado-Islas, O and Maeda, T and Rodríguez-Zavala, JS and Marín-Hernández, Á and García-Contreras, R and Jasso-Chávez, R}, title = {Transplant of gut microbiota ameliorates metabolic and heart disorders in rats fed with a hypercaloric diet by modulating microbial metabolism and diversity.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {181}, number = {}, pages = {117667}, doi = {10.1016/j.biopha.2024.117667}, pmid = {39546851}, issn = {1950-6007}, abstract = {Metabolic syndrome (MS) is a cluster of metabolic disorders which have a tight correlation with dysbiosis of gut microbiota (GM) that have to be treated to avoid higher risks for health. In this work, probiotics obtained from healthy cultured GM were provided to rats with metabolic syndrome (MSR) as therapy in treating MS through the correction of dysbiosis. MSR showed obesity, high blood pressure, abnormal blood chemistry parameters and high heart rate respect to control rats (CNTR). Cultivated GM from feces of MSR in media favoring anaerobic species, showed dysbiosis as judged by differences in the 16S rRNA metabarcoding analysis and by affected intermediary metabolism (methane and SCFA production, nutrients consumption and enzyme activities) compared to CNTR. The metabarcoding analysis of cultured healthy GM identified 211 species, which were further transplanted alive in MSR once a week for 9 weeks. Thereafter, in transplanted MSR the excess of Clostridium and Lactobacillus diminished, while Prevotella, Eubacterium, Faecalibacterium and methanogens, among others increased, leading to the recovery of the microbial metabolic capacity. The presence of butyric acid-producing bacteria in the transplanted GM correlated with increased levels of anti-inflammatory cytokines. Therefore, transplanted MSR recovered the normal levels of weight, blood glucose, triglycerides and cholesterol as well as the heart function. Data suggested that the great diversity of species contained in the GM transplanted restored the microbial metabolism, consuming excessive nutrients and secondary metabolites produced by MS. The use of cultivated GM as probiotics may be a safer alternative for the treatment of different diseases.}, } @article {pmid39545921, year = {2024}, author = {Ullern, A and Holm, K and Røssevold, AH and Andresen, NK and Bang, C and Lingjærde, OC and Naume, B and Hov, JR and Kyte, JA}, title = {Gut microbiota diversity is prognostic and associated with benefit from chemo-immunotherapy in metastatic triple-negative breast cancer.}, journal = {Molecular oncology}, volume = {}, number = {}, pages = {}, doi = {10.1002/1878-0261.13760}, pmid = {39545921}, issn = {1878-0261}, support = {2017100//Helse Sør-Øst RHF/ ; 2017122//Helse Sør-Øst RHF/ ; 182632//Kreftforeningen/ ; 214972/WT_/Wellcome Trust/United Kingdom ; 802544/ERC_/European Research Council/International ; }, abstract = {The gut microbiota influences multiple aspects of human health and disease. Several studies have indicated an association between the gut microbiota and response to immune checkpoint inhibitors in various cancers, but there is scarce data from breast cancer. The randomized ALICE trial demonstrated improved progression-free survival (PFS) from adding the programmed cell death 1 ligand 1 (PD-L1) inhibitor atezolizumab (atezo) to immunomodulating chemotherapy (chemo) in metastatic triple-negative breast cancer (mTNBC), even for PD-L1[negative] disease. Herein, we investigated the microbiota composition and dynamics in the ALICE patients and their association with clinical outcome, by analyzing fecal samples collected at baseline and after 8 weeks. We applied 16S (V3-V4) rRNA sequencing to characterize the diversity and taxonomic composition. Kaplan-Meier and Cox proportional hazard models were used for time-to-event analyses. We found that high alpha diversity by Faith's phylogenetic diversity (PD) at baseline was associated with prolonged PFS in the total study population and in the atezo-chemo arm, but not in the placebo-chemo arm. Moreover, Faith's PD appeared to be predictive of benefit from atezolizumab. Patients with high Faith's PD exhibited a PFS hazard ratio of 0.34 (P = 0.018) in favor of the atezo-chemo arm, compared to 0.83 (P = 0.62) in the low Faith's PD group. Faith's PD was significantly reduced during treatment. At baseline, Bifidobacterium was significantly overrepresented in patients without clinical benefit in the atezo-chemo arm, but not in the placebo-chemo arm. These findings suggest that alpha diversity by Faith's PD should be further investigated as a prognostic and predictive biomarker in patients with mTNBC receiving chemo-immunotherapy.}, } @article {pmid39543390, year = {2024}, author = {Islam, J and Ohtani, N and Shimizu, Y and Tanimizu, M and Goto, Y and Sato, M and Makino, E and Shimada, T and Ueda, C and Matsuo, A and Suyama, Y and Sakai, Y and Karrow, NA and Yoneyama, H and Hirakawa, R and Furukawa, M and Tanaka, H and Nochi, T}, title = {Freeze-dried fecal microorganisms as an effective biomaterial for the treatment of calves suffering from diarrhea.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {28078}, pmid = {39543390}, issn = {2045-2322}, support = {Livestock Promotional Subsidy//Japan Racing Association/ ; 20K15478//Japan Society for the Promotion of Science/ ; 22H00393//Japan Society for the Promotion of Science/ ; 18H03969//Japan Society for the Promotion of Science/ ; }, mesh = {Animals ; Cattle ; *Diarrhea/therapy/microbiology/veterinary ; *Fecal Microbiota Transplantation/methods ; *Feces/microbiology ; *Freeze Drying ; Gastrointestinal Microbiome ; Cattle Diseases/therapy/microbiology ; Biocompatible Materials ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is a therapeutic modality for treating neonatal calf diarrhea. Several practical barriers, including donor selection, fecal collection, and a limited timeframe for FMT, are the main constraints to using fresh feces for implementing on-farm FMT. We report the utility of FMT with pretreated ready-to-use frozen (F) or freeze-dried (FD) microorganisms for treating calf diarrhea. In total, 19 FMT (F-FMT, n = 10 and FD-FMT, n = 9) treatments were conducted. Both FMT treatments were 100% clinically effective; however, multi-omics analysis showed that FD-FMT was superior to F-FMT. Machine learning analysis with SourceTracker confirmed that donor microbiota was retained four times better in the recipient calves treated with FD-FMT than F-FMT. A predictive model based on receiver operating characteristic curve analysis and area under the curve showed that FD-FMT was more discriminative than F-FMT of the observed changes in microbiota and metabolites during disease recovery. These results provide new insights into establishing methods for preparing fecal microorganisms to increase the quality of FMT in animals and may contribute to FMT in humans.}, } @article {pmid39541983, year = {2024}, author = {Urtecho, G and Moody, T and Huang, Y and Sheth, RU and Richardson, M and Descamps, HC and Kaufman, A and Lekan, O and Zhang, Z and Velez-Cortes, F and Qu, Y and Cohen, L and Ricaurte, D and Gibson, TE and Gerber, GK and Thaiss, CA and Wang, HH}, title = {Spatiotemporal dynamics during niche remodeling by super-colonizing microbiota in the mammalian gut.}, journal = {Cell systems}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cels.2024.10.007}, pmid = {39541983}, issn = {2405-4720}, abstract = {While fecal microbiota transplantation (FMT) has been shown to be effective in reversing gut dysbiosis, we lack an understanding of the fundamental processes underlying microbial engraftment in the mammalian gut. Here, we explored a murine gut colonization model leveraging natural inter-individual variations in gut microbiomes to elucidate the spatiotemporal dynamics of FMT. We identified a natural "super-donor" consortium that robustly engrafts into diverse recipients and resists reciprocal colonization. Temporal profiling of the gut microbiome showed an ordered succession of rapid engraftment by early colonizers within 72 h, followed by a slower emergence of late colonizers over 15-30 days. Moreover, engraftment was localized to distinct compartments of the gastrointestinal tract in a species-specific manner. Spatial metagenomic characterization suggested engraftment was mediated by simultaneous transfer of spatially co-localizing species from the super-donor consortia. These results offer a mechanism of super-donor colonization by which nutritional niches are expanded in a spatiotemporally dependent manner. A record of this paper's transparent peer review process is included in the supplemental information.}, } @article {pmid39540836, year = {2024}, author = {Charles, P and Kumar, S and Girish Kumar, CP and Parameswaran, S and Viswanathan, P and Nachiappa Ganesh, R}, title = {Association of gut microbiota with allograft injury in kidney transplant recipients: a comparative profiling through 16S metagenomics and quantitative PCR.}, journal = {Journal of medical microbiology}, volume = {73}, number = {11}, pages = {}, doi = {10.1099/jmm.0.001934}, pmid = {39540836}, issn = {1473-5644}, mesh = {Humans ; *Kidney Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Male ; *RNA, Ribosomal, 16S/genetics ; Female ; Middle Aged ; *Metagenomics/methods ; Adult ; Prospective Studies ; Longitudinal Studies ; *Graft Rejection/microbiology ; Real-Time Polymerase Chain Reaction/methods ; Bacteria/classification/genetics/isolation & purification ; Feces/microbiology ; Allografts/microbiology ; Transplant Recipients ; }, abstract = {Introduction. The existence of a mutual relationship between gut microbiota and immune homeostasis highlights its importance in the context of kidney transplantation.Gap statement. The translational utility of gut microbiota as a biomarker for allograft injury has not been assessed before.Aim. In this study, we aimed to characterize the gut microbial diversity in kidney transplant recipients and investigate the alterations in the gut microbial composition in association with allograft injury such as histopathological graft rejection and calcineurin inhibitor toxicity. In addition, we compared the gut microbial quantitation using 16S metagenomics and quantitative PCR (qPCR) to assess its translational utility.Methodology. In this prospective longitudinal cohort study, we enrolled 38 kidney transplant recipients and collected serial faecal specimens (n=114), once before the induction therapy, and twice after transplant, during the first and third month. We characterized the gut microbial composition through 16S rRNA sequencing and qPCR from the DNA isolates of the samples. The recipients were clinically followed up for a median of 600 days post-transplant. Histopathological evidence of allograft rejection and calcineurin inhibitor toxicity were used for the correlational analysis with gut microbial diversity.Results. Significant differences in the gut microbial diversity were observed between the pre- and post-transplant samples. Pre-transplant gut microbiota revealed a higher relative abundance of phylum Bacteroidetes in the allograft rejection group, and a higher relative abundance of phylum Firmicutes was observed in the histopathological features of calcineurin inhibitor toxicity (hCNI toxicity) group. We found a high concordance between 16S metagenomics and qPCR outputs for assessing the gut microbial diversity. Furthermore, the receiver operating characteristic curve analysis has also proven that the pre-transplant levels of gut microbial dysbiosis, as a potential predictive biomarker for allograft injury.Conclusion. Our pilot study found a strong statistical association of gut microbial dysbiosis with kidney allograft injury, highlighting the potential of gut microbiota as a predictive biomarker and that qPCR serves as a more reliable and economic tool for assessing dysbiosis paving the way for its translational utility.}, } @article {pmid39539436, year = {2024}, author = {Abood, NA and Kadhim, DJ and Hussein, RJ}, title = {Medication-related burden among Iraqi patients with ulcerative colitis: a cross-sectional study.}, journal = {Journal of medicine and life}, volume = {17}, number = {8}, pages = {800-805}, pmid = {39539436}, issn = {1844-3117}, mesh = {Humans ; *Colitis, Ulcerative/drug therapy ; Iraq ; Male ; Cross-Sectional Studies ; Female ; Adult ; Surveys and Questionnaires ; Middle Aged ; Cost of Illness ; Drug-Related Side Effects and Adverse Reactions/epidemiology ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by recurring periods of inflammation and remission, primarily affecting the colon. The concept of medication-related burden, which refers to the adverse effects experienced by patients due to conventional medical treatments, is relatively new in the field. This study aimed to measure medication-related burden among patients with ulcerative colitis in Iraq. The study was conducted at the Gastroenterology and Hepatology Teaching Hospital, Medical City, Baghdad, Iraq, from December 2022 to May 2023. We used the Arabic version of the Living with Medicines Questionnaire version 3 (LMQ-3) to explore medication-related burdens experienced by patients with UC. Eighty-six patients with ulcerative colitis were included. The mean of the total medication-related burden score was 107.5 ± 20.7. The findings showed that 45.3% of patients with UC had a moderate degree of medication-related burden, followed by minimum burden (44.2%), high burden (5.8%), and no burden (4.7%). The lowest median burden scores emerged in five domains: interactions with healthcare professionals, practical difficulties with medication use, medication side effects, medication effectiveness, and the impact on daily life. Conversely, the highest-burden scores were noted in the cost, concerns about medication use, and autonomy to vary the regimen domains. In multivariate analysis, none of the patient-related variables was independently correlated with the total medication-related burden score. A large proportion of the patients with UC who participated in the current study reported varying degrees of medication-related burden, with the majority having a minimum to moderate medication-related burden.}, } @article {pmid39539028, year = {2024}, author = {Kovynev, A and Ying, Z and Zhang, S and Olgiati, E and Lambooij, JM and Visentin, C and Guigas, B and Ducarmon, QR and Rensen, PCN and Schönke, M}, title = {Timing Matters: Late, but Not Early, Exercise Training Ameliorates MASLD in Part by Modulating the Gut-Liver Axis in Mice.}, journal = {Journal of pineal research}, volume = {76}, number = {8}, pages = {e70003}, doi = {10.1111/jpi.70003}, pmid = {39539028}, issn = {1600-079X}, support = {//This work was supported by the Novo Nordisk Foundation (grant NNF18OC0032394 to M.S.), The Netherlands Cardiovascular Research Initiative CVON-GENIUS-2 (grant to P.C.N.R.), the Chinese Scholarship Council (grants to Z.Y. and S.Z.). A.K. is supported by a PhD grant from Leiden University Medical Center (to M.S.)./ ; }, mesh = {Animals ; Mice ; Male ; *Physical Conditioning, Animal ; *Gastrointestinal Microbiome ; *Liver/metabolism ; Fatty Liver/therapy/metabolism ; Non-alcoholic Fatty Liver Disease/metabolism/therapy ; Diet, High-Fat ; Mice, Transgenic ; }, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) affects two billion people worldwide and is currently mostly treatable via lifestyle interventions, such as exercise training. However, it is unclear whether the positive effects of exercise are restricted to unique circadian windows. We therefore aimed to study whether the timing of exercise training differentially modulates MASLD development. Twenty weeks old male APOE*3-Leiden.CETP mice were fed a high fat-high cholesterol diet to induce MASLD and treadmill-trained for 1 h five times per week for 12 weeks either early (ZT13; E-RUN) or late (ZT22; L-RUN) in the dark phase while corresponding sedentary groups (E-SED and L-SED) did not. Late, but not early exercise training decreased the MASLD score, body weight, fat mass, and liver triglycerides, accompanied by an altered composition of the gut microbiota. Specifically, only late exercise training increased the abundance of short-chain fatty acid-producing bacterial families and genera, such as Akkermansia, Lachnospiraceae, and Rikenella. To assess the role of the gut microbiota in training-induced effects, the study was repeated and trained (ZT22 only, RUN) or sedentary mice (SED) served as fecal donors for sedentary recipient mice (RUN FMT and SED FMT). Fecal microbiota transplantation reduced liver weight and plasma triglycerides in RUN FMT compared to SED FMT and tended to lower the MASLD score and liver triglycerides. Timing of exercise training is a critical factor for the positive effect on MASLD in this preclinical model, and the effect of late exercise is partially mediated via the gut-liver axis.}, } @article {pmid39538028, year = {2024}, author = {Emile, SH and Wignakumar, A and Horesh, N and Garoufalia, Z and Strassmann, V and Boutros, M and Wexner, SD}, title = {Systematic literature review and meta-analysis of surgical treatment of complete rectal prolapse in male patients.}, journal = {Techniques in coloproctology}, volume = {28}, number = {1}, pages = {158}, pmid = {39538028}, issn = {1128-045X}, mesh = {Adult ; Humans ; Male ; Middle Aged ; Constipation/etiology/surgery/epidemiology ; Digestive System Surgical Procedures/methods/adverse effects ; Fecal Incontinence/etiology/epidemiology ; Operative Time ; Perineum/surgery ; Postoperative Complications/etiology/epidemiology ; *Rectal Prolapse/surgery ; Rectum/surgery ; Recurrence ; Surgical Mesh ; Treatment Outcome ; }, abstract = {BACKGROUND: Rectal prolapse often affects women but may also affect men. This systematic review aimed to provide outcomes of surgery for complete rectal prolapse reported in studies with a predominantly male population.

METHODS: This PRISMA-compliant systematic literature review searched PubMed and Scopus between January 2000 and February 2024; Google Scholar was queried for studies reporting outcomes of complete rectal prolapse surgery in predominately (> 90%) male populations. Main outcome measures were recurrence, complications, operative time, and bowel function.

RESULTS: Eight studies (452 patients; median age 45.6 years) were included; 80.5% of patients underwent abdominal procedures whereas 19.5% underwent perineal procedures. The prevalence of recurrence was 11.2% after ventral mesh rectopexy (VMR), 0.8% after posterior mesh rectopexy (PMR), 0 after resection rectopexy, and 19.3% after perineal procedures. The prevalence of complications was 13.9% after VMR, 13.1% after PMR, 43.3% after resection rectopexy, and 17.4% after perineal procedures. The most improvement in constipation was noted after resection rectopexy (83.3-100%) and in fecal incontinence (FI) was noted after posterior mesh rectopexy (86.4-90%). Abdominal procedures had lower rates of recurrence (6% vs. 19.3%, RR 0.50, 95% CI 0.21-1.18, p = 0.113), similar complication rates (14.3% vs. 13.6%, RR 0.41, 95% CI 0.06-2.9, p = 0.374), and longer operative times (116 ± 47.2 vs. 74.2 ± 23.6 min, p < 0.001).

CONCLUSIONS: Treatment of rectal prolapse in male patients undergoing abdominal procedures was associated with longer operative times, lower recurrence rates, and similar complications to perineal procedures. PMR and resection rectopexy had the lowest recurrence. The most improvement in FI and constipation was noted after PMR and resection rectopexy, respectively.}, } @article {pmid39536754, year = {2024}, author = {Wang, T and Fan, Y and Tan, S and Wang, Z and Li, M and Guo, X and Yu, X and Lin, Q and Song, X and Xu, L and Li, L and Li, S and Gao, L and Liang, X and Li, C and Ma, C}, title = {Probiotics and their metabolite spermidine enhance IFN-γ[+]CD4[+] T cell immunity to inhibit hepatitis B virus.}, journal = {Cell reports. Medicine}, volume = {}, number = {}, pages = {101822}, doi = {10.1016/j.xcrm.2024.101822}, pmid = {39536754}, issn = {2666-3791}, abstract = {The therapeutic potential of commensal microbes and their metabolites is promising in the functional cure of chronic hepatitis B virus (HBV) infection, which is defined as hepatitis B surface antigen (HBsAg) loss. Here, using both specific-pathogen-free and germ-free mice, we report that probiotics significantly promote the decline of HBsAg and inhibit HBV replication by enhancing intestinal homeostasis and provoking intrahepatic interferon (IFN)-γ[+]CD4[+] T cell immune response. Depletion of CD4[+] T cells or blockage of IFN-γ abolishes probiotics-mediated HBV inhibition. Specifically, probiotics-derived spermidine accumulates in the gut and transports to the liver, where it exhibits a similar anti-HBV effect. Mechanistically, spermidine enhances IFN-γ[+]CD4[+] T cell immunity by autophagy. Strikingly, administration of probiotics in HBV patients reveals a preliminary trend to accelerate the decline of serum HBsAg. In conclusion, probiotics and their derived spermidine promote HBV clearance via autophagy-enhanced IFN-γ[+]CD4[+] T cell immunity, highlighting the therapeutic potential of probiotics and spermidine for the functional cure of HBV patients.}, } @article {pmid39534584, year = {2024}, author = {Hrubesz, G and Leigh, J and Ng, TL}, title = {Understanding the relationship between breast cancer, immune checkpoint inhibitors, and gut microbiota: a narrative review.}, journal = {Translational breast cancer research : a journal focusing on translational research in breast cancer}, volume = {5}, number = {}, pages = {31}, pmid = {39534584}, issn = {2218-6778}, abstract = {BACKGROUND AND OBJECTIVE: The composition of gut microbiota plays an important role in predicting and influencing outcomes of cancer treated with immunotherapy. Our objective is to summarize the role of gut microbiota and immunotherapy in breast cancer.

METHODS: A systematic search from inception until July 2024 of key search terms including immunity, breast neoplasm, gastrointestinal microbiome/microbiota, fecal microbiota transplantation, pro- and prebiotics, antibiotics and immunotherapy using EMBASE, MEDLINE and CENTRAL was conducted. The results were screened by two reviewers independently and synthesized and presented descriptively.

KEY CONTENT AND FINDINGS: Thirteen studies (5 clinical, 8 pre-clinical) met the eligibility criteria and were published from 2020-2024. Clinical studies showed that the composition and diversity of gut microbiota was associated with patient response to immunotherapy. In pre-clinical studies, dysbiotic states induced by obesity, antibiotics, and diet were associated with immunosuppression and influenced response to programmed cell death-ligand 1 (PD-L1) inhibitors. Microbiota-modulating treatments such as probiotics showed the ability to enhance response to immunotherapy, indicating their potential use as adjunct therapies in breast cancer treatment.

CONCLUSIONS: The composition of gut microbiota could help predict the chance of response to immunotherapy, and modulating gut microbiota has the potential to enhance the efficacy of chemo-immunotherapy in breast cancer. However, the available data relating to breast cancer are limited. Larger prospective studies are required to further elucidate their role as a biomarker and treatment.}, } @article {pmid38978509, year = {2024}, author = {Cantón, R and De Lucas Ramos, P and García-Botella, A and García-Lledó, A and Hernández-Sampelayo, T and Gómez-Pavón, J and González Del Castillo, J and Martín-Delgado, MC and Martín Sánchez, FJ and Martínez-Sellés, M and Molero García, JM and Moreno Guillén, S and Rodríguez-Artalejo, FJ and Reigadas, E and Del Campo, R and Serrano, S and Ruiz-Galiana, J and Bouza, E}, title = {Human intestinal microbiome: Role in health and disease.}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {37}, number = {6}, pages = {438-453}, doi = {10.37201/req/056.2024}, pmid = {38978509}, issn = {1988-9518}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; Prebiotics ; Fecal Microbiota Transplantation ; }, abstract = {The study of the microbiota and the microbiome, and specifically the intestinal one, has determined great interest due to the possible association of their alterations with numerous diseases. These include entities as diverse as Crohn's disease, autism, diabetes, cancer or situations as prevalent today as obesity. In view of this situation, different recommendations have been performed regarding the use of probiotics, prebiotics, and postbiotics as modulators of the microbiota and the microbiome, seeking both preventive and therapeutic effects, and faecal material transfer (FMT) is proposed as an alternative. The latter has emerged as the only proven beneficial intervention on the intestinal microbiome, specifically in the treatment of recurrent colitis associated with Clostridioides difficile (R-CDI). In the rest of the entities, the lowering of laboratory costs has favored the study of the microbiome, which is resolved by delivering reports with catalogs of microorganisms, metabolites or supposed biomarkers without consensus on their composition associated with healthy or diseased microbiota and the disease. There is still insufficient evidence in any disease for interventions on the microbiome beyond FMT and R-CDI. Multi- and multi-disciplinary work with extensive research and the application of artificial intelligence in this field may shed light on the questions raised currently. Ethical issues must also be resolved in light of possible interventions within the umbrella of personalized medicine.}, } @article {pmid39534519, year = {2024}, author = {Jeyaraman, N and Jeyaraman, M and Mariappan, T and Muthu, S and Ramasubramanian, S and Sharma, S and Santos, GS and da Fonseca, LF and Lana, JF}, title = {Insights of gut-liver axis in hepatic diseases: Mechanisms, clinical implications, and therapeutic potentials.}, journal = {World journal of gastrointestinal pharmacology and therapeutics}, volume = {15}, number = {6}, pages = {98146}, pmid = {39534519}, issn = {2150-5349}, abstract = {With the rising prevalence of chronic liver diseases worldwide, there exists a need to diversify our artillery to incorporate a plethora of diagnostic and therapeutic methods to combat this disease. Currently, the most common causes of liver disease are non-alcoholic fatty liver disease, hepatitis, and alcoholic liver disease. Some of these chronic diseases have the potential to transform into hepatocellular carcinoma with advancing fibrosis. In this review, we analyse the relationship between the gut and liver and their significance in liver disease. This two-way relationship has interesting effects on each other in liver diseases. The gut microbiota, through its metabolites, influences the metabolism in numerous ways. Careful manipulation of its composition can lead to the discovery of numerous therapeutic potentials that can be applied in the treatment of various liver diseases. Numerous cohort studies with a pan-omics approach are required to understand the association between the gut microbiome and hepatic disease progression through which we can identify effective ways to deal with this issue.}, } @article {pmid39534419, year = {2024}, author = {Wang, J and Meng, Y and Guo, ZG}, title = {Contribution of gut microbiota to the development of Crohn's disease: Insights gained from fecal microbiota transplantation studies in mice.}, journal = {World journal of gastroenterology}, volume = {30}, number = {41}, pages = {4514-4517}, pmid = {39534419}, issn = {2219-2840}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Crohn Disease/microbiology/immunology/therapy ; *Gastrointestinal Microbiome/immunology ; Mice ; *Disease Models, Animal ; Humans ; Mesentery ; Feces/microbiology ; Intestines/microbiology/immunology ; Adipose Tissue/immunology ; }, abstract = {We would like to present some new thoughts on the publication in the journal published in August 2024 in World Journal of Gastroenterology. We specifically focused on the alterations in the intestinal tract, mesenteric adipose tissue (MAT), and systemic inflammatory changes in mice following fecal flora transplantation into a mouse model of Crohn's disease (CD). Accumulating evidence suggests that the occurrence of CD is influenced by environmental factors, host immune status, genetic susceptibility, and flora imbalance. One microbiota-based intervention, fecal microbiota transplantation, has emerged as a potential treatment option for CD. The MAT is considered a "second barrier" around the inflamed intestine. The interaction between gut microbes and inflammatory changes in MAT has attracted considerable interest. In the study under discussion, the authors transplanted fetal fecal microorganisms from patients with CD and clinically healthy donors, respectively, into 2,4,6-trinitrobenzene sulfonic acid-induced CD mice. The research explored the complex interplay between MAT, creeping fat, inflammation, and intestinal flora in CD by evaluating intestinal and mesenteric lesions, along with the systemic inflammatory state in the mice. This article provides several important insights. First, the transplantation of intestinal flora holds significant potential as a therapeutic strategy for CD, offering hope for patients with CD. Second, it presents a novel approach to the diagnosis and treatment of CD: The inflammatory response in CD could potentially be assessed through pathological or imaging changes in the MAT, and CD could be treated by targeting the inflammation of the MAT.}, } @article {pmid39529641, year = {2024}, author = {Kirsch, P and Rauch, J and Delau, O and Axelrad, J and Chang, S and Shaukat, A}, title = {Prevalence of Active Pouch Symptoms and Patient Perception of Symptom Control and Quality of Life in an Outpatient Practice.}, journal = {Gastro hep advances}, volume = {3}, number = {8}, pages = {1069-1078}, pmid = {39529641}, issn = {2772-5723}, abstract = {BACKGROUND AND AIMS: Pouchitis is an inflammatory condition affecting the ileal pouch in patients' status after ileal pouch anal anastomosis (IPAA). This affects a significant portion of IPAA patients. Our aim was to study the prevalence of active pouch symptoms among currently treated outpatients with endoscopic pouchitis and understand patients' perspective of disease control and quality of life.

METHODS: We cross-sectionally reviewed the medical charts of patients who had undergone pouchoscopy at NYU Langone Health from 2010 to 2022 and recorded demographic, clinical, and endoscopic data. Based on the most recent data in the medical record, we defined active pouch symptoms as 2 or more current clinical symptoms and "endoscopic pouchitis" as "moderate" or "severe" by pouchoscopy. We also administered surveys in March 2023 to 296 patients with an IPAA to understand symptom control, quality of life, and interest in fecal microbiota transplant.

RESULTS: We identified 282 unique patients. The median age of patients was 46 (interquartile range 33-59), with 54.3% males. Of these, 37.2% of patients currently had active pouch symptoms, 36.9% had endoscopic pouchitis, and 14.9% met the criteria for both. Of the 296 surveys sent to patients with IPAA, 74 (25%) responded. The median age of respondents was 49.5 (interquartile range 34-62). 59.5% were male. Average treatment satisfaction score (scale of 0-10) was 6.4 and quality of life score was 5.8. A majority (64.9%) expressed interest in fecal microbiota transplant.

CONCLUSION: Outpatients with active pouch symptoms or endoscopic pouchitis have high prevalence of active disease and report ongoing symptoms. The results underscore the inadequacy of current treatments and highlight the need for additional therapeutic options.}, } @article {pmid39533632, year = {2024}, author = {Philips, CA and Ahamed, R and Oommen, TT and Nahaz, N and Tharakan, A and Rajesh, S and Augustine, P}, title = {Clinical outcomes and associated bacterial and fungal microbiota changes after high dose probiotic therapy for severe alcohol-associated hepatitis: An observational study.}, journal = {Medicine}, volume = {103}, number = {45}, pages = {e40429}, pmid = {39533632}, issn = {1536-5964}, mesh = {Humans ; *Hepatitis, Alcoholic/therapy ; Male ; *Probiotics/administration & dosage/therapeutic use ; Middle Aged ; Female ; *Gastrointestinal Microbiome/drug effects ; *Fecal Microbiota Transplantation/methods ; Adult ; Treatment Outcome ; Adrenal Cortex Hormones/administration & dosage/therapeutic use ; Mycobiome ; Dysbiosis/therapy/microbiology ; }, abstract = {Alcohol-associated hepatitis (AH) is a critical condition with high mortality rates and is worsened by infections. Organ failure is strongly associated with intestinal dysbiosis. Emerging research suggests that gut microbiota modulation with probiotics can improve AH outcomes. This study investigated the clinical and microbiome effects of high-dose probiotic infusion (HDPI) compared with corticosteroid therapy (CST) and fecal microbiota transplantation (FMT) in severe AH. Patients with biopsy-proven severe-AH were enrolled from March 2019 to June 2020 and matched for age and disease severity. The patients received HDPI (n = 20), FMT (n = 16), or CST (n = 14). HDPI consists of a potent probiotic mix delivered via a nasoduodenal tube for 6 days. The primary outcome was survival at 90-days. Stool samples were subjected to 16S and 18S rRNA sequencing to assess significant bacterial and fungal taxa and their interactions at baseline and post treatment. At 90-days, survival rates were 55%, 64.3%, and 87.5% (HDPI, CST, respectively). HDPI did not beneficially impact bacterial alpha-diversity but significantly altered beta-diversity. Notably, the number of pathogenic bacteria, such as Bilophila and Roseburia increased. Fungal analysis revealed no significant changes in alpha diversity, but significant dissimilarities in beta diversity post-HDPI. New fungal genera such as Basidiomycota and Phragmoplastophyta have emerged, with significant deleterious expansion in fungal communities and damaging modifications between fungal-bacterial interactions. HDPI failed to outperform CST in improving the clinical outcomes of patients with severe AH. While HDPI influenced both bacterial and fungal microbiomes, it also led to the persistence of pathogenic communities. FMT showed superior survival outcomes, highlighting the urgent need for further controlled trials.}, } @article {pmid39533343, year = {2024}, author = {Guo, X and Xu, J and Zhao, Y and Wang, J and Fu, T and Richard, ML and Sokol, H and Wang, M and Li, Y and Liu, Y and Wang, H and Wang, C and Wang, X and He, H and Wang, Y and Ma, B and Peng, S}, title = {Melatonin alleviates heat stress-induced spermatogenesis dysfunction in male dairy goats by regulating arachidonic acid metabolism mediated by remodeling the gut microbiota.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {233}, pmid = {39533343}, issn = {2049-2618}, support = {32072815//National Natural Science Foundation of China/ ; 2022YFD1300200//National Key Research and Development Program of China/ ; 2023-YBNY-140//General Project of the Key R & D Plan of Shaanxi Province/ ; TG20221184//Ningbo Second Hormone Factory/ ; }, mesh = {Animals ; *Melatonin/pharmacology ; Male ; *Spermatogenesis/drug effects ; *Goats ; *Gastrointestinal Microbiome/drug effects ; *Testis/drug effects/metabolism ; Mice ; *Heat-Shock Response/drug effects ; *Arachidonic Acid/metabolism ; Spermatozoa/drug effects ; Oxidative Stress/drug effects ; }, abstract = {BACKGROUND: Heat stress (HS) commonly occurring in summer has gradually become a factor threatening the reproductive performance of male dairy goats by reducing their fecundity. Despite the melatonin is applied to relieve HS, it is still unclear whether melatonin protects against reproductive damage induced by HS in dairy goats and how it works. The purpose of the present study is to evaluate the role of melatonin in alleviating HS-induced spermatogenesis dysfunction in male dairy goats and further explore its mechanism.

RESULTS: HS impaired spermatogenesis, sperm formation in the testes, and sperm maturation in the epididymis of dairy goats, resulting in decreased sperm quality. Melatonin rescued the decrease of sperm quality induced by HS via decreasing inflammatory and oxidative stress levels in testicular tissue and enhancing intercellular barrier function within the testes. Amplicon-based microbiota analysis revealed that despite gut microbiota differences between melatonin-treated dairy goats and NC dairy goats to some extent, melatonin administration tends to return the gut microbiota of male dairy goats under HS to the levels of natural control dairy goats. To explore whether the protective role of melatonin in sperm quality is mediated by regulating gut microbiota, fecal microbiota of HS dairy goats with or without melatonin treatment were transferred to HS mice, respectively. We found HS mice that had received fecal bacteria of HS dairy goats experienced serious testicular injury and dyszoospermia, while this phenomenon was ameliorated in HS mice that had received fecal bacteria of dairy goats treated with melatonin, indicating melatonin alleviates HS-induced spermatogenic damage in a microbiota dependent manner. We further found that the testicular tissue of both HS dairy goats and mice transplanted with HS dairy goat feces produced large amounts of arachidonic acid (AA)-related metabolites, which were closely associated with semen quality. Consistently, supplementation with AA has been shown to elevate the levels of inflammation and oxidative stress in the testicular tissue of mice, disrupting intercellular connections and ultimately leading to spermatogenic disorders.

CONCLUSION: This study has revealed that melatonin can effectively alleviate spermatogenic disorders in dairy goats caused by HS. This beneficial effect was primarily achieved through the modulation of gut microbiota, which subsequently inhibited the excessive synthesis of AA in testicular tissue. These discoveries are of great significance for preventing or improving the decline in male livestock reproductive performance caused by HS, enhancing the reproductive efficiency of elite male breeds, and ultimately improving the production efficiency of animal husbandry. Video Abstract.}, } @article {pmid39531305, year = {2024}, author = {Tursumetova, DR and Khan, Y and Tkacheva, LV and Rayevskii, KP}, title = {[The role and features of the gut microbiota in Alzheimer's disease.].}, journal = {Advances in gerontology = Uspekhi gerontologii}, volume = {37}, number = {4}, pages = {442-452}, pmid = {39531305}, issn = {1561-9125}, mesh = {*Alzheimer Disease/microbiology/therapy/physiopathology ; Humans ; *Gastrointestinal Microbiome/physiology ; *Probiotics/administration & dosage/therapeutic use ; Fecal Microbiota Transplantation/methods ; Prebiotics/administration & dosage ; Brain-Gut Axis/physiology ; Disease Progression ; }, abstract = {Alzheimer's disease causes gradual, persistent deterioration of cognitive function in the elderly, causing social and economic damage to society. Over the past decades, mankind has made significant progress in the study of Alzheimer's disease, but there are no methods to fully control the disease. The lack of effectiveness of existing treatment methods emphasizes the need to search for new approaches. The present review is devoted to the study of the latest data regarding the role of microbiota in the mechanisms of formation and progression of Alzheimer's disease, possible therapeutic ways to influence the processes of neurodegeneration through microbiota and taking into account identified relationships. The article considers the axis «gut microbiota-brain» as a link in the pathogenesis of neuroinflammation. New data on the influence of gut microbiota on neurodegenerative processes through metabolic, nervous, and immune mechanisms is analyzed. New data reveals correlations between microbiota specifics and the origin and/or progression of Alzheimer's disease, expanding the understanding of disease pathogenesis. The role of the oral microbiota in neurodegeneration processes is mentioned, emphasizing the diverse mechanisms of this disease. Available therapies for Alzheimer's disease are discussed, including probiotics and prebiotics, fecal microbiota transplantation, and dietary correction.}, } @article {pmid39530534, year = {2024}, author = {Kao, D and Wong, K and Jijon, H and Moayyedi, P and Franz, R and McDougall, C and Hotte, N and Panaccione, R and Semlacher, E and Kroeker, KI and Peerani, F and MacDonald, KV and Xu, H and Narula, N and Turbide, C and Marshall, DA and Madsen, KL}, title = {Preliminary results from a multicenter, randomized trial using fecal microbial transplantation to induce remission in patients with mild to moderate Crohn's disease.}, journal = {The American journal of gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ajg.0000000000003196}, pmid = {39530534}, issn = {1572-0241}, abstract = {INTRODUCTION: Fecal microbial transplantation (FMT) has shown promise at inducing remission in ulcerative colitis. This study is the first of its kind to evaluate the efficacy and safety of FMT at inducing remission in Crohn's disease (CD).

METHODS: This double-blind, placebo-controlled trial was conducted in three Canadian academic centers; randomized patients with mild to moderate CD received FMT or placebo. The first treatment was administered by colonoscopy followed by weekly fecal capsules for 7 weeks. Primary endpoint was clinical and endoscopic remission at week 8. Secondary outcomes included clinical and endoscopic response, adverse events, and health-related quality of life using generic and disease-specific instruments.

RESULTS: From July 2017 to June 2021, 21 and 13 patients were randomized to FMT and placebo groups, respectively. The trial terminated early due to futility. At week 8, 0% (0/15) of patients in the FMT group versus 8.3% (1/11) in the placebo group reached the primary endpoint of combined clinical and endoscopic remission as per protocol analysis. There were no differences between the groups in clinical or endoscopic responses. One participant in each group had worsening of CD. Although both groups experienced statistically significant improvements in health-related quality of life, only the FMT group had a significant decrease in activity impairment. Although there were no significant changes in microbial diversity or composition, participants who achieved clinical response became more similar to their donors in stool microbial composition.

DISCUSSION: FMT was not effective at inducing clinical and endoscopic remission in CD using the FMT regimen in this study. Future studies may use other strategies to enhance treatment response, including longer intervention, antibiotic pretreatment, optimized donor-recipient pairing, and concomitant anti-inflammatory diet, biologic or small molecule therapies.}, } @article {pmid39528920, year = {2024}, author = {Laperrousaz, B and Levast, B and Fontaine, M and Nancey, S and Dechelotte, P and Doré, J and Lehert, P}, title = {Safety comparison of single-donor and pooled fecal microbiota transfer product preparation in ulcerative colitis: systematic review and meta-analysis.}, journal = {BMC gastroenterology}, volume = {24}, number = {1}, pages = {402}, pmid = {39528920}, issn = {1471-230X}, mesh = {*Colitis, Ulcerative/therapy/microbiology ; Humans ; *Fecal Microbiota Transplantation/methods ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {BACKGROUND: Multiple studies have evaluated fecal microbiota transfer (FMT) in patients with ulcerative colitis (UC) using single-donor (SDN) and multidonor (MDN) products. Systematic review and meta-analysis were performed to compare the safety of SDN and MDN products.

METHODS: Systematic searches were performed in Web of Science, Scopus, PubMed, and Orbit Intelligence to identify studies that compared FMT products manufactured using SDN or MDN strategies against control treatment in patients with UC. Fifteen controlled studies were selected for meta-analysis (11 randomized controlled trials and 4 controlled cohort trials). Safety of each treatment type was assessed using the counts of adverse events and serious adverse events using fixed- and random-effects models. Significance of the indirect difference between FMT preparations was assessed using a network approach. Benefit-risk ratios were calculated by multiplicative utility model, incorporating geometric mean of risk ratios (RRs) of efficacy and safety.

RESULTS: Safety data was collected for a total of 587 patients (193 exposed to SDN products, 114 exposed to MDN products and 280 exposed to control treatment). The 12 studies showed similar overall safety event counts for MDN and SDN versus placebo (RRs: 0.90 and 1.09, respectively [P = 0.206 and P = 0.420, respectively]). Results indicated similar risk of safety events for MDN compared to SDN (RR: 0.83, P = 0.159). Positive benefit-risk ratios were demonstrated for MDN and SDN versus placebo (RRs: 1.70 and 1.16, respectively [P = 0.003 and P = 0.173, respectively]). MDN had a greater benefit-risk ratio compared to SDN (RR: 1.46, P = 0.072).

CONCLUSION: Similar safety profiles were observed for MDN and SDN strategies. Alongside previously described superior efficacy, treatment with MDN has greater benefit-risk ratio than SDN in patients with UC. Further development of MDN FMT treatment for UC should be considered.}, } @article {pmid39524804, year = {2024}, author = {Zhang, Y and Wu, Y and Guan, Y and Lu, Y and Zhu, W and Ping, F and Wang, Y}, title = {Maidong Dishao Decoction mitigates submandibular gland injury in NOD mice through modulation of gut microbiota and restoration of Th17/Treg immune balance.}, journal = {Heliyon}, volume = {10}, number = {21}, pages = {e38421}, pmid = {39524804}, issn = {2405-8440}, abstract = {BACKGROUND: Primary Sjogren's syndrome (pSS) is a common chronic autoimmune disease that presents limited treatment options and poses significant challenges for patients. Maidong Dishao Decoction (MDDST), a traditional Chinese medicine compound, has demonstrated potential in alleviating dryness symptoms associated with pSS. Therefore, it is important to study the specific mechanism of its therapeutic effect.

OBJECTIVE: This study aims to investigate the effects of MDDST on gut microbiota, short-chain fatty acids (SCFAs), and the Th17/Treg immune balance in non-obese diabetes (NOD) mice.

METHODS: The study employed ultrahigh-performance liquid chromatography coupled with quadrupole-exactive mass spectrometry (UHPLC-QE-MS) to identify the primary components of MDDST. Subsequently, hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assays (ELISA), and flow cytometry analyses were conducted to evaluate the therapeutic effects of MDDST in NOD mice. Additionally, 16S rDNA sequencing and gas chromatography-mass spectrometry (GC-MS) were utilized to assess the influence of MDDST on gut microbiota and SCFAs. Finally, fecal microbiota transplantation (FMT) and SCFA-based interventions were performed to elucidate the mechanisms through which MDDST exerts its effects.

RESULTS: The research findings demonstrate that MDDST exerts therapeutic effects on NOD mice, primarily manifested as reduced inflammation, decreased water intake, ameliorated pathological changes and lowered levels of Sjogren's syndrome antigen A (SSA) and immunoglobulin G (IgG). Additionally, MDDST significantly decreased serum levels of interleukin-6 (IL-6) and interleukin-17 (IL-17), while enhancing levels of interleukin-10 (IL-10) and transforming growth factor beta (TGF-β), thereby regulating the Th17/Treg immune balance. Further investigations revealed that MDDST treatment induces alterations in gut microbiota composition and elevates SCFA levels in the gut. Subsequent FMT and SCFA intervention experiments demonstrated a downregulation of pSS-related phenotypes.

CONCLUSION: In summary, MDDST demonstrates protective effects against pSS by restoring the balance between Th17 and Treg cells. The therapeutic effects can be partially attributed to its regulation of gut microbiota and SCFAs. Our finding provides a new option for treating pSS.}, } @article {pmid39526563, year = {2024}, author = {Tessier, MEM and Schraw, JM and Beer, S and Harpavat, S and Kyle Jensen, M and Magee, JC and Ng, V and Scheurer, ME and Taylor, SA and Shneider, BL}, title = {The association of human milk intake and outcomes in biliary atresia.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1002/jpn3.12403}, pmid = {39526563}, issn = {1536-4801}, support = {5K23-DK119567//National Institute of Diabetes, Digestive and Kidney Diseases/ ; U01DK103140//University of Utah/ ; U01DK062453//Children's Hospital Colorado/ ; U01DK062456//The University of Michigan/ ; U01DK103149//Texas Children's Hospital/ ; U01DK103135//The Hospital for Sick Children/ ; U24DK062456//ChiLDReN's Scientific Data Coordinating Center, Ann Arbor, MI/ ; }, abstract = {OBJECTIVES: Human milk intake has many benefits which could influence outcomes in biliary atresia (BA). However, the role of human milk in BA has not been examined. We hypothesized that human milk intake would be associated with improved outcomes in BA.

METHODS: We assessed the impact of any human milk (AHM) as compared to formula only (FO) intake before Kasai portoenterostomy (KP) on outcomes in 447 infants with BA using the PROBE database (NCT00061828) post hoc. The primary outcome was clearance of jaundice (COJ = total bilirubin (TB) < 2 mg/dL by 3 months post-KP). Secondary outcomes included 2-year native liver survival (SNL), bilirubin levels, cholangitis, ascites, and growth. We assessed the fecal microbiome (n = 8) comparing AHM versus FO.

RESULTS: At baseline, 211 infants received AHM and 215 received FO. 53.9% of AHM and 50.5% of FO achieved COJ (p = NS). SNL was insignificantly increased in AHM (odds ratio = 1.47, 95% confidence interval: 1.00-2.12, p = 0.053). TB decreased in AHM from 4 weeks to 3 months post-KP [4.8-4.0 mg/dL (p = 0.01)] unlike the FO group (4.9-4.9 mg/dL, p = 0.4). At 3 months post-KP, AHM infants had greater weight gain (1.88 ± 0.66 vs. 1.57 ± 0.73 kg, p < 0.001) and mid-upper arm circumference (12.9 ± 1.4 vs. 12.2 ± 1.7 cm, p < 0.001). Other secondary outcomes were not different. Microbiome differences were seen between AHM and FO.

CONCLUSIONS: Human milk intake in infants with BA did not significantly improve COJ or SNL. However, growth parameters were improved, and TB 3 months post-KP was decreased. Thus, human milk intake should not be discouraged. Prospective studies with detailed assessment of human milk intake are needed.}, } @article {pmid39523344, year = {2024}, author = {You, X and Yan, J and Herzog, J and Nobakhti, S and Campbell, R and Hoke, A and Hammamieh, R and Sartor, RB and Shefelbine, S and Kacena, MA and Chakraborty, N and Charles, JF}, title = {Bone loss with aging is independent of gut microbiome in mice.}, journal = {Bone research}, volume = {12}, number = {1}, pages = {65}, pmid = {39523344}, issn = {2095-4700}, support = {R01-AG046257//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; P30-AR070253//U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)/ ; P40-OD010995//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; P30-DK034987//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; 997397//Crohn's and Colitis Foundation (Crohn's & Colitis Foundation)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Aging/physiology ; Male ; Mice ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Bone Resorption/microbiology ; Germ-Free Life ; }, abstract = {Emerging evidence suggests a significant role of gut microbiome in bone health. Aging is well recognized as a crucial factor influencing the gut microbiome. In this study, we investigated whether age-dependent microbial change contributes to age-related bone loss in CB6F1 mice. The bone phenotype of 24-month-old germ-free (GF) mice was indistinguishable compared to their littermates colonized by fecal transplant at 1-month-old. Moreover, bone loss from 3 to 24-month-old was comparable between GF and specific pathogen-free (SPF) mice. Thus, GF mice were not protected from age-related bone loss. 16S rRNA gene sequencing of fecal samples from 3-month and 24-month-old SPF males indicated an age-dependent microbial shift with an alteration in energy and nutrient metabolism potential. An integrative analysis of 16S predicted metagenome function and LC-MS fecal metabolome revealed an enrichment of protein and amino acid biosynthesis pathways in aged mice. Microbial S-adenosyl methionine metabolism was increased in the aged mice, which has previously been associated with the host aging process. Collectively, aging caused microbial taxonomic and functional alteration in mice. To demonstrate the functional importance of young and old microbiome to bone, we colonized GF mice with fecal microbiome from 3-month or 24-month-old SPF donor mice for 1 and 8 months. The effect of microbial colonization on bone phenotypes was independent of the microbiome donors' age. In conclusion, our study indicates age-related bone loss occurs independent of gut microbiome.}, } @article {pmid39522895, year = {2024}, author = {Wan, J and Wang, F and Xiao, Y and Cheng, Y and Zhen, S and Jiang, Q and Tan, B and Li, X and Chen, J and Liao, S}, title = {Poria cocos polysaccharides alleviate dextran sulphate sodium-induced ulcerative colitis in mice by modulating intestinal inflammatory responses and microbial dysbiosis.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {137450}, doi = {10.1016/j.ijbiomac.2024.137450}, pmid = {39522895}, issn = {1879-0003}, abstract = {Poria cocos polysaccharide (PCP), one of the main active components of P. cocos, is extensively used worldwide and exhibits strong pharmacological effects. However, whether PCP can attenuate inflammatory bowel disease remains unclear. In this study, we assessed the effects of PCP supplementation on dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) in mice. We found that PCP supplementation mitigated UC symptoms in DSS-treated mice, as evidenced by reductions in body weight loss, colon length shortening and disease activity index score. Importantly, PCP supplementation enhanced colonic barrier integrity by increasing tight junction protein abundance and exerted anti-inflammatory effects by suppressing nuclear factor-κB (NF-κB) activation in DSS-treated mice. Furthermore, PCP supplementation reversed DSS-induced dysbiosis in colonic microbiota by increasing the colonic abundance of beneficial bacteria (e.g. Akkermansiaceae) and decreasing the colonic abundance of harmful bacteria (e.g. Erysipelotrichaceae) in DSS-treated mice. Although PCP supplementation failed to ameliorate DSS-induced UC in antibiotic-treated mice, faecal microbiota transplantation from PCP-administered mice ameliorated DSS-induced UC in antibiotic-treated mice. In summary, PCP alleviates UC in mice by attenuating intestinal inflammation via the inhibition of NF-κB activation and modulating the intestinal microbiota.}, } @article {pmid39522254, year = {2024}, author = {Li, X and Khan, I and Han, R and Huang, G and Xia, W and Yin, L and Leong, WK and Su, L and Law, BY and Wong, VKW and Wu, Q and Guo, X and Hsiao, WLW}, title = {Gynostemma pentaphyllum saponins shield mice from peanut allergy by modulation of gut microbiota: A novel approach for peanut allergy management.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156101}, doi = {10.1016/j.phymed.2024.156101}, pmid = {39522254}, issn = {1618-095X}, abstract = {BACKGROUND: Food allergies, particularly peanut (PN) allergies, are a growing concern, with fatal anaphylaxis incidents often reported. While palforzia is the sole FDA-approved drug for managing PN allergies, it is not universally effective.

PURPOSE: This study aimed to investigate the potential of Gynostemma pentaphyllum saponins (GpS) as a novel therapeutic agent for PN allergy through modulation of gut microbiota, addressing the limitations of current treatments.

METHODS: To elucidate the role of GpS on peanut allergy, we first built a PN-sensitized C57BL/6J model mice. Through comprehensive sequencing analysis, we identified Parabacteroides distasonis as a key bacterium triggering PN sensitization. Employing the same mouse model, GpS was evaluated for its effects on anaphylactic symptoms, serum immunoglobulin levels, and allergy-related biomarkers. 16S rRNA sequencing and transcriptomic analysis were applied to investigate the impact of GpS on the host's gut epithelium and microbiome.

RESULTS: GpS treatment effectively reduced anaphylactic symptoms in PN-sensitized mice, as shown by decreased IgG1, total IgE, and PN-specific IgE levels. It also modulated the immune response by suppressing proinflammatory cytokines (IL-1β, IFN-γ, IL-21) and chemokines (CCL5, CCL12, CCL17, CCL22), while enhancing anti-inflammatory cytokines (IL-4, IL-10, IL-12, IL-13). Fecal microbial transplant from GpS-treated Model mice to PN-sensitized mice displayed anti-peanut allergy effects. Additionally, the administration of GpS-enhanced bacteria (Clostridium aldenese or Lactobacillus murinus), alleviated anaphylactic symptoms and reduced serum allergy markers in PN-sensitized mice.

CONCLUSION: To conclude, we revealed the intestinal environment, signaling molecules, mucosal cytokines, and commensal microbial profiles in the peanut-sensitized mouse model. We further presented evidence for the protective effect of GpS against PN allergen sensitization by downregulating a series of food-allergy-associated biomarkers and cytokines via the modulation of gut bacteria. More importantly, supported by both in vitro and in vivo experiments, we demonstrated that the protective effect of GpS against PN-allergy is through the enhancement of two commensal bacteria, Clostridium aldenese, and Lactobacillus murinus.}, } @article {pmid39521596, year = {2024}, author = {Hurtado-Lorenzo, A and Swantek, JL}, title = {The landscape of new therapeutic opportunities for IBD.}, journal = {Advances in pharmacology (San Diego, Calif.)}, volume = {101}, number = {}, pages = {1-83}, doi = {10.1016/bs.apha.2024.10.011}, pmid = {39521596}, issn = {1557-8925}, mesh = {Humans ; *Inflammatory Bowel Diseases/drug therapy/therapy/immunology ; Animals ; Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; }, abstract = {This chapter presents an overview of the emerging strategies to address the unmet needs in the management of inflammatory bowel diseases (IBD). IBD poses significant challenges, as over half of patients experience disease progression despite interventions, leading to irreversible complications, and a substantial proportion do not respond to existing therapies, such as biologics. To overcome these limitations, we describe a diverse array of novel therapeutic approaches. In the area of immune homeostasis restoration, the focus is on targeting cytokine networks, leukocyte trafficking, novel immune pathways, and cell therapies involving regulatory T cells and mesenchymal stem cells (MSC). Recognizing the critical role of impaired intestinal barrier integrity in IBD, we highlight therapies aimed at restoring barrier function and promoting mucosal healing, such as those targeting cell proliferation, tight junctions, and lipid mediators. Addressing the challenges posed by fibrosis and fistulas, we describe emerging targets for reversing fibrosis like kinase and cytokine inhibitors and nuclear receptor agonists, as well as the potential of MSC for fistulas. The restoration of a healthy gut microbiome, through strategies like fecal microbiota transplantation, rationally defined bacterial consortia, and targeted antimicrobials, is also highlighted. We also describe innovative approaches to gut-targeted drug delivery to enhance efficacy and minimize side effects. Reinforcing these advancements is the critical role of precision medicine, which emphasizes the use of multiomics analysis for the discovery of biomarkers to enable personalized IBD care. Overall, the emerging landscape of therapeutic opportunities for IBD holds great potential to surpass the therapeutic ceiling of current treatments.}, } @article {pmid39521225, year = {2024}, author = {Yang, X and Zhang, X and Ma, Y and Li, S and Wang, Q and Hong, JS and Yu, G and Qi, B and Wang, J and Liu, C and Shang, Q and Wu, X and Zhao, J}, title = {Fucoidan ameliorates rotenone-induced Parkinsonism in mice by regulating the microbiota-gut-brain axis.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {137373}, doi = {10.1016/j.ijbiomac.2024.137373}, pmid = {39521225}, issn = {1879-0003}, abstract = {Microbiota-gut-brain axis, the bidirectional relationship between the gut microbiota and the brain, has been increasingly appreciated in the pathogenesis of Parkinson's disease (PD). Fucoidan, a sulphate-rich polysaccharide, has been shown to be neuroprotective by reducing oxidative stress in PD models. However, the role of microbiota-gut-brain axis in the neuroprotective activity of fucoidan has not been revealed. In this study, the therapeutic effects of fucoidan and involvement of microbiota-gut-brain axis in rotenone (ROT)-induced PD were investigated. The results showed that fucoidan gavage attenuated neuroinflammation, dopamine neuronal damage and motor dysfunction in ROT-induced PD mice. In addition, fucoidan treatment ameliorated gut dysfunction, intestinal inflammation and disruption of the intestinal barrier in PD mice. Fucoidan also affected the composition of gut microbiota in PD mice, indicated particularly by decreased abundance of Akkermansia muciniphila and Lactobacillus johnsonii and increased abundance of Lactobacillus murinus. Mechanistic studies showed that fecal microbiota transplantation (FMT) from the fucoidan-treated mice and probiotic Lactobacillus murinus supplement are as potent as fucoidan treatment in attenuating peripheral and central inflammation and ameliorating dopamine neuronal damage, which might be attributed to the downregulation of LPS/TLR4/NF-κB signaling pathway. Our study suggests that fucoidan might be potential candidates for the treatment of PD.}, } @article {pmid39507519, year = {2024}, author = {Claassen-Weitz, S and du Toit, E and Gardner-Lubbe, S and Kullin, B and Bellairs, G and Hilton, C and Chicken, A and Welp, K and Livingstone, H and Brink, A}, title = {Knowledge and perceptions of South African blood donors towards biobanking and stool donation.}, journal = {Southern African journal of infectious diseases}, volume = {39}, number = {1}, pages = {645}, pmid = {39507519}, issn = {2313-1810}, abstract = {BACKGROUND: The complexity of contexts and varied purposes for which biome donation are requested are unknown in South Africa.

OBJECTIVES: The aim of this study was to provide strategic data towards actualisation of whether a stool donor bank may be established as a collaborative between Western Cape Blood Services (WCBS) and the University of Cape Town (UCT).

METHOD: We designed a cross-sectional, questionnaire-based survey to determine willingness of WCBS blood donors to donate stool specimens for microbiome biobanking. The study was conducted between 01 June 2022 and 01 July 2022 at three WCBS donation centres in Cape Town, South Africa. Anonymous blood donors who met the inclusion criteria were enrolled. Anonymised demographic and interview data were analysed statistically.

RESULTS: Analysis of responses from 209/231 blood donors demonstrated in a logistic regression model that compensation (p < 0.001) and 'societal benefit outweighs inconvenience' beliefs (p = 7.751e-05) were covariates significantly associated with willingness to donate stool. Age was borderline significant at a 5% level (p = 0.0556). Most willing stool donors indicated that donating stool samples would not affect blood donations (140/157, 90%). Factors decreasing willingness to donate were stool collection being unpleasant or embarrassing.

CONCLUSION: The survey provides strategic data for the establishment of a stool bank and provided an understanding of the underlying determinants regarding becoming potential donors.

CONTRIBUTION: This is the first report on the perspectives of potential participants in donating samples towards a stool microbiome biobank in South Africa, a necessity for faecal microbiota transplantation (FMT).}, } @article {pmid39519488, year = {2024}, author = {Pinto, C and Carrasco-Loncharic, T and González-Mienert, E and de Solminihac, J and Gálvez-Jirón, F and Cifuentes, F and Pino-Lagos, K}, title = {IL-33 Induces a Switch in Intestinal Metabolites Revealing the Tryptophan Pathway as a Target for Inducing Allograft Survival.}, journal = {Nutrients}, volume = {16}, number = {21}, pages = {}, doi = {10.3390/nu16213655}, pmid = {39519488}, issn = {2072-6643}, support = {1210654//Fondo Nacional de Desarrollo Científico y Tecnológico (Fondecyt)/ ; }, mesh = {Animals ; *Tryptophan/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Graft Survival/drug effects ; *Interleukin-33/metabolism ; *Skin Transplantation ; *T-Lymphocytes, Regulatory/metabolism ; Mice ; *Mice, Inbred C57BL ; Intestines/drug effects ; Allografts ; Mice, Inbred BALB C ; Male ; Kynurenic Acid/metabolism ; Dysbiosis ; }, abstract = {BACKGROUND: IL-33, a pleiotropic cytokine, has been associated with a plethora of immune-related processes, both inflammatory and anti-inflammatory. T regulatory (Treg) cells, the main leukocyte population involved in immune tolerance, can be induced by the administration of IL-33, the local microbiota, and its metabolites. Here, we demonstrate that IL-33 drastically induces the production of intestinal metabolites involved on tryptophan (Trp) metabolism.

METHODS: naïve mice were treated with IL-33 for 4 days and leukocyte populations were analyzed by flow cytometry, and feces were processed for microbiota and intestinal metabolites studies. Using a murine skin transplantation model, the effect of Kynurenic acid (KA) on allograft survival was tested.

RESULTS: Under homeostatic conditions, animals treated with IL-33 showed an increment in Treg cell frequencies. Intestinal bacterial abundance analysis indicates that IL-33 provokes dysbiosis, demonstrated by a reduction in Enterobacteria and an increment in Lactobacillus genera. Furthermore, metabolomics analysis showed a dramatic IL-33 effect on the abundance of intestinal metabolites related to amino acid synthesis pathways, highlighting molecules linked to Trp metabolism, such as kynurenic acid (KA), 5-Hydroxyindoleacetic acid (5-HIAA), and 6-Hydroxynicotinic acid (6-HNA), which was supported by an enhanced expression of Ido and Kat mRNA in MLN cells, which are two enzymes involved on KA synthesis. Interestingly, animals receiving KA in drinking water and subjected to skin transplantation showed allograft acceptance, which is associated with an increment in Treg cell frequencies.

CONCLUSIONS: Our study reveals a new property for IL-33 as a modulator of the intestinal microbiota and metabolites, especially those involved with Trp metabolism. In addition, we demonstrate that KA favors Tregs in vivo, positively affecting skin transplantation survival.}, } @article {pmid39519055, year = {2024}, author = {Misiąg, P and Molik, K and Kisielewska, M and Typek, P and Skowron, I and Karwowska, A and Kuźnicki, J and Wojno, A and Ekiert, M and Choromańska, A}, title = {Amelanotic Melanoma-Biochemical and Molecular Induction Pathways.}, journal = {International journal of molecular sciences}, volume = {25}, number = {21}, pages = {}, doi = {10.3390/ijms252111502}, pmid = {39519055}, issn = {1422-0067}, mesh = {Humans ; *Melanoma, Amelanotic/metabolism/genetics/pathology ; Proto-Oncogene Proteins B-raf/genetics/metabolism/antagonists & inhibitors ; Biomarkers, Tumor/metabolism ; Proto-Oncogene Proteins c-kit/genetics/metabolism/antagonists & inhibitors ; Skin Neoplasms/metabolism/genetics/pathology/therapy ; Melanins/metabolism/biosynthesis ; Signal Transduction ; }, abstract = {Amelanotic melanoma (AM) is a subtype of hypomelanotic or completely amelanotic melanoma. AM is a rare subtype of melanoma that exhibits a higher recurrence rate and aggressiveness as well as worse surveillance than typical melanoma. AM shows a dysregulation of melanin production, cell cycle control, and apoptosis pathways. Knowing these pathways has an application in medicine due to targeted therapies based on the inhibiting elements of the abovementioned pathways. Therefore, we summarized and discussed AM biochemical and molecular induction pathways and personalized medicine approaches, clinical management, and future directions due to the fact that AM is relatively rare. AM is commonly misdiagnosed. Hence, the role of biomarkers is becoming significant. Nonetheless, there is a shortage of biomarkers specific to AM. BRAF, NRAS, and c-KIT genes are the main targets of therapy. However, the role of BRAF and KIT in AM varied among studies. BRAF inhibitors combined with MAK inhibitors demonstrate better results. Immune checkpoint inhibitors targeting CTLA-4 combined with a programmed death receptor 1 (PD-1) show better outcomes than separately. Fecal microbiota transplantation may overcome resistance to immune checkpoint therapy of AM. Immune-modulatory vaccines against indoleamine 2,3-dioxygenase (IDO) and PD ligand (PD-L1) combined with nivolumab may be efficient in melanoma treatment.}, } @article {pmid39518717, year = {2024}, author = {Brusnic, O and Onisor, D and Boicean, A and Hasegan, A and Ichim, C and Guzun, A and Chicea, R and Todor, SB and Vintila, BI and Anderco, P and Porr, C and Dura, H and Fleaca, SR and Cristian, AN}, title = {Fecal Microbiota Transplantation: Insights into Colon Carcinogenesis and Immune Regulation.}, journal = {Journal of clinical medicine}, volume = {13}, number = {21}, pages = {}, doi = {10.3390/jcm13216578}, pmid = {39518717}, issn = {2077-0383}, abstract = {Colorectal cancer (CRC) constitutes a significant global health challenge, with recent studies underscoring the pivotal role of the gut microbiome in its pathogenesis and progression. Fecal microbiota transplantation (FMT) has emerged as a compelling therapeutic approach, offering the potential to modulate microbial composition and optimize treatment outcomes. Research suggests that specific bacterial strains are closely linked to CRC, influencing both its clinical management and therapeutic interventions. Moreover, the gut microbiome's impact on immunotherapy responsiveness heralds new avenues for personalized medicine. Despite the promise of FMT, safety concerns, particularly in immunocompromised individuals, remain a critical issue. Clinical outcomes vary widely, influenced by genetic predispositions and the specific transplantation methodologies employed. Additionally, rigorous donor selection and screening protocols are paramount to minimize risks and maximize therapeutic efficacy. The current body of literature advocates for the establishment of standardized protocols and further clinical trials to substantiate FMT's role in CRC management. As our understanding of the microbiome deepens, FMT is poised to become a cornerstone in CRC treatment, underscoring the imperative for continued research and clinical validation.}, } @article {pmid39515099, year = {2024}, author = {Yu, ZQ and Du, HX and Gao, S and Liang, CZ}, title = {Eriocalyxin B ameliorated experimental autoimmune prostatitis via modulation of macrophage polarization through gut microbiota-mediated vitamin D3 alteration.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156191}, doi = {10.1016/j.phymed.2024.156191}, pmid = {39515099}, issn = {1618-095X}, abstract = {BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a often heterogeneous condition in urology. Accumulating evidence suggests that the autoimmune response against prostate antigens is related to CP/CPPS. The gut microbiota may be a possible cause of a number of autoimmune diseases. Eriocalyxin B (EriB) is used as an anti-inflammatory treatment for autoimmune disorders. The underlying mechanism of fecal metabolome involved in CP/CPPS treatment by EriB remains unclear.

METHODS: The experimental autoimmune prostatitis (EAP) mouse model was generated by subcutaneous immunization. Macrophages, inflammatory cytokines, intestinal microbiota, and fecal metabolome of the mice were analyzed. The alteration of the fecal metabolome was investigated in detail in EriB-treated EAP mice and confirmed by in vitro experiments.

RESULTS: EriB ameliorated significantly decreased prostate inflammation in EAP mice and promoted macrophage phenotype polarizing from M1 to M2. The gut microbiome was altered, and intestinal barrier damage was improved by EriB treatment. Furthermore, the enrichment of vitamin digestion and absorption pathways in the fecal metabolome revealed that vitamin D3 was altered by EriB. In vitro experiments confirmed that macrophage polarization from M1 to M2 was promoted by vitamin D3. Finally, fecal transplantation from EriB-treated mice markedly reduced inflammatory indicators and the macrophage M1/M2 ratio in pseudogerm-free EAP mice. In our study, the immune state of macrophage regulated by gut microbiota-mediated vitamin D3 alteration was first time revealed in EAP treatment.

CONCLUSIONS: EriB ameliorated in mice with EAP, the gut microbiota mediates vitamin D3 alterations to modulate macrophage phenotype polarizing from M1 to M2.}, } @article {pmid39515036, year = {2024}, author = {Sun, B and Hu, C and Li, J and Yang, Z and Chen, L}, title = {Interaction between young fecal transplantation and perfluorobutanesulfonate endocrine disrupting toxicity in aged recipients: An estrobolome perspective.}, journal = {Environment international}, volume = {193}, number = {}, pages = {109133}, doi = {10.1016/j.envint.2024.109133}, pmid = {39515036}, issn = {1873-6750}, abstract = {Transplanting young feces into the aged was found to effectively counteract the endocrine disrupting effects of perfluorobutanesulfonate (PFBS) pollutant, showing promise in the maintenance of healthy aging. However, the interactive mechanisms between young fecal transplantation and PFBS endocrine disruption during aging remain unclear. In this follow-up study, aged zebrafish were administered young donor feces and then exposed to environmentally relevant concentrations of PFBS (0 and 100 μg/L). Alterations in the holistic estrobolome along gut-liver axis were investigated. The results showed that PFBS singular exposure significantly increased blood estradiol concentration in the aged, inducing an estrogenic activity. Concentrations of other estrogen forms, including estrone and estriol, were also disrupted by PFBS. Interestingly, young fecal transplant effectively mitigated the estrogenic toxicity of PFBS and largely restored estrogen equilibrium. After PFBS exposure, the transcriptions of estrogen metabolic genes were consistently upregulated in aged livers, causing the accumulation of 2-methoxyestradiol-3-methylether metabolite. In contrast, aged livers coexposed to young fecal transplant and PFBS enhanced the glucuronidation process, successfully facilitating the elimination and detoxification of estrogen metabolites. In aged gut, PFBS exposure inhibited β-glucuronidase enzyme activity, implying the suppression of estrogen deconjugation and recycle. However, in the combined group, β-glucuronidase activity was significantly stimulated, thus reestablishing estrobolome dynamics. Overall, current findings provide mechanistic insights into the antagonistic interaction between young fecal transplant and PFBS on reproductive endocrinology. Gut microbiota manipulation appears appealing to maintain healthy aging progression albeit the interruption of environmental xenobiotics.}, } @article {pmid39513042, year = {2024}, author = {Park, KJ and Gao, Y}, title = {Gut-brain axis and neurodegeneration: mechanisms and therapeutic potentials.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1481390}, doi = {10.3389/fnins.2024.1481390}, pmid = {39513042}, issn = {1662-4548}, abstract = {This paper reviews the effects of gut microbiota in regulating neurodegenerative diseases through controlling gut-brain axis. Specific microbial populations and their metabolites (short-chain fatty acids and tryptophan derivatives) regulate neuroinflammation, neurogenesis and neural barrier integrity. We then discuss ways by which these insights lead to possible interventions - probiotics, prebiotics, dietary modification, and fecal microbiota transplantation (FMT). We also describe what epidemiological and clinical studies have related certain microbiota profiles with the courses of neurodegenerative diseases and how these impact the establishment of microbiome-based diagnostics and individualized treatment options. We aim to guide microbial ecology research on this key link to neurodegenerative disorders and also to highlight collaborative approaches to manage neurological health by targeting microbiome-related factors.}, } @article {pmid39510500, year = {2024}, author = {Scull, CE and Hu, Y and Jennings, S and Wang, G}, title = {Normalization of CF Immune System Reverses Intestinal Neutrophilic Inflammation and Significantly Improves the Survival of CF Mice.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {}, number = {}, pages = {101424}, doi = {10.1016/j.jcmgh.2024.101424}, pmid = {39510500}, issn = {2352-345X}, abstract = {BACKGROUND & AIMS: Cystic fibrosis (CF) is an autosomal recessive genetic disorder, affecting multiple organ systems. CF intestinal disease develops early, manifesting as intestinal bacterial overgrowth/dysbiosis, neutrophilic inflammation and obstruction. As unresolvable infection and inflammation reflect host immune deficiency, we sought to determine if the CF-affected immune system plays any significant role in CF intestinal disease pathogenesis.

METHODS: CF and sibling wild-type (WT) mice underwent reciprocal bone marrow transplantation. After immune reconstitution, their mortality, intestinal transit, fecal inflammatory markers, and mucosal immune cell composition were assessed. Moreover, reciprocal neutrophil transfusion was conducted to determine if neutrophil function affects intestinal movement. Furthermore, expression of induced nitric oxide synthase (iNOS) and production of nitric oxide (NO) in CF and WT neutrophils were compared. Lastly, specific iNOS inhibitor 1400W was tested to prevent CF intestinal obstruction.

RESULTS: Immune restoration in CF mice reversed the intestinal neutrophilic inflammation, improved the intestinal dysmotility, and rescued the mice from mortality. Transfusion of WT neutrophils into CF mice ameliorated the retarded bowel movement. CF neutrophils expressed significantly more iNOS and produced significantly more NO. Pharmaceutical blocking of iNOS significantly improved intestinal transit and survival of CF mice.

CONCLUSION: CF immune defect plays a critical role in CF intestinal disease development. Activation of iNOS in inflammatory cells produces excessive NO, slows the bowel movement, and facilitates intestinal paralysis and obstruction in CF. Thus, normalization of the CF immune system may offer a novel therapy to treat CF intestinal disease.}, } @article {pmid39510376, year = {2024}, author = {Huang, Y and You, Y and Wang, W and Chen, YH and Zhang, H and Li, QP and Liu, L and Tong, K and Sun, N and Hao, JR and Gao, C}, title = {Adenosine regulates depressive behavior in mice with chronic social defeat stress through gut microbiota.}, journal = {Neuropharmacology}, volume = {262}, number = {}, pages = {110209}, doi = {10.1016/j.neuropharm.2024.110209}, pmid = {39510376}, issn = {1873-7064}, abstract = {Major depressive disorder (MDD) is recognized as the most prevalent affective disorder worldwide. Metagenomic studies increasingly support a critical role for dysbiosis of gut microbiota in the development of depression. Previous studies have demonstrated that adenosine alleviates gut dysbiosis, suggesting that elevating adenosine levels could be a novel intervention for MDD; however, the mechanisms underlying this effect remain unclear. This study utilized 16S rRNA gene sequencing, fecal microbiota transplantation (FMT) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to test the hypothesis that increased adenosine alleviates depressive behaviors in male mice subjected to chronic social defeat stress (CSDS) through alterations to gut microbiota. The data showed that depression-susceptible (SUS) mice exhibited gut dysbiosis, and FMT from SUS mice increased depression-like behaviors in healthy recipients. In SUS mice, adenosine supplementation ameliorated both depression-like behaviors and abnormalities in gut microbiota, and co-administration of probiotics and adenosine not only mitigated depression-like behaviors but also enhanced gut barrier integrity. By including 83 depressed adolescents and 67 healthy controls, this study found that the level of short-chain fatty acids (SCFAs) in the depression group was reduced, this finding parallels reductions seen in SUS mice and in recipient mice after FMT from SUS donors. Conversely, supplementation with either adenosine or probiotics led increased SCFAs concentrations in the serum of SUS mice. These findings suggest that adenosine may alleviate depression-like behaviors in CSDS mice by modulating the gut microbiota. This effect is likely associated with increased serum SCFAs, metabolites produced by the gut microbiota, following adenosine supplementation.}, } @article {pmid39510013, year = {2024}, author = {Yang, D and Lv, G and Wu, Y and Guo, W and Wang, Y and Hu, J and Li, N and Zheng, F and Dai, Y and Pi, Z and Yue, H}, title = {Licorice-regulated gut-joint axis for alleviating collagen-induced rheumatoid arthritis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156203}, doi = {10.1016/j.phymed.2024.156203}, pmid = {39510013}, issn = {1618-095X}, abstract = {BACKGROUND: Rheumatoid arthritis (RA) is partially affected by the integrity of the intestinal barrier. Licorice (GC), a medicinal and food-related herb, exhibits potent anti-inflammatory activity; however, studies on its mechanisms of action in RA are limited.

METHOD: Using a bovine type-II collagen-induced arthritis rat model, this study examined how GC influences the gut-joint axis to decrease RA. The Th17/Treg cell ratios in the blood, colon, and joints were also measured. Metabolomics and 16S rRNA sequencing were applied to explore the effects of variations in gut flora and metabolites.

RESULTS: The arthropathological slices, inflammation markers, and joint inflammation index scores in the GC treatment group significantly differed from those in the CIA group. Studies on the effect of GC on the gut-joint axis showed changes in the levels of lipopolysaccharide and diamine oxidase, both directly associated with intestinal permeability. ZO-1, occludin, and claudin-1, three intestinal tight-junction proteins, may express themselves more when exposed to GC. By maintaining an appropriate Th17/Treg cell ratio in the blood, colon, and joints, GC may reduce impaired to the intestinal barrier. An imbalance in the intestinal microenvironment, caused by modifications in gut flora and endogenous substances, can damage the intestinal barrier. GC may modify the relative abundances of Papillibacter, Clostridium, Eubacterium, Helicobacter, Provotella, and Barnesiella during RA treatment by repairing the intestinal barrier. The metabolic differences were mainly related to primary bile acid biosynthesis, pyrimidine metabolism, steroid biosynthesis, biotin metabolism, and sphingolipid metabolism. A fecal microbiota transplantation experiment confirmed the involvement of the gut microbiota and its metabolites in GC-mediated RA therapy.

CONCLUSION: The results demonstrated that GC repairs the intestinal barrier and adjusts the gut-joint axis to manage immunological imbalance in RA.}, } @article {pmid39509684, year = {2024}, author = {L'Huillier, JC and Guo, WA}, title = {The always evolving diagnosis and management of Clostridioides difficile colitis: What you need to know.}, journal = {The journal of trauma and acute care surgery}, volume = {}, number = {}, pages = {}, doi = {10.1097/TA.0000000000004474}, pmid = {39509684}, issn = {2163-0763}, abstract = {The diagnosis, pharmacologic management, and surgical options for Clostridioides difficile infection (CDI) are rapidly evolving, which presents a challenge for the busy surgeon to remain up to date on the latest clinical guidelines. This review provides an evidence-based practical guide for CDI management tailored to the needs of surgeons and surgical intensivists. Historically, the diagnosis of CDI relied on slow cell culture cytotoxicity neutralization assays, but now, the rapidly resulting nucleic acid amplification tests and enzyme immunoassays have become mainstream. In terms of antibiotic therapy, metronidazole and oral vancomycin were the main "workhorse" antibiotics in the early 2000s, but large randomized controlled trials have now demonstrated that fidaxomicin produces superior results. Regarding surgical intervention, total abdominal colectomy was once the only procedure of choice; however, diverting loop ileostomy with colonic lavage is emerging as a viable alternative. Finally, novel adjuncts such as fecal microbiota transplantation and targeted therapy against toxin B (bezlotoxumab) are playing an increasingly important role in the management of CDI.}, } @article {pmid39508236, year = {2024}, author = {Shen, H and Zhang, C and Zhang, Q and Lv, Q and Liu, H and Yuan, H and Wang, C and Meng, F and Guo, Y and Pei, J and Yu, C and Tie, J and Chen, X and Yu, H and Zhang, G and Wang, X}, title = {Gut microbiota modulates depressive-like behaviors induced by chronic ethanol exposure through short-chain fatty acids.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {290}, pmid = {39508236}, issn = {1742-2094}, support = {82271931//National Natural Science Foundation of China/ ; 82101979//National Natural Science Foundation of China/ ; 2022-MS-220//Natural Science Foundation of Liaoning Province/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects/physiology ; Mice ; *Ethanol/toxicity/administration & dosage/pharmacology ; *Depression/chemically induced/metabolism ; *Fatty Acids, Volatile/metabolism ; Male ; *Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Anxiety/chemically induced ; Central Nervous System Depressants/pharmacology/toxicity ; }, abstract = {BACKGROUND: Chronic ethanol exposure (CEE) is recognized as an important risk factor for depression, and the gut-brain axis has emerged as a key mechanism underlying chronic ethanol exposure-induced anxiety and depression-like behaviors. Short-chain fatty acids (SCFAs), which are the key metabolites generated by gut microbiota from insoluble dietary fiber, exert protective roles on the central nervous system, including the reduction of neuroinflammation. However, the link between gut microbial disturbances caused by chronic ethanol exposure, production of SCFAs, and anxiety and depression-like behaviors remains unclear.

METHODS: Initially, a 90-day chronic ethanol exposure model was established, followed by fecal microbiota transplantation model, which was supplemented with SCFAs via gavage. Anxiety and depression-like behaviors were determined by open field test, forced swim test, and elevated plus-maze. Serum and intestinal SCFAs levels were quantified using GC-MS. Changes in related indicators, including the intestinal barrier, intestinal inflammation, neuroinflammation, neurotrophy, and nerve damage, were detected using Western blotting, immunofluorescence, and Nissl staining.

RESULTS: Chronic ethanol exposure disrupted with gut microbial homeostasis, reduced the production of SCFAs, and led to anxiety and depression-like behaviors. Recipient mice transplanted with fecal microbiota that had been affected by chronic ethanol exposure exhibited impaired intestinal structure and function, low levels of SCFAs, intestinal inflammation, activation of neuroinflammation, a compromised blood-brain barrier, neurotrophic defects, alterations in the GABA system, anxiety and depression-like behaviors. Notably, the negative effects observed in these recipient mice were significantly alleviated through the supplementation of SCFAs.

CONCLUSION: SCFAs not only mitigate damage to intestinal structure and function but also alleviate various lesions in the central nervous system, such as neuroinflammation, and reduce anxiety and depression-like behaviors, which were triggered by transplantation with fecal microbiota that had been affected by chronic ethanol exposure, adding more support that SCFAs serve as a bridge between the gut and the brain.}, } @article {pmid39502702, year = {2024}, author = {Han, YJ and Kim, S and Shin, H and Kim, HW and Park, JD}, title = {Protective effect of gut microbiota restored by fecal microbiota transplantation in a sepsis model in juvenile mice.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1451356}, pmid = {39502702}, issn = {1664-3224}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Sepsis/therapy/microbiology/immunology ; Mice ; *Disease Models, Animal ; Male ; Cytokines/metabolism/blood ; Anti-Bacterial Agents/therapeutic use ; Dysbiosis/therapy ; Feces/microbiology ; Mice, Inbred C57BL ; }, abstract = {INTRODUCTION: Restoring a balanced, healthy gut microbiota through fecal microbiota transplantation (FMT) has the potential to be a treatment option for sepsis, despite the current lack of evidence. This study aimed to investigate the effect of FMT on sepsis in relation to the gut microbiota through a sepsis model in juvenile mice.

METHODS: Three-week-old male mice were divided into three groups: the antibiotic treatment (ABX), ABX-FMT, and control groups. The ABX and ABX-FMT groups received antibiotics for seven days. FMT was performed through oral gavage in the ABX-FMT group over the subsequent seven days. On day 14, all mice underwent cecal ligation and puncture (CLP) to induce abdominal sepsis. Blood cytokine levels and the composition of fecal microbiota were analyzed, and survival was monitored for seven days post-CLP.

RESULTS: Initially, the fecal microbiota was predominantly composed of the phyla Bacteroidetes and Firmicutes. After antibiotic intake, an extreme predominance of the class Bacilli emerged. FMT successfully restored antibiotic-induced fecal dysbiosis. After CLP, the phylum Bacteroidetes became extremely dominant in the ABX-FMT and control groups. Alpha diversity of the microbiota decreased after antibiotic intake, was restored after FMT, and decreased again following CLP. In the ABX group, the concentrations of interleukin-1β (IL-1β), IL-2, IL-6, IL-10, granulocyte macrophage colony-stimulating factor, tumor necrosis factor-α, and C-X-C motif chemokine ligand 1 increased more rapidly and to a higher degree compared to other groups. The survival rate in the ABX group was significantly lower (20.0%) compared to other groups (85.7%).

CONCLUSION: FMT-induced microbiota restoration demonstrated a protective effect against sepsis. This study uniquely validates the effectiveness of FMT in a juvenile mouse sepsis model, offering potential implications for clinical research in critically ill children.}, } @article {pmid39502523, year = {2024}, author = {Anouti, A and Kerr, TA and Mitchell, MC and Cotter, TG}, title = {Advances in the management of alcohol-associated liver disease.}, journal = {Gastroenterology report}, volume = {12}, number = {}, pages = {goae097}, pmid = {39502523}, issn = {2052-0034}, abstract = {Alcohol-associated liver disease (ALD) is a significant global health challenge, encompassing a spectrum from steatotic liver disease to cirrhosis and alcohol-associated hepatitis, and contributed to 25% of global cirrhosis deaths in 2019. The identification of both modifiable (e.g. heavy drinking, metabolic syndromes) and non-modifiable risk factors (e.g. genetic predispositions) is crucial for effective disease management. Alcohol use assessment and treatment, by using both behavioral therapy and pharmacotherapeutic modalities, nutrition support, and optimization of liver disease modifiers, form the cornerstone of management. Advances in medical therapies, such as fecal microbiota transplantation and novel agents such as IL-22, are being explored for their therapeutic potential. A unifying theme in ALD care is the need for a personalized approach to management, accounting for the spectrum of the disease and individual patient characteristics, to tailor interventions effectively. Finally, it is essential to address the challenges to effective ALD treatment, including socioeconomic, logistical, and stigma-related barriers, to improve patient outcomes. This review discusses the current knowledge on ALD, including epidemiology, pathophysiology, risk factors, and management strategies, highlighting the critical role of integrated care models.}, } @article {pmid39500537, year = {2024}, author = {Slizovskiy, IB and Bonin, N and Bravo, JE and Ferm, PM and Singer, J and Boucher, C and Noyes, NR}, title = {Factors impacting target-enriched long-read sequencing of resistomes and mobilomes.}, journal = {Genome research}, volume = {}, number = {}, pages = {}, doi = {10.1101/gr.279226.124}, pmid = {39500537}, issn = {1549-5469}, abstract = {We investigated the efficiency of target-enriched long-read sequencing (TELSeq) for detecting antimicrobial resistance genes (ARGs) and mobile genetic elements (MGEs) within complex matrices. We aimed to overcome limitations associated with traditional antimicrobial resistance (AMR) detection methods, including short-read shotgun metagenomics, which can lack sensitivity, specificity, and the ability to provide detailed genomic context. By combining biotinylated probe-based enrichment with long-read sequencing, we facilitated the amplification and sequencing of ARGs, eliminating the need for bioinformatic reconstruction. Our experimental design included replicates of human fecal microbiota transplant material, bovine feces, pristine prairie soil, and a mock human gut microbial community, allowing us to examine variables including genomic DNA input and probe set composition. Our findings demonstrated that TELSeq markedly improves the detection rates of ARGs and MGEs compared to traditional sequencing methods, underlining its potential for accurate AMR monitoring. A key insight from our research is the importance of incorporating mobilome profiles to better predict the transferability of ARGs within microbial communities, prompting a recommendation for the use of combined ARG-MGE probe sets for future studies. We also reveal limitations for ARG detection from low-input workflows, and describe the next steps for ongoing protocol refinement to minimize technical variability and expand utility in clinical and public health settings. This effort is part of our broader commitment to advancing methodologies that address the global challenge of AMR.}, } @article {pmid39500027, year = {2024}, author = {Hua, Y and Zhou, C and Fan, R and Benazzouz, S and Shen, J and Xiao, R and Ma, W}, title = {Altered intestinal microbiota induced by high-fat diets affect cognition differently in mice.}, journal = {Nutrition research (New York, N.Y.)}, volume = {132}, number = {}, pages = {67-84}, doi = {10.1016/j.nutres.2024.09.019}, pmid = {39500027}, issn = {1879-0739}, abstract = {The role of the gut microbiota in the association between high-fat diet and cognition is not clear. We hypothesized that a high-fat diet may influence cognition by altering the intestinal microbiota. Fecal microbiota isolated from male C57BL/6J mice feeding on various high-fat diets and a control basic diet were transplanted to antibiotic-treated recipient mice. The measurement of weight and plasma lipids, novel object recognition test, 16S rRNA gene sequencing of feces, and hematoxylin-eosin staining of the hippocampal cornu ammonis 1 and cornu ammonis 3 areas were performed for all mice. Compared with those in the control and n-3 polyunsaturated fatty acid (n-3 PUFA) groups, donor obese mice fed with diets high in long-chain saturated fatty acids, n-6 polyunsaturated fatty acids (n-6 PUFAs), and trans fatty acids exhibited significant cognitive impairment (all P < .05). There were fewer neurons in the hippocampal area in the n-6 PUFA group than in the n-3 PUFA group (P < .05). Similar effect on cognition and neurons in hippocampal area in corresponding recipient mice were revealed after fecal microbiota transplantation. In addition, the composition of intestinal microbiota differed among recipient mice after fecal microbiota transplantation from donor mice. According to these results, it was concluded that diets rich in long-chain saturated fatty acids, n-6 PUFAs, and trans fatty acids may lead to cognitive impairment by damaging the structure of the hippocampus through influencing the intestinal microbiota in mice, whereas a diet high in n-3 PUFAs may exhibit a beneficial effect.}, } @article {pmid39499189, year = {2024}, author = {Ghani, R and Chrysostomou, D and Roberts, LA and Pandiaraja, M and Marchesi, JR and Mullish, BH}, title = {Faecal (or intestinal) microbiota transplant: a tool for repairing the gut microbiome.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2423026}, pmid = {39499189}, issn = {1949-0984}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Gastrointestinal Microbiome ; *Clostridium Infections/therapy/microbiology ; Animals ; Feces/microbiology ; Clostridioides difficile/physiology ; Treatment Outcome ; Donor Selection ; }, abstract = {Faecal/intestinal microbiota transplant (FMT/IMT) is an efficacious treatment option for recurrent Clostridioides difficile infection, which has prompted substantial interest in FMT's potential role in the management of a much broader range of diseases associated with the gut microbiome. Despite its promise, the success rates of FMT in these other settings have been variable. This review critically evaluates the current evidence on the impact of clinical, biological, and procedural factors upon the therapeutic efficacy of FMT, and identifies areas that remain nebulous. Due to some of these factors, the optimal therapeutic approach remains unclear; for example, the preferred timing of FMT administration in a heavily antibiotic-exposed hematopoietic cell transplant recipient is not standardized, with arguments that can be made in alternate directions. We explore how these factors may impact upon more informed selection of donors, potential matching of donors to recipients, and aspects of clinical care of FMT recipients. This includes consideration of how gut microbiome composition and functionality may strategically inform donor selection criteria. Furthermore, we review how the most productive advances within the FMT space are those where clinical and translational outcomes are assessed together, and where this model has been used productively in recent years to better understand the contribution of the gut microbiome to human disease, and start the process toward development of more targeted microbiome therapeutics.}, } @article {pmid39495286, year = {2024}, author = {Zhang, H and Zhou, W and Gao, P and Li, Z and Li, C and Li, J and Bian, J and Gong, L and He, C and Han, L and Wang, M}, title = {Ellagic Acid Protects against Alcohol-Related Liver Disease by Modulating the Hepatic Circadian Rhythm Signaling through the Gut Microbiota-NPAS2 Axis.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {45}, pages = {25103-25117}, doi = {10.1021/acs.jafc.4c06992}, pmid = {39495286}, issn = {1520-5118}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Circadian Rhythm ; Animals ; *Basic Helix-Loop-Helix Transcription Factors/metabolism/genetics ; *Liver/metabolism/drug effects ; *Liver Diseases, Alcoholic/metabolism/prevention & control/microbiology/drug therapy ; Mice ; Male ; Humans ; *Ellagic Acid/pharmacology ; *Mice, Inbred C57BL ; Signal Transduction/drug effects ; Nerve Tissue Proteins/genetics/metabolism ; Bacteria/classification/genetics/metabolism/isolation & purification/drug effects ; Protective Agents/pharmacology/administration & dosage ; }, abstract = {Alcohol-related liver disease (ALD) encompasses a spectrum of hepatic disorders resulting from alcohol abuse, which constitutes the predominant etiology of morbidity and mortality associated with hepatic pathologies globally. Excessive alcohol consumption disrupts the integrity of the intestinal barrier and perturbs the balance of gut microbiota, thereby facilitating the progression of ALD. Ellagic acid (EA) has been extensively reported to be an effective intervention for alleviating liver symptoms. However, the target molecules of EA in improving ALD and its underlying mechanism remain elusive. First, our study indicates that EA ameliorated ALD through the hepatic circadian rhythm signaling by up-regulating neuronal PAS domain protein 2 (NPAS2). Furthermore, analysis of the intestinal microbiome showed that EA significantly enhanced the abundance of beneficial bacteria, which was positively correlated with NPAS2 expression and negatively correlated with liver injury. Finally, antibiotic treatment and fecal microbiota transplantation (FMT) experiments established a causal relationship between the reshaped microbiota and NPAS2 in the amelioration of ALD. In summary, our study demonstrates novel evidence that EA attenuated ALD by modulating the hepatic circadian rhythm signaling pathway via the gut microbiota-NPAS2 axis, providing valuable insights for EA and microbiome-targeted interventions against ALD.}, } @article {pmid39494101, year = {2024}, author = {Singh, AK and Durairajan, SSK and Iyaswamy, A and Williams, LL}, title = {Elucidating the role of gut microbiota dysbiosis in hyperuricemia and gout: Insights and therapeutic strategies.}, journal = {World journal of gastroenterology}, volume = {30}, number = {40}, pages = {4404-4410}, pmid = {39494101}, issn = {2219-2840}, mesh = {*Dysbiosis ; Humans ; *Gout/microbiology/therapy/complications ; *Gastrointestinal Microbiome/physiology ; *Hyperuricemia/microbiology/blood/therapy/diagnosis ; *Uric Acid/blood/metabolism ; *Probiotics/therapeutic use/administration & dosage ; *Prebiotics/administration & dosage ; Gout Suppressants/therapeutic use ; }, abstract = {Hyperuricemia (HUA) is a condition associated with a high concentration of uric acid (UA) in the bloodstream and can cause gout and chronic kidney disease. The gut microbiota of patients with gout and HUA is significantly altered compared to that of healthy people. This article focused on the complex interconnection between alterations in the gut microbiota and the development of this disorder. Some studies have suggested that changes in the composition, diversity, and activity of microbes play a key role in establishing and progressing HUA and gout pathogenesis. Therefore, we discussed how the gut microbiota contributes to HUA through purine metabolism, UA excretion, and intestinal inflammatory responses. We examined specific changes in the composition of the gut microbiota associated with gout and HUA, highlighting key bacterial taxa and the metabolic pathways involved. Additionally, we discussed the effect of conventional gout treatments on the gut microbiota composition, along with emerging therapeutic approaches that target the gut microbiome, such as the use of probiotics and prebiotics. We also provided insights into a study regarding the gut microbiota as a possible novel therapeutic intervention for gout treatment and dysbiosis-related diagnosis.}, } @article {pmid39493843, year = {2024}, author = {Duan, X and Nie, Y and Xie, X and Zhang, Q and Zhu, C and Zhu, H and Chen, R and Xu, J and Zhang, J and Yang, C and Yu, Q and Cai, K and Wang, Y and Tian, W}, title = {Sex differences and testosterone interfere with the structure of the gut microbiota through the bile acid signaling pathway.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1421608}, pmid = {39493843}, issn = {1664-302X}, abstract = {BACKGROUND: The gut microbiome has a significant impact on human wellness, contributing to the emergence and progression of a range of health issues including inflammatory and autoimmune conditions, metabolic disorders, cardiovascular problems, and psychiatric disorders. Notably, clinical observations have revealed that these illnesses can display differences in incidence and presentation between genders. The present study aimed to evaluate whether the composition of gut microbiota is associated with sex-specific differences and to elucidate the mechanism.

METHODS: 16S-rRNA-sequencing technology, hormone analysis, gut microbiota transplantation, gonadectomy, and hormone treatment were employed to investigate the correlation between the gut microbiome and sex or sex hormones. Meanwhile, genes and proteins involved bile acid signaling pathway were analyzed both in the liver and ileum tissues.

RESULTS: The composition and diversity of the microbiota from the jejunum and feces and the level of sex hormones in the serum differed between the sexes in young and middle-aged Sprague Dawley (SD) rats. However, no similar phenomenon was found in geriatric rats. Interestingly, whether in young, middle-aged, or old rats, the composition of the microbiota and bacterial diversity differed between the jejunum and feces in rats. Gut microbiota transplantation, gonadectomy, and hormone replacement also suggested that hormones, particularly testosterone (T), influenced the composition of the gut microbiota in rats. Meanwhile, the mRNA and protein level of genes involved bile acid signaling pathway (specifically SHP, FXR, CYP7A1, and ASBT) exhibited gender-specific differences, and T may play a significant role in mediating the expression of this pathway.

CONCLUSION: Sex-specific differences in the structure of the gut microbiota are mediated by T through the bile acid signaling pathway, pointing to potential targets for disease prevention and management techniques by indicating that sex differences and T levels may alter the composition of the gut microbiota via the bile acid signaling pathway.}, } @article {pmid39493719, year = {2024}, author = {Wang, L and Yu, L and Liu, Z and Che, C and Wang, Y and Zhao, Y and Zhu, M and Yang, G and Cao, A}, title = {FMT intervention decreases urine 5-HIAA levels: a randomized double-blind controlled study.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1411089}, pmid = {39493719}, issn = {2296-858X}, abstract = {BACKGROUND: Autism spectrum disorder (ASD) is often linked to gastrointestinal issues and altered serotonin metabolism. Emerging evidence suggests gut microbiota influence both, with fecal microbiota transplantation (FMT) offering a potential therapeutic approach. However, its impact on serotonin metabolism and ASD symptoms is not well understood. In this study, we aimed to evaluate the clinical effects of FMT and examine changes in specific urinary metabolites in children with ASD.

METHODS: A randomized double-blind controlled trial was performed to evaluate the clinical effects of FMT on GI and ASD-related symptoms. Gastrointestinal symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS), and the ASD-related symptoms were assessed using the Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), and Social Responsiveness Scale (SRS) scores. Urinary metabolites were analyzed by homogeneous enzyme immunoassay using commercially available kits.

RESULTS: Significant improvements in GI and core ASD symptoms were observed following FMT intervention. The average GSRS scores decreased from 30.17 (before) to 19 (after; p < 0.0001), CARS scores decreased from 36.22 to 33.33 (p < 0.0001), SRS scores decreased from 151.17 to 137.5 (p = 0.0002), and the ABC scores decreased 76.39 to 53.17 (p < 0.0001) in the FMT group. However, in the placebo group, GSRS, CARS, and SRS scores showed no significant changes, while ABC scores decreased from 72 to 58.75 (p = 0.034). The FMT group also showed a significant reduction in urinary 5-hydroxyindoleacetic acid (5-HIAA) levels from 8.6 to 7.32 mg/L (p = 0.022), while other metabolites showed no significant changes.

CONCLUSION: FMT is a safe and effective treatment for improving GI and core symptoms in children with ASD, with 5-HIAA showing potential as a urinary biomarker for treatment response.}, } @article {pmid39492827, year = {2024}, author = {Jiang, L and Fan, JG}, title = {Gut microbiota in gastrointestinal diseases: Insights and therapeutic strategies.}, journal = {World journal of gastroenterology}, volume = {30}, number = {39}, pages = {4329-4332}, pmid = {39492827}, issn = {2219-2840}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Dysbiosis ; Inflammatory Bowel Diseases/microbiology/therapy ; Hypertension, Portal/microbiology/therapy/diagnosis/etiology ; Liver/microbiology/metabolism ; Gastrointestinal Diseases/microbiology/therapy ; Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {Considering the bidirectional crosstalk along the gut-liver axis, gut-derived microorganisms and metabolites can be released into the liver, potentially leading to liver injury. In this editorial, we comment on several studies published in the recent issue of the World Journal of Gastroenterology. We focus specifically on the roles of gut microbiota in selected gastrointestinal (GI) diseases that are prevalent, such as inflammatory bowel disease, metabolic dysfunction-associated steatotic liver disease, and hepatitis B virus-related portal hypertension. Over the past few decades, findings from both preclinical and clinical studies have indicated an association between compositional and metabolic changes in the gut microbiota and the pathogenesis of the aforementioned GI disorders. However, studies elucidating the mechanisms underlying the host-microbiota interactions remain limited. The purpose of this editorial is to summarize current findings and provide insights regarding the context-specific roles of gut microbiota. Ultimately, the discovery of microbiome-based biomarkers may facilitate disease diagnosis and the development of personalized medicine.}, } @article {pmid39492826, year = {2024}, author = {Kong, MW and Yu, Y and Wang, P and Wan, Y and Gao, Y and Zhang, CX}, title = {Advances in the research of intestinal fungi in Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {30}, number = {39}, pages = {4318-4323}, pmid = {39492826}, issn = {2219-2840}, mesh = {*Crohn Disease/microbiology/immunology ; Humans ; *Gastrointestinal Microbiome ; Animals ; *Dysbiosis/microbiology ; *Fecal Microbiota Transplantation ; *Fungi/pathogenicity ; *Disease Models, Animal ; Intestines/microbiology ; Mice ; Adipose Tissue/microbiology ; Mesentery/microbiology ; }, abstract = {This article reviews of the original research published by Wu et al in the World Journal of Gastroenterology, delving into the pivotal role of the gut microbiota in the pathogenesis of Crohn's disease (CD). Insights were gained from fecal microbiota transplantation (FMT) in mouse models, revealing the intricate interplay between the gut microbiota, mesenteric adipose tissue (MAT), and creeping fat. The study uncovered the characteristics of inflammation and fibrosis in the MAT and intestinal tissues of patients with CD; moreover, through the FMT mouse model, it observed the impact of samples from healthy patients and those with CD on symptoms. The pathogenesis of CD is complex, and its etiology remains unclear; however, it is widely believed that gut microbiota dysbiosis plays a significant role. Recently, with the development and application of next-generation sequencing technology, research on the role of fungi in the pathogenesis and chronicity of CD has deepened. This editorial serves as a supplement to the research by Wu et al who discussed advances related to the study of fungi in CD.}, } @article {pmid39491642, year = {2024}, author = {Shimokawa, C}, title = {The gut microbiome-helminth-immune axis in autoimmune diseases.}, journal = {Parasitology international}, volume = {104}, number = {}, pages = {102985}, doi = {10.1016/j.parint.2024.102985}, pmid = {39491642}, issn = {1873-0329}, abstract = {The global prevalence of autoimmune diseases has surged in recent decades. Consequently, environmental triggers have emerged as crucial contributors to autoimmune diseases, equally relevant to classical risk factors, such as genetic polymorphisms, infections, and smoking. Sequencing-based approaches have demonstrated distinct gut microbiota compositions in individuals with autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, type 1 diabetes mellitus (T1D), and systemic lupus erythematosus, compared to healthy controls. Furthermore, fecal microbiota transplantation and microbial inoculation experiments have supported the hypothesis that alterations in the gut microbiota can influence autoimmune responses and disease outcomes. Herein, we propose that intestinal helminths may serve as a critical factor in inducing alterations in the gut microbiota. The concept of helminth-mediated suppression of autoimmune diseases in humans is supported by substantial evidence, aligning with the long-standing "hygiene hypothesis." This review focused on T1D to explore the interactions between parasites, gut microbiota, and the immune system-a topic that remains a black box within this intricate triangular relationship.}, } @article {pmid39491609, year = {2024}, author = {Chen, D and Xie, J and Chen, X and Qin, B and Kong, D and Luo, J}, title = {Fecal microbiota transplantation alleviates neuronal Apoptosis, necroptosis and M1 polarization of microglia after ischemic stroke.}, journal = {Neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neuroscience.2024.10.053}, pmid = {39491609}, issn = {1873-7544}, abstract = {OBJECTIVE: This study aims to delve into the mechanisms underlying the improvement of neurological function in rats with ischemic stroke through fecal microbiota transplantation.

METHODS: A total of fifty male Sprague-Dawley rats were categorized into three groups: sham surgery, model, and fecal transplantation. We assessed behavioral and pathological alterations in the rats using modified neurological function scoring and TTC staining. Additionally, Western blot and immunofluorescence techniques were employed to examine the expression levels of RIP1, RIP3, MLKL, p-MLKL, Bcl-2, Bax, and cleaved caspase-3 in neurons of ischemic brain tissue, while iNOS and Arg1 were analyzed to evaluate microglial polarization.

RESULTS: The fecal transplantation group exhibited a decline in neurological function score compared to the model group, accompanied by a reduction in infarct volume (P < 0.05). Relative to the sham surgery group, the model group displayed a significant increase in the expression levels of necroptosis-related proteins RIP1, RIP3, p-MLKL, apoptotic proteins Bax and cleaved caspase-3, and the M1 microglial cell marker iNOS in ischemic brain tissue, while Bcl-2 expression was notably decreased (P < 0.05). Conversely, compared to the model group, the fecal transplantation group demonstrated decreased expression levels of RIP1, RIP3, p-MLKL, Bax, cleaved caspase-3, and iNOS, along with increased expression of Bcl-2.

CONCLUSION: Fecal microbiota transplantation presents a promising avenue for enhancing neurological function in rats with ischemic stroke by inhibiting neuronal apoptosis, necroptosis, and M1 polarization of microglial cells.}, } @article {pmid39491142, year = {2023}, author = {Zhao, T and Lv, J and Peng, M and Mi, J and Zhang, S and Liu, J and Chen, T and Sun, Z and Niu, R}, title = {Fecal microbiota transplantation and short-chain fatty acids improve learning and memory in fluorosis mice by BDNF-PI3K/AKT pathway.}, journal = {Chemico-biological interactions}, volume = {}, number = {}, pages = {110786}, doi = {10.1016/j.cbi.2023.110786}, pmid = {39491142}, issn = {1872-7786}, abstract = {Fluoride, an environmental toxicant, not only arouses intestinal microbiota dysbiosis, but also causes neuronal apoptosis and a decline in learning and memory ability. The purpose of this study was to explore whether fecal microbiota transplantation (FMT) from healthy mice and bacteria-derived metabolites short-chain fatty acids (SCFAs) supplement protect against fluoride-induced learning and memory impairment. Results showed that FMT reversed the elevated percentage of working memory errors (WME) and reference memory errors (RME) in fluorosis mice during the eight-arm maze test. Nissl and TUNEL staining presented that fluoride led to a decreased proportion of Nissl bodies area in the hippocampal CA3 region and an increased apoptotic ratio of nerve cells in CA1, CA3 and DG areas, whereas FMT alleviated those pathological damages. Moreover, the expressions of mRNA in hippocampal BDNF, PDK1, AKT, Bcl-2, and Bcl-xL were downregulated in mice exposed to fluoride, but the levels of PI3K, Bax, Bak, and Caspase-7 mRNA were upregulated. NaF treatment had an increase in PI3K and Caspase-3 protein levels and reduced the expressions of these four proteins, including BDNF, p-PI3K, AKT and p-AKT. By contrast, FMT enhanced the expression of BDNF and thus activated the PI3K/AKT pathway. Besides, the 16S rRNA sequencing revealed that fluoride caused a reduction in certain SCFA producers in the colon as evidenced by a decline in Erysipelatoclostridiaceae, and a downward trend in Akkermansia, Blautia and Alistipes. However, the disordered gut microbiome was restored via frequent FMT. Of note, SCFAs administration also increased BDNF levels and regulated its downstream pathways, which contributed to cell survival and learning and memory function recovery. In conclusion, FMT and SCFAs may activate the BDNF-PI3K/AKT pathway to play an anti-apoptotic role and ultimately improve learning and memory deficits in fluorosis mice.}, } @article {pmid39490563, year = {2024}, author = {Wu, J and Zhang, R and Yin, Z and Chen, X and Mao, R and Zheng, X and Yuan, M and Li, H and Lu, Y and Liu, S and Gao, X and Sun, Q}, title = {Gut microbiota-driven metabolic alterations reveal the distinct pathogenicity of chemotherapy-induced cachexia in gastric cancer.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {107476}, doi = {10.1016/j.phrs.2024.107476}, pmid = {39490563}, issn = {1096-1186}, abstract = {Cachexia affects approximately 50-80% of advanced cancer patients, particularly those with gastric cancer (GC). Therefore, early detection of cachexia is essential to prevent its progression. Targeting the gut microbiota may be a promising approach for preventing and treating cachexia in patients with GC. Chemotherapy significantly reduced gut microbiota diversity in GC patients. Specifically, the abundance of bacterial genera such as Bacteroides, Streptococcus, and Prevotella was increased in the gut of patients postchemotherapy, which was closely associated with the development of cachexia. Serum metabolic analysis revealed a strong link between specific microbes and metabolite in patients with chemotherapy-induced GC cachexia. We further constructed a random forest model based on the top 6 genera in terms of abundance for the prediction of chemotherapy-related GC cachexia development; this model had an area under the receiver operating characteristic curve (AUC) of 93.5% [95% confidence interval (CI), 86.6%-100%], with a specificity and accuracy above 75%. Additionally, we identified Enterotoxin Bacteroides fragilis (ETBF) as a key factor in chemotherapy-induced GC cachexia. In an in vivo GC model, the colonization of ETBF in the intestines of mice significantly accelerated the muscle and adipose tissue consumption induced by chemotherapy, resulting in cachexia symptoms. Furthermore, ETBF damaged the intestinal mucosal barrier by disrupting cell connections and attracting M1 macrophages, which advances GC cachexia. In conclusion, our findings indicate that gut microbiota imbalance is crucial in GC cachexia development, suggesting potential biomarkers for early diagnosis. Clinical trial registration: http://www.chictr.org.cn, Identification No: ChiCTR2200064547.}, } @article {pmid39489477, year = {2024}, author = {Chen, W and Liu, Y and Pu, J and Gui, S and Wang, D and Zhong, X and Tao, W and Chen, X and Chen, X and Chen, Y and Zhao, L and Wu, Q and Chen, X and Zhang, Y and Xie, A and Xie, P}, title = {Comparative transcriptional analyses of the striatum in the chronic social defeat stress model in C57BL/6J male mice and the gut microbiota-dysbiosis model in Kumming mice.}, journal = {Neuroscience}, volume = {562}, number = {}, pages = {217-226}, doi = {10.1016/j.neuroscience.2024.10.057}, pmid = {39489477}, issn = {1873-7544}, abstract = {Depression is a complex disorder with multiple contributing factors, and chronic stress has previously been recognized as a major causative factor, while gut microbes have also been found to be involved in depression recently. However, gene expression in depression models with different etiologies is unclear. Here, we compared the transcriptomes of the striatum in chronic social defeat stress (CSDS) model of C57BL/6J male mice and fecal microbiota transplant (FMT) model of Kumming male mice. We found that the proportion of shared differentially expressed genes (DEGs) between the two models was only 24 %. The specific DEGs of FMT model were enriched in immune and inflammatory, and are associated with changes in vascular and ciliated ependymal cells. The specific DEGs of CSDS model were enriched in neuron and synapse. The results of network analysis suggested the expression patterns and biological function of depressive-like behaviors-related modules in the two models are different. Further, the alternative splicing events of CSDS are more than FMT. Our results suggested models of depression induced by different etiologies differ significantly in gene expression and biological function. Our study also suggested us to pay attention to the characteristics of models of depression of different etiologies and provided a more comprehensive understanding of the heterogeneity of depression.}, } @article {pmid39487198, year = {2024}, author = {Chatthanathon, P and Leelahavanichkul, A and Cheibchalard, T and Wilantho, A and Hirankarn, N and Somboonna, N}, title = {Comparative time-series analyses of gut microbiome profiles in genetically and chemically induced lupus-prone mice and the impacts of fecal transplantation.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {26371}, pmid = {39487198}, issn = {2045-2322}, support = {CU_FRB65_hea(68)_131_23_61//Thailand Science Research and Innovation Fund Chulalongkorn University/ ; }, mesh = {Animals ; *Lupus Erythematosus, Systemic/microbiology/immunology/genetics ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Mice ; *Receptors, IgG/genetics ; *Dysbiosis/microbiology ; *Disease Models, Animal ; Female ; Feces/microbiology ; Mice, Knockout ; Terpenes ; Mice, Inbred C57BL ; }, abstract = {Although the association between gut dysbiosis (imbalance of the microbiota) in systemic lupus erythematosus (SLE) is well-known, the simultaneous exploration in gut dysbiosis in fecal and different intestinal sections before and after lupus onset (at 2, 4, 6, 8, and 10 months old) resulting from the loss of inhibitory Fc gamma receptor IIb (FcGIIb) and pristane induction have never been conducted. Anti-dsDNA (an important lupus autoantibody) and proteinuria developed as early as 6 months old in both models, with higher levels in FcGRIIb deficient (FcGRIIb-/-) mice. Compared to the healthy control at 2 and 4 months, the lupus mice (both FcGRRIIb-/- and pristane) and healthy mice at 6 months old demonstrated an alteration as indicated by the Shannon alpha diversity index, highlighting influences of lupus- and age-induced dysbiosis, respectively. Non-metric multidimensional scaling (NMDS) revealed that the fecal microbiota of FcGRIIb-/- mice were distinct from the age-matched healthy control at all timepoints (at 6 month, p < 0.05), while pristane mice showed divergence at only some timepoints. Analyses of different intestinal sections revealed similarity among microbiota in the cecum, colon, and feces, contrasting with those in the small intestines (duodenum, jejunum, and ileum). Subtle differences were found between FcGRIIb-/- and pristane mice in feces and the intestinal sections as assessed by several analyses, for examples, the similar or dissimilar distances (NMDS), the neighbor-joining clustering, and the potential metabolisms (KEGG pathway analysis). Due to the differences between the gut microbiota (feces and intestinal sections) in the lupus mice and the healthy control, rebalancing of the microbiota using rectal administration of feces from the healthy control (fecal transplantation; FMT) to 7-month-old FcGIIb-/- mice (the established lupus; positive anti-dsDNA and proteinuria) was performed. In comparison to FcGRIIb-/- mice without FMT, FMT mice (more effect on the female than the male mice) showed the lower anti-dsDNA levels with similar fecal microbiome diversity (16s DNA gene copy number) and microbiota patterns to the healthy control. In conclusion, gut microbiota (feces and intestinal sections) of lupus mice (FcGRIIb-/- and pristane) diverged from the control as early as 4-6 months old, correlating with lupus characteristics (anti-dsDNA and proteinuria). The different gut microbiota in FcGRIIb-/- and pristane suggested a possible different gut microbiota in lupus with various molecular causes. Furthermore, FMT appeared to mitigate gut dysbiosis and reduce anti-dsDNA, supporting the benefit of the rebalancing gut microbiota in lupus, with more studies are warranted.}, } @article {pmid39488230, year = {2024}, author = {Rubak, T and Baunwall, SMD and Gregersen, M and Paaske, SE and Asferg, M and Barat, I and Secher-Johnsen, J and Riis, MG and Rosenbæk, JB and Hansen, TK and Ørum, M and Steves, CJ and Veilbæk, H and Hvas, CL and Damsgaard, EMS}, title = {Early geriatric assessment and management in older patients with Clostridioides difficile infection in Denmark (CLODIfrail): a randomised trial.}, journal = {The lancet. Healthy longevity}, volume = {}, number = {}, pages = {100648}, doi = {10.1016/j.lanhl.2024.100648}, pmid = {39488230}, issn = {2666-7568}, abstract = {BACKGROUND: Clostridioides difficile infection causes diarrhoea and colitis. Older patients with C difficile infection are often frail and have comorbidities, leading to high mortality rates. The frailty burden in older people might restrict access to treatments, such as C difficile infection-specific antibiotics and faecal microbiota transplantation. We aimed to investigate the clinical effects of early comprehensive geriatric assessment (CGA) and frailty evaluation, including home visits and assessment for faecal microbiota transplantation, in older patients with C difficile infection.

METHODS: In this randomised, quality improvement trial with a pragmatic design, patients from the Central Denmark Region aged 70 years or older with a positive PCR test for C difficile toxin were randomly assigned (1:1) to CGA or standard care, both with equal access to faecal microbiota transplantation. Patients and investigators were unmasked to treatment. The primary outcome was 90-day mortality, and was compared in the study groups according to the intention-to-treat principle. The study is registered with ClinicalTrials.gov, NCT05447533.

FINDINGS: Between Sept 1, 2022, and May 3, 2023, we randomly assigned 217 patients to CGA (n=109) or standard care (n=108). The median patient age was 78 years (IQR 74-84). 116 (53%) of 217 patients were female and 101 (47%) were male. 16 (15%; 95% CI 9-23) of 109 patients in the CGA group and 22 (20%; 14-29) of 108 patients in the standard-care group died within 90 days (odds ratio 0·66, 95% CI 0·32-1·38. No serious adverse events or deaths related to patient assessment or faecal microbiota transplantation were recorded in either group. Deaths directly attributable to C difficile infection were lower in the CGA group (seven [44%] of 16 deaths vs 18 [82%] of 22 deaths in the standard-care group; p=0·020).

INTERPRETATION: Older patients who received CGA had a 90-day mortality rate similar to that of patients who received standard care, but with fewer deaths directly attributable to C difficile infection.

FUNDING: Innovation Fund Denmark, Novo Nordisk Foundation, and Helsefonden.}, } @article {pmid39486524, year = {2024}, author = {Kapoor, B and Biswas, P and Gulati, M and Rani, P and Gupta, R}, title = {Gut microbiome and Alzheimer's disease: what we know and what remains to be explored.}, journal = {Ageing research reviews}, volume = {}, number = {}, pages = {102570}, doi = {10.1016/j.arr.2024.102570}, pmid = {39486524}, issn = {1872-9649}, abstract = {With advancement in human microbiome research, an increasing number of scientific evidences have endorsed the key role of gut microbiota in the pathogenesis of Alzheimer disease. Microbiome dysbiosis, characterized by altered diversity and composition, as well as rise of pathobionts influence not only various gut disorder but also central nervous system disorders such as AD. On the basis of accumulated evidences of past few years now it is quite clear that the gut microbiota can control the functions of the central nervous system (CNS) through the gut-brain axis, which provides a new prospective into the interactions between the gut and brain. The main focus of this review is on the molecular mechanism of the crosstalk between the gut microbiota and the brain through the gut-brain axis, and on the onset and development of neurological disorders triggered by the dysbiosis of gut microbiota. Due to microbiota dysbiosis the permeability of the gut and blood brain barrier is increased which may mediate or affect AD. Along with this, bacterial population of the gut microbiota can secrete amyloid proteins and lipopolysaccharides in a large quantity which may create a disturbance in the signaling pathways and the formation of proinflammatory cytokines associated with the pathogenesis of AD. These topics are followed by a critical analysis of potential intervention strategies targeting gut microbiota dysbiosis, including the use of probiotics, prebiotics, metabolites, diets and fecal microbiota transplantation. The main purpose of this review includes the summarization and discussion on the recent finding that may explain the role of the gut microbiota in the development of AD. Understanding of these fundamental mechanisms may provide a new insight into the novel therapeutic strategies for AD.}, } @article {pmid39486483, year = {2024}, author = {Lu, H and Xie, L and Guo, L and Gu, X and Zhu, R and Yang, Y and Tang, F and Li, M and Liu, C and Wang, D and Li, M and Tian, Y and Cai, S}, title = {EGCG protects intestines of mice and pelvic cancer patients against radiation injury via the gut microbiota/D-tagatose/AMPK axis.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {}, number = {}, pages = {110608}, doi = {10.1016/j.radonc.2024.110608}, pmid = {39486483}, issn = {1879-0887}, abstract = {BACKGROUND AND PURPOSE: Radiation-induced intestinal injury (RIII) compromises the clinical utility of pelvic radiotherapy (RT). We aimed to explore the protective effect and underlying mechanism of (-)-epigallocatechin-3-gallate (EGCG) on RIII.

MATERIALS AND METHODS: We evaluated the protective effect of EGCG on intestine in RIII mouse model and pelvic cancer patients, while explored the underlying mechanism through (1) 16S rRNA sequencing, (2) metabolomic profiles, (3) fresh sterile fecal filtrate (SFF) transplantation, and (4) transcriptome sequencing.

RESULTS: EGCG efficiently prevented RIII in mouse, as reflected by improved survival, alleviated intestinal structure damage, promoted intestinal regeneration, and ameliorated gut microbiota dysbiosis. Prophylactic EGCG intervention reduced the severity of RIII in patients receiving pelvic RT. Mechanistically, the protective effect of EGCG could be transferred to other mice by SFF transplantation. EGCG enriched gut microbiota-derived metabolite D-tagatose, and oral administration of D-tagatose reproduced the radio-protective effect of EGCG via activating AMPK.

CONCLUSION: Oral EGCG may be a promising strategy for preventing RIII clinically, and warrant further investigation in prospective randomized phase III trials.}, } @article {pmid39486191, year = {2024}, author = {Singh, R and Panganiban, K and Au, E and Ravikumar, R and Pereira, S and Prevot, TD and Mueller, DJ and Remington, G and Agarwal, SM and Verdu, EF and Bercik, P and De Palma, G and Hahn, MK}, title = {Human-fecal microbiota transplantation in relation to gut microbiome signatures in animal models for schizophrenia: A scoping review.}, journal = {Asian journal of psychiatry}, volume = {102}, number = {}, pages = {104285}, doi = {10.1016/j.ajp.2024.104285}, pmid = {39486191}, issn = {1876-2026}, abstract = {More recently, attention has turned to the putative role of gut microbiome (GMB) in pathogenesis, symptomatology, treatment response and/or resistance in schizophrenia (SCZ). It is foreseeable that fecal microbiota transplantation (FMT) from SCZ patients (SCZ-FMT) to germ-free mice could represent a suitable experimental framework for a better understanding of the relationship between GMB and SCZ. Thus, we set out to identify literature (i) characterizing the GMB in animal models of SCZ, and (ii) employing SCZ-FMT into rodents to model SCZ in relation to behavioral and molecular phenotypes. Five studies examining animal models of SCZ suggest distinct GMB composition compared to respective control groups, which was correlated with SCZ-like behavioral phenotypes. Four additional studies investigated SCZ-FMT into rodents in relation to behavioral phenotypes, including spontaneous hyperlocomotion, social deficits, exaggerated startle response, and cognitive impairments, resembling those observed in SCZ patients. Mice receiving SCZ-FMT showed altered neurochemical and metabolic pathways in the brain. Animal models of SCZ have shown altered GMB composition, whereas reported behavioral and neurochemical alterations following FMT from patients into rodents suggest early face and construct validity for SCZ-FMT animal models. However, the predictive validity of these models remains to be validated.}, } @article {pmid38052097, year = {2024}, author = {Cooper, J and Markovinovic, A and Coward, S and Herauf, M and Shaheen, AA and Swain, M and Panaccione, R and Ma, C and Lu, C and Novak, K and Kroeker, KI and Ng, SC and Kaplan, GG}, title = {Incidence and Prevalence of Primary Sclerosing Cholangitis: A Meta-analysis of Population-based Studies.}, journal = {Inflammatory bowel diseases}, volume = {30}, number = {11}, pages = {2019-2026}, pmid = {38052097}, issn = {1536-4844}, support = {PJT-162393/CAPMC/CIHR/Canada ; G-2106-04697//Leona M. and Harry B. Helmsley Charitable Trust/ ; //Study of Inflammatory Bowel Disease/ ; PJT-162393/CAPMC/CIHR/Canada ; }, mesh = {*Cholangitis, Sclerosing/epidemiology ; Humans ; Incidence ; Prevalence ; Asia/epidemiology ; }, abstract = {BACKGROUND: Primary sclerosing cholangitis is a chronic liver disease associated with significant morbidity, mortality, and healthcare utilization. We conducted a systematic review and meta-analysis of population-based studies of the incidence and prevalence of primary sclerosing cholangitis.

METHODS: Medline and Embase were systematically searched to identify population-based studies of a defined geographic area and reported the incidence or prevalence of primary sclerosing cholangitis in the general population. Meta-analyses, using random-effects, were performed to calculate overall and country-specific incidence (per 100 000 persons/year) and prevalence rates (per 100 000 persons) with 95% confidence intervals.

RESULTS: The 14 studies on incidence and the 12 for prevalence originated from North America, Asia, Europe, and Oceania. Incidence and prevalence rates of primary sclerosing cholangitis were 0.87 (95% confidence interval, 0.59-1.29) and 13.53 (95% confidence interval, 10.20-17.94) per 100 000 persons, respectively.

CONCLUSIONS: Both the prevalence and incidence of primary sclerosing cholangitis is low in the general population. Future studies on the incidence and prevalence of primary sclerosing cholangitis in the general population should be directed at Asia, Africa, and Latin America to allow for a more robust assessment of the global epidemiology of primary sclerosing cholangitis.}, } @article {pmid39484201, year = {2024}, author = {Cheng, X and Ren, C and Mei, X and Jiang, Y and Zhou, Y}, title = {Gut microbiota and irritable bowel syndrome: status and prospect.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1429133}, pmid = {39484201}, issn = {2296-858X}, abstract = {Irritable bowel syndrome (IBS) is a very common gastrointestinal disease that, although not as aggressive as tumors, affects patients' quality of life in different ways. The cause of IBS is still unclear, but more and more studies have shown that the characteristics of the gut microbiota, such as diversity, abundance, and composition, are altered in patients with IBS, compared to the healthy population, which confirms that the gut microbiota plays a crucial role in the development of IBS. This paper aims to identify the commonalities by reviewing a large body of literature. Changes in the characteristics of gut microbiota in patients with different types of IBS are discussed, relevant mechanisms are described, and the treatment modalities of gut microbiota in IBS are summarized. Although there are more clinical trials that have made good progress, more standardized, more generalized, larger-scale, multi-omics clinical studies are what is missing. Overall, gut microbiota plays a crucial role in the development of IBS, and there is even more potential for treating IBS by modulating gut microbiota.}, } @article {pmid39484168, year = {2024}, author = {Duo, H and Yang, Y and Zhang, G and Chen, Y and Cao, Y and Luo, L and Pan, H and Ye, Q}, title = {Comparative effectiveness of treatments for recurrent Clostridioides difficile infection: a network meta-analysis of randomized controlled trials.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1430724}, pmid = {39484168}, issn = {1663-9812}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) is the most common cause of healthcare-associated infectious diarrhea. A major clinical challenge is recurrent CDI (rCDI) without effective standard drug-based therapy. Additionally, a comprehensive comparison of various therapy effectiveness in rCDI patients is still under investigation.

METHODS: A Bayesian network meta-analysis (NMA) of randomized control trials up to March 2024 was performed to investigate the efficacy of rCDI interventions.

RESULTS: Seventeen trials were included, comprising 4,148 CDI patients with ten interventions, including fecal microbiota transplantation (FMT) by lower gastrointestinal (LGI), FMT by upper gastrointestinal (UGI), Autologous FMT (AFMT), vancomycin + FMT, vancomycin, placebo, fidaxomicin, Vowst (SER109), Rebyota (RBX2660), and monoclonal antibody. NMA showed that FMT by LGI had the highest efficacy in treating rCDIs with an odds ratio (95% confidence interval) of 32.33 (4.03, 248.69) compared with placebo. FMT by UGI also showed high efficacy, whereas the efficacy comparison between FMT by LGI and UGI was not statistically significant (ORs) (95% CI), 1.72 (0.65, 5.21). The rankogram and surface under the cumulative ranking curve (SUCRA) also showed FMT by LGI ranked at the top and FMT by UGI ranked second in the curative effect.

CONCLUSION: NMA demonstrates FMT's significant efficacy in rCDI management, regardless of administration route (lower or upper gastrointestinal). Despite its significant benefits, FMT's safety is a concern due to the lack of standardized FDAcompliant manufacturing and oversight. Microbiota-based therapies also exhibit potential. However, limited research mandates further clinical exploration. Antibiotics, in contrast, display comparatively reduced efficacy in rCDI, potentially linked to disruptions in native gut microflora balance.

SYSTEMATIC REVIEW: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=368435, Identifier CRD42022368435.}, } @article {pmid39483608, year = {2024}, author = {Aslam, MR and Perala, A and Wishart, AV and Hamouda, RK and Elsaady, E and Khan, S}, title = {Therapeutic Potential of Fecal Microbiota Transplantation in Type 2 Diabetes Mellitus: A Systematic Review.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e70642}, pmid = {39483608}, issn = {2168-8184}, abstract = {Diabetes mellitus is a chronic metabolic disease characterized by insulin resistance and hyperglycemia. It can cause various complications, which result in significant morbidity and mortality. There are multiple treatment options available to combat this disease; however, despite this, the incidence of type 2 diabetes mellitus is continuously increasing. Some promising results have shown that dysbiosis has a role in the pathogenesis of type 2 diabetes mellitus and fecal microbiota transplantation (FMT) in animals; however, the usage of FMT in humans needs further clarification and review. We explored PubMed, Popline, and Cochrane Library to identify relevant papers. Eight articles were then finalized after screening and applying eligibility criteria. These articles explored the role of the therapeutic efficacy of FMT in insulin resistance and hyperglycemia. The studies showed that the FMT had a positive impact on managing hyperglycemia and insulin resistance, which is evident in the decline of blood glucose and HBA1c levels and the rise of insulin and C-peptides. In addition, FMT also helped to control other risk factors such as hyperlipidemia and blood pressure; however, the impact on weight loss is not convincing. FMT also influenced the levels of some microbiota, which could be involved in controlling hyperglycemia and insulin resistance. Due to limited control trials and study periods and the small sample size of diabetic patients, more research is needed to explore the impact of FMT in controlling type 2 diabetes mellitus.}, } @article {pmid39482760, year = {2024}, author = {Nie, D and Wang, D and Wang, Z and Fang, Q and Wang, H and Xie, W and Li, C and Zhang, Y}, title = {The gut microbiome in patients with Cushing's disease affects depression- and anxiety-like behavior in mice.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {225}, pmid = {39482760}, issn = {2049-2618}, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; *Pituitary ACTH Hypersecretion/microbiology/psychology/physiopathology ; *Depression/microbiology ; *Anxiety/microbiology ; Humans ; *Disease Models, Animal ; Male ; Behavior, Animal ; Feces/microbiology ; Female ; Corticosterone/blood ; Bacteria/classification/isolation & purification ; Adult ; Middle Aged ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Depression and anxiety significantly impact the quality of life in individuals with Cushing's disease (CD), which originates from pituitary neuroendocrine tumors (PitNETs), yet our understanding of the underlying mechanisms is limited. There is substantial evidence linking gut microbes to depression, anxiety, and endocrinology.

RESULTS: The gut bacterial phenotype of patients with Cushing's disease was significantly different from that of the control group, and when the mice were treated with fecal bacteria from these patients, both anxiety- and depression-like behavior were significantly increased. However, this effect can be alleviated by supplementing with 2-(14, 15-epoxyeicosatrienoyl) glycerol (2-14,15-EG) which was found at reduced levels in the peripheral blood of mice treated with coprofecal bacteria from Cushing's disease. In this process, the effects of hormone levels and immune factors were not significant. In addition, in an animal model, corticosterone has been observed to affect behavioral changes in mice through gut microbiota composition, clarifying the cause-and-effect relationship between hormones, microbiota, and behavior. Finally, there was no significant difference in gut microbiome composition and its effects on mouse behavior in patients with Cushing's disease with different levels of depression and anxiety.

CONCLUSIONS: In summary, this research enhances our current understanding of how gut microbes in patients with Cushing's disease contribute to depression and anxiety, offering novel insights for clinical treatment approaches. Video Abstract.}, } @article {pmid39485288, year = {2024}, author = {Minaya, DM and Kim, JS and Kirkland, R and Allen, J and Cullinan, S and Maclang, N and de Lartigue, G and de La Serre, C}, title = {Transfer of microbiota from lean donors in combination with prebiotics prevents excessive weight gain and improves gut-brain vagal signaling in obese rats.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2421581}, doi = {10.1080/19490976.2024.2421581}, pmid = {39485288}, issn = {1949-0984}, mesh = {Animals ; *Obesity/microbiology/metabolism ; Male ; *Gastrointestinal Microbiome/drug effects ; Rats ; *Prebiotics/administration & dosage ; *Brain-Gut Axis/physiology ; *Diet, High-Fat/adverse effects ; *Vagus Nerve ; *Weight Gain/drug effects ; Dysbiosis/microbiology ; Rats, Sprague-Dawley ; Bacteria/classification/isolation & purification/genetics/metabolism ; Fecal Microbiota Transplantation ; Brain/metabolism ; Signal Transduction ; }, abstract = {Gastrointestinal (GI) microbiota plays an active role in regulating the host's immune system and metabolism, as well as certain pathophysiological processes. Diet is the main factor modulating GI microbiota composition and studies have shown that high fat (HF) diets induce detrimental changes (dysbiosis) in the GI bacterial makeup. HF diet induced dysbiosis has been associated with structural and functional changes in gut-brain vagally mediated signaling system, associated with overeating and obesity. Although HF-driven changes in microbiota composition are sufficient to alter vagal signaling, it is unknown if improving microbiota composition after diet-induced obesity has been established can ameliorate gut-brain signaling and metabolic outcomes. In this study, we evaluated the effect of lean gut microbiota transfer in obese, vagally compromised, rats on gut-brain communication, food intake, and body weight. Male rats were maintained on regular chow or 45% HF diet for nine weeks followed by three weeks of microbiota depletion using antibiotics. The animals were then divided into four groups (n = 10 each): LF - control fed regular chow, LF-LF - chow fed animals that received microbiota from chow fed donors, HF-LF - HF fed animals that received microbiota from chow fed donors, and HF-HF - HF fed animals that received microbiota from HF fed donors. HF-LF animals received inulin as a prebiotic to aid the establishment of the lean microbiome. We found that transferring a LF microbiota to HF fed animals (HF-LF) reduced caloric intake during the light phase when compared with HF-HF rats and prevented additional excessive weight gain. HF-LF animals displayed an increase in postprandial activation of both primary sensory neurons innervating the GI tract and brainstem secondary neurons. We concluded from these data that improving microbiota composition in obese rats is sufficient to ameliorate gut-brain communication and restore normal feeding patterns which was associated with a reduction in weight gain.}, } @article {pmid39484785, year = {2024}, author = {Li, Y and Song, X and Dai, L and Wang, Y and Luo, Q and Lei, L and Pu, Y}, title = {Mechanism of action of exercise regulating intestinal microflora to improve spontaneous hypertension in rats.}, journal = {Biomolecules & biomedicine}, volume = {}, number = {}, pages = {}, doi = {10.17305/bb.2024.11174}, pmid = {39484785}, issn = {2831-090X}, abstract = {Hypertension is a prevalent cardiovascular disease. Exercise is widely recognized as an effective treatment for hypertension, and it may also influence the composition of the intestinal microflora. However, it remains unclear whether exercise can specifically regulate the intestinal microflora in the context of hypertension treatment. In this study, tail blood pressure in spontaneously hypertensive rats (SHR) was measured using a blood pressure meter after exercise intervention and fecal bacteria transplantation following exercise. Blood lipid levels were assessed using an automatic biochemical analyzer, and 16S rRNA sequencing was employed to analyze the intestinal microflora. Histological examinations of ileal tissue were conducted using HE and Masson staining. Intestinal permeability, inflammatory status, and sympathetic activity were evaluated by measuring the levels of diamine oxidase, D-lactic acid, C-reactive protein, interleukin-6, tumor necrosis factor-α, lipopolysaccharide, norepinephrine, angiotensin II, cyclic adenosine monophosphate, and cyclic guanosine monophosphate. Exercise was found to reduce blood pressure and blood lipid levels in SHR. It also improved the composition of the intestinal microflora, as evidenced by a reduced Firmicutes/Bacteroidetes ratio, an increase in bacteria that produce acetic and butyric acid, and higher Chao 1 and Shannon diversity indices. Furthermore, exercise reduced the thickness of the fibrotic and muscular layers in the ileum, increased the goblet cell/villus ratio and villus length, and decreased intestinal permeability, inflammatory markers, and sympathetic nerve activity. The intestinal microbial flora regulated by exercise demonstrated similar effects on hypertension. In conclusion, exercise appears to regulate the intestinal microflora, and this exercise-induced change in flora may contribute to improvements in hypertension in rats.}, } @article {pmid39482823, year = {2024}, author = {Zhang, T and Li, X and Li, J and Sun, F and Duan, L}, title = {Gut microbiome-targeted therapies as adjuvant treatments in inflammatory bowel diseases: a systematic review and network meta-analysis.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.16795}, pmid = {39482823}, issn = {1440-1746}, support = {2021YFA1301300//National Key Research and Development Program of China/ ; 82170557//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND AND AIM: Gut microbiome-targeted therapies (MTTs), including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation (FMT), have been widely used in inflammatory bowel diseases (IBD), but the best MTTs has not yet been confirmed. We performed a network meta-analysis (NMA) to examine this in ulcerative colitis (UC) and Crohn's disease (CD).

METHODS: We searched for randomized controlled trials (RCTs) on the efficacy and safety of MTTs as adjuvant therapies for IBD until December 10, 2023. Data were pooled using a random effects model, with efficacy reported as pooled relative risks with 95% CIs, and interventions ranked according to means of surfaces under cumulative ranking values.

RESULTS: Thirty-eight RCTs met the inclusion criteria. Firstly, we compared the efficacy of MTTs in IBD patients. Only FMT and probiotics were superior to placebo in all outcomes, but FMT ranked best in improving clinical response rate and clinical and endoscopic remission rate, and probiotics ranked second in reducing clinical relapse rate showed significant efficacy, while prebiotics ranked first showed nonsignificant efficacy. Subsequently, we conducted NMA for specific MTT formulations in UC and CD separately, which revealed that FMT, especially combined FMT via colonoscopy and enema, showed significant efficacy and was superior in improving clinical response and remission rate of active UC patients. As for endoscopic remission and clinical relapse, multistrain probiotics based on specific genera of Lactobacillus and Bifidobacterium showed significant efficacy and ranked best in UC. In CD, we found that no MTTs were significantly better than placebo, but synbiotics comprising Bifidobacterium and fructo-oligosaccharide/inulin mix and Saccharomyces ranked best in improving clinical remission and reducing clinical relapse, respectively. Moreover, FMT was safe in both UC and CD.

CONCLUSIONS: FMT and multistrain probiotics showed superior efficacy in UC. However, the efficacy of MTTs varies among different IBD subtypes and disease stages; thus, the personalized treatment strategies of MTTs are necessary.}, } @article {pmid39481287, year = {2024}, author = {Gautam, R and Maan, P and Patel, AK and Vasudevan, S and Arora, T}, title = {Unveiling the complex interplay between gut microbiota and polycystic ovary syndrome: A narrative review.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {43}, number = {12}, pages = {199-208}, doi = {10.1016/j.clnu.2024.10.028}, pmid = {39481287}, issn = {1532-1983}, abstract = {BACKGROUND & AIM: Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder that affects women throughout their reproductive age and characterised via polycystic ovaries, hyperandrogenism, and irregular menstruation. There is rising evidence that the pathophysiology of PCOS is significantly affected via the gut microbiota and its metabolic products.

METHODS: This narrative review synthesizes current literature exploring the relationship between gut microbiota and PCOS. A comprehensive search of electronic databases was conducted to identify relevant studies. Further this review also analysed therapeutic options of probiotics, prebiotics, Fecal Microbiota Transplant (FMT), high fiber and poly phenol rich diet and novel therapeutic agents in treatment of PCOS.

RESULTS: Emerging evidence suggests alterations in the composition and diversity of gut microbiota in women with PCOS. The current literature showed a complex relationship of gut microbiota, short chain fatty acids (SCFAs) metabolism, intestinal permeability and LPS (Lipid Polysaccharide) metabolism, gut-brain axis and bile acid (BA) pathway within etiology and pathophysiology of PCOS. Additionally, the factors such as diet, lifestyle, genetics, and environmental influences may all contribute to alterations in gut microbiota that could potentially exacerbate or mitigate PCOS symptoms.

CONCLUSION: The review provides valuable insights into the intricate interplay between the gut and female reproductive health. The present evidence suggested that alterations in diversity and function of the gut microbiota may lead to specific pathogenic changes that lead to development of PCOS. A comprehensive understanding of these microbial dynamics may lead to new therapeutic approaches that target the gut micro biome.}, } @article {pmid39480487, year = {2024}, author = {Deda, O and Armitage, EG and Mouskeftara, T and Kachrimanidou, M and Zervos, I and Malousi, A and Loftus, NJ and Taitzoglou, I and Gika, H}, title = {Unraveling Cecal Alterations in Clostridioides difficile Colonized Mice through Comprehensive Metabolic Profiling.}, journal = {Journal of proteome research}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jproteome.4c00578}, pmid = {39480487}, issn = {1535-3907}, abstract = {The disruption of gut microbiota caused by antibiotics favors the intestinal colonization of Clostridioides difficile - a Gram-positive, spore-forming anaerobic bacterium that causes potentially fatal gastrointestinal infections. In an endeavor to elucidate the complexities of the gut-brain axis in the context of Clostridium difficile infection (CDI), a murine model has been used to investigate the potential effects of antibiotic administration and subsequent colonization by C. difficile, as well as the impact of three different 10-day treatments (metronidazole, probiotics, and fecal microbiota transplantation), on the cecal metabolome for the first time. This follows our previous research which highlighted the metabolic effect of CDI and these treatments in the brain and employs the same four different metabolomics-based methods (targeted GC-MS/MS, targeted HILIC-MS/MS, untargeted RP-LC-HRMS/MS and untargeted GC-MS). A total of 286 unique metabolites have been identified in the mouse cecal profiles and statistical analysis revealed that CDI, as well as the subsequent treatments, significantly alters cecal metabolites and lipids implicated in various biochemical pathways centered around amino acid metabolism, glycerophospholipid metabolism, and central carbon metabolism. To our knowledge, this study represents the first exploration of the effects of C. difficile-induced colitis and potential treatments on the cecal tissue metabolome.}, } @article {pmid38988278, year = {2024}, author = {Yan, M and Man, S and Ma, L and Guo, L and Huang, L and Gao, W}, title = {Immunological mechanisms in steatotic liver diseases: An overview and clinical perspectives.}, journal = {Clinical and molecular hepatology}, volume = {30}, number = {4}, pages = {620-648}, doi = {10.3350/cmh.2024.0315}, pmid = {38988278}, issn = {2287-285X}, support = {82074069//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Fatty Liver/complications/therapy/pathology ; Dysbiosis/complications ; Fecal Microbiota Transplantation ; Animals ; }, abstract = {Steatotic liver diseases (SLD) are the principal worldwide cause of cirrhosis and end-stage liver cancer, affecting nearly a quarter of the global population. SLD includes metabolic dysfunction-associated alcoholic liver disease (MetALD) and metabolic dysfunction-associated steatotic liver disease (MASLD), resulting in asymptomatic liver steatosis, fibrosis, cirrhosis and associated complications. The immune processes include gut dysbiosis, adiposeliver organ crosstalk, hepatocyte death and immune cell-mediated inflammatory processes. Notably, various immune cells such as B cells, plasma cells, dendritic cells, conventional CD4+ and CD8+ T cells, innate-like T cells, platelets, neutrophils and macrophages play vital roles in the development of MetALD and MASLD. Immunological modulations targeting hepatocyte death, inflammatory reactions and gut microbiome include N-acetylcysteine, selonsertib, F-652, prednisone, pentoxifylline, anakinra, JKB-121, HA35, obeticholic acid, probiotics, prebiotics, antibiotics and fecal microbiota transplantation. Understanding the immunological mechanisms underlying SLD is crucial for advancing clinical therapeutic strategies.}, } @article {pmid39479215, year = {2024}, author = {Huang, J and Xu, T and Quan, G and Li, Y and Yang, X and Xie, W}, title = {Current progress on the microbial therapies for acute liver failure.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1452663}, pmid = {39479215}, issn = {1664-302X}, abstract = {Acute liver failure (ALF), associated with a clinical fatality rate exceeding 80%, is characterized by severe liver damage resulting from various factors in the absence of pre-existing liver disease. The role of microbiota in the progression of diverse liver diseases, including ALF, has been increasingly recognized, with the interactions between the microbiota and the host significantly influencing both disease onset and progression. Despite growing interest in the microbiological aspects of ALF, comprehensive reviews remain limited. This review critically examines the mechanisms and efficacy of microbiota-based treatments for ALF, focusing on their role in prevention, treatment, and prognosis over the past decade.}, } @article {pmid39473963, year = {2024}, author = {Wang, YN and Zhai, XY and Wang, Z and Gao, CL and Mi, SC and Tang, WL and Fu, XM and Li, HB and Yue, LF and Li, PF and Xi, SY}, title = {Jianpi-Huatan-Huoxue-Anshen formula ameliorates gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with H22 hepatocellular carcinoma.}, journal = {World journal of gastrointestinal oncology}, volume = {16}, number = {10}, pages = {4209-4231}, pmid = {39473963}, issn = {1948-5204}, abstract = {BACKGROUND: Jianpi-Huatan-Huoxue-Anshen formula [Tzu-Chi cancer-antagonizing & life-protecting II decoction (TCCL)] is a Chinese medical formula that has been clinically shown to reduce the gastrointestinal side effects of chemotherapy in cancer patients and improve their quality of life. However, its effect and mechanism on the intestinal microecology after chemotherapy are not yet clear.

AIM: To discover the potential mechanisms of TCCL on gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with hepatocellular carcinoma (HCC).

METHODS: Ninety-six mice were inoculated subcutaneously with HCC cells. One week later, the mice received a large dose of 5-fluorouracil by intraperitoneal injection to establish a HCC chemotherapy model. Thirty-six mice were randomly selected before administration, and feces, ileal tissue, and ileal contents were collected from each mouse. The remaining mice were randomized into normal saline, continuous chemotherapy, Yangzheng Xiaoji capsules-treated, and three TCCL-treated groups. After treatment, feces, tumors, liver, spleen, thymus, stomach, jejunum, ileum, and colon tissues, and ileal contents were collected. Morphological changes, serum levels of IL-1β, IL-6, IL-8, IL-10, IL-22, TNF-α, and TGF-β, intestinal SIgA, and protein and mRNA expression of ZO-1, NF-κB, Occludin, MUC-2, Claudin-1, and IκB-α in colon tissues were documented. The effect of TCCL on the abundance and diversity of intestinal flora was analyzed using 16S rDNA sequencing.

RESULTS: TCCL treatment improved thymus and spleen weight, thymus and spleen indexes, and body weight, decreased tumor volumes and tumor tissue cell density, and alleviated injury to gastric, ileal, and colonic mucosal tissues. Among proteins and genes associated with inflammation, IL-10, TGF-β, SIgA, ZO-1, MUC-2, and Occludin were upregulated, whereas NF-κB, IL-1β, IL-6, TNF-α, IL-22, IL-8, and IκB-α were downregulated. Additionally, TCCL increased the proportions of fecal Actinobacteria, AF12, Adlercreutzia, Clostridium, Coriobacteriaceae, and Paraprevotella in the intermediate stage of treatment, decreased the proportions of Mucipirillum, Odoribacter, RF32, YS2, and Rikenellaceae but increased the proportions of p_Deferribacteres and Lactobacillus at the end of treatment. Studies on ileal mucosal microbiota showed similar findings. Moreover, TCCL improved community richness, evenness, and the diversity of fecal and ileal mucosal flora.

CONCLUSION: TCCL relieves pathological changes in tumor tissue and chemotherapy-induced gastrointestinal injury, potentially by reducing the release of pro-inflammatory factors to repair the gastrointestinal mucosa, enhancing intestinal barrier function, and maintaining gastrointestinal microecological balance. Hence, TCCL is a very effective adjuvant to chemotherapy.}, } @article {pmid39471749, year = {2024}, author = {Liu, X and Lu, B and Tang, H and Jia, X and Zhou, Q and Zeng, Y and Gao, X and Chen, M and Xu, Y and Wang, M and Tan, B and Li, J}, title = {Gut microbiome metabolites, molecular mimicry, and species-level variation drive long-term efficacy and adverse event outcomes in lung cancer survivors.}, journal = {EBioMedicine}, volume = {109}, number = {}, pages = {105427}, doi = {10.1016/j.ebiom.2024.105427}, pmid = {39471749}, issn = {2352-3964}, abstract = {BACKGROUND: The influence of the gut microbiota on long-term immune checkpoint inhibitor (ICI) efficacy and immune-related adverse events (irAEs) is poorly understood, as are the underlying mechanisms.

METHODS: We performed gut metagenome and metabolome sequencing of gut microbiotas from patients with lung cancer initially treated with anti-PD-1/PD-L1 therapy and explored the underlying mechanisms mediating long-term (median follow-up 1167 days) ICI responses and immune-related adverse events (irAEs). Results were validated in external, publicly-available datasets (Routy, Lee, and McCulloch cohorts).

FINDINGS: The ICI benefit group was enriched for propionate (P = 0.01) and butyrate/isobutyrate (P = 0.12) compared with the resistance group, which was validated in the McCulloch cohort (propionate P < 0.001, butyrate/isobutyrate P = 0.002). The acetyl-CoA pathway (P = 0.02) in beneficial species mainly mediated butyrate production. Microbiota sequences from irAE patients aligned with antigenic epitopes found in autoimmune diseases. Microbiotas of responsive patients contained more lung cancer-related antigens (P = 0.07), which was validated in the Routy cohort (P = 0.02). Escherichia coli and SGB15342 of Faecalibacterium prausnitzii showed strain-level variations corresponding to clinical phenotypes. Metabolome validation reviewed more abundant acetic acid (P = 0.03), propionic acid (P = 0.09), and butyric acid (P = 0.02) in the benefit group than the resistance group, and patients with higher acetic, propionic, and butyric acid levels had a longer progression-free survival and lower risk of tumor progression after adjusting for histopathological subtype and stage (P < 0.05).

INTERPRETATION: Long-term ICI survivors have coevolved a compact microbial community with high butyrate production, and molecular mimicry of autoimmune and tumor antigens by microbiota contribute to outcomes. These results not only characterize the gut microbiotas of patients who benefit long term from ICIs but pave the way for "smart" fecal microbiota transplantation. Registered in the Chinese Clinical Trial Registry (ChiCTR2000032088).

FUNDING: This work was supported by Beijing Natural Science Foundation (7232110), National High Level Hospital Clinical Research Funding (2022-PUMCH-A-072, 2023-PUMCH-C-054), CAMS Innovation Fund for Medical Sciences (CIFMS) (2022-I2M-C&T-B-010).}, } @article {pmid39471538, year = {2024}, author = {Levitte, S and Nilkant, R and Jensen, AR and Zhang, KY}, title = {Unlocking the promise of mesenchymal stem cells and extracorporeal photopheresis to address rejection and graft failure in intestinal transplant recipients.}, journal = {Human immunology}, volume = {85}, number = {6}, pages = {111160}, doi = {10.1016/j.humimm.2024.111160}, pmid = {39471538}, issn = {1879-1166}, abstract = {INTRODUCTION: In patients with irreversible intestinal failure, intestinal transplant has become a standard treatment option. Graft failure secondary to acute or chronic cellular rejection continues to be a significant challenge following transplant. Even with optimal immune suppression, some patients continue to struggle with refractory rejection. Both extracorporeal photopheresis (ECP) and extracellular vesicles derived from mesenchymal stem cells (EVs) have been used to treat refractory rejection following intestinal transplantation, although their use remains limited and consistent treatment protocols are lacking.

METHODS: Intestinal transplant recipients who received ECP only or ECP and EVs as rescue therapy for acute cellular rejection or chronic inflammation between 2016 and 2022 were included in this single-center retrospective analysis. Baseline demographics, pre- and post-treatment histopathology, endoscopic and biochemical findings, and long-term transplant outcomes were analyzed.

RESULTS: Three patients (two pediatric and one adult) with acute steroid- and biologic-refractory rejection were treated with ECP and/or EVs, as was one patient (pediatric) with chronic graft rejection and inflammation. Patients received twice weekly ECP for 4 weeks and once weekly thereafter. EVs were administered in three doses each separated by 72 h. Immunosuppression at the time of treatment initiation included high-dose tacrolimus and sirolimus. Histologic resolution of rejection was achieved in all patients over 12-16 weeks. Steroids were weaned to low-dose or withdrawn in every patient within 4 weeks of ECP/EV treatment. C-reactive protein decreased from an average of 14.75 to 1.6 mg/dL post-treatment and fecal calprotectin decreased from average 800 mg/g to 31 mg/g. Donor-induced cytotoxic T cell populations were quantified for two of the patients with acute rejection, and in both cases decreased dramatically following treatment. There were no complications associated with either treatment.

CONCLUSION: Both ECP and EVs present novel opportunities to address graft rejection and inflammation in bowel transplant recipients. More work will be needed to define the optimal therapeutic parameters for each treatment modality.}, } @article {pmid39470619, year = {2024}, author = {Liu, X and Luo, Y and Chen, X and Wu, M and Xu, X and Tian, J and Gao, Y and Zhu, J and Wang, Z and Zhou, Y and Zhang, Y and Wang, X and Li, W and Lu, Q and Yao, X}, title = {Fecal microbiota transplantation against moderate-to-severe atopic dermatitis: A randomized, double-blind controlled explorer trial.}, journal = {Allergy}, volume = {}, number = {}, pages = {}, doi = {10.1111/all.16372}, pmid = {39470619}, issn = {1398-9995}, support = {//Nanjing Incubation Program for National Clinical Research Center/ ; //National Key Research and Development Program of China/ ; //CAMS Innovation Fund for Medical Sciences/ ; //Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences/ ; //National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a novel treatment for inflammatory diseases. Herein, we assess its safety, efficacy, and immunological impact in patients with moderate-to-severe atopic dermatitis (AD).

METHODS: In this randomized, double-blind, placebo-controlled clinical trial, we performed the efficacy and safety assessment of FMT for moderate-to-severe adult patients with AD. All patients received FMT or placebo once a week for 3 weeks, in addition to their standard background treatments. Patients underwent disease severity assessments at weeks 0, 1, 2, 4, 8, 12, and 16, and blood and fecal samples were collected for immunologic analysis and metagenomic shotgun sequencing, respectively. Safety was monitored throughout the trial.

RESULTS: Improvements in eczema area and severity index (EASI) scores and percentage of patients achieving EASI 50 (50% reduction in EASI score) were greater in patients treated with FMT than in placebo-treated patients. No serious adverse reactions occurred during the trial. FMT treatment decreased the Th2 and Th17 cell proportions among the peripheral blood mononuclear cells, and the levels of TNF-α, and total IgE in serum. By contrast, the expression levels of IL-12p70 and perforin on NK cells were increased. Moreover, FMT altered the abundance of species and functional pathways of the gut microbiota in the patients, especially the abundance of Megamonas funiformis and the pathway for 1,4-dihydroxy-6-naphthoate biosynthesis II.

CONCLUSION: FMT was a safe and effective therapy in moderate-to-severe adult patients with AD; the treatment changed the gut microbiota compositions and functions.}, } @article {pmid39470206, year = {2024}, author = {Todd, CL and Johnson, EE and Stewart, F and Wallace, SA and Bryant, A and Woodward, S and Norton, C}, title = {Conservative, physical and surgical interventions for managing faecal incontinence and constipation in adults with central neurological diseases.}, journal = {The Cochrane database of systematic reviews}, volume = {10}, number = {10}, pages = {CD002115}, pmid = {39470206}, issn = {1469-493X}, mesh = {Humans ; *Constipation/therapy/etiology ; *Fecal Incontinence/therapy/etiology ; *Randomized Controlled Trials as Topic ; Adult ; *Central Nervous System Diseases/complications ; Conservative Treatment/methods ; Quality of Life ; Bias ; }, abstract = {BACKGROUND: People with central neurological disease or injury have a much higher risk of both faecal incontinence (FI) and constipation than the general population. There is often a fine line between the two symptoms, with management intended to ameliorate one risking precipitating the other. Bowel problems are observed to be the cause of much anxiety and may reduce quality of life in these people. Current bowel management is largely empirical, with a limited research base. The review is relevant to individuals with any disease directly and chronically affecting the central nervous system (post-traumatic, degenerative, ischaemic or neoplastic), such as multiple sclerosis, spinal cord injury, cerebrovascular disease, Parkinson's disease and Alzheimer's disease. This is an update of a Cochrane Review first published in 2001 and subsequently updated in 2003, 2006 and 2014.

OBJECTIVES: To assess the effects of conservative, physical and surgical interventions for managing FI and constipation in people with a neurological disease or injury affecting the central nervous system.

SEARCH METHODS: We searched the Cochrane Incontinence Specialised Register (searched 27 March 2023), which includes searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP as well as handsearching of journals and conference proceedings; and all reference lists of relevant articles.

SELECTION CRITERIA: We included randomised, quasi-randomised (where allocation is not strictly random), cross-over and cluster-randomised trials evaluating any type of conservative, physical or surgical intervention against placebo, usual care or no intervention for the management of FI and constipation in people with central neurological disease or injury.

DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed the risk of bias in eligible trials using Cochrane's 'Risk of bias' tool and independently extracted data from the included trials using a range of prespecified outcome measures. We produced summary of findings tables for our main outcome measures and assessed the certainty of the evidence using GRADE.

MAIN RESULTS: We included 25 studies with 1598 participants. The studies were generally at high risk of bias due to lack of blinding of participants and personnel to the intervention. Half of the included studies were also at high risk of bias in terms of selective reporting. Outcomes were often reported heterogeneously across studies, making it difficult to pool data. We did not find enough evidence to be able to analyse the effects of interventions on individual central neurological diseases. Additionally, very few studies reported on the primary outcomes of self-reported improvement in FI or constipation, or Neurogenic Bowel Dysfunction Score. Conservative interventions compared with usual care, no active treatment or placebo Thirteen studies assessed this comparison. The interventions included assessment-based nursing, holistic nursing, probiotics, psyllium, faecal microbiota transplantation, and a stepwise protocol of increasingly invasive evacuation methods. Conservative interventions may result in a large improvement in faecal incontinence (standardised mean difference (SMD) -1.85, 95% confidence interval (CI) -3.47 to -0.23; 3 studies; n = 410; low-certainty evidence). We interpreted SMD ≥ 0.80 as a large effect. It was not possible to pool all data from studies that assessed improvement in constipation, but the evidence suggested that conservative interventions may improve constipation symptoms (data not pooled; 8 studies; n = 612; low-certainty evidence). Conservative interventions may lead to a reduction in mean time taken on bowel care (data not pooled; 5 studies; n = 526; low-certainty evidence). The evidence is uncertain about the effects of conservative interventions on condition-specific quality of life and adverse events. Neurogenic Bowel Dysfunction Score was not reported. Physical therapy compared with usual care, no active treatment or placebo Twelve studies assessed this comparison. The interventions included massage therapy, standing, osteopathic manipulative treatment, electrical stimulation, transanal irrigation, and conventional physical therapy with visceral mobilisation. Physical therapies may make little to no difference to self-reported faecal continence assessed using the St Mark's Faecal Incontinence Score, where the minimally important difference is five, or the Cleveland Constipation Score (MD -2.60, 95% CI -4.91 to -0.29; 3 studies; n = 155; low-certainty evidence). Physical therapies may result in a moderate improvement in constipation symptoms (SMD -0.62, 95% CI -1.10 to -0.14; 9 studies; n = 431; low-certainty evidence). We interpreted SMD ≥ 0.5 as a moderate effect. However, physical therapies may make little to no difference in Neurogenic Bowel Dysfunction Score as the minimally important difference for this tool is 3 (MD -1.94, 95% CI -3.36 to -0.51; 7 studies; n = 358; low-certainty evidence). We are very uncertain about the effects of physical therapies on the time spent on bowel care, condition-specific quality of life and adverse effects (all very low-certainty evidence). Surgical interventions compared with usual care, no active treatment or placebo No studies were found for surgical interventions that met the inclusion criteria for this review.

AUTHORS' CONCLUSIONS: There remains little research on this common and, for patients, very significant issue of bowel management. The available evidence is almost uniformly of low methodological quality. The clinical significance of some of the research findings presented here is difficult to interpret, not least because each intervention has only been addressed in individual trials, against control rather than compared against each other, and the interventions are very different from each other. Understanding whether there is a clinically-meaningful difference from the results of available trials is largely hampered by the lack of uniform outcome measures. This is due to an absence of core outcome sets, and development of these needs to be a research priority to allow studies to be compared directly. Some studies used validated constipation, incontinence or condition-specific measures; however, others used unvalidated analogue scales to report effectiveness. Some studies did not use any patient-reported outcomes and focused on physiological outcome measures, which is of relatively limited significance in terms of clinical implementation. There was evidence in favour of some conservative interventions, but these findings need to be confirmed by larger, well-designed controlled trials, which should include evaluation of the acceptability of the intervention to patients and the effect on their quality of life.}, } @article {pmid39468666, year = {2024}, author = {Lian, J and Xia, L and Wang, G and Wu, W and Yi, P and Li, M and Su, X and Chen, Y and Li, X and Dou, F and Wang, Z}, title = {Multi-omics evaluation of clinical-grade human umbilical cord-derived mesenchymal stem cells in synergistic improvement of aging related disorders in a senescence-accelerated mouse model.}, journal = {Stem cell research & therapy}, volume = {15}, number = {1}, pages = {383}, pmid = {39468666}, issn = {1757-6512}, support = {3502220214001//Xiamen Cell Therapy Research Center/ ; 3502Z20234008//Key Healthcare Projects of Xiamen City/ ; 202212631066//Xiamen Medical College Undergraduate Innovation and Entrepreneurship Training Program/ ; 2022//Xiamen Medical College Undergraduate Innovation and Entrepreneurship Training Program/ ; 2023QNB003//Health science and technology project of Fujian Province/ ; 3502Z202372072//Natural Science Foundation of Xiamen/ ; 3502Z20244ZD1009//Natural Science Foundation of Xiamen/ ; }, mesh = {Animals ; Mice ; *Mesenchymal Stem Cells/metabolism/cytology ; Humans ; *Umbilical Cord/cytology/metabolism ; *Aging ; *Disease Models, Animal ; Mesenchymal Stem Cell Transplantation/methods ; Gastrointestinal Microbiome ; Male ; DNA Damage ; Multiomics ; }, abstract = {BACKGROUND: The prevalence of age-related disorders, particularly in neurological and cardiovascular systems, is an increasing global health concern. Mesenchymal stem cell (MSC) therapy, particularly using human umbilical cord-derived MSCs (HUCMSCs), has shown promise in mitigating these disorders. This study investigates the effects of HUCMSCs on aging-related conditions in a senescence-accelerated mouse model (SAMP8), with a focus on DNA damage, gut microbiota alterations, and metabolic changes.

METHODS: SAMP8 mice were treated with clinical-grade HUCMSCs via intraperitoneal injections. Behavioral and physical assessments were conducted to evaluate cognitive and motor functions. The Single-Strand Break Mapping at Nucleotide Genome Level (SSiNGLe) method was employed to assess DNA single-strand breaks (SSBs) across the genome, with particular attention to exonic regions and transcription start sites. Gut microbiota composition was analyzed using 16S rRNA sequencing, and carboxyl metabolomic profiling was performed to identify changes in circulating metabolites.

RESULTS: HUCMSC treatment significantly improved motor coordination and reduced anxiety in SAMP8 mice. SSiNGLe analysis revealed a notable reduction in DNA SSBs in MSC-treated mice, especially in critical genomic regions, suggesting that HUCMSCs may mitigate age-related DNA damage. The functional annotation of the DNA breaktome indicated a potential link between reduced DNA damage and altered metabolic pathways. Additionally, beneficial alterations in gut microbiota were observed, including an increase in short-chain fatty acid (SCFA)-producing bacteria, which correlated with improved metabolic profiles.

CONCLUSION: The administration of HUCMSCs in SAMP8 mice not only reduces DNA damage but also induces favorable changes in gut microbiota and metabolism. The observed alterations in DNA break patterns, along with specific changes in microbiota and metabolic profiles, suggest that these could serve as potential biomarkers for evaluating the efficacy of HUCMSCs in treating age-related disorders. This highlights a promising avenue for the development of new therapeutic strategies that leverage these biomarkers, to enhance the effectiveness of HUCMSC-based treatments for aging-associated diseases.}, } @article {pmid39468065, year = {2024}, author = {Wang, G and Cao, L and Li, S and Zhang, M and Li, Y and Duan, J and Li, Y and Hu, Z and Wu, J and Ni, J and Lan, D and Li, T and Lu, J}, title = {Gut microbiota dysbiosis-mediated ceramides elevation contributes to corticosterone-induced depression by impairing mitochondrial function.}, journal = {NPJ biofilms and microbiomes}, volume = {10}, number = {1}, pages = {111}, pmid = {39468065}, issn = {2055-5008}, support = {82371176//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81801331//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Mitochondria/metabolism ; *Corticosterone ; Mice ; *Depression ; *Ceramides/metabolism ; *Dysbiosis ; *Hippocampus/metabolism ; Fecal Microbiota Transplantation ; Male ; Disease Models, Animal ; Feces/microbiology ; Mice, Inbred C57BL ; Neurogenesis ; Behavior, Animal/drug effects ; }, abstract = {The role of gut microbiota (GM) dysbiosis in the pathogenesis of depression has received widespread attention, but the mechanism remains elusive. Corticosterone (CORT)-treated mice showed depression-like behaviors, reduced hippocampal neurogenesis, and altered composition of the GM. Fecal microbial transplantation from CORT-treated mice transferred depression-like phenotypes and their dominant GM to the recipients. Fecal metabolic profiling exposed remarkable increase of gut ceramides in CORT-treated and recipient mice. Oral gavage with Bifidobacterium pseudolongum and Lactobacillus reuteri could induce elevations of gut ceramides in mice. Ceramides-treated mice showed depressive-like phenotypes, significant downregulation of oxidative phosphorylation-associated genes, and hippocampal mitochondrial dysfunction. Our study demonstrated a link between chronic exposure to CORT and its impact on GM composition, which induces ceramides accumulation, ultimately leading to hippocampal mitochondrial dysfunction. This cascade of events plays a critical role in reducing adult hippocampal neurogenesis and is strongly associated with the development of depression-like behaviors.}, } @article {pmid39467697, year = {2024}, author = {Qu, J and Meng, F and Wang, Z and Xu, W}, title = {Unlocking Cardioprotective Potential of Gut Microbiome: Exploring Therapeutic Strategies.}, journal = {Journal of microbiology and biotechnology}, volume = {34}, number = {12}, pages = {1-12}, doi = {10.4014/jmb.2405.05019}, pmid = {39467697}, issn = {1738-8872}, abstract = {The microbial community inhabiting the human gut resembles a bustling metropolis, wherein beneficial bacteria play pivotal roles in regulating our bodily functions. These microorganisms adeptly break down resilient dietary fibers to fuel our energy, synthesize essential vitamins crucial for our well-being, and maintain the delicate balance of our immune system. Recent research indicates a potential correlation between alterations in the composition and activities of these gut microbes and the development of coronary artery disease (CAD). Consequently, scientists are delving into the intriguing realm of manipulating these gut inhabitants to potentially mitigate disease risks. Various promising strategies have emerged in this endeavor. Studies have evidenced that probiotics can mitigate inflammation and enhance the endothelial health of our blood vessels. Notably, strains such as Lactobacilli and Bifidobacteria have garnered substantial attention in both laboratory settings and clinical trials. Conversely, prebiotics exhibit anti-inflammatory properties and hold potential in managing conditions like hypertension and hypercholesterolemia. Synbiotics, which synergistically combine probiotics and prebiotics, show promise in regulating glucose metabolism and abnormal lipid profiles. However, uncertainties persist regarding postbiotics, while antibiotics are deemed unsuitable due to their potential adverse effects. On the other hand, TMAO blockers, such as 3,3-dimethyl-1-butanol, demonstrate encouraging outcomes in laboratory experiments owing to their anti-inflammatory and tissue-protective properties. Moreover, fecal transplantation, despite yielding mixed results, warrants further exploration and refinement. In this comprehensive review, we delve into the intricate interplay between the gut microbiota and CAD, shedding light on the multifaceted approaches researchers are employing to leverage this understanding for therapeutic advancements.}, } @article {pmid39466773, year = {2024}, author = {Partida-Rodríguez, O and Brown, EM and Woodward, SE and Cirstea, M and Reynolds, LA and Petersen, C and Vogt, SL and Peña-Díaz, J and Thorson, L and Arrieta, MC and Hernández, EG and Rojas-Velázquez, L and Moran, P and González Rivas, E and Serrano-Vázquez, A and Pérez-Juárez, H and Torres, J and Ximénez, C and Finlay, BB}, title = {Fecal microbiota transplantation from protozoa-exposed donors downregulates immune response in a germ-free mouse model, its role in immune response and physiology of the intestine.}, journal = {PloS one}, volume = {19}, number = {10}, pages = {e0312775}, pmid = {39466773}, issn = {1932-6203}, mesh = {Animals ; *Fecal Microbiota Transplantation ; Mice ; *Germ-Free Life ; Gastrointestinal Microbiome/immunology ; Cytokines/metabolism ; T-Lymphocytes, Regulatory/immunology ; Intestines/immunology/parasitology/microbiology ; Mice, Inbred C57BL ; Intestinal Mucosa/immunology/metabolism ; Down-Regulation ; Female ; Spleen/immunology/metabolism ; }, abstract = {Intestinal parasites are part of the intestinal ecosystem and have been shown to establish close interactions with the intestinal microbiota. However, little is known about the influence of intestinal protozoa on the regulation of the immune response. In this study, we analyzed the regulation of the immune response of germ-free mice transplanted with fecal microbiota (FMT) from individuals with multiple parasitic protozoans (P) and non-parasitized individuals (NP). We determined the production of intestinal cytokines, the lymphocyte populations in both the colon and the spleen, and the genetic expression of markers of intestinal epithelial integrity. We observed a general downregulation of the intestinal immune response in mice receiving FMT-P. We found significantly lower intestinal production of the cytokines IL-6, TNF, IFN-γ, MCP-1, IL-10, and IL-12 in the FMT-P. Furthermore, a significant decrease in the proportion of CD3+, CD4+, and Foxp3+ T regulatory cells (Treg) was observed in both, the colon and spleen with FMT-P in contrast to FMT-NP. We also found that in FMT-P mice there was a significant decrease in tjp1 expression in all three regions of the small intestine; ocln in the ileum; reg3γ in the duodenum and relmβ in both the duodenum and ileum. We also found an increase in colonic mucus layer thickness in mice colonized with FMT-P in contrast with FMT-NP. Finally, our results suggest that gut protozoa, such as Blastocystis hominis, Entamoeba coli, Endolimax nana, Entamoeba histolytica/E. dispar, Iodamoeba bütschlii, and Chilomastix mesnili consortia affect the immunoinflammatory state and induce functional changes in the intestine via the gut microbiota. Likewise, it allows us to establish an FMT model in germ-free mice as a viable alternative to explore the effects that exposure to intestinal parasites could have on the immune response in humans.}, } @article {pmid39463943, year = {2024}, author = {Dai, A and Adintori, PA and Funnell, T and Jogia, WP and Fei, T and Waters, NR and Rangesa, M and Ballweg, A and Gipson, B and Raj, S and Hayase, E and Markey, KA and Burgos da Silva, M and Miltiadous, O and Brambilla, CZ and Buchan, ML and Peets, T and Gradissimo, A and Smith, N and Katsamakis, Z and Warren, A and Amoretti, LA and Duan, C and Zhang, C and Matheis, F and Sullivan, AP and Slingerland, JB and Clurman, A and Brereton, DG and Giardina, PA and Gomes, ALC and Johnson, AJ and Knights, D and Jenq, RR and Perales, MA and Giralt, SA and Schluter, J and van den Brink, MRM and Peled, J}, title = {Sugar-rich foods exacerbate antibiotic-induced microbiome injury.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.10.14.617881}, pmid = {39463943}, issn = {2692-8205}, abstract = {Intestinal microbiota composition is implicated in several diseases; understanding the factors that influence it are key to elucidating host-commensal interactions and to designing microbiome-targeted therapies. We quantified how diet influences microbiome dynamics in hospitalized patients. We recorded 9,419 meals consumed by 173 patients undergoing hematopoietic cell transplantation and profiled the microbiome in 1,009 longitudinally collected stool samples from 158 of them. Caloric intake was correlated with fecal microbiota diversity. Bayesian inference revealed associations between intake of sweets or sugars during antibiotic exposure with microbiome disruption, as assessed by low diversity or expansion of the pathobiont Enterococcus. We validated this observation experimentally, finding that sucrose exacerbated antibiotic-induced Enterococcus expansion in mice. Taken together, our results suggest that avoiding sugar-rich foods during antibiotic treatment may reduce microbiome injury.}, } @article {pmid39462615, year = {2024}, author = {Ozaki, Y and Suzuki, Y and Suzuki, H}, title = {[Gut Microbiota as a Potential Biomarker for Immune Checkpoint Inhibitors].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {9}, pages = {862-864}, pmid = {39462615}, issn = {0385-0684}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Immune Checkpoint Inhibitors/therapeutic use ; *Lung Neoplasms/drug therapy/immunology/microbiology ; Biomarkers, Tumor/immunology ; }, abstract = {Immune checkpoint inhibitors(ICIs)currently play a predominant role in the standard treatment of non-small cell lung cancer(NSCLC)across all stages. While PD-L1 positivity has traditionally been used as the sole effective biomarker, evidence suggests that certain efficacy exists even in PD-L1-negative lung cancers. Various investigations have been conducted to identify biomarkers predicting the therapeutic efficacy of ICIs, focusing on both tumor-local and host-related factors. Among indicators reflecting the host status, the gut microbiota has garnered attention, with its composition and diversity potentially influencing the efficacy of ICI therapy. The presence of specific gut microbiota has been frequently reported to enhance the effectiveness of ICI treatment. Furthermore, the use of antibiotics may diminish the effects of ICIs, while fecal microbiota transplantation has shown potential to enhance ICI therapy. In our department, analysis of the gut microbiota in patients receiving anti-PD-1 antibody treatment has been conducted, yielding promising results through the identification of specific bacterial species and the search for these species using real-time PCR, suggesting avenues for further research. Recently, attention has also been drawn to the lung microbiota and tumor microbiota in the context of lung cancer, with reports suggesting that increased diversity in these microbial communities may correlate with the efficacy of ICI therapy. However, none of these findings alone provide sufficient evidence as standalone biomarkers, necessitating future research to advance from both the host environment, including the gut microbiota, and the microenvironment of the tumor site, such as the lung and tumor microbiota.}, } @article {pmid39462312, year = {2024}, author = {Garcia-Martinez, Y and Alexandrova, E and Iebba, V and Ferravante, C and Spinelli, M and Franci, G and Amoresano, A and Weisz, A and Trepiccione, F and Borriello, M and Ingrosso, D and Perna, AF}, title = {Does gut microbiota dysbiosis impact the metabolic alterations of hydrogen sulfide and lanthionine in patients with chronic kidney disease?.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {436}, pmid = {39462312}, issn = {1471-2180}, support = {Grant agreement No [860329]//European Union's Horizon 2020 research and innovation program/ ; Grant agreement No [860329]//European Union's Horizon 2020 research and innovation program/ ; Grant agreement No [860329]//European Union's Horizon 2020 research and innovation program/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Hydrogen Sulfide/metabolism ; *Renal Insufficiency, Chronic/microbiology/metabolism ; Male ; Female ; Middle Aged ; *Dysbiosis/microbiology ; *Feces/microbiology/chemistry ; Aged ; Sulfides/metabolism ; Adult ; Renal Dialysis ; Bacteria/classification/isolation & purification/metabolism/genetics ; Alanine/analogs & derivatives/metabolism ; Case-Control Studies ; }, abstract = {BACKGROUND: Chronic Kidney Disease (CKD) is characterized by a methionine-related metabolic disorder involving reduced plasma levels of hydrogen sulfide (H2S) and increased lanthionine. The gut microbiota influences methionine metabolism, potentially impacting sulfur metabolite dysfunctions in CKD. We evaluated whether gut microbiota dysbiosis contributes to H2S and lanthionine metabolic alterations in CKD.

METHODS: The gut microbiota of 88 CKD patients (non-dialysis, hemodialysis, and transplant patients) and 26 healthy controls were profiled using 16 S-amplicon sequencing. H2S and lanthionine concentrations were measured in serum and fecal samples using the methylene blue method and LC-MS/MS, respectively.

RESULTS: The CKD population exhibited a tenfold increase in serum lanthionine associated with kidney dysfunction. Despite lanthionine retention, hemodialysis and transplant patients had significantly lower serum H2S than healthy controls. Fecal H2S levels were not altered or related to bloodstream H2S concentrations. Conversely, fecal lanthionine was significantly increased in CKD compared to healthy controls and associated with kidney dysfunction. Microbiota composition varied among CKD groups and healthy controls, with the greatest dissimilarity observed between hemodialysis and transplant patients. Changes relative to the healthy group included uneven Ruminococcus gnavus distribution (higher in transplant patients and lower in non-dialysis CKD patients), reduced abundance of the short-chain fatty acid-producing bacteria Alistipes indistinctus and Coprococcus eutactus among transplant patients, and depleted Streptococcus salivarius in non-dialysis CKD patients. A higher abundance of Methanobrevibacter smithii, Christensenella minuta, and Negativibacillus massiliensis differentiated hemodialysis patients from controls. No correlation was found between differentially abundant species and the metabolic profile that could account for the H2S and lanthionine alterations observed.

CONCLUSIONS: The metabolic deregulation of H2S and lanthionine observed in the study was not associated with alterations in the gut microbiota composition in CKD patients. Further research on microbial sulfur pathways may provide a better understanding of the role of gut microbiota in maintaining H2S and lanthionine homeostasis.}, } @article {pmid39462039, year = {2024}, author = {Zhou, X and Shen, S and Wang, Z}, title = {Genetic evidence of bidirectional mendelian randomization study on the causality between gut microbiome and respiratory diseases contributes to gut-lung axis.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {25550}, pmid = {39462039}, issn = {2045-2322}, support = {82174302//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Mendelian Randomization Analysis ; *Gastrointestinal Microbiome/genetics ; *Genome-Wide Association Study ; Lung/microbiology/pathology ; Respiratory Tract Diseases/microbiology/genetics ; Risk Factors ; }, abstract = {Observational studies and clinical trials have suggested the relationship between the gut microbiome and respiratory diseases, but the causality between them remains unclear. Firstly, we selected eight respiratory diseases Genome-wide association study (GWAS) datasets mainly from the FinnGen collaboration as outcomes. The exposure was based on GWAS statistics about the gut microbiome, sourced from the MiBioGen consortium, including gut microbial taxa. The causal link between the gut microbiome and respiratory illnesses was then estimated using a Two-sample Mendelian randomization (MR) analysis, including the inverse-variance weighted (IVW), weighted median, MR-Egger, simple mode, and weighted mode. To ensure reliability, F-statistics and sensitivity tests were conducted. Furthermore, we performed a reverse MR analysis of the pre-Mendelian positive findings to possible reverse causality. For the 196 gut microbe taxa, the IVW analysis suggested 88 potential associations with eight clinically prevalent respiratory diseases. Among them, 30 causal associations were found in more than one MR method. Multiple statistical corrections have confirmed three causal associations: genus Holdemanella was a risk factor for chronic obstructive pulmonary disease (COPD) (P = 1.3 × 10[-4], OR = 1.18), family FamilyXIII was a protective factor for COPD (P = 1.3 × 10[-3], OR = 0.75), and genus Oxalobacter was a risk factor for asthma (P = 2.1 × 10[-4], OR = 1.09). Our MR analysis results indicate that there would be a causal relationship between the gut microbiome and respiratory diseases, contributing to the gut-lung axis. This finding offers new insights into the gut microbiome's roles in respiratory diseases' clinical prevention, pathogenesis, and improvement of clinical symptoms. Further randomized controlled trials are necessary to clarify the protective effect of probiotics and fecal microbial transplantation on respiratory health.}, } @article {pmid39461299, year = {2024}, author = {Verbiest, A and Hvistendahl, MK and Bolognani, F and Li, C and Youssef, NN and Huh, S and Menys, A and Bhatnagar, G and Vanslembrouck, R and Peeters, R and Sartoris, R and Vermeersch, P and Wauters, L and Verbeke, K and Jeppesen, PB and Joly, F and Vanuytsel, T}, title = {Efficacy and safety of apraglutide in short bowel syndrome with intestinal failure and colon-in-continuity: A multicenter, open-label, metabolic balance study.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {43}, number = {12}, pages = {158-166}, doi = {10.1016/j.clnu.2024.10.011}, pmid = {39461299}, issn = {1532-1983}, abstract = {BACKGROUND: Apraglutide is a novel long-acting GLP-2 analog in development for short bowel syndrome with intestinal failure (SBS-IF). This multicenter, open-label, phase 2 study in SBS-IF and colon-in-continuity (CiC) investigates the safety and efficacy of apraglutide.

METHODS: This was a 52-week phase 2 metabolic balance study (MBS) in 9 adult patients with SBS-IF-CiC receiving once-weekly subcutaneous apraglutide injections. Safety was the primary endpoint. Secondary endpoints included changes in absorption parameters (MBS at baseline, after 4 weeks with stable parenteral support (PS), and 48 weeks), PS needs (48-week PS adjustment period based on monthly 48-h fluid balances) and intestinal morphology and motility (static and cine MRI at baseline and 4, 24 and 48 weeks).

RESULTS: PS volume decreased by -4702 mL/week (-52 %; p < 0.001) at week 52. Seven patients (78 %) achieved ≥1 day off PS at week 52. At 4 weeks, fecal output was reduced by 253 g/day (p = 0.013). At 48 weeks, increases in wet weight absorption by 316 g/day (p = 0.039), energy absorption by 1134 kJ/day (p = 0.041) and carbohydrate absorption by 56.1 g/day (p = 0.024) were observed. Moreover, small bowel length increased from 29.7 to 40.7 cm (p = 0.012), duodenal wall thickness increased by 0.8 mm (p = 0.02) and motility in the proximal colon was reduced (p = 0.031). A total of 127 adverse events was reported, which were mostly mild to moderate.

CONCLUSION: Apraglutide had an acceptable safety profile and was associated with significant reductions in PS needs and days off PS, improvements in intestinal absorption, and structural and functional intestinal changes in patients with SBS-IF-CiC.

CLINICALTRIALS: gov, Number NCT04964986.}, } @article {pmid39460926, year = {2024}, author = {Magnusson, C and Ölfvingsson, E and Hjortswang, H and Östholm, Å and Serrander, L}, title = {Improved health-related quality of life in patients with recurrent Clostridioides difficile infection after treatment with faecal microbiota transplantation.}, journal = {Infectious diseases (London, England)}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/23744235.2024.2415694}, pmid = {39460926}, issn = {2374-4243}, abstract = {BACKGROUND: Clostridioides difficile is a major burden for both healthcare systems and the patients. Faecal microbiota transplantation (FMT) is becoming more common as a treatment since it reduces the risk of recurrent Clostridioides difficile infection (rCDI).

OBJECTIVES: To evaluate how treatment with FMT is affecting the health-related quality of life (HRQoL) in patients with rCDI.

METHODS: A prospective observational cohort study was conducted where patients who were offered FMT as a treatment for rCDI were asked to fill in a questionnaire based on the Short Health Scale (SHS) and EuroQol 5-Dimensions 5-Levels (EQ-5D-5L) about their HRQoL before and after treatment.

RESULTS: Patients with rCDI had poor HRQoL, which improved following FMT.

CONCLUSIONS: Since FMT cures, reduces the risk of new recurrences of CDI and improves the HRQoL of the patients, it should be offered as a treatment for patients with rCDI. Also, SHS is a useful and reliable instrument for measuring HRQoL in patients with rCDI.}, } @article {pmid39460538, year = {2024}, author = {Yang, J and Liang, J and Hu, N and He, N and Liu, B and Liu, G and Qin, Y}, title = {The Gut Microbiota Modulates Neuroinflammation in Alzheimer's Disease: Elucidating Crucial Factors and Mechanistic Underpinnings.}, journal = {CNS neuroscience & therapeutics}, volume = {30}, number = {10}, pages = {e70091}, pmid = {39460538}, issn = {1755-5949}, support = {2024yjscx013//Innovative Research Project for Postgraduate Students of Heilongjiang University of Traditional Chinese Medicine/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; *Alzheimer Disease/microbiology/metabolism/pathology ; Humans ; *Neuroinflammatory Diseases/microbiology/metabolism ; Animals ; Dysbiosis ; Blood-Brain Barrier/metabolism/microbiology ; Fecal Microbiota Transplantation ; Probiotics ; }, abstract = {BACKGROUND AND PURPOSE: Alzheimer's disease (AD) is characterized by progressive cognitive decline and neuronal loss, commonly linked to amyloid-β plaques, neurofibrillary tangles, and neuroinflammation. Recent research highlights the gut microbiota as a key player in modulating neuroinflammation, a critical pathological feature of AD. Understanding the role of the gut microbiota in this process is essential for uncovering new therapeutic avenues and gaining deeper insights into AD pathogenesis.

METHODS: This review provides a comprehensive analysis of how gut microbiota influences neuroinflammation and glial cell function in AD. A systematic literature search was conducted, covering studies from 2014 to 2024, including reviews, clinical trials, and animal studies. Keywords such as "gut microbiota," "Alzheimer's disease," "neuroinflammation," and "blood-brain barrier" were used.

RESULTS: Dysbiosis, or the imbalance in gut microbiota composition, has been implicated in the modulation of key AD-related mechanisms, including neuroinflammation, blood-brain barrier integrity, and neurotransmitter regulation. These disruptions may accelerate the onset and progression of AD. Additionally, therapeutic strategies targeting gut microbiota, such as probiotics, prebiotics, and fecal microbiota transplantation, show promise in modulating AD pathology.

CONCLUSIONS: The gut microbiota is a pivotal factor in AD pathogenesis, influencing neuroinflammation and disease progression. Understanding the role of gut microbiota in AD opens avenues for innovative diagnostic, preventive, and therapeutic strategies.}, } @article {pmid39459579, year = {2024}, author = {Alswat, AS}, title = {The Influence of the Gut Microbiota on Host Health: A Focus on the Gut-Lung Axis and Therapeutic Approaches.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {10}, pages = {}, pmid = {39459579}, issn = {2075-1729}, abstract = {The human gut microbiota is a complex ecosystem harboring thousands of microbial strains that play a crucial role in maintaining the overall well-being of its host. The composition of the gut microbiota varies with age from infancy to adulthood and is influenced by dietary habits, environment, and genetic disposition. Recent advances in culture-independent techniques and nucleic acid sequencing have improved our understanding of the diversity of the gut microbiota. The microbial species present in the gut release short-chain fatty acids (SCFAs), which have anti-inflammatory properties. The gut microbiota also plays a substantial role in modulating the host's immune system, promoting immune tolerance, and maintaining homeostasis. The impact of the gut microbiota on the health of the host is quite evident, as gut dysbiosis has been linked to various diseases, including metabolic disorders, autoimmune diseases, allergies, and inflammatory bowel diseases. The gut microbiota has bidirectional communication with the respiratory system, creating the gut-lung axis, which has been associated with different respiratory diseases. Therapeutic approaches targeting the gut microbiota, such as probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation (FMT), aim to restore microbial balance and promote the growth of beneficial strains in the gut. Nonetheless, gaining knowledge of the complex interactions between the gut microbiota and the host is necessary to develop personalized medicine approaches and microbiota-based therapies for various conditions. This review summarizes studies related to the gut-lung axis with particular emphasis on the role of the microbiota. Future research directions are also discussed.}, } @article {pmid39458553, year = {2024}, author = {Borrego-Ruiz, A and Borrego, JJ}, title = {Nutritional and Microbial Strategies for Treating Acne, Alopecia, and Atopic Dermatitis.}, journal = {Nutrients}, volume = {16}, number = {20}, pages = {}, pmid = {39458553}, issn = {2072-6643}, mesh = {Humans ; *Dermatitis, Atopic/therapy/microbiology ; *Gastrointestinal Microbiome ; *Acne Vulgaris/therapy/microbiology ; *Probiotics/therapeutic use/administration & dosage ; *Alopecia/therapy/microbiology ; Synbiotics/administration & dosage ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; Diet ; Skin/microbiology ; }, abstract = {BACKGROUND/OBJECTIVES: Diet is one of the major determinants of the composition and function of the gut microbiome, and diverse studies have established directional connections between gut microbiome dysbiosis and skin dyshomeostasis. Furthermore, a significant link between the gut and certain skin-related disorders has been reported. This work reviews the mechanisms underlying the relationship between nutritional factors, gut microbiome, and certain skin diseases such as acne vulgaris, alopecia, and atopic dermatitis. In addition, it explores how the modulation of the gut microbiome and human skin through diet and various microbial strategies, including probiotics, synbiotics, postbiotics, and fecal microbiota transplantation, may serve as future treatments for skin diseases, possibly replacing traditional methods such as antibiotic, topical corticosteroid, and laser therapies.

RESULTS: The adequate intake of certain foods can promote a balanced gut microbiome, potentially reducing skin inflammation and improving overall skin health, while poor dietary choices may lead to worse outcomes by disrupting gut homeostasis. In this regard, diets high in antioxidants, fiber, and phytonutrients appear to be beneficial for enhancing skin health and preventing associated comorbidities. In addition, the administration of probiotics, synbiotics, and postbiotics in the treatment of cutaneous diseases has been shown to restore skin dyshomeostasis and to improve the symptoms of the reviewed skin conditions.

CONCLUSIONS: Consuming a healthy, plant-based diet can reduce skin inflammation and enhance overall skin health. Although the application of probiotics, synbiotics, and postbiotics has demonstrated promise in modulating inflammation, enhancing tissue regeneration, and inhibiting pathogenic colonization, further research is required.}, } @article {pmid39458486, year = {2024}, author = {Gómez-Pérez, AM and Muñoz-Garach, A and Lasserrot-Cuadrado, A and Moreno-Indias, I and Tinahones, FJ}, title = {Microbiota Transplantation in Individuals with Type 2 Diabetes and a High Degree of Insulin Resistance.}, journal = {Nutrients}, volume = {16}, number = {20}, pages = {}, pmid = {39458486}, issn = {2072-6643}, support = {PI15/011114//Instituto de Salud Carlos III/ ; EPIGEN-MICROBIOTA NCT05076656, PI15/01114//CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Fondo de Investigación para la Salud/ ; CPII21/00013//Instituto de Salud Carlos III-FEDER: Miguel Servet II programm/ ; B-0033-2014//Servicio Andaluz de Salud/ ; }, mesh = {Humans ; *Diabetes Mellitus, Type 2/therapy/blood/microbiology ; Female ; Male ; *Insulin Resistance ; Middle Aged ; *Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; Aged ; *Blood Glucose/metabolism ; Single-Blind Method ; Glucose Tolerance Test ; Gastrointestinal Microbiome ; Insulin/blood ; Body Mass Index ; Lactobacillus delbrueckii ; Treatment Outcome ; Glycated Hemoglobin/metabolism ; }, abstract = {The objective of this study was to determine the results of fecal microbiota transplantation (FMT) from healthy lean subjects in patients with type 2 diabetes (T2D); Methods: We designed a phase II, randomized, single-blind, parallel-arm clinical trial. Twenty-one subjects (12 men [57.1%] and 9 women [42.9%]), who had previously signed an informed consent were randomized to FMT from lean donors, a probiotic (Lactobacillus delbrueckii spp. bulgaricus LB-14), or placebo. Mean age at baseline was 62.5 ± 5.8 years and mean body mass index (BMI) at baseline was approximately 32.4 ± 2.4 kg/m[2]. Anthropometric measures, biochemical variables, oral glucose tolerance test (OGTT), and a stool microbiota analysis were performed (baseline, 4 and 12 weeks). The trial was conducted following the Declaration of Helsinki, Good Clinical Practice Guides (CPMP/ICH/135/95) and the current Spanish legislation regarding clinical trials (RD 223/2004).; Results: FMT changes occurred at the expense of the species found in the donor. No differences in weight, body mass index, HbA1c, or the results of the OGTT for glucose and insulin were found between groups after the intervention, although a decrease in uric acid was observed in the probiotic group (-0.5 mg/dL; p = 0.037) and a mild increase in HbA1c in the FMT group (+0.25%; p = 0.041); Conclusions: In our sample, neither FMT from healthy and lean donors nor a probiotic were effective in improving insulin sensitivity and HbA1c in patients with T2D.}, } @article {pmid39458368, year = {2024}, author = {Marsiglia, R and Pane, S and Del Chierico, F and Russo, A and Vernocchi, P and Romani, L and Cardile, S and Diamanti, A and Galli, L and Tamborino, A and Terlizzi, V and De Angelis, P and Angelino, G and Putignani, L}, title = {Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infections in a Cystic Fibrosis Child Previously Screen Positive, Inconclusive Diagnosis (CFSPID): A Case Report.}, journal = {Microorganisms}, volume = {12}, number = {10}, pages = {}, pmid = {39458368}, issn = {2076-2607}, support = {Current Research funds//Italian Ministry of Health/ ; }, abstract = {Clostridioides difficile infection (CDI) is generally treated with vancomycin, metronidazole or fidaxomicin, although fecal microbiota transplantation (FMT) represents a promising therapeutic option for antibiotic-resistant recurrent C. difficile infections (rCDIs) in adults. In pediatric cystic fibrosis (CF) patients, CDIs are generally asymptomatic and respond to treatment. Here, we present the case of an 8-year-old female, initially diagnosed as "CFTR-related metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis" (CMRS/CFSPID), who then progressed to CF at 12 months. In the absence of CF-related symptoms, she presented multiple and disabling episodes of bloody diarrhoea with positive tests for C. difficile antigen and A/B toxin. After conventional treatments failed and several CDI relapses, FMT was proposed. Donor screening and GM donor-receiver matching identified her mother as a donor. Metataxonomy and targeted metabolomics provided, through a pre- and post-FMT time course, gut microbiota (GM) profiling to assess GM engraftment. At first, the GM map revealed severe dysbiosis, with a prevalence of Bacteroidetes and Proteobacteria (i.e., Klebsiella spp., Escherichia coli), a reduction in Firmicutes, a GM nearly entirely composed of Enterococcaceae (i.e., Enterococcus) and an almost complete depletion of Verrucomicrobia and Actinobacteria, mostly represented by Veillonella dispar. Post FMT, an increment in Bifidobacterium spp. and Collinsella spp. with a decrease in V. dispar restored intestinal eubiosis. Consistently, four weeks after FMT treatment, the child's gut symptoms cleared, without CDI recurrence.}, } @article {pmid39458032, year = {2024}, author = {Piccioni, A and Spagnuolo, F and Candelli, M and Voza, A and Covino, M and Gasbarrini, A and Franceschi, F}, title = {The Gut Microbiome in Sepsis: From Dysbiosis to Personalized Therapy.}, journal = {Journal of clinical medicine}, volume = {13}, number = {20}, pages = {}, pmid = {39458032}, issn = {2077-0383}, abstract = {Sepsis is a complex clinical syndrome characterized by an uncontrolled inflammatory response to an infection that may result in septic shock and death. Recent research has revealed a crucial link between sepsis and alterations in the gut microbiota, showing that the microbiome could serve an essential function in its pathogenesis and prognosis. In sepsis, the gut microbiota undergoes significant dysbiosis, transitioning from a beneficial commensal flora to a predominance of pathobionts. This transformation can lead to a dysfunction of the intestinal barrier, compromising the host's immune response, which contributes to the severity of the disease. The gut microbiota is an intricate system of protozoa, fungi, bacteria, and viruses that are essential for maintaining immunity and metabolic balance. In sepsis, there is a reduction in microbial heterogeneity and a predominance of pathogenic bacteria, such as proteobacteria, which can exacerbate inflammation and negatively influence clinical outcomes. Microbial compounds, such as short-chain fatty acids (SCFAs), perform a crucial task in modulating the inflammatory response and maintaining intestinal barrier function. However, the role of other microbiota components, such as viruses and fungi, in sepsis remains unclear. Innovative therapeutic strategies aim to modulate the gut microbiota to improve the management of sepsis. These include selective digestive decontamination (SDD), probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT), all of which have shown potential, although variable, results. The future of sepsis management could benefit greatly from personalized treatment based on the microbiota. Rapid and easy-to-implement tests to assess microbiome profiles and metabolites associated with sepsis could revolutionize the disease's diagnosis and management. These approaches could not only improve patient prognosis but also reduce dependence on antibiotic therapies and promote more targeted and sustainable treatment strategies. Nevertheless, there is still limited clarity regarding the ideal composition of the microbiota, which should be further characterized in the near future. Similarly, the benefits of therapeutic approaches should be validated through additional studies.}, } @article {pmid39457652, year = {2024}, author = {Zhang, J and Gan, H and Duan, X and Li, G}, title = {Targeting the Intestinal Microbiota: A Novel Direction in the Treatment of Inflammatory Bowel Disease.}, journal = {Biomedicines}, volume = {12}, number = {10}, pages = {}, pmid = {39457652}, issn = {2227-9059}, support = {82170617//National Natural Science Foundation of China/ ; }, abstract = {Over the past decade, there has been a rapid increase in the incidence of inflammatory bowel disease. It has been suggested that multifactorial interactions of environmental factors, genetic factors, immune response and intestinal microbiota are involved in the pathogenesis of inflammatory bowel disease. It is widely recognized that the intestinal microbiota are essential for human metabolism, the immune system and pathogen resistance, and are integral to human health. Therefore, the dysbiosis of the microbiota is a critical step leading to intestinal mucosal damage and a key factor in the pathogenesis of inflammatory bowel disease. Regulating the microbiota through interventions such as enteral nutrition, fecal microbiota transplantation, and probiotic supplementation has the potential to prevent or even reverse intestinal dysbiosis, opening up new perspectives for the treatment of inflammatory bowel disease.}, } @article {pmid39457040, year = {2024}, author = {Mousa, WK and Al Ali, A}, title = {The Gut Microbiome Advances Precision Medicine and Diagnostics for Inflammatory Bowel Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {20}, pages = {}, pmid = {39457040}, issn = {1422-0067}, mesh = {Humans ; *Inflammatory Bowel Diseases/microbiology/therapy/diagnosis/genetics ; *Gastrointestinal Microbiome ; *Precision Medicine/methods ; *Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Animals ; Metabolomics/methods ; }, abstract = {The gut microbiome emerges as an integral component of precision medicine because of its signature variability among individuals and its plasticity, which enables personalized therapeutic interventions, especially when integrated with other multiomics data. This promise is further fueled by advances in next-generation sequencing and metabolomics, which allow in-depth high-precision profiling of microbiome communities, their genetic contents, and secreted chemistry. This knowledge has advanced our understanding of our microbial partners, their interaction with cellular targets, and their implication in human conditions such as inflammatory bowel disease (IBD). This explosion of microbiome data inspired the development of next-generation therapeutics for treating IBD that depend on manipulating the gut microbiome by diet modulation or using live products as therapeutics. The current landscape of artificial microbiome therapeutics is not limited to probiotics and fecal transplants but has expanded to include community consortia, engineered probiotics, and defined metabolites, bypassing several limitations that hindered rapid progress in this field such as safety and regulatory issues. More integrated research will reveal new therapeutic targets such as enzymes or receptors mediating interactions between microbiota-secreted molecules that drive or modulate diseases. With the shift toward precision medicine and the enhanced integration of host genetics and polymorphism in treatment regimes, the following key questions emerge: How can we effectively implement microbiomics to further personalize the treatment of diseases like IBD, leveraging proven and validated microbiome links? Can we modulate the microbiome to manage IBD by altering the host immune response? In this review, we discuss recent advances in understanding the mechanism underpinning the role of gut microbes in driving or preventing IBD. We highlight developed targeted approaches to reverse dysbiosis through precision editing of the microbiome. We analyze limitations and opportunities while defining the specific clinical niche for this innovative therapeutic modality for the treatment, prevention, and diagnosis of IBD and its potential implication in precision medicine.}, } @article {pmid39456641, year = {2024}, author = {Wu, M and Tian, C and Zou, Z and Jin, M and Liu, H}, title = {Gastrointestinal Microbiota in Gastric Cancer: Potential Mechanisms and Clinical Applications-A Literature Review.}, journal = {Cancers}, volume = {16}, number = {20}, pages = {}, pmid = {39456641}, issn = {2072-6694}, support = {WJ2023M92//Scientific research project of Hubei Provincial Health Commission/ ; 320.6750.2023-19-7 and 320.6750.2024-10-2//Clinical Research Special Fund of Wu Jieping Medical Foundation/ ; WX23A31//Medical Science Research Fundation of Wuhan/ ; }, abstract = {Emerging evidence highlights the crucial role of gastrointestinal microbiota in the pathogenesis of gastric cancer. Helicobacter pylori (H. pylori) infection stands out as a primary pathogenic factor. However, interventions such as anti-H. pylori therapy, gastric surgeries, immunotherapy, and chronic inflammation significantly remodel the gastric microbiome, implicating a broader spectrum of microorganisms in cancer development. These microbial populations can modulate gastric carcinogenesis through various mechanisms, including sustained chronic inflammation, bacterial genotoxins, alterations in short-chain fatty acids, elevated gastrointestinal bile acids, impaired mucus barrier function, and increased concentrations of N-nitrosamines and lactic acid. The dynamic changes in gut microbiota also critically influence the outcomes of anti-cancer therapies by modifying drug bioavailability and metabolism, thus affecting therapeutic efficacy and side effect profiles. Additionally, the effectiveness of radiotherapy can be significantly impacted by gut microbiota alterations. Novel therapeutic strategies targeting the microbiome, such as dietary interventions, probiotic and synbiotic supplementation, and fecal microbiota transplantation, are showing promise in cancer treatment. Understanding the intricate relationship between the gut microbiota and gastric cancer is essential for developing new, evidence-based approaches to the prevention and treatment of this malignancy.}, } @article {pmid39455910, year = {2024}, author = {Tang, BB and Su, CX and Wen, N and Zhang, Q and Chen, JH and Liu, BB and Wang, YQ and Huang, CQ and Hu, YL}, title = {FMT and TCM to treat diarrhoeal irritable bowel syndrome with induced spleen deficiency syndrome- microbiomic and metabolomic insights.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {433}, pmid = {39455910}, issn = {1471-2180}, support = {2023ZR004//TCM science and technology project of Zhejiang Province/ ; 2024KY869//Zhejiang Provincial Medical and Health Science and Technology Project/ ; 2022020801020508//Knowledge Innovation Program of Wuhan Shuguang Project/ ; 2022020801020584//Knowledge Innovation Program of Wuhan Shuguang Project/ ; 82374205//National Natural Science Foundation of China/ ; 2020020601012244//Wuhan Applied Foundational Frontier Project/ ; }, mesh = {Animals ; *Irritable Bowel Syndrome/therapy/microbiology/drug therapy ; *Gastrointestinal Microbiome/drug effects ; Rats ; *Fecal Microbiota Transplantation ; *Diarrhea/microbiology/therapy/drug therapy ; *Medicine, Chinese Traditional/methods ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *Disease Models, Animal ; *Metabolomics ; Splenic Diseases/therapy/microbiology/drug therapy ; Male ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; Spleen/microbiology/metabolism ; }, abstract = {BACKGROUND: Diarrheal irritable bowel syndrome (IBS-D) is a functional bowel disease with diarrhea, and can be associated with common spleen deficiency syndrome of the prevelent traditional Chinese medicine (TCM) syndrome. Fecal microbiota transplantation (FMT) could help treating IBS-D, but may provide variable effects. Our study evaluated the efficacy of TCM- shenling Baizhu decoction and FMT in treating IBS-D with spleen deficiency syndrome, with significant implications on gut microbiome and serum metabolites.

METHODS: The new borne rats were procured from SPF facility and separated as healthy (1 group) and IBS-D model (3 groups) rats were prepared articially using mother's separation and senna leaf treatment. 2 groups of IBS-D models were further treated with TCM- shenling Baizhu decoction and FMT. The efficacy was evaluated by defecation frequency, bristol stool score, and intestinal tight junction proteins (occludin-1 and claudin-1) expression. Microbiomic analysis was conducted using 16 S rRNA sequencing and bioinformatics tools. Metabolomics were detected in sera of rats by LC-MS and annotated by using KEGG database.

RESULTS: Significant increment in occludin-1 and claudin-1 protein expression alleviated the diarrheal severity in IBS-D rats (P < 0.05) after treatment with FMT and TCM. FMT and TCM altered the gut microbiota and regulated the tryptophan metabolism, steroid hormone biosynthesis and glycerophospholipid metabolism of IBS-D rats with spleen deficiency syndrome.The microbial abundance were changed in each case e.g., Monoglobus, Dubosiella, and Akkermansia and othe metabolic profiles.

CONCLUSION: FMT and TCM treatment improved the intestinal barrier function by regulating gut microbiota and improved metabolic pathways in IBS-D with spleen deficiency syndrome.}, } @article {pmid39454127, year = {2024}, author = {Ran, X and Li, Y and Guo, W and Li, K and Guo, W and Wang, X and Liu, J and Bi, J and Fu, S}, title = {Angelica sinensis Polysaccharide Alleviates Staphylococcus aureus-Induced Mastitis by Regulating The Intestinal Flora and Gut Metabolites.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c06094}, pmid = {39454127}, issn = {1520-5118}, abstract = {The modulation of intestinal flora by various polysaccharides has been shown to mitigate disease progression. Recent research reveals a significant link between intestinal flora and the progression of mastitis. This study demonstrates that the oral administration of Angelica sinensis polysaccharide (ASP) reduces mammary inflammation and blood-milk barrier (BMB) damage induced by Staphylococcus aureus in mice, primarily through the modulation of intestinal flora. The beneficial effects of ASP were negated when antibiotics disrupted the gut microbiota in mice. Furthermore, fecal microbiota transplantation (FMT) from ASP-treated mice to recipients markedly alleviated symptoms of S. aureus-induced mastitis. Oral ASP not only enhances gut microbial diversity but also shifts its composition, increasing the abundance of Lachnospiraceae_NK4A136 while reducing Erysipelatoclostridium. Metabolomic analysis revealed that ASP alters intestinal metabolic pathways, elevating levels of metabolites, such as tabersonine and riboflavin. Notably, tabersonine was found to ameliorate S. aureus-induced mastitis. These results suggest that targeting intestinal flora and metabolism through polysaccharides could serve as a promising strategy for mastitis intervention and potentially for other infectious diseases, as well.}, } @article {pmid39452187, year = {2024}, author = {Niyazi, D and Vergiev, S and Markovska, R and Stoeva, T}, title = {Prevalence and Molecular Epidemiology of Intestinal Colonization by Multidrug-Resistant Bacteria among Hematopoietic Stem-Cell Transplantation Recipients: A Bulgarian Single-Center Study.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {13}, number = {10}, pages = {}, pmid = {39452187}, issn = {2079-6382}, support = {19019/2019//Medical University of Varna/ ; }, abstract = {Background/Objectives: Intestinal colonization by multidrug-resistant (MDR) bacteria is considered one of the main risk factors for invasive infections in the hematopoietic stem-cell transplant (HSCT) setting, associated with hard-to-eradicate microorganisms. The aim of this study was to assess the rate of intestinal colonization by MDR bacteria and their microbial spectrum in a group of post-HSCT patients to study the genetic determinants of beta-lactam and glycopeptide resistance in the recovered isolates, as well as to determine the epidemiological relation between them. Methods: The intestinal colonization status of 74 patients admitted to the transplantation center of University Hospital "St. Marina"-Varna in the period January 2019 to December 2021 was investigated. Stool samples/rectal swabs were screened for third-generation cephalosporin and/or carbapenem-resistant Gram-negative bacteria, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and Stenotrophomonas maltophilia. Identification and antimicrobial susceptibility testing were performed by Phoenix (BD, Sparks, MD, USA) and MALDI Biotyper sirius (Bruker, Bremen, Germany). Molecular genetic methods (PCR, DNA sequencing) were used to study the mechanisms of beta-lactam and glycopeptide resistance in the collected isolates, as well as the epidemiological relationship between them. Results: A total of 28 patients (37.8%) were detected with intestinal colonization by MDR bacteria. Forty-eight non-duplicate MDR bacteria were isolated from their stool samples. Amongst them, the Gram-negative bacteria prevailed (68.8%), dominated by ESBL-producing Escherichia coli (30.3%), and followed by carbapenem-resistant Pseudomonas sp. (24.2%). The Gram-positive bacteria were represented exclusively by Enterococcus faecium (31.2%). The main beta-lactam resistance mechanisms were associated with CTX-M and VIM production. VanA was detected in all vancomycin-resistant enterococci. A clonal relationship was observed among Enterobacter cloacae complex and among E. faecium isolates. Conclusions: To the best of our knowledge, this is the first Bulgarian study that presents detailed information about the prevalence, resistance genetic determinants, and molecular epidemiology of MDR gut-colonizing bacteria in HSCT patients.}, } @article {pmid39449276, year = {2024}, author = {Zhang, H and Luo, M and Li, Y and Liu, L and Bian, J and Gong, L and He, C and Han, L and Wang, M}, title = {Ellagic acid ameliorates alcohol-induced cognitive and social dysfunction through the gut microbiota-mediated CCL21-CCR7 axis.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d4fo03985h}, pmid = {39449276}, issn = {2042-650X}, abstract = {Chronic alcohol consumption disrupts the balance of the gut microbiome, resulting in alcohol-induced cognitive and social dysfunction (AICSD), and serves as a primary etiological factor for early-onset dementia. Ellagic acid (EA) is a polyphenolic compound belonging to the ellagitannin family, showing potential as a dietary intervention for alleviating cognitive impairments. Nonetheless, the protective effects and underlying mechanisms of EA on AICSD remain unclear. In our study, we employed a multi-omics approach to elucidate the microbiome-mediated mechanism underlying the beneficial effects of EA on AICSD. Firstly, our findings demonstrate that EA significantly ameliorated cognitive and social behavioral deficits as well as neuroinflammation induced by alcohol. Moreover, RNA-seq analysis of hippocampi indicates that EA regulated the KEGG pathway of cytokine-cytokine receptor interaction signaling by downregulating the CCL21-CCR7 axis. Furthermore, we observed that EA effectively restored the dysbiosis of gut microbiota and their derived metabolites induced by chronic alcohol consumption. Strong connections were observed between EA-regulated genes, microbiota and metabolites. Finally, the causal relationship between the microbiome and behavioral changes was further confirmed through antibiotic treatment and fecal microbiota transplantation experiments. Overall, our study provides innovative evidence supporting the role of EA in improving AICSD via regulation of the cytokine-cytokine receptor interaction signaling pathway through the microbiota-mediated CCl21-CCR7 axis. These findings offer valuable insights into both EA-based interventions as well as microbial interventions against AICSD.}, } @article {pmid39449261, year = {2024}, author = {Lee, JW and Kim, N}, title = {[Efficacy of Fecal Microbial Transplantation for Improving Symptoms of Irritable Bowel Syndrome - A Pilot Study for Voluntary Participants in Korea].}, journal = {The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi}, volume = {84}, number = {4}, pages = {168-176}, doi = {10.4166/kjg.2024.107}, pmid = {39449261}, issn = {2233-6869}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy/diagnosis ; *Fecal Microbiota Transplantation ; Male ; Female ; Adult ; Middle Aged ; Pilot Projects ; Surveys and Questionnaires ; Republic of Korea ; Severity of Illness Index ; Treatment Outcome ; Feces/microbiology ; }, abstract = {BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a chronic, intractable functional disease. It is inferred that fecal microbiota transplantation (FMT) may have favorable efficacy on IBS by gut microbial modification. The aim of this study was to investigate the efficacy of FMT for improving severity in patients with IBS.

METHODS: Patients who voluntarily wanted FMT were consecutively enrolled. The study subjects were classified by subtype of IBS by the ROME IV criteria. The IBS-symptom severity score (IBS-SSS) was used to evaluate the efficacy of FMT. The subjects completed a questionnaire at baseline week 0 and weeks 4, 12, and 24 after FMT. FMT was performed by esophagogastroduodenoscopy using frozen stock stool solution. If the follow-up IBS-SSS achieved less than 75 points, it was defined as remission. Adverse events were also gathered.

RESULTS: Twenty-one subjects were included from October 2023 until July 2024. There were 7 patients with IBS-C, 10 patients with IBS-D, 2 patients with IBS-M, and 2 patients with IBS-U type. The mean SSS of the IBS-D group was 244.0±64.2, which was higher than IBS-C group (192.9±85.4). Alleviations in IBS-SSS after FMT were observed in 19 subjects (19/21, 90.5%) at week 4. At week 12, 71.4% (5/7) in the IBS-C group and 20.0% (2/10) in the IBS-D group achieved remission. The remission states were maintained up to week 24 and no serious adverse events were reported.

CONCLUSIONS: FMT might be an effective treatment option for improving symptoms of mild to moderate IBS, especially IBS-C.}, } @article {pmid39449004, year = {2024}, author = {Munoz-Pinto, MF and Candeias, E and Melo-Marques, I and Esteves, AR and Maranha, A and Magalhães, JD and Carneiro, DR and Sant'Anna, M and Pereira-Santos, AR and Abreu, AE and Nunes-Costa, D and Alarico, S and Tiago, I and Morgadinho, A and Lemos, J and Figueiredo, PN and Januário, C and Empadinhas, N and Cardoso, SM}, title = {Gut-first Parkinson's disease is encoded by gut dysbiome.}, journal = {Molecular neurodegeneration}, volume = {19}, number = {1}, pages = {78}, pmid = {39449004}, issn = {1750-1326}, support = {SC01//Cure Parkinson's Trust/ ; PTDC/MED-NEU/3644/2020//Instituto Nacional de Ciência e Tecnologia de Ciência Animal/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Parkinson Disease/metabolism/microbiology/immunology ; Mice ; *Dysbiosis/immunology ; Male ; *Mice, Inbred C57BL ; Humans ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: In Parkinson's patients, intestinal dysbiosis can occur years before clinical diagnosis, implicating the gut and its microbiota in the disease. Recent evidence suggests the gut microbiota may trigger body-first Parkinson Disease (PD), yet the underlying mechanisms remain unclear. This study aims to elucidate how a dysbiotic microbiome through intestinal immune alterations triggers PD-related neurodegeneration.

METHODS: To determine the impact of gut dysbiosis on the development and progression of PD pathology, wild-type male C57BL/6 mice were transplanted with fecal material from PD patients and age-matched healthy donors to challenge the gut-immune-brain axis.

RESULTS: This study demonstrates that patient-derived intestinal microbiota caused midbrain tyrosine hydroxylase positive (TH +) cell loss and motor dysfunction. Ileum-associated microbiota remodeling correlates with a decrease in Th17 homeostatic cells. This event led to an increase in gut inflammation and intestinal barrier disruption. In this regard, we found a decrease in CD4 + cells and an increase in pro-inflammatory cytokines in the blood of PD transplanted mice that could contribute to an increase in the permeabilization of the blood-brain-barrier, observed by an increase in mesencephalic Ig-G-positive microvascular leaks and by an increase of mesencephalic IL-17 levels, compatible with systemic inflammation. Furthermore, alpha-synuclein aggregates can spread caudo-rostrally, causing fragmentation of neuronal mitochondria. This mitochondrial damage subsequently activates innate immune responses in neurons and triggers microglial activation.

CONCLUSIONS: We propose that the dysbiotic gut microbiome (dysbiome) in PD can disrupt a healthy microbiome and Th17 homeostatic immunity in the ileum mucosa, leading to a cascade effect that propagates to the brain, ultimately contributing to PD pathophysiology. Our landmark study has successfully identified new peripheral biomarkers that could be used to develop highly effective strategies to prevent the progression of PD into the brain.}, } @article {pmid39447641, year = {2024}, author = {Li, YL and Chen, BY and Feng, ZH and Zhou, LJ and Liu, T and Lin, WZ and Zhu, H and Xu, S and Bai, XB and Meng, XQ and Zhang, J and Liu, Y and Pu, J and Jiang, M and Duan, SZ}, title = {Roles of oral and gut microbiota in acute myocardial infarction.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2024.10.009}, pmid = {39447641}, issn = {2090-1224}, abstract = {INTRODUCTION: The significance of oral/gut microbiota in acute myocardial infarction (AMI) has been increasingly appreciated. However, correlations between oral/gut microbiota and AMI parameter, as well as the key microbiota that may have a crucial function in this process, remain unclear.

OBJECTIVES: To investigate the composition and structure of oral and gut microbiota associated with AMI and explore the roles of specific bacterial species in the progression of AMI.

METHODS: We conducted a case-control study with 37 AMI patients and 36 controls. Oral and gut sample were collected and sequenced. Using correlation analysis, we combined bioinformatics data with AMI clinical parameters and obtained heatmaps of correlation coefficients. Additionally, we used antibiotics to eliminate the gut microbiota of C57BL/6J mice, followed by the transplantation of selected bacteria to verify the gut colonization of oral bacteria and their impact on AMI.

RESULTS: The component of oral and gut microbiota of AMI group showed significant alterations when compared to the control group. 17 salivary genera, 21 subgingival genera, and 8 gut genera in AMI group substantially differed from those in control group. Additionally, 19 genera from saliva, 19 genera from subgingival plaque, and 11 genera from feces substantially correlated with AMI clinical parameters. Orally administrated S.o (Streptococcus oralis subsp. dentisani), S.p (Streptococcus parasanguinis), and S.s (Streptococcus salivarius) were able to colonize in the gut and exacerbate myocardial infarction.

CONCLUSION: There is a strong correlation between oral/gut microbiota and AMI. Streptococcus spp. is capable to transmit from oral to gut and exacerbate myocardial infarction in mice. Monitoring and control of specific oral microbiota may be an effective new strategy for improving the therapy of AMI.}, } @article {pmid39445550, year = {2024}, author = {Wu, Q and Li, P and Li, X and Ma, L and Chen, K and Man, S}, title = {Pueraria Extract Ameliorates Alcoholic Liver Disease via the Liver-Gut-Brain Axis: Focus on Restoring the Intestinal Barrier and Inhibiting Alcohol Metabolism.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c05365}, pmid = {39445550}, issn = {1520-5118}, abstract = {Alcoholic liver disease (ALD) is one of the causes of hepatocellular carcinoma, accompanied by intestinal leakage and microbial changes. Pueraria has protective effects on liver injury. The aim of this study was to investigate the mechanism of pueraria in the treatment of ALD. UPLC-Q/TOF-MS was used to analyze the composition of the pueraria extract (PUE). Acute and chronic ALD models were established to evaluate the antialcoholic and hepatoprotective effects of PUE. As a result, PUE treatment reduced the serum levels of ALT, AST, TC, and TG and inflammatory factors and alleviated liver inflammation and drunk state. PUE decreased the gene expression of ADH1 and the serum level of acetaldehyde (ACH) to inhibit the generation of ACH from ethanol metabolism, increased the gene level of ALDH2 to accelerate the decomposition of ACH, and thereby alleviated liver inflammation and intestinal barrier damage. Meanwhile, 16 S rDNA revealed that PUE altered the microbiota composition, reduced the amount of Proteobacteria and Desulfobacterota, and thus inhibited the generation of lipopolysaccharide and its downstream-like TLR4/MyD88/NF-κB pathway. PUE also increased the abundance of Bacteroides, Ruminococcus, and Prevotella and producted short-chain fatty acids to protect the intestinal wall. Treatment with fecal microbiota transplantation further confirmed that PUE gut microbiota dependently alleviated ALD. Therefore, PUE regulated gut microbiota and inhibited ethanol metabolism to alleviate ALD through the liver-gut-brain axis. It has good prospects in the future.}, } @article {pmid39444759, year = {2024}, author = {Yaghmaei, H and Bahanesteh, A and Soltanipur, M and Takaloo, S and Rezaei, M and Siadat, SD}, title = {The Role of Gut Microbiota Modification in Nonalcoholic Fatty Liver Disease Treatment Strategies.}, journal = {International journal of hepatology}, volume = {2024}, number = {}, pages = {4183880}, pmid = {39444759}, issn = {2090-3448}, abstract = {One of the most common chronic liver diseases is nonalcoholic fatty liver disease (NAFLD), which affects many people around the world. Gut microbiota (GM) dysbiosis seems to be an influential factor in the pathophysiology of NAFLD because changes in GM lead to fundamental changes in host metabolism. Therefore, the study of the effect of dysbiosis on the pathogenicity of NAFLD is important. European clinical guidelines state that the best advice for people with NAFLD is to lose weight and improve their lifestyle, but only 40% of people can achieve this goal. Accordingly, it is necessary to provide new treatment approaches for prevention and treatment. In addition to dietary interventions and lifestyle modifications, GM modification-based therapies are of interest. These therapies include probiotics, synbiotics, fecal microbiota transplantation (FMT), and next-generation probiotics. All of these treatments have had promising results in animal studies, and it can be imagined that acceptable results will be obtained in human studies as well. However, further investigations are required to generalize the outcomes of animal studies to humans.}, } @article {pmid39442873, year = {2024}, author = {Wang, R and Chen, RL and Wu, C and Zhang, XC and Wu, WY and Dai, C and Wang, Y and Li, G}, title = {The gut microbiotas with metabolites regulate the protective role of miR-30a-5p in myocardial infarction.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2024.10.017}, pmid = {39442873}, issn = {2090-1224}, abstract = {INTRODUCTION: Gut microbial homeostasis is closely associated with myocardial infarction (MI). However, little is known about how gut microbiota influences miRNAs-regulated MI.

OBJECTIVES: This study aims to elucidate the connections between miR-30a-5p, MI, gut microbiota, and gut microbial metabolite-related pathways, to explore potential strategy for preventing and treating MI.

METHODS: We evaluated the effects of knocking out (KO) or overexpressing (OE) miR-30a-5p on MI by assessing cardiac structure and function, myocardial enzyme levels, and apoptosis. Then, we applied 16S rDNA sequencing and metabolomics to explore how intestinal microecology and its microorganisms affect miR-30a-5p-regulated MI.

RESULTS: The results showed that KO exacerbated MI, whereas OE improved MI damage, compared to the wild-type (WT) mice. KO exacerbated intestinal barrier structure deterioration and further downregulated the expression of Cloudin-1, Occludin, and ZO-1 in MI mice. 16S rDNA sequencing-analyzed gut microbiome of KO and WT mice found that KO mainly reduced g_Lactobacillus. Transplanting fecal microorganisms from KO mice aggravated MI damage in WT mice. However, administering probiotics (mainly containing lactobacilli) helped neutralize these damages. Intriguingly, fecal microbiota transplantation from OE mice reduced MI damage. Analysis of intestinal microbial metabolites in KO and WT mice found that KO may mainly affect ABC transporters. ABCC1 was identified as the target of KO-aggravated MI. Furthermore, fecal transplantation microorganisms of MI patients aggravated MI injury in mice and miR-30a-5p and ABCC1 were involved in the process.

CONCLUSIONS: Our findings demonstrate that miR-30a-5p regulates MI by affecting intestinal microbiota homeostasis and targeting ABCC1. This highlights the critical importance of maintaining a healthy gut microbiota homeostasis in MI management.}, } @article {pmid39442743, year = {2024}, author = {Bénard, MV and de Goffau, MC and Blonk, J and Hugenholtz, F and van Buuren, J and Paramsothy, S and Kaakoush, NO and D'Haens, GRAM and Borody, TJ and Kamm, MA and Ponsioen, CY}, title = {Fecal Microbiota Transplantation Outcome and Gut Microbiota Composition in Ulcerative Colitis: a Systematic Review and Meta-analysis.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2024.10.001}, pmid = {39442743}, issn = {1542-7714}, abstract = {BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis (UC), yet its efficacy needs improvement. We conducted a comprehensive evaluation of the current literature on microbial factors affecting outcome, as well as a meta-analysis on some of the largest datasets regarding composition.

METHODS: MEDLINE, Embase and Cochrane were systematically searched through August 2024 for relevant studies. The quality of studies was analyzed with Joanna Briggs tools and a composite critical appraisal-score. Additionally, species-level data from two landmark FMT-trials (TURN and FOCUS) were re-analyzed from a compositional perspective.

RESULTS: Out of 3755 citations identified, 56 met the inclusion criteria, of which 29 fulfilled quality standards. Higher microbial α-diversity, either in donors or recipients (at baseline or following FMT treatment), was associated with better clinical response rates. Engraftment of the donors' microbiota could not be clearly linked with clinical response, possibly because not every donor has an ideal microbiome. Butyrate producing species from the Lachnospiraceae and Oscillospiraceae families were often related with response, whereas the reverse was true for Fusobacteria, many Proteobacteria and Ruminococcus gnavus. Compositional analyses showed that clinical response is associated with a shift from a low-diversity, often Bacteroides dominant composition to one with higher diversity, either dominated by various butyrate producers, the Christensenellaceae-Methanobrevibacter trophic network, or a moderate/high diversity composition with abundant but not excessive levels of Prevotella copri.

CONCLUSION: This systematic review/meta-analysis yielded a coherent picture from a compositional perspective, which may help identify beneficial donor profiles and guide personalized FMT approaches.}, } @article {pmid39442742, year = {2024}, author = {Claytor, JD and Faith, JJ}, title = {Fecal Microbiota Transplantation (FMT) in Ulcerative Colitis: Holding Out for a Superdonor?.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2024.07.047}, pmid = {39442742}, issn = {1542-7714}, } @article {pmid39442279, year = {2024}, author = {Yang, X and Xin, Y and Gu, Y and Wang, Y and Hu, X and Ying, G and Zhang, Q and He, X}, title = {Total alkaloids of Aconitum carmichaelii Debx alleviate cisplatin-induced acute renal injury by inhibiting inflammation and oxidative stress related to gut microbiota metabolism.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156128}, doi = {10.1016/j.phymed.2024.156128}, pmid = {39442279}, issn = {1618-095X}, abstract = {BACKGROUND: Cisplatin-induced acute kidney injury (AKI) is a complex and serious clinical issue, representing a major cause of hospital-acquired AKI. Alkaloids are the main active constituents of Aconitum carmichaelii Debx, which exhibit protective effects in several kidney disease models and against other acute organ injuries. However, its activity and mechanism of action in AKI treatment remain unclear.

PURPOSE: This study aimed to elucidate the effect of Aconitum carmichaelii Debx (ACA) in a model of cisplain-induced AKI and comprehensively investigate its underlying mechanisms.

METHODS: The major alkaloids in ACA were analyzed using high-performance liquid chromatography. Blood urea nitrogen (BUN) and serum creatine levels were measured using automated biochemical instruments. 16S rRNA sequencing, short-chain fatty acid (SCFA) analysis, fecal microbiota transplantation (FMT), non-targeted metabolomics, and transcriptomics were performed to systematically identify prospective biomarkers after ACA treatment. Anti-inflammatory and anti-oxidative stress activities were monitored using ELISA and western blotting.

RESULTS: Four main compounds (fuziline, neoline, talatisamine, and songorine) were identified in ACA. ACA significantly alleviated cisplatin-induced AKI by reducing (BUN) and serum creatine levels and improving histopathological scores. Moreover, ACA balanced cisplatin-mediated confoundments in microbial composition and function, including decreasing the levels of Escherichia-Shigella, Clostridium, and Ruminococcus, as well as increasing Ligilactobacillus, Anaerotruncus, Bacteroides and Desulfovibrio levels, accompanied by uremic toxin reduction, and augmenting serum SCFAs. The FMT experiments further confirmed that ACA exerts anti-AKI effects by affecting gut microbiota. A multi-omics study has shown that ACA regulates glutathione and tryptophan metabolism and mediates pathways that trigger inflammatory responses. Finally, ACA reduced serum levels of inflammatory factors (IL-1β, IL-6, and TNF-α), restored enzymes of the antioxidative system (SOD and CAT) and GSH values, and decreased monoester diterpene alkaloid levels in the kidney by inhibiting the expression of NF-κB pathway-related proteins and increasing Nrf2/HO-1 pathway-related protein expression.

CONCLUSION: ACA protects against cisplatin-induced AKI through its anti-inflammatory and antioxidant functions, which may be associated with the restoration of gut microbiota metabolism. ACA is a potential drug for AKI and other forms of organ damage related to the disruption of the gut microbiota.}, } @article {pmid39439945, year = {2024}, author = {Chen, W and Zou, H and Xu, H and Cao, R and Zhang, H and Zhang, Y and Zhao, J}, title = {The potential influence and intervention measures of gut microbiota on sperm: it is time to focus on testis-gut microbiota axis.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1478082}, pmid = {39439945}, issn = {1664-302X}, abstract = {As the global male infertility rate continues to rise, there is an urgent imperative to investigate the underlying causes of sustained deterioration in sperm quality. The gut microbiota emerges as a pivotal factor in host health regulation, with mounting evidence highlighting its dual influence on semen. This review underscores the interplay between the Testis-Gut microbiota axis and its consequential effects on sperm. Potential mechanisms driving the dual impact of gut microbiota on sperm encompass immune modulation, inflammatory responses mediated by endotoxins, oxidative stress, antioxidant defenses, gut microbiota-derived metabolites, epigenetic modifications, regulatory sex hormone signaling. Interventions such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and Traditional natural herbal extracts are hypothesized to rectify dysbiosis, offering avenues to modulate gut microbiota and enhance Spermatogenesis and motility. Future investigations should delve into elucidating the mechanisms and foundational principles governing the interaction between gut microbiota and sperm within the Testis-Gut microbiota Axis. Understanding and modulating the Testis-Gut microbiota Axis may yield novel therapeutic strategies to enhance male fertility and combat the global decline in sperm quality.}, } @article {pmid39438902, year = {2024}, author = {Díaz-García, C and Moreno, E and Talavera-Rodríguez, A and Martín-Fernández, L and González-Bodí, S and Martín-Pedraza, L and Pérez-Molina, JA and Dronda, F and Gosalbes, MJ and Luna, L and Vivancos, MJ and Huerta-Cepas, J and Moreno, S and Serrano-Villar, S}, title = {Fecal microbiota transplantation alters the proteomic landscape of inflammation in HIV: identifying bacterial drivers.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {214}, pmid = {39438902}, issn = {2049-2618}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *HIV Infections/therapy ; *Gastrointestinal Microbiome ; *Inflammation ; Male ; Middle Aged ; Female ; *Proteomics/methods ; Adult ; *Feces/microbiology ; Pilot Projects ; Double-Blind Method ; Bacteria/classification/isolation & purification/metabolism ; }, abstract = {BACKGROUND: Despite effective antiretroviral therapy, people with HIV (PWH) experience persistent systemic inflammation and increased morbidity and mortality. Modulating the gut microbiome through fecal microbiota transplantation (FMT) represents a novel therapeutic strategy. We aimed to evaluate proteomic changes in inflammatory pathways following repeated, low-dose FMT versus placebo.

METHODS: This double-masked, placebo-controlled pilot study assessed the proteomic impacts of weekly FMT versus placebo treatment over 8 weeks on systemic inflammation in 29 PWH receiving stable antiretroviral therapy (ART). Three stool donors with high Faecalibacterium and butyrate profiles were selected, and their individual stools were used for FMT capsule preparation. Proteomic changes in 345 inflammatory proteins in plasma were quantified using the proximity extension assay, with samples collected at baseline and at weeks 1, 8, and 24. Concurrently, we characterized shifts in the gut microbiota composition and annotated functions through shotgun metagenomics. We fitted generalized additive models to evaluate the dynamics of protein expression. We selected the most relevant proteins to explore their correlations with microbiome composition and functionality over time using linear mixed models.

RESULTS: FMT significantly reduced the plasma levels of 45 inflammatory proteins, including established mortality predictors such as IL6 and TNF-α. We found notable reductions persisting up to 16 weeks after the final FMT procedure, including in the expression of proteins such as CCL20 and CD22. We identified changes in 46 proteins, including decreases in FT3LG, IL6, IL10RB, IL12B, and IL17A, which correlated with multiple bacterial species. We found that specific bacterial species within the Ruminococcaceae, Succinivibrionaceae, Prevotellaceae families, and the Clostridium genus, in addition to their associated genes and functions, were significantly correlated with changes in inflammatory markers.

CONCLUSIONS: Targeting the gut microbiome through FMT effectively decreased inflammatory proteins in PWH, with sustained effects. These findings suggest the potential of the microbiome as a therapeutic target to mitigate inflammation-related complications in this population, encouraging further research and development of microbiome-based interventions. Video Abstract.}, } @article {pmid39437686, year = {2024}, author = {Cao, Z and Wang, X and Liu, H and Yang, Z and Zeng, Z}, title = {Gut microbiota mediate the alleviation effect of Xiehuo-Guzheng granules on β cell dedifferentiation in type 2 diabetes mellitus.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156151}, doi = {10.1016/j.phymed.2024.156151}, pmid = {39437686}, issn = {1618-095X}, abstract = {BACKGROUND: Type 2 diabetes mellitus (T2DM) is a worldwide public health problem characterized by a progressive decline in β cell function. In traditional Chinese medicine (TCM) theory, 'fire' and 'healthy qi deficiency' are important pathogeneses of T2DM, and purging 'fire' and reinforcing the 'healthy qi' (Pinyin name: Xiehuo-Guzheng, XHGZ) are important method of treatment. Over the years, we have observed its benefit for diabetes. However, the underlying mechanisms remain unclear.

PURPOSE: To investigate the mechanism of XHGZ granules against β cell dedifferentiation in T2DM based on gut microbiota.

METHODS: Rats with T2DM, induced by intraperitoneal injection of streptozotocin after eight weeks of high-fat diet, were randomly allocated to receive XHGZ granules, metformin, or distilled water for eight consecutive weeks. Changes in metabolic parameters, β cell dedifferentiation, inflammatory cytokines, gut microbiota, and microbial metabolites (lipopolysaccharide (LPS) and short-chain fatty acids (SCFAs)), were detected. Furthermore, faecal microbiota transplantation (FMT) was performed to confirm the anti-diabetic effect of XHGZ granule-regulated gut microbiota in pseudo-germ-free T2DM rats.

RESULTS: XHGZ granules significantly ameliorated hyperglycaemia, improved islet function and pathology, and reduced β cell dedifferentiation and pro-inflammatory cytokines in T2DM rats. 16S rRNA sequencing revealed that XHGZ granules decreased the LPS-containing microbiota (e.g., Colidextribacter, Desulfovibrionaceae, and Morganella) and increased the SCFAs-producing bacteria (e.g., Prevotella, Alloprevotella, and Muribaculaceae) and Lactobacillus_intestinalis. Correspondingly, it strengthened intestinal barrier, lowered LPS, and elevated acetic and butyric acids. Tax4Fun analysis indicated that XHGZ granules restored abnormal metabolism, lipopolysaccharide biosynthesis, and pantothenate and CoA biosynthesis. Moreover, the XHGZ granule-regulated microbiota also exhibited the effects of anti-diabetes, anti-β cell dedifferentiation, and anti-inflammation along with the reduction of LPS and the increase of SCFAs in pseudo-germ-free T2DM rats.

CONCLUSION: Our results show that XHGZ granules alleviate β cell dedifferentiation via regulating gut microbiota and their metabolites in T2DM, suggesting its potential as a promising complementary treatment for T2DM. As far as we know, there are very few studies on the alleviation of β cell dedifferentiation by TCM, and investigations into the mechanism from the perspective of intestinal flora and microbial metabolites are yet to be reported.}, } @article {pmid39437444, year = {2024}, author = {Ciernikova, S and Sevcikova, A and Mego, M}, title = {Targeting the gut and tumor microbiome in cancer resistance.}, journal = {American journal of physiology. Cell physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpcell.00201.2024}, pmid = {39437444}, issn = {1522-1563}, support = {2/0069/22//Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; 1/0071/24//Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; }, abstract = {Therapy resistance represents a significant challenge in oncology, occurring in various therapeutic approaches. Recently, animal models and an increasing set of clinical trials highlight the crucial impact of the gut and tumor microbiome on treatment response. The intestinal microbiome contributes to cancer initiation, progression, and formation of distant metastasis. In addition, tumor-associated microbiota is considered a critical player in influencing tumor microenvironment and regulating local immune processes. Intriguingly, numerous studies have successfully identified pathogens within the gut and tumor microbiome that might be linked to a poor response to different therapeutic modalities. The unfavorable microbial composition with the presence of specific microbes participates in cancer resistance and progression via several mechanisms, including upregulation of oncogenic pathways, macrophage polarization reprogramming, metabolism of chemotherapeutic compounds, autophagy pathway modulation, enhanced DNA damage repair, inactivation of a pro-apoptotic cascade, and bacterial secretion of extracellular vesicles, promoting the processes in the metastatic cascade. Targeted elimination of specific intratumoral bacteria appears to enhance treatment response. However, broad-spectrum antibiotic pre-treatment is mostly connected to reduced efficacy due to gut dysbiosis and lower diversity. Mounting evidence supports the potential of microbiota modulation by probiotics and fecal microbiota transplantation to improve intestinal dysbiosis and increase microbial diversity, leading to enhanced treatment efficacy while mitigating adverse effects. In this context, further research concerning the identification of clinically relevant microbiome signatures followed by microbiota-targeted strategies presents a promising approach to overcoming immunotherapy and chemotherapy resistance in refractory patients, improving their outcomes.}, } @article {pmid39435211, year = {2024}, author = {Koneru, HM and Sarwar, H and Bandi, VV and Sinha, M and Tarar, P and Bishara, R and Malasevskaia, I}, title = {A Systematic Review of Gut Microbiota Diversity: A Key Player in the Management and Prevention of Diabetes Mellitus.}, journal = {Cureus}, volume = {16}, number = {9}, pages = {e69687}, pmid = {39435211}, issn = {2168-8184}, abstract = {Diabetes mellitus represents a significant global health challenge, characterized by impaired insulin production and action, leading to elevated blood glucose levels. This systematic review investigates the association between gut microbiota composition and diversity, along with the structural and functional characteristics of the gut microbiome, and their implications for the risk, prevention, and management of both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, a comprehensive search across multiple databases yielded 16 studies that met the inclusion criteria. The findings highlight the potential of gut microbiota interventions, such as fecal microbiota transplantation and probiotic supplementation, in improving metabolic parameters and glycemic control. Notably, the review underscores the importance of dietary interventions and the role of specific microbial populations in influencing diabetes outcomes. Despite the promising results, the variability in study designs, sample sizes, and methodologies poses challenges for generalizability and interpretation. This review emphasizes the need for further research to elucidate the mechanisms underlying these associations and to explore personalized microbiome-based therapies in diabetes management. The insights gained could pave the way for innovative therapeutic strategies aimed at harnessing gut health to mitigate the burden of diabetes mellitus.}, } @article {pmid39434180, year = {2024}, author = {Yan, S and Du, R and Yao, W and Zhang, H and Xue, Y and Teligun, and Li, Y and Bao, H and Zhao, Y and Cao, S and Cao, G and Li, X and Bao, S and Song, Y}, title = {Host-microbe interaction-mediated resistance to DSS-induced inflammatory enteritis in sheep.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {208}, pmid = {39434180}, issn = {2049-2618}, mesh = {Animals ; Sheep/microbiology ; Mice ; *Dextran Sulfate ; *Gastrointestinal Microbiome ; *Disease Models, Animal ; *Feces/microbiology ; *Colitis/microbiology/chemically induced ; Host Microbial Interactions ; Fecal Microbiota Transplantation ; Disease Resistance ; Enteritis/microbiology/veterinary ; Sheep Diseases/microbiology ; Bacteria/classification/isolation & purification/genetics ; }, abstract = {BACKGROUND: The disease resistance phenotype is closely related to immunomodulatory function and immune tolerance and has far-reaching implications in animal husbandry and human health. Microbes play an important role in the initiation, prevention, and treatment of diseases, but the mechanisms of host-microbiota interactions in disease-resistant phenotypes are poorly understood. In this study, we hope to uncover and explain the role of microbes in intestinal diseases and their mechanisms of action to identify new potential treatments.

METHODS: First, we established the colitis model of DSS in two breeds of sheep and then collected the samples for multi-omics testing including metagenes, metabolome, and transcriptome. Next, we made the fecal bacteria liquid from the four groups of sheep feces collected from H-CON, H-DSS, E-CON, and E-DSS to transplant the fecal bacteria into mice. H-CON feces were transplanted into mice named HH group and H-DSS feces were transplanted into mice named HD group and Roseburia bacteria treatment named HDR groups. E-CON feces were transplanted into mice named EH group and E-DSS feces were transplanted into mice in the ED group and Roseburia bacteria treatment named EDR groups. After successful modeling, samples were taken for multi-omics testing. Finally, colitis mice in HD group and ED group were administrated with Roseburia bacteria, and the treatment effect was evaluated by H&E, PAS, immunohistochemistry, and other experimental methods.

RESULTS: The difference in disease resistance of sheep to DSS-induced colitis disease is mainly due to the increase in the abundance of Roseburia bacteria and the increase of bile acid secretion in the intestinal tract of Hu sheep in addition to the accumulation of potentially harmful bacteria in the intestine when the disease occurs, which makes the disease resistance of Hu sheep stronger under the same disease conditions. However, the enrichment of harmful microorganisms in East Friesian sheep activated the TNFα signalling pathway, which aggravated the intestinal injury, and then the treatment of FMT mice by culturing Roseburia bacteria found that Roseburia bacteria had a good curative effect on colitis.

CONCLUSION: Our study showed that in H-DSS-treated sheep, the intestinal barrier is stabilized with an increase in the abundance of beneficial microorganisms. Our data also suggest that Roseburia bacteria have a protective effect on the intestinal barrier of Hu sheep. Accumulating evidence suggests that host-microbiota interactions are associated with IBD disease progression. Video Abstract.}, } @article {pmid39432486, year = {2024}, author = {Ebrahimi, R and Masouri, MM and Salehi Amniyeh Khozani, AA and Ramadhan Hussein, D and Nejadghaderi, SA}, title = {Safety and efficacy of fecal microbiota transplantation for viral diseases: A systematic review of clinical trials.}, journal = {PloS one}, volume = {19}, number = {10}, pages = {e0311731}, pmid = {39432486}, issn = {1932-6203}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Virus Diseases/therapy ; COVID-19/therapy ; Gastrointestinal Microbiome ; Hepatitis B/therapy ; HIV Infections/therapy/microbiology ; Clinical Trials as Topic ; Treatment Outcome ; Clostridium Infections/therapy/microbiology ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Gut microbiota play important roles in several diseases like viral infections. In this systematic review, our objective was to assess the efficacy and safety of fecal microbiota transplantation (FMT) in treating various viral diseases.

METHODS: We conducted searches on databases including PubMed, Web of Science, Scopus, and Google Scholar until November 2023. Clinical trials reported outcomes related to safety of FMT or its efficacy in patients with viral diseases were included. We excluded other types of studies that enrolled healthy individuals or patients with other disorders and did not use FMT. The assessment of bias risk was conducted using the National Institutes of Health (NIH) study quality evaluation tool.

RESULTS: Eight studies with total 196 participants were included. Viral diseases were human immunodeficiency virus (HIV), hepatitis B, COVID-19 and Clostridioides difficile coinfection, and cytomegalovirus colitis. In hepatitis B cases, HBeAg clearance was significant in those received FMT (p<0.01), while it was not significant in another one (p = 0.19). A clinical response was noted in 37.5% of patients with cytomegalovirus colitis, with an equal percentage achieving clinical remission post-FMT. There was a significant reduction in Clostridioides difficile relapse rate in FMT group than controls in coinfection of Clostridioides difficile and COVID-19 (2.17% vs. 42.5%, p<0.05). In patients with HIV, partial engraftment of the donor microbiome and increases in alpha diversity were observed after FMT. No severe adverse events were reported. Most studies had fair or good qualities.

CONCLUSIONS: Our findings revealed FMT as a promising, safe treatment for some viral diseases. It improved viral clearance, clinical outcomes, and inflammation. However, the varying responses and small sample sizes call for more trials on FMT in viral diseases.}, } @article {pmid39431286, year = {2024}, author = {Liu, T and Zhou, L and Dong, R and Qu, Y and Liu, Y and Song, W and Lv, J and Wu, S and Peng, W and Shi, L}, title = {Isomalto-Oligosaccharide Potentiates Alleviating Effects of Intermittent Fasting on Obesity-Related Cognitive Impairment during Weight Loss and the Rebound Weight Gain.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c07351}, pmid = {39431286}, issn = {1520-5118}, abstract = {Obesity-related cognitive dysfunction poses a significant threat to public health. The present study demonstrated mitigating effects of intermittent fasting (IF) and its combination with isomalto-oligosaccharides and IF (IF + IMO) on cognitive impairments induced by a high-fat-high-fructose (HFHF) diet in mice, with IF + IMO exhibiting superior effects. Transcriptomic analysis of the hippocampus revealed that the protective effects on cognition might be attributed to the suppression of toll-like receptor 4 (TLR4)/NFκB signaling, oxidative phosphorylation, and neuroinflammation. Moreover, both IF and IF + IMO modulated the gut microbiome and promoted the production of short-chain fatty acids, with IF + IMO displaying more pronounced effects. IF + IMO-modulated gut microbiota, metabolites, and molecular targets associated with cognitive impairments were further corroborated using human data from public databases Gmrepo and gutMgene. Furthermore, the fecal microbiome transplantation confirmed the direct impacts of IF + IMO-derived microbiota on improving cognition functions by suppressing TLR4/NFκB signaling and increasing BDNF levels. Notably, prior exposure to IF + IMO prevented weight-regain-induced cognitive decline, suppressed TLR4/NFκB signaling and inflammatory cytokines in the hippocampus, and mitigated weight regain-caused gut dysbacteriosis without altering body weight. Our study underscores that IMO-augmented alleviating effects of IF on obesity-related cognitive impairment particularly during weight-loss and weight-regain periods, presenting a novel nutritional strategy to tackle obesity-related neurodegenerative disorders.}, } @article {pmid39427741, year = {2024}, author = {Sun, Z and Zeng, Z and Chen, LX and Xu, JD and Zhou, J and Kong, M and Shen, H and Mao, Q and Wu, CY and Long, F and Zhou, SS and Li, SL}, title = {Integrated anti-fatigue effects of polysaccharides and small molecules coexisting in water extracts of ginseng: Gut microbiota-mediated mechanisms.}, journal = {Journal of ethnopharmacology}, volume = {337}, number = {Pt 3}, pages = {118958}, doi = {10.1016/j.jep.2024.118958}, pmid = {39427741}, issn = {1872-7573}, abstract = {Both clinical and animal studies have demonstrated that ginseng has curative effects on fatigue. Our previous study found that water extracts of ginseng (WEG) could significantly mitigate exercise-induced fatigue (EF). Notably, polysaccharides (GP) and small molecules (GS, mainly ginsenosides) coexist in WEG. Whether and how GP and GS contribute to the anti-EF effects of WEG remains unknown.

AIM OF THE STUDY: To evaluate the contribution of GP and GS to the anti-EF effects of WEG and clarify the potential gut microbiota-mediated mechanisms.

MATERIALS AND METHODS: Firstly, the anti-EF effects of WEG, GP and GS were comparatively investigated by determining fatigue phenotypes (energy metabolism and oxidative stress parameters), gut microbiota composition as well as exogenous and endogenous metabolites in EF modeling rats. Then, the gut microbiota mediated mechanisms were verified by antibiotics (ABX) intervention and fecal microbial transplantation (FMT).

RESULTS: GP, GS and WEG each exhibited distinct anti-EF effects in differentially improving EF-induced energy metabolism abnormality and oxidative stress, reshaping gut microbiota composition, and elevating systemic metabolites. Notably, WEG showed stronger anti-EF effects than both GP and GS, characterized by better alleviation of disturbances in energy metabolism (e.g. Glc) and oxidative stress parameters (e.g. SOD), regulation of gut microbiota homeostasis (e.g. enriching the genus Coprococcus and species Collinsella provencensis etc.), as well as increases in exogenous secondary ginsenosides (e.g. 20(S)-Rg3, 20(R)-Rg3, CK), endogenous bile acids (BAs) (e.g. CA, DCA, LCA), and short chain fatty acids (SCFAs) (e.g. butyric acid). The stronger anti-EF effects of WEG compared to GP and GS could be abolished by ABX intervention, and transferred by FMT.

CONCLUSION: GP and GS could collectively contribute to the anti-EF effects of WEG through integrated actions. Gut microbiota mediate the integrated anti-EF effects of GP and GS in WEG, potentially by regulating the levels of exogenous bioactive secondary ginsenosides, as well as endogenous BAs and SCFAs, thereby alleviating fatigue-related energy metabolic abnormalities and oxidative stress.}, } @article {pmid39426981, year = {2024}, author = {Lu, C and Liu, D and Wu, Q and Zeng, J and Xiong, Y and Luo, T}, title = {EphA2 blockage ALW-II-41-27 alleviates atherosclerosis by remodeling gut microbiota to regulate bile acid metabolism.}, journal = {NPJ biofilms and microbiomes}, volume = {10}, number = {1}, pages = {108}, pmid = {39426981}, issn = {2055-5008}, support = {2023NSFSC1631//Department of Science and Technology of Sichuan Province (Sichuan Provincial Department of Science and Technology)/ ; 2023YFS0116//Department of Science and Technology of Sichuan Province (Sichuan Provincial Department of Science and Technology)/ ; 2022YFS0604//Department of Science and Technology of Sichuan Province (Sichuan Provincial Department of Science and Technology)/ ; Q22066//Education Department of Sichuan Province/ ; }, mesh = {Animals ; *Atherosclerosis/metabolism/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Bile Acids and Salts/metabolism ; Mice ; *Receptor, EphA2/metabolism ; *Diet, High-Fat/adverse effects ; Male ; Humans ; Disease Models, Animal ; Plaque, Atherosclerotic/etiology ; Mice, Inbred C57BL ; Bacteria/classification/isolation & purification/genetics/metabolism ; Dysbiosis ; }, abstract = {Coronary artery disease (CAD), a critical condition resulting from systemic inflammation, metabolic dysfunction, and gut microbiota dysbiosis, poses a global public health challenge. ALW-II-41-27, a specific inhibitor of the EphA2 receptor, has shown anti-inflammatory prosperities. However, the impact of ALW-II-41-27 on atherosclerosis has not been elucidated. This study aimed to examine the roles of pharmacologically inhibiting EphA2 and the underlying mechanism in ameliorating atherosclerosis. ALW-II-41-27 was administered to apoE[-/-] mice fed a high-fat diet via intraperitoneal injection. We first discovered that ALW-II-41-27 led to a significant reduction in atherosclerotic plaques, evidenced by reduced lipid and macrophage accumulation, alongside an increase in collagen and smooth muscle cell content. ALW-II-41-27 also significantly lowered plasma and hepatic cholesterol levels, as well as the colonic inflammation. Furthermore, gut microbiota was analyzed by metagenomics and plasma metabolites by untargeted metabolomics. ALW-II-41-27-treated mice enriched Enterococcus, Akkermansia, Eggerthella and Lactobaccilus, accompanied by enhanced secondary bile acids production. To explore the causal link between ALW-II-41-27-associated gut microbiota and atherosclerosis, fecal microbiota transplantation was employed. Mice that received ALW-II-41-27-treated mouse feces exhibited the attenuated atherosclerotic plaque. In clinical, lower plasma DCA and HDCA levels were determined in CAD patients using quantitative metabolomics and exhibited a negative correlation with higher monocytes EphA2 expression. Our findings underscore the potential of ALW-II-41-27 as a novel therapeutic agent for atherosclerosis, highlighting its capacity to modulate gut microbiota composition and bile acid metabolism, thereby offering a promising avenue for CAD.}, } @article {pmid39426255, year = {2024}, author = {Liu, SJ and Fu, JJ and Liao, ZY and Liu, YX and He, J and He, LY and Bai, J and Yang, JY and Niu, SQ and Guo, JL}, title = {Z-ligustilide alleviates atherosclerosis by reconstructing gut microbiota and sustaining gut barrier integrity through activation of cannabinoid receptor 2.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156117}, doi = {10.1016/j.phymed.2024.156117}, pmid = {39426255}, issn = {1618-095X}, abstract = {BACKGROUND: Z-Ligustilide (ZL) is an essential phthalide found in Ligusticum chuanxiong Hort, a commonly used traditional Chinese medicine for treating atherosclerosis (AS) clinically. ZL has been shown to be effective in treating AS. However, the underlying mechanism of ZL against AS and its potential targets remain elusive.

PURPOSE: The purpose of this research was to assess the influence of ZL on AS and explore the role of the gut microbiome in mediating this effect.

METHODS: A well-established AS mouse model, apolipoprotein E deficient (ApoE[-/-]) mice was used to examine the effects of ZL on AS, inflammation, and the intestinal barrier. To analyze the changes in gut microbial community, we employed the 16S rRNA gene sequencing. Antibiotic cocktail and fecal microbiota transplantation (FMT) were employed to clarify the contribution of the gut microbiota to the anti-AS effects of ZL. The mechanism through which ZL provided protective effects on AS and the intestinal barrier was explored by untargeted metabolomics, as well as by validating the involvement of cannabinoid receptor 2 (CB2R) in mice and Caco-2 cells.

RESULTS: Oral administration of ZL inhibited the development of atherosclerotic lesions, improved plaque stability, inhibited the increase in serum and atherosclerotic inflammation, and improved intestinal barrier function. Fecal bacteria from ZL-treated mice induced similar beneficial effects on AS and the intestinal barrier. We used 16S RNA gene sequencing to reveal a significant increase in Rikenella abundance in both ZL-treated mice and ZL-FMT mice, which was associated with the beneficial effects of ZL. Further function prediction analysis of the gut microbiota and CB2R antagonist intervention experiment in mice and Caco-2 cells showed that the activation of CB2R resulted in the enhancement of the intestinal barrier by ZL. Furthermore, the analysis of metabolomic profiling revealed the enrichment of capsaicin upon ZL treatment, which induced the activation of CB2R in human colon epithelial cells.

CONCLUSION: Our study is the first to demonstrate that oral treatment with ZL has the potential to alleviate AS by reducing inflammation levels and enhancing the intestinal barrier function. This mechanism relies on the gut microbiota in a CB2R-dependent manner, suggesting promising strategies and ideas for managing AS. This study provides insights into a novel mechanism for treating AS with ZL.}, } @article {pmid39425119, year = {2024}, author = {Qian, X and Lin, X and Hu, W and Zhang, L and Chen, W and Zhang, S and Ge, S and Xu, X and Luo, K}, title = {Intestinal homeostasis disrupted by Periodontitis exacerbates Alzheimer's Disease in APP/PS1 mice.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {263}, pmid = {39425119}, issn = {1742-2094}, support = {81860197//the National Natural Science Foundation of China/ ; 2020Y9032//the Joint Funds for the Innovation of Science and Technology/ ; JAT220078//the Educational Research Project for Young and Middle-aged Teachers of Fujian Provincial Department of Education/ ; 82301103//National Outstanding Youth Science Fund Project of National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Alzheimer Disease/pathology/metabolism ; Mice ; *Homeostasis/physiology ; *Mice, Transgenic ; *Periodontitis/pathology/complications/microbiology ; *Amyloid beta-Protein Precursor/genetics/metabolism ; *Gastrointestinal Microbiome/physiology ; *Presenilin-1/genetics ; Intestines/pathology ; Mice, Inbred C57BL ; Disease Models, Animal ; }, abstract = {Periodontitis exacerbates Alzheimer's disease (AD) through multiple pathways. Both periodontitis and AD are intricately correlated to intestinal homeostasis, yet there is still a lack of direct evidence regarding whether periodontitis can regulate the progression of AD by modulating intestinal homeostasis. The current study induced experimental periodontitis in AD mice by bilaterally ligating the maxillary second molars with silk and administering Pg-LPS injections in APP[swe]/PS1[ΔE9] (APP/PS1) mice. Behavioral tests and histological analyses of brain tissue were conducted after 8 weeks. Gut microbiota was analyzed and colon tissue were also evaluated. Then, fecal microbiota from mice with periodontitis was transplanted into antibiotic-treated mice to confirm the effects of periodontitis on AD and the potential mechanism was explored. The results indicated periodontitis exacerbated cognitive impairment and anxious behaviour in APP/PS1 mice, with increased Aβ deposition, microglial overactivation and neuroinflammation in brain. Moreover, the intestinal homeostasis of AD mice was altered by periodontitis, including affecting gut microbiota composition, causing colon inflammation and destroyed intestinal epithelial barrier. Furthermore, AD mice that underwent fecal transplantation from mice with periodontitis exhibited worsened AD progression and disrupted intestinal homeostasis. It also impaired intestinal barrier function, elevated peripheral inflammation, damaged blood-brain barrier (BBB) and caused neuroinflammation and synapses impairment. Taken together, the current study demonstrated that periodontitis could disrupt intestinal homeostasis to exacerbate AD progression potential via causing gut microbial dysbiosis, intestinal inflammation and intestinal barrier impairment to induce peripheral inflammation and damage BBB, ultimately leading to neuroinflammation and synapse impairment. It underscores the importance of maintaining both periodontal health and intestinal homeostasis to reduce the risk of AD.}, } @article {pmid39423571, year = {2024}, author = {Li, Y and Yan, M and Zhang, M and Zhang, B and Xu, B and Ding, X and Wang, J and Wang, Z}, title = {Scutellarin alleviated ulcerative colitis through gut microbiota-mediated cAMP/PKA/NF-κB pathway.}, journal = {Biochemical and biophysical research communications}, volume = {735}, number = {}, pages = {150837}, doi = {10.1016/j.bbrc.2024.150837}, pmid = {39423571}, issn = {1090-2104}, abstract = {PURPOSE: Ulcerative colitis (UC) is a chronic, non-specific inflammatory condition of the colon, characterized by recurrent episodes and a notable lack of effective pharmacological treatments. Scutellarin, a natural component, exhibits appreciable pharmacological effects and therapeutic potential for various diseases. However, its effects on UC are not fully understood, and the precise mechanisms remain to be deciphered. This study aimed to assess the therapeutic efficacy of scutellarin and elucidate its underlying mechanisms in treating UC.

METHODS: This study utilized dextran sulfate sodium (DSS)-induced mice to evaluate the therapeutic potential of scutellarin against UC and to elucidate the mechanisms involving the gut microbiota. An antibiotics cocktail (ABX) and fecal microbiota transplantation (FMT) were also used to determine the mechanistic role of the gut microbiota. An integrative approach combining fecal metabolomics and network pharmacology analysis was used to explore the gut microbiota-directed molecular mechanism.

RESULTS: The results showed that scutellarin provided various therapeutic benefits in UC management, including alleviating weight loss, slowing disease progression, and reducing inflammatory damage in colon structures. The improved gut microbiota after scutellarin administration contributed to these effects. Fecal metabolome revealed that scutellarin selectively mitigated DSS-induced dysregulation of gut microbiota-derived metabolites, including glycolic acid, γ-aminobutyric acid, glutamate, tryptophan, xanthine, and β-hydroxypyruvate. Network pharmacology analysis, along with in vivo experimental verification, implicated the cAMP/PKA/NF-κB pathway in the action of these metabolites in treating UC, which may be the mechanism responsible for scutellarin's curative effects on UC.

CONCLUSION: This study demonstrates the potential of scutellarin in alleviating UC by activating the cAMP/PKA/NF-κB pathway through gut microbiota-derived metabolites, highlighting scutellarin as a promising therapeutic agent for UC.}, } @article {pmid39423480, year = {2024}, author = {Xiao, Q and Luo, L and Zhu, X and Yan, Y and Li, S and Chen, L and Wang, X and Zhang, J and Liu, D and Liu, R and Zhong, Y}, title = {Formononetin alleviates ulcerative colitis via reshaping the balance of M1/M2 macrophage polarization in a gut microbiota-dependent manner.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156153}, doi = {10.1016/j.phymed.2024.156153}, pmid = {39423480}, issn = {1618-095X}, abstract = {BACKGROUND: Ulcerative colitis (UC), a type of inflammatory bowel disease, presents substantial challenges in clinical treatment due to the limitations of current medications. Formononetin (FN), a naturally compound with widespread availability, exhibits anti-inflammatory, antioxidant, and immunomodulatory properties.

PURPOSE: This study aimed to investigate the efficacy of FN against UC and its potential regulatory mechanism.

METHODS: Here, dextran sulfate sodium (DSS) was employed to replicate experimental colitis in mice with concomitant FN treatment. The distribution and localisation of CD68 and F4/80 macrophages in colonic tissues were visualized by immunofluorescence, their chemokine and inflammatory cytokine concentrations were determined by ELISA, and macrophages and M1/M2 subpopulations were determined by flow cytometry. Additionally, 16 s rRNA and LC-MS techniques were used to detect the colonic intestinal microbiota and metabolite profiles, respectively. Correlation analyses was performed to clarify the interactions between differential bacteria, metabolites and M1/M2 macrophages, and pseudo sterile mice were constructed by depletion of gut flora with quadruple antibiotics, followed by faecal microbial transplantation to evaluate its effects on colitis and M1/M2 macrophage polarisation.

RESULTS: FN dose-dependently alleviated clinical symptoms and inflammatory injury in colonic tissues of colitis mice, with its high-dose efficacy comparable to that of 5-ASA. Concurrently, FN not only inhibited inflammatory infiltration of macrophages and their M1/M2 polarisation balance in colitis mice, but also improved the composition of colonic microbiota and metabolite profiles. However, FN lost its protective effects against DSS-induced colitis and failed to restore the equilibrium of M1/M2 macrophage differentiation following intestinal flora depletion through quadruple antibiotic treatment. Importantly, fecal microbiota transplantation from FN-treated mice restored FN's protective effects against DSS-induced colitis and reestablished its regulatory role in M1/M2 macrophage polarization.

CONCLUSION: Collectively, FN ameliorated UC through modulating the balance of M1/M2 macrophage polarization in a gut microbiota-dependent manner.}, } @article {pmid39421003, year = {2024}, author = {Hansen, MM and Rågård, N and Andreasen, PW and Paaske, SE and Dahlerup, JF and Mikkelsen, S and Erikstrup, C and Baunwall, SMD and Hvas, CL}, title = {Encapsulated donor faeces for faecal microbiota transplantation: the Glyprotect protocol.}, journal = {Therapeutic advances in gastroenterology}, volume = {17}, number = {}, pages = {17562848241289065}, pmid = {39421003}, issn = {1756-283X}, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is a highly effective treatment for Clostridioides difficile infection. Its use is backed by solid evidence, but application methods differ. Encapsulated FMT is a non-invasive, patient-friendly and scalable application method that may be preferred over colonoscopy or nasoduodenal tube application.

OBJECTIVES: We describe a detailed protocol, the Glyprotect protocol, for producing glycerol-based capsules to increase FMT accessibility.

DESIGN: Using iterative quality improvement methods, we developed and validated the Glyprotect protocol as a reproducible protocol for cryopreserving minimally processed donor faeces in a standard hospital laboratory setting.

METHODS: We describe detailed standard operating procedures for producing glycerol-based capsules, including all necessary materials and troubleshooting guidelines. Capsule integrity was tested at various temperatures and pH levels. Flow cytometry was used to measure microbiota counts and dose accuracy.

RESULTS: The Glyprotect protocol has been used for more than 2500 capsule-based FMT treatments and complies with European tissue and cell standards. The protocol is optimised to preserve microbes and minimise modulation of the donated microbiota by removing debris and water, which also reduces the number of capsules needed per FMT treatment. The intestinal microbiota is preserved in glycerol for cryoprotection and to prevent capsule leakage. Each capsule contains 650 µL microbe-glycerol mass, estimated to contain an average of 2.5 × 10[8] non-specified bacteria.

CONCLUSION: The Glyprotect protocol enables hospitals and tissue establishments to set up capsule production in a standard laboratory, improving patients' access to FMT. The protocol facilitates the scalability of FMT services because capsule FMT is less time-consuming and less expensive than liquid-suspension FMT applied by colonoscopy or nasojejunal tube.

TRIAL REGISTRATION: Not applicable.}, } @article {pmid39420836, year = {2024}, author = {Qu, W and Xu, Y and Yang, J and Shi, H and Wang, J and Yu, X and Chen, J and Wang, B and Zhuoga, D and Luo, M and Liu, R}, title = {Berberine alters the gut microbiota metabolism and impairs spermatogenesis.}, journal = {Acta biochimica et biophysica Sinica}, volume = {}, number = {}, pages = {}, doi = {10.3724/abbs.2024174}, pmid = {39420836}, issn = {1745-7270}, abstract = {Berberine (BBR) is used to treat diarrhea clinically. However, its reproductive toxicity is unclear. This study aims to investigate the impact of BBR on the male reproductive system. Intragastric BBR administration for 14 consecutive days results in a significant decrease in the serum testosterone concentration, epididymal sperm concentration, mating rate and fecundity of male mice. Testicular treatment with testosterone propionate (TP) partially reverses the damage caused by BBR to the male reproductive system. Mechanistically, the decrease in Muribaculaceae abundance in the gut microbiota of mice is the principal cause of the BBR-induced decrease in the sperm concentration. Both fecal microbiota transplantation (FMT) and polyethylene glycol (PEG) treatment demonstrate that Muribaculaceae is necessary for spermatogenesis. The intragastric administration of Muribaculaceae intestinale to BBR-treated mice restores the sperm concentration and testosterone levels. Metabolomic analysis reveals that BBR affects arginine and proline metabolism, of which ornithine level is downregulated. Combined analysis via 16S rRNA metagenomics sequencing and metabolomics shows that Muribaculaceae regulates ornithine level. The transcriptomic results of the testes indicate that the expressions of genes related to the low-density lipoprotein receptor (LDLR)-mediated testosterone synthesis pathway decrease after BBR administration. The transcriptional activity of the Ldlr gene in TM3 cells is increased with increased ornithine supplementation in the culture media, leading to increased testosterone synthesis. Overall, this study reveals an association between a BBR-induced decrease in Muribaculaceae abundance and defective spermatogenesis, providing a prospective therapeutic approach for addressing infertility-related decreases in serum testosterone triggered by changes in the gut microbiota composition.}, } @article {pmid39420603, year = {2024}, author = {Poupard, L and Page, G and Thoreau, V and Kaouah, Z}, title = {Relationships between Gut Microbiota and Autism Spectrum Disorders: Development and Treatment.}, journal = {Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology}, volume = {22}, number = {4}, pages = {554-564}, doi = {10.9758/cpn.24.1179}, pmid = {39420603}, issn = {1738-1088}, abstract = {Many studies have demonstrated the impact of intestinal microbiota on normal brain development. Moreover, the gut microbiota (GM) is impacted by multiple endogenous and environmental factors that may promote gut dysbiosis (GD). An increasing number of studies are investigating the possible role of the GD in the development of neurological and behavioral disorders. For autism spectrum disorders (ASD), specific intestinal bacterial signatures have been identified, knowing that gastrointestinal symptoms are frequently found in ASD. In this review, the peri and post-natal factors modulating the GM are described and the specific gut bacterial signature of ASD children is detailed. Through bidirectional communication between the GM and the brain, several mechanisms are involved in the development of ASD, such as cytokine-mediated neuroinflammation and decreased production of neuroprotective factors such as short-chain fatty acids by the GM. Imbalance of certain neurotransmitters such as serotonin or gamma-aminobutyric acid could also play a role in these gut-brain interactions. Some studies show that this GD in ASD is partly reversible by treatment with pre- and probiotics, or fecal microbiota transplantation with promising results. However, certain limitations have been raised, in particular concerning the short duration of treatment, the small sample sizes and the diversity of protocols. The development of standardized therapeutics acting on GD in large cohort could rescue the gastrointestinal symptoms and behavioral impairments, as well as patient management.}, } @article {pmid39420082, year = {2024}, author = {Zhang, HJ and Wang, HW and Tian, FY and Yang, CZ and Zhao, M and Ding, YX and Wang, XY and Cui, XY}, title = {Decolonization strategies for ESBL-producing or carbapenem-resistant Enterobacterales carriage: a systematic review and meta-analysis.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {24349}, pmid = {39420082}, issn = {2045-2322}, support = {2024L090//Shanxi Provincial Education Department/ ; 2017041037-2//Shanxi Provincial Science and Technology Department/ ; 202303021211121//Natural Science Foundation of Shanxi Province/ ; }, mesh = {Humans ; *beta-Lactamases/metabolism ; *Enterobacteriaceae Infections/drug therapy/microbiology ; *Carbapenem-Resistant Enterobacteriaceae/drug effects ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Carbapenems/therapeutic use/pharmacology ; Enterobacteriaceae/drug effects ; Carrier State/microbiology/drug therapy ; }, abstract = {The prevalence of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) and carbapenem-resistant Enterobacterales (CRE) has become a global public health problem. ESBL-E/CRE colonization can increase the risk of infection in patients and lead to poor disease prognosis. We conducted a systematic review and meta-analysis to evaluate current decolonization strategies regarding ESBL-E/CRE and their efficacy. A literature search was conducted until August 2023 on the five databases to review decolonization strategies associated with ESBL-E/CRE. A meta-analysis was conducted using RevMan 5.4 to compare differences in the decolonization strategy with placebo controls. The primary outcome was decolonization rates, with secondary outcomes of attributable death and adverse events. Quality of identified studies was determined using the Newcastle-Ottawa scale and cochrane risk assessment tool. Random and fixed effects meta-analyses were performed to calculate pooled value. A total of 25 studies were included. In five randomized controlled trial (RCT) studies, the decolonization effect of selective digestive decontamination(SDD) on ESBL-E/CRE at the end of treatment was significantly better in the experimental group than the controls [risk radio (RR): 3.30; 95% CI 1.78-6.14]. In three n-RCT studies, the decolonization effect in the experimental group was still better than the controls one month after SDD therapy [odds ratio (OR): 4.01; 95% CI 1.88-8.56]. The combined decolonization rates reported by six single-arm trial studies of SDD therapy ranged from 53.8 to 68.0%. Additionally, TSA analysis confirmed the effectiveness of SDD therapy. In studies on Faecal microbiota transplantation (FMT) therapy, the decolonization effect of the experimental group was significantly better than the controls 1 month after treatment (OR: 2.57; 95% CI 1.07-6.16). In studies without a control group and with varying follow-up times, the decolonization rates varied widely but indicated the effectiveness trend of FMT therapy (61.3-81.2%). Currently, research on the decolonization effect of probiotic therapy on ESBL-E/CRE is insufficient, and only a systematic review was conducted. SDD and FMT strategies have short-term benefits for ESBL-E/CRE decolonization, but long-term effects are unclear. The effect of probiotic therapy on ESBL-E/CRE decolonization is an interesting topic that still requires further investigation.}, } @article {pmid39420033, year = {2024}, author = {Majzoub, ME and Paramsothy, S and Haifer, C and Parthasarathy, R and Borody, TJ and Leong, RW and Kamm, MA and Kaakoush, NO}, title = {The phageome of patients with ulcerative colitis treated with donor fecal microbiota reveals markers associated with disease remission.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {8979}, pmid = {39420033}, issn = {2041-1723}, support = {988415//Crohn's and Colitis Foundation (Crohn's & Colitis Foundation)/ ; APP2011047//Department of Health | National Health and Medical Research Council (NHMRC)/ ; Investigator grant//Department of Health | National Health and Medical Research Council (NHMRC)/ ; Scientia fellowship//University of New South Wales (UNSW Australia)/ ; }, mesh = {Humans ; *Colitis, Ulcerative/therapy/microbiology/virology ; *Fecal Microbiota Transplantation ; *Bacteriophages/genetics/isolation & purification/physiology ; *Gastrointestinal Microbiome/genetics ; *Feces/microbiology/virology ; Double-Blind Method ; Male ; Female ; Metagenomics/methods ; Adult ; Dysbiosis/microbiology/therapy ; Middle Aged ; Virome/genetics ; Remission Induction ; Anti-Bacterial Agents/therapeutic use ; Biomarkers ; }, abstract = {Bacteriophages are influential within the human gut microbiota, yet they remain understudied relative to bacteria. This is a limitation of studies on fecal microbiota transplantation (FMT) where bacteriophages likely influence outcome. Here, using metagenomics, we profile phage populations - the phageome - in individuals recruited into two double-blind randomized trials of FMT in ulcerative colitis. We leverage the trial designs to observe that phage populations behave similarly to bacterial populations, showing temporal stability in health, dysbiosis in active disease, modulation by antibiotic treatment and by FMT. We identify a donor bacteriophage putatively associated with disease remission, which on genomic analysis was found integrated in a bacterium classified to Oscillospiraceae, previously isolated from a centenarian and predicted to produce vitamin B complex except B12. Our study provides an in-depth assessment of phage populations during different states and suggests that bacteriophage tracking has utility in identifying determinants of disease activity and resolution.}, } @article {pmid39419539, year = {2024}, author = {Scher, JU and Nayak, R and Clemente, JC}, title = {Microbiome research in autoimmune and immune-mediated inflammatory diseases: lessons, advances and unmet needs.}, journal = {Annals of the rheumatic diseases}, volume = {}, number = {}, pages = {}, doi = {10.1136/ard-2024-225735}, pmid = {39419539}, issn = {1468-2060}, abstract = {The increasing prevalence of autoimmune and immune-mediated diseases (AIMDs) underscores the need to understand environmental factors that contribute to their pathogenesis, with the microbiome emerging as a key player. Despite significant advancements in understanding how the microbiome influences physiological and inflammatory responses, translating these findings into clinical practice remains challenging. This viewpoint reviews the progress and obstacles in microbiome research related to AIMDs, examining molecular techniques that enhance our understanding of microbial contributions to disease. We discuss significant discoveries linking specific taxa and metabolites to diseases such as rheumatoid arthritis, systemic lupus erythematosus and spondyloarthritis, highlighting the role of gut dysbiosis and host-microbiome interactions. Furthermore, we explore the potential of microbiome-based therapeutics, including faecal microbiota transplantation and pharmacomicrobiomics, while addressing the challenges of identifying robust microbial targets. We advocate for integrative, transdisease studies and emphasise the need for diverse cohort research to generalise findings across populations. Understanding the microbiome's role in AIMDs will pave the way for personalised medicine and innovative therapeutic strategies.}, } @article {pmid39418776, year = {2024}, author = {Xie, Q and Sun, J and Sun, M and Wang, Q and Wang, M}, title = {Perturbed microbial ecology in neuromyelitis optica spectrum disorder: Evidence from the gut microbiome and fecal metabolome.}, journal = {Multiple sclerosis and related disorders}, volume = {92}, number = {}, pages = {105936}, doi = {10.1016/j.msard.2024.105936}, pmid = {39418776}, issn = {2211-0356}, abstract = {BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system inflammatory demyelinating immune-mediated ailment, which is influenced by genetic, epigenetic, and environmental elements. The escalating incidence of NMOSD in recent years implies alterations in environmental risk factors. Recent research has established a correlation between gut microbiomes and the development of NMOSD.

METHODS: Metagenomic shotgun sequencing and gas chromatography-mass spectrometry (GC-MS) were employed to assess alterations of the structure and function in the fecal microbiome, as well as levels of short-chain fatty acids (SCFAs) in fecal and blood samples, among individuals with neuromyelitis optica spectrum disorder (NMOSD) during the acute phase (n = 25), the remission phase (n = 11), and a group of healthy controls (HCs) (n = 24). We further explored the correlation between gut microbiota and the pathogenesis of NMOSD through fecal microbiota transplantation (FMT). The gut microbiome from human donors diagnosed with NMOSD or HCs was transplanted into germ-free mice, followed by an analysis of the alterations in the structure and functionality of the transplanted mice's gut microbiome. Additionally, the impact of microbiome transfer on the immunity and spinal cord of germ-free mice was assessed through various techniques, including ELISA, flow cytometry, western blot, histopathology, and transcriptome sequencing.

RESULTS: (1) At the taxonomic levels of genus and species, there were significant differences in the α-diversity of the microbiome between HCs and NMOSD patients in the acute phase, with NMOSD patients having higher species diversity. (2) In the acute phase, the gut microbiota of NMOSD patients was characterized by Ruminococcaceae_unclassified, Campylobacter, Parabacteroides, Lactobacillus, Akkermansia, Streptococcus oralis, Clostridium leptum, Clostridium asparagiforme, Firmicutes bacterium CAG 238, and Lactobacillus fermentum. (3) The relative abundances of Coprobacter, Turicimonas, Gemmiger, Enterobacter, Roseburia sp.CAG 471, Veillonella tobetsuensis, Proteobacteria bacterium CAG 139, Ruminococcus bicirculans, Lactococcus lactis, Flavonifractor plautii, and Streptococcus cristatus were notably lower in patients experiencing remission compared to NMOSD patients in the acute phase, On the other hand, the relative abundances of Flavonifractor (P = 0.049) and Clostridium aldenense (P = 0.049) were significantly higher. Following medication, the gut microbiome distribution in NMOSD patients during remission closely resembled that of healthy controls (HCs). (4) Compared with HCs, acetate levels in the feces of patients with NMOSD in the acute phase were significantly lower. (5) In addition, we transplanted feces from NMOSD patients into germ-free mice and revealed a significant increase in the levels of IL-6, IL-17A, and IL-23 in the blood of mice belonging to the NMOSD fecal transplantation (NFMT) group. Additionally, the IL-10 level exhibited a significant reduction. Moreover, the proportion of Th17 cells displayed a significant increase, while the proportion of Treg cells exhibited a significant decrease in the spleens of NFMT mice.

CONCLUSION: Patients in the acute phase of neuromyelitis optica spectrum disorder (NMOSD) exhibited imbalances in their gut microbiota and a deficiency in short-chain fatty acids (SCFAs). Following drug treatment, the composition of intestinal microbes in NMOSD patients during the remission phase closely resembled that of the healthy control population. The FMT experiment provided evidence of the significant association between intestinal flora and the pathogenesis of NMOSD. Consequently, investigating gut microbiota and identifying novel microbial markers hold promise for the diagnosis and treatment of NMOSD patients.}, } @article {pmid39412514, year = {2024}, author = {Han, M and Wang, X and Su, L and Pan, S and Liu, N and Li, D and Liu, L and Cui, J and Zhao, H and Yang, F}, title = {Intestinal microbiome dysbiosis increases Mycobacteria pulmonary colonization in mice by regulating the Nos2-associated pathways.}, journal = {eLife}, volume = {13}, number = {}, pages = {}, pmid = {39412514}, issn = {2050-084X}, support = {242102521045//Science and Technology Research Project of Henan Province/ ; 242102310202//Science and Technology Research Project of Henan Province/ ; LHGJ20230525//Project of Health Commission of Henan Province/ ; Open Project of the Institute of Tuberculosis XYJHB20210//Xinxiang Medical University/ ; Tuberculosis Capacity Improvement Project 2023-68//Henan Provincial Health Commission/ ; }, mesh = {Animals ; *Dysbiosis/microbiology ; *Gastrointestinal Microbiome/physiology ; Mice ; *Lung/microbiology ; *Nitric Oxide Synthase Type II/metabolism/genetics ; Mice, Inbred C57BL ; Mycobacterium tuberculosis ; Tuberculosis/microbiology ; }, abstract = {Increasing researches reveal gut microbiota was associated with the development of tuberculosis (TB). How to prevent or reduce Mycobacterium tuberculosis colonization in the lungs is a key measure to prevent TB. However, the data on gut microbiota preventing Mycobacterium colonization in the lungs were scarce. Here, we established the clindamycin-inducing intestinal microbiome dysbiosis and fecal microbial transplantation models in mice to identify gut microbiota's effect on Mycobacterium's colonization in the mouse lungs and explore its potential mechanisms. The results showed that clindamycin treatment altered the diversity and composition of the intestinal bacterial and fungal microbiome, weakened the trans-kingdom network interactions between bacteria and fungi, and induced gut microbiome dysbiosis in the mice. Gut microbiota dysbiosis increases intestinal permeability and enhances the susceptibility of Mycobacterium colonization in the lungs of mice. The potential mechanisms were gut microbiota dysbiosis altered the lung transcriptome and increased Nos2 expression through the 'gut-lung axis'. Nos2 high expression disrupts the intracellular antimicrobial and anti-inflammatory environment by increasing the concentration of nitric oxide, decreasing the levels of reactive oxygen species and Defb1 in the cells, and promoting Mycobacteria colonization in the lungs of mice. The present study raises a potential strategy for reducing the risks of Mycobacteria infections and transmission by regulating the gut microbiome balance.}, } @article {pmid39410876, year = {2024}, author = {Wen, J and Feng, Y and Xue, L and Yuan, S and Chen, Q and Luo, A and Wang, S and Zhang, J}, title = {High-fat diet-induced L-saccharopine accumulation inhibits estradiol synthesis and damages oocyte quality by disturbing mitochondrial homeostasis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2412381}, pmid = {39410876}, issn = {1949-0984}, mesh = {Animals ; Female ; *Diet, High-Fat/adverse effects ; *Estradiol/metabolism/biosynthesis ; *Oocytes/metabolism/drug effects ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Mitochondria/metabolism/drug effects ; *Dysbiosis/microbiology ; *Homeostasis ; *Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Infertility, Female/microbiology/metabolism/etiology ; Ovary/metabolism/microbiology ; }, abstract = {High-fat diet (HFD) has been linked to female infertility. However, the specific age at which HFD impacts ovarian function and the underlying mechanisms remain poorly understood. Here, we administered a HFD to female mice at various developmental stages: pre-puberty (4 weeks old), post-puberty (6 weeks old), young adult (9 weeks old), and middle age (32 weeks old). Our observations indicated that ovarian function was most significantly compromised when HFD was initiated at post-puberty. Consequently, post-puberty mice were chosen for further investigation. Through transplantation of fecal bacteria from the HFD mice to the mice on a normal diet, we confirmed that gut microbiota dysbiosis contributed to HFD-induced deteriorated fertility and disrupted estradiol synthesis. Utilizing untargeted and targeted metabolomics analyses, we identified L-saccharopine as a key metabolite, which was enriched in the feces, serum, and ovaries of HFD and HFD-FMT mice. Subsequent in vitro and in vivo experiments demonstrated that L-saccharopine disrupted mitochondrial homeostasis by impeding AMPKα/MFF-mediated mitochondrial fission. This disruption ultimately hindered estradiol synthesis and compromised oocyte quality. AICAR, an activator of AMPKα, ameliorated L-saccharopine induced mitochondrial damage in granulosa cells and oocytes, thereby enhancing E2 synthesis and improving oocyte quality. Collectively, our findings indicate that the accumulation of L-saccharopine may play a pivotal role in mediating HFD-induced ovarian dysfunction. This highlights the potential therapeutic benefits of targeting the gut microbiota-metabolite-ovary axis to address HFD-induced ovarian dysfunction.}, } @article {pmid39409832, year = {2024}, author = {Kang, HJ and Kim, SW and Kim, SM and La, TM and Hyun, JE and Lee, SW and Kim, JH}, title = {Altered Gut Microbiome Composition in Dogs with Hyperadrenocorticism: Key Bacterial Genera Analysis.}, journal = {Animals : an open access journal from MDPI}, volume = {14}, number = {19}, pages = {}, pmid = {39409832}, issn = {2076-2615}, abstract = {Hyperadrenocorticism (HAC) is a common endocrine disorder in dogs, which is associated with diverse metabolic abnormalities. We hypothesized that elevated cortisol levels in dogs with HAC disrupt the gut microbiome (GM), and this disruption persists even after trilostane treatment. This study explored GM composition in dogs with HAC. We included 24 dogs, 15 with HAC and 9 healthy controls, and followed up with 5 dogs with HAC who received trilostane treatment. The GM analysis revealed significant compositional changes in dogs with HAC, including reduced microbiome diversity compared to healthy controls, particularly in rare taxa, as indicated by the Shannon index (p = 0.0148). Beta diversity analysis further showed a distinct clustering of microbiomes in dogs with HAC, separating them from healthy dogs (p < 0.003). Specifically, an overrepresentation of Proteobacteria (Pseudomonadota), Actinobacteria, Bacteroides, Enterococcus, Corynebacterium, Escherichia, and Proteus populations occurred alongside a decreased Firmicutes (Bacillota) population. Despite trilostane treatment, gut dysbiosis persisted in dogs with HAC at a median of 41 d post treatment, suggesting its potential role in ongoing metabolic issues. We identified GM dysbiosis in dogs with HAC by examining key bacterial genera, offering insights into potential interventions like probiotics or fecal microbiota transplants for better HAC management.}, } @article {pmid39408940, year = {2024}, author = {Luppi, S and Aldegheri, L and Azzalini, E and Pacetti, E and Barucca Sebastiani, G and Fabiani, C and Robino, A and Comar, M}, title = {Unravelling the Role of Gut and Oral Microbiota in the Pediatric Population with Type 1 Diabetes Mellitus.}, journal = {International journal of molecular sciences}, volume = {25}, number = {19}, pages = {}, pmid = {39408940}, issn = {1422-0067}, support = {RC 26/22 (Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy)//Ministero della Salute/ ; }, mesh = {Humans ; *Diabetes Mellitus, Type 1/microbiology ; *Gastrointestinal Microbiome ; *Dysbiosis/microbiology ; Child ; Mouth/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; Microbiota ; }, abstract = {Type 1 Diabetes Mellitus (T1DM) is a chronic autoimmune disease that results in the destruction of pancreatic β cells, leading to hyperglycaemia and the need for lifelong insulin therapy. Although genetic predisposition and environmental factors are considered key contributors to T1DM, the exact causes of the disease remain partially unclear. Recent evidence has focused on the relationship between the gut, the oral cavity, immune regulation, and systemic inflammation. In individuals with T1DM, changes in the gut and oral microbial composition are commonly observed, indicating that dysbiosis may contribute to immune dysregulation. Gut dysbiosis can influence the immune system through increased intestinal permeability, altered production of short chain fatty acids (SCFAs), and interactions with the mucosal immune system, potentially triggering the autoimmune response. Similarly, oral dysbiosis may contribute to the development of systemic inflammation and thus influence the progression of T1DM. A comprehensive understanding of these relationships is essential for the identification of biomarkers for early diagnosis and monitoring, as well as for the development of therapies aimed at restoring microbial balance. This review presents a synthesis of current research on the connection between T1DM and microbiome dysbiosis, with a focus on the gut and oral microbiomes in pediatric populations. It explores potential mechanisms by which microbial dysbiosis contributes to the pathogenesis of T1DM and examines the potential of microbiome-based therapies, including probiotics, prebiotics, synbiotics, and faecal microbiota transplantation (FMT). This complex relationship highlights the need for longitudinal studies to monitor microbiome changes over time, investigate causal relationships between specific microbial species and T1DM, and develop personalised medicine approaches.}, } @article {pmid39408584, year = {2024}, author = {Guevara-Ramírez, P and Cadena-Ullauri, S and Paz-Cruz, E and Ruiz-Pozo, VA and Tamayo-Trujillo, R and Cabrera-Andrade, A and Zambrano, AK}, title = {Gut Microbiota Disruption in Hematologic Cancer Therapy: Molecular Insights and Implications for Treatment Efficacy.}, journal = {International journal of molecular sciences}, volume = {25}, number = {19}, pages = {}, pmid = {39408584}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Hematologic Neoplasms/therapy/microbiology ; Probiotics/therapeutic use ; Treatment Outcome ; Antineoplastic Agents/therapeutic use ; Fecal Microbiota Transplantation ; Animals ; }, abstract = {Hematologic malignancies (HMs), including leukemia, lymphoma, and multiple myeloma, involve the uncontrolled proliferation of abnormal blood cells, posing significant clinical challenges due to their heterogeneity and varied treatment responses. Despite recent advancements in therapies that have improved survival rates, particularly in chronic lymphocytic leukemia and acute lymphoblastic leukemia, treatments like chemotherapy and stem cell transplantation often disrupt gut microbiota, which can negatively impact treatment outcomes and increase infection risks. This review explores the complex, bidirectional interactions between gut microbiota and cancer treatments in patients with HMs. Gut microbiota can influence drug metabolism through mechanisms such as the production of enzymes like bacterial β-glucuronidases, which can alter drug efficacy and toxicity. Moreover, microbial metabolites like short-chain fatty acids can modulate the host immune response, enhancing treatment effectiveness. However, therapy often reduces the diversity of beneficial bacteria, such as Bifidobacterium and Faecalibacterium, while increasing pathogenic bacteria like Enterococcus and Escherichia coli. These findings highlight the critical need to preserve microbiota diversity during treatment. Future research should focus on personalized microbiome-based therapies, including probiotics, prebiotics, and fecal microbiota transplantation, to improve outcomes and quality of life for patients with hematologic malignancies.}, } @article {pmid39407442, year = {2024}, author = {Lamminpää, I and Niccolai, E and Amedei, A}, title = {Probiotics as adjuvants to mitigate adverse reactions and enhance effectiveness in Food Allergy Immunotherapy.}, journal = {Scandinavian journal of immunology}, volume = {}, number = {}, pages = {e13405}, doi = {10.1111/sji.13405}, pmid = {39407442}, issn = {1365-3083}, abstract = {In the past decades, food allergies became increasingly dominant since early childhood, leading to a lower quality of life and to increasing costs addressed by the health care system. Beside standard avoidance of specific allergens and drug treatments following allergen exposure, a great deal of research has lately focused on Food Allergy Allergen Immunotherapy (FA-AIT). SCIT and EPIT (Subcutaneous and Epicutaneous Immunotherapy), OIT (Oral Immunotherapy), and SLIT (Sublingual Immunotherapy) consist in gradual exposure to allergens to desensitize and achieve tolerance once therapy has ended. Although promising, FA-AIT may bring acute local and systemic adverse reactions. To enhance efficacy, safety and convenience of AIT, the quest of potential adjuvants to mitigate the adverse reactions becomes crucial. Immunomodulatory activities, such as that of increasing the regulatory T cells and decreasing the IgE, have been observed in specific probiotics' strains and multiple studies elucidated the role of gut microbiota as a major interplayer among the host and its immune system. In this review, the microbiome modulation is shown as potential AIT adjuvant, nevertheless the need of more clinical studies in the near future is pivotal to assess the efficacy of targeted bacterial therapies and faecal microbiota transplantation.}, } @article {pmid39407244, year = {2024}, author = {Huang, Y and Wang, Y and Huang, X and Yu, X}, title = {Unveiling the overlooked fungi: the vital of gut fungi in inflammatory bowel disease and colorectal cancer.}, journal = {Gut pathogens}, volume = {16}, number = {1}, pages = {59}, pmid = {39407244}, issn = {1757-4749}, support = {NSFC 32260024, 32060040//the National Natural Science Foundation of China/ ; 20232BAB216091, 20202BAB206062//The Jiangxi Natural Science Foundation/ ; jxsq2023201019//The Double-Thousand Talent Program of Jiangxi Province/ ; }, abstract = {The fungi of the human microbiota play important roles in the nutritional metabolism and immunological balance of the host. Recently, research has increasingly emphasised the role of fungi in modulating inflammation in intestinal diseases and maintaining health in this environment. It is therefore necessary to understand more clearly the interactions and mechanisms of the microbiota/pathogen/host relationship and the resulting inflammatory processes, as well as to offer new insights into the prevention, diagnosis and treatment of inflammatory bowel disease (IBD), colorectal cancer (CRC) and other intestinal pathologies. In this review, we comprehensively elucidate the fungal-associated pathogenic mechanisms of intestinal inflammation in IBD and related CRC, with an emphasis on three main aspects: the direct effects of fungi and their metabolites on the host, the indirect effects mediated by interactions with other intestinal microorganisms and the immune regulation of the host. Understanding these mechanisms will enable the development of innovative approaches based on the use of fungi from the resident human microbiota such as dietary interventions, fungal probiotics and faecal microbiota transplantation in the prevention, diagnosis and treatment of intestinal diseases.}, } @article {pmid39406549, year = {2024}, author = {Li, K and Guo, L and Yu, J and Yang, Y and Wei, L and Min, C and Xu, X and Li, F and Liu, J and Zhou, G and Zhang, J}, title = {Kui-Jie-Ling capsule inhibits ulcerative colitis by modulating inflammation and gut microbiota.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.16758}, pmid = {39406549}, issn = {1440-1746}, support = {81202882//National Natural Science Foundation of China/ ; SNG2021022//Suzhou Science and Technology Planning Project in Jiangsu Province of China/ ; SYS2020079//Suzhou Science and Technology Planning Project in Jiangsu Province of China/ ; Z2020063//Jiangsu Health Commission Medical Research Projects, China/ ; JCZ21130//Science and Technology Bureau of Haian City, China/ ; SZWZYTD202205//Scientific and Technological Innovation Team Building Program of Suzhou Vocational Health College/ ; PAPD//Priority Academic Program Development of the Jiangsu Higher Education Institutes, China/ ; SZWZY202401//Science and Technology Planning Project of Suzhou Vocational Health College/ ; }, abstract = {BACKGROUND AND AIM: Kui-Jie-Ling capsule (Kui-Jie-Ling) is a hospital preparation for ulcerative colitis (UC) in China. This study aimed at evaluating the protective effects and mechanisms of Kui-Jie-Ling and Kui-Jie-Ling combined with adalimumab on UC induced by dextran sulfate sodium (DSS).

METHODS: Network pharmacology was combined with an animal experiment to reveal the targets of Kui-Jie-Ling alleviating UC. The UC model was established by drinking 2.5% DSS solution for 7 days. On the second day, the mice in the Kui-Jie-Ling group were orally administered with Kui-Jie-Ling (1.5 and 3.0 g/kg) daily for seven consecutive days, and the mice in the combination group were orally administered with Kui-Jie-Ling (3.0 g/kg) once a day for seven consecutive days and received one subcutaneous injection of adalimumab. The disease activity index, the colon length, the spleen index, the cytokines, the colon, the short-chain fatty acid content, and the gut microbiota in the colon were analyzed. The role of gut microbiota against UC was verified by fecal microbiota transplantation experiments.

RESULTS: The animal study's results were consistent with the network pharmacology analysis, which reflected that Kui-Jie-Ling alleviated UC via multi-pathway. Kui-Jie-Ling ameliorated UC by inhibiting the formation of neutrophil extracellular traps (NETs), regulating inflammatory factors through the lipopolysaccharide-toll-like receptor 4/nuclear factor kappa B and interleukin-23-Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway, and restoring intestinal homeostasis.

CONCLUSION: These studies provided the experimental basis for the clinical administration of Kui-Jie-Ling and Kui-Jie-Ling combined with adalimumab against UC.}, } @article {pmid39189787, year = {2024}, author = {Arcay, R and Barceló-Nicolau, M and Suárez, L and Martín, L and Reigada, R and Höring, M and Liebisch, G and Garrido, C and Cabot, G and Vílchez, H and Cortés-Lara, S and González de Herrero, E and López-Causapé, C and Oliver, A and Barceló-Coblijn, G and Mena, A}, title = {Gut microbiome and plasma lipidome analysis reveals a specific impact of Clostridioides difficile infection on intestinal bacterial communities and sterol metabolism.}, journal = {mBio}, volume = {15}, number = {10}, pages = {e0134724}, pmid = {39189787}, issn = {2150-7511}, support = {co-PI of the SYN17/12//Health Research Institute of the Balearic Islands (IdISBa)/ ; JUNIOR18/02//Health Research Institute of the Balearic Islands (IdISBa)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Clostridium Infections/microbiology/blood/therapy ; *Sterols/metabolism/blood ; *Lipid Metabolism ; *Clostridioides difficile/metabolism ; Bacteria/classification/metabolism/isolation & purification/genetics ; Male ; Lipidomics ; Female ; Middle Aged ; Aged ; Feces/microbiology ; Lipids/blood ; Adult ; Fecal Microbiota Transplantation ; }, abstract = {UNLABELLED: Clostridioides difficile infection (CDI) causes alterations in the intestinal microbiota, frequently associated with changes in the gut metabolism of bile acids and cholesterol. In addition to the impact on microbiome composition and given the metabolic changes occurring during CDI, our work focuses on the importance to know the effects at the local and systemic levels, both during the infection and its treatment, by paying particular attention to plasma lipid metabolism due to its relationship with CDI pathogenesis. Specific changes, characterized by a loss of microbial richness and diversity and related to a reduction in short-chain acid-producing bacteria and an increase in bile salt hydrolase-producing bacteria, were observed in the gut microbiota of CDI patients, especially in those suffering from recurrent CDI (RCDI). However, gut microbiota showed its ability to restore itself after treatment, resembling healthy individuals, in those patients treated by fecal microbiome transfer (FMT), in contrast with those treated with antibiotics, and displaying increased levels of Eubacterium coprostanoligenes, a cholesterol-reducing anaerobe. Interestingly, changes in plasma lipidome revealed a global depletion in circulating lipids in CDI, with the largest impact on cholesteryl esters. CDI patients also showed a specific and consistent decrease in the levels of lipid species containing linoleic acid-an essential fatty acid-which were only partially recovered after antibiotic treatment. Analysis of the plasma lipidome reflects CDI impact on the gut microbiota and its metabolism, evidencing changes in sterol and fatty acid metabolism that are possibly related to specific alterations observed in gut microbial communities of CDI patients.

IMPORTANCE: There is increasing evidence about the influence the changes in microbiota and its metabolism has on numerous diseases and infections such as Clostridioides difficile infection (CDI). The knowledge of these changes at local and systemic levels can help us manage this infection to avoid recurrences and apply the best therapies, such as fecal microbiota transfer (FMT). This study shows a better restoration of the gut in FMT-treated patients than in antibiotic-treated patients, resembling healthy controls and showing increased levels of cholesterol-reducing bacteria. Furthermore, it evidences the CDI impact on plasma lipidome. We observed in CDI patients a global depletion in circulating lipids, particularly cholesteryl esters, and a specific decrease in linoleic acid-containing lipids, an essential fatty acid. Our observations could impact CDI management because the lipid content was only partially recovered after treatment, suggesting that continued nutritional support, aiming to restore healthy lipid levels, could be essential for a full recovery.}, } @article {pmid39404715, year = {2024}, author = {Maev, IV and Velikolug, KA}, title = {[Cytomegalovirus infection in gastroenterology].}, journal = {Terapevticheskii arkhiv}, volume = {96}, number = {8}, pages = {723-731}, doi = {10.26442/00403660.2024.08.202814}, pmid = {39404715}, issn = {0040-3660}, mesh = {Humans ; *Cytomegalovirus Infections/diagnosis/drug therapy ; *Antiviral Agents/therapeutic use ; Cytomegalovirus/genetics/isolation & purification ; Gastrointestinal Diseases/virology/diagnosis/therapy/etiology ; Risk Factors ; Polymerase Chain Reaction/methods ; DNA, Viral/analysis ; }, abstract = {AIM: To highlight the relevance of gastrointestinal manifestations of cytomegalovirus infection (CMVI), to highlight the main risk factors for the development of this pathology, current trends in diagnosis and treatment.

KEY POINTS: CMVI is one of the most common opportunistic diseases, characterized by a variety of manifestations from asymptomatic to severe generalized forms affecting internal organs and body systems. The prevalence of CMVI worldwide ranges from 20 to 95%. Particular attention is paid to timely diagnosis, treatment and prevention of CMVI. The "gold standard" in the diagnosis of digestive diseases associated with CMVI is immunohistochemical examination and detection of cytomegalovirus (CMV) DNA in tissues using the polymerase chain reaction (PCR). Of undoubted interest in the diagnosis of CMV is the detection of CMV DNA in stool using digital PCR. Compared to quantitative PCR, digital PCR has higher accuracy and sensitivity. As first-line therapy, the drugs of choice are ganciclovir and valganciclovir. Maribavir has been successfully used to treat patients with CMV infection refractory to one or more previous therapies. One of the promising directions in the treatment of cytomegalovirus colitis in patients with ulcerative colitis is fecal microbiota transplantation.

CONCLUSION: Timely identification of risk factors for the development of CMV infection, the introduction of innovative methods and approaches in diagnosis, and the use of effective methods for treating diseases of the digestive system associated with CMV infection can improve the prognosis of the underlying disease and reduce the risk of developing urgent conditions in gastroenterology.}, } @article {pmid39403342, year = {2024}, author = {Bertin, L and Crepaldi, M and Zanconato, M and Lorenzon, G and Maniero, D and De Barba, C and Bonazzi, E and Facchin, S and Scarpa, M and Ruffolo, C and Angriman, I and Buda, A and Zingone, F and Savarino, EV and Barberio, B}, title = {Refractory Crohn's Disease: Perspectives, Unmet Needs and Innovations.}, journal = {Clinical and experimental gastroenterology}, volume = {17}, number = {}, pages = {261-315}, pmid = {39403342}, issn = {1178-7023}, abstract = {Crohn's disease (CD) is a complex, chronic inflammatory bowel disease characterized by unpredictable flare-ups and periods of remission. Despite advances in treatment, CD remains a significant health burden, leading to substantial direct healthcare costs and out-of-pocket expenses for patients, especially in the first-year post-diagnosis. The impact of CD on patients' quality of life is profound, with significant reductions in physical, emotional, and social well-being. Despite advancements in therapeutic options, including biologics, immunomodulators, and small molecules, many patients struggle to achieve or maintain remission, leading to a considerable therapeutic ceiling. This has led to an increased focus on novel and emerging treatments. This context underscores the importance of exploring advanced and innovative treatment options for managing refractory CD. By examining the latest approaches, including immunomodulators, combination therapies, stem cell therapies, and emerging treatments like fecal microbiota transplantation and dietary interventions, there is an opportunity to gain a comprehensive understanding of how best to address and manage refractory cases of CD.}, } @article {pmid39403201, year = {2024}, author = {Napiórkowska-Baran, K and Biliński, J and Pujanek, M and Hałakuc, P and Pietryga, A and Szymczak, B and Deptuła, A and Rosada, T and Bartuzi, Z}, title = {Fecal microbiota transplantation in a patient with chronic diarrhea and primary and secondary immunodeficiency (common variable immunodeficiency and splenectomy).}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1456672}, pmid = {39403201}, issn = {2235-2988}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Diarrhea/microbiology/therapy ; Middle Aged ; *Splenectomy ; *Common Variable Immunodeficiency/complications/therapy ; *Gastrointestinal Microbiome ; Feces/microbiology/virology ; Cytomegalovirus Infections ; Male ; Treatment Outcome ; Valganciclovir/therapeutic use/administration & dosage ; Chronic Disease ; Immunocompromised Host ; Dysbiosis/therapy/microbiology ; Clostridioides difficile ; }, abstract = {The gut microbiota serves a crucial role in the development of host immunity. Immunocompromised patients are particularly vulnerable to dysbiosis not only by virtue of a defect in the immune system but also due to increased susceptibility to infection and multiple courses of antibiotic therapy. Fecal microbiota transplantation is by far the most effective option for restoring gastrointestinal homeostasis. However, it is contraindicated in patients with significant primary and secondary immunodeficiencies. This article presents the case of a 59-year-old patient with common variable immunodeficiency, after splenectomy at age 39 for primary immune thrombocytopenia, who manifested diarrhea of up to 10 stools per day accompanied by secondary malnutrition and cachexia. The patient was admitted to the hospital on multiple occasions due to this condition, with stool PCR tests confirming a HHV-5 (Cytomegalovirus, CMV) infection. Following the administration of valganciclovir, the patient's complaints diminished, although, upon cessation of the drug, the symptoms recurred. In addition, the patient had an intestinal infection with C. difficile etiology. Given that the patient's therapeutic options had been exhausted, after obtaining informed consent from the patient and approval from the bioethics committee to conduct a medical experiment, treatment of diarrhea was undertaken by fecal microbiota transplantation with the certified preparation Mbiotix HBI from the Human Biome Institute. The patient underwent two transplants, with a one-week interval between them. The initial procedure was performed using the endoscopic method, while the subsequent was conducted using the capsule method. Following the administration of the applied treatment, the patient's symptoms were successfully alleviated, and no adverse effects were observed. A microbiological analysis of the intestinal microbiota was conducted prior to and following transplantation via next-generation sequencing (NGS). No recurrence of symptoms was observed during the two-year follow-up period. To the best of our knowledge, this is the first fecal microbiota transplantation in an adult patient with primary and secondary immunodeficiency.}, } @article {pmid39403173, year = {2024}, author = {Huang, J and Wang, X and Zhang, J and Li, Q and Zhang, P and Wu, C and Jia, Y and Su, H and Sun, X}, title = {Fecal microbiota transplantation alleviates food allergy in neonatal mice via the PD-1/PD-L1 pathway and change of the microbiota composition.}, journal = {The World Allergy Organization journal}, volume = {17}, number = {10}, pages = {100969}, pmid = {39403173}, issn = {1939-4551}, abstract = {BACKGROUND: Food allergy (FA) is a common disorder in children and affects the health of children worldwide. The gut microbiota is closely related to the occurrence and development of FA. Fecal microbiota transplantation (FMT) is a way to treat diseases by reconstituting the microbiota; however, the role and mechanisms of FA have not been validated.

METHODS: In this study, we established an ovalbumin (OVA)-induced juvenile mouse model and used 16S RNA sequencing, pathological histological staining, molecular biology, and flow-through techniques to evaluate the protective effects of FMT treatment on FA and to explore the mechanisms.

RESULTS: OVA-induced dysregulation of the gut microbiota led to impaired intestinal function and immune dysregulation in FA mice. FMT treatment improved the structure, diversity, and composition of the gut microbiota and restored it to a near-donor state. FMT treatment reduced levels of Th2-associated inflammatory factors, decreased intestinal tissue inflammation, and reduced IgE production. In addition, FMT reduced the number of mast cells and eosinophils and suppressed OVA-specific antibodies. Further mechanistic studies revealed that FMT treatment induced immune tolerance by inducing the expression of CD103[+]DCs and programmed cell death ligand 1 (PD-L1) in mesenteric lymph nodes and promoting the production of Treg through the programmed cell death protein 1 (PD-1)/PD-L1 pathway. Meanwhile, Th2 cytokines, OVA-specific antibodies, and PD-1/PD-L1 showed a significant correlation with the gut microbiota.

CONCLUSIONS: FMT could regulate the gut microbiota and Th1/Th2 immune balance and might inhibit FA through the PD-1/PD-L1 pathway, which would provide a new idea for the treatment of FA.}, } @article {pmid39403057, year = {2024}, author = {Liang, C and Pereira, R and Zhang, Y and Rojas, OL}, title = {Gut Microbiome in Alzheimer's Disease: from Mice to Humans.}, journal = {Current neuropharmacology}, volume = {22}, number = {14}, pages = {2314-2329}, pmid = {39403057}, issn = {1875-6190}, mesh = {*Alzheimer Disease/microbiology/therapy ; *Gastrointestinal Microbiome/physiology ; Humans ; Animals ; *Brain-Gut Axis/physiology ; Mice ; Probiotics/therapeutic use ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Prebiotics ; }, abstract = {Alzheimer's disease (AD) is the most prevalent type of dementia, but its etiopathogenesis is not yet fully understood. Recent preclinical studies and clinical evidence indicate that changes in the gut microbiome could potentially play a role in the accumulation of amyloid beta. However, the relationship between gut dysbiosis and AD is still elusive. In this review, the potential impact of the gut microbiome on AD development and progression is discussed. Pre-clinical and clinical literature exploring changes in gut microbiome composition is assessed, which can contribute to AD pathology including increased amyloid beta deposition and cognitive impairment. The gut-brain axis and the potential involvement of metabolites produced by the gut microbiome in AD are also highlighted. Furthermore, the potential of antibiotics, prebiotics, probiotics, fecal microbiota transplantation, and dietary interventions as complementary therapies for the management of AD is summarized. This review provides valuable insights into potential therapeutic strategies to modulate the gut microbiome in AD.}, } @article {pmid39401017, year = {2024}, author = {Yang, T and Liu, Y and Yin, J and Tian, Y and Zhou, F and Li, Y and Yang, L and Han, L and Huang, X}, title = {Transplantation of fecal microbiota from different breed improved intestinal barrier condition and modulated ileal microflora of recipient pigs.}, journal = {Journal of animal science}, volume = {}, number = {}, pages = {}, doi = {10.1093/jas/skae314}, pmid = {39401017}, issn = {1525-3163}, abstract = {In this study, we investigated the effects of transplanting Ningxiang pig fecal bacteria on ileum microflora and intestinal barrier of Duroc × Landrace × Large White (DLY) pigs. Thirty-two DLY pigs at 90-d-old were equally assigned to either control groups (fed the basal diet) or test group (fed the basal diet + 10ml fecal microbiota suspension from Ningxiang pig). Results showed that fecal microbiota transplantation (FMT) did not influence the growth performance, but increased the number of ileum goblet cells and the expression level of mucin-2. Additionally, the mucosal levels of anti-inflammatory cytokines interlukin-4 and interlukin-10 were upregulated, but the level of pro-inflammatory cytokine interferon-γ was downregulated by FMT. Moreover, FMT increased the expression level of porcine β defensin-114 in ileum mucus. 16S rRNA gene sequencing of ileal digesta showed that FMT modulated the diversity and composition of ileal microbiota of DLY pigs by increasing the relative abundances of beneficial bacteria, while decreasing the abundance of the pathogenic bacterium Streptococcus. Taken together, the study showed that FMT of Ningxiang pigs could improve intestinal barrier condition of DLY pigs by improving intestinal microflora and promoting intestinal health.}, } @article {pmid39400011, year = {2024}, author = {Lu, D and Ji, L and Liu, F and Liu, H and Sun, Z and Yan, J and Wu, H}, title = {Fecal Microbiota Transplantation Induced by Wumei Pills Improves Chemotherapy-Induced Intestinal Mucositis in BALB/c Mice by Modulating the TLR4/MyD88/NF-κB Signaling Pathway.}, journal = {Current drug delivery}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115672018304338241003095955}, pmid = {39400011}, issn = {1875-5704}, abstract = {BACKGROUND: Our previous studies have found that Wumei Pills can regulate the intestinal flora to inhibit chemotherapy-induced intestinal mucositis (CIM). However, there is still insufficient evidence to confirm that intestinal flora is the main link in the regulation of CIM by Wumei Pills, and its downstream mechanism is still unclear.

METHOD: We first obtained the signal pathway of the intervention of Wumei Pill on CIM through network pharmacological analysis and then transplanted the bacterial solution into CIM mice, combined with Western Blot, HE, ELISA and other biological technology-related proteins and inflammatory factors.

RESULTS: It showed that 97 kinds of effective ingredients and 205 kinds of targets of Wumei pills were screened out and the potential mechanism of Wumei Pills on CIM may be the NF-κB signaling pathway. In contrast with the control group, the results displayed that the weight, food intake, and mice's colon length were apparently decreased in the 5-Fu group, while the diarrhea score was increased. However, FMT reversed this change, and the difference was statistically significant. Additionally, FMT could improve the pathological state of inflammatory cell infiltration in mice, reduce histopathological scores of colon and jejunum, decrease the expression levels of IL-1β, MPO, TNF-α, and IL-6, reverse the activation of signaling pathway named TLR4/Myd88/ NF-κB and down-regulate protein expression, thereby exerting its anti-inflammatory activities. Further experiments have found that FMT could reverse the decreasing of tight junction proteins and mucins caused by 5-Fu, thereby repairing the intestinal mucosal barrier, and FMT could also increase the content of acetic acid, propanoic acid, and butanoic acid in the feces of 5-Fu group.

CONCLUSION: FMT can defend the intestinal mucosal barrier integrality by increasing the content of exercise fatty acids, and its mechanism may be in connection with its inhibition of TLR4/My- D88/NF-κB signal pathway to relieve inflammation.}, } @article {pmid39399248, year = {2024}, author = {Scott, A and Khoruts, A and Freeman, ML and Beilman, G and Ramanathan, K and Bellin, MD and Trikudanathan, G}, title = {Successful Use of Fecal Microbiota Transplantation in Management of Nonobstructive Recurrent Cholangitis Following Total Pancreatectomy and Islet Autotransplant.}, journal = {ACG case reports journal}, volume = {11}, number = {10}, pages = {e01527}, pmid = {39399248}, issn = {2326-3253}, abstract = {Alterations in the gut microbiome have been implicated in various pathologies. Fecal microbiota transplantation (FMT) has been offered as a novel treatment for conditions implicated in the disruption of the gut-microbiota axis. This case report details the successful treatment of recurrent nonobstructive cholangitis following a single FMT application in a patient who had previously undergone a hepatobiliary tract surgical diversion. Cholangitis was suspected secondary to reflux of an altered microbiome into the surgically reanastomosed biliary tract, and FMT was justified based on the history of recurrent Clostridioides difficile infections. This case supports the further evaluation of the utility of FMT as one potential treatment of post hepatobiliary surgical diversion cholangitis.}, } @article {pmid39398388, year = {2024}, author = {Liu, T and Lei, C and Huang, Q and Song, W and Li, C and Sun, N and Liu, Z}, title = {Hesperidin and Fecal Microbiota Transplantation Modulate the Composition of the Gut Microbiota and Reduce Obesity in High Fat Diet Mice.}, journal = {Diabetes, metabolic syndrome and obesity : targets and therapy}, volume = {17}, number = {}, pages = {3643-3656}, pmid = {39398388}, issn = {1178-7007}, abstract = {INTRODUCTION: Obesity, which is associated with gut microbiota dysbiosis, low-grade chronic inflammation and intestinal barrier dysfunction, can cause a variety of chronic metabolic diseases. Phytochemical flavonoids have a variety of biological activities, among which there may be safe and effective anti-obesity solutions.

METHODS: We tested a plant-derived flavonoid hesperidin and fecal microbiota transplantation (FMT) to alleviate diet-induced obesity. High-fat diet (HFD)-fed mice were treated with hesperidin (100 and 200 mg/kg BW) and FMT.

RESULTS: Results indicated that hesperidin had the effects of reducing obesity as indicated by reduction of body weight, fat accumulation and blood lipids, reducing inflammation as indicated by reduction of pro-inflammation factors including TNFα, IL-6, IL-1βand iNOS, and improving gut integrity as indicated by increasing colon length, reducing plasma gut permeability indicators iFABP and LBP, increased mRNA expression of mucus protein Muc2, tight junction p Claudin 2, Occludin and ZO-1 in the HFD-fed mice. The anti-obesity effects of hesperidin treatment have a dose-dependent manner. In addition, 16S rRNA-based gut microbiota analysis revealed that hesperidin selectively promoted the growth of Lactobacillus salivarius, Staphylococcus sciuri and Desulfovibrio C21_c20 while inhibiting Bifidobacterium pseudolongum, Mucispirillum schaedleri, Helicobacter ganmani and Helicobacter hepaticus in the HFD-fed mice. Horizontal feces transfer from the normal diet (ND)-fed mice to the HFD-fed mice conferred anti-obesity effects and transmitted some of the HFD-modulated microbes.

CONCLUSION: We concluded that hesperidin and FMT both affect the reduction of body weight and improve HFD-related disorders in the HFD-fed mice possibly through modulating the composition of the gut microbiota.}, } @article {pmid39397472, year = {2024}, author = {Ding, H and Wang, Q and Liao, G and Hao, Z}, title = {[Diagnosis and treatment of gastrointestinal bleeding after kidney transplantation].}, journal = {Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences}, volume = {56}, number = {5}, pages = {902-907}, pmid = {39397472}, issn = {1671-167X}, mesh = {Humans ; *Kidney Transplantation ; *Gastrointestinal Hemorrhage/etiology/diagnosis/therapy ; Retrospective Studies ; *Kidney Failure, Chronic/therapy/complications ; Gastroscopy ; Male ; Embolization, Therapeutic ; }, abstract = {OBJECTIVE: To analyze the clinical characteristics of acute and chronic gastrointestinal bleeding in patients with end-stage renal disease (ESRD) after kidney transplantation, to improve the understanding of the causes, diagnosis, treatment and prevention of this complication, and to improve the management of patients with gastrointestinal bleeding after kidney transplantation.

METHODS: The clinical, imaging and pathological data of patients with gastrointestinal bleeding after kidney transplantation in the Department of Urology of The First Affiliated Hospital of Anhui Medical University from August, 2015 to December, 2020 were collected. The etiology, early clinical manifestations, abnormal laboratory tests and examinations, treatment procedures, late prevention and treatment measures and outcomes of gastrointestinal bleeding were retrospectively studied, and the relevant literature was summarized and reviewed.

RESULTS: A total of 17 patients were included in this study. Nine patients had chronic small amount of bleeding, hemoglobin gradually decreased, melena and fecal occult blood positive in the early stage, and the general condition was good, vital signs were stable, and were cured by drug treatment. Gastroscopy showed small ulcers with active bleeding foci in 2 cases, and the bleeding was stopped by titanium clips, and the prognosis was good. Gastroscopy showed that the anterior wall longitudinal ulcer at the junction of gastric antrum body was not effective in 1 case, and the small branch of right gastroepithelial artery was embolized, and the patient recovered and discharged after 2 weeks. Gastroscopy showed deep pit ulcer at the lesser curvature of gastric antrum in 1 patient, who underwent distal gastroduodenal artery embolization and had a good prognosis. Gastroscopy showed huge multiple ulcers in the stomach and duodenal bulb in 2 patients, who underwent subtotal gastrectomy and partial duodenectomy, duodenal stump exclusion and remnant gastrojejunostomy. One patient recovered and was discharged, and the other patient died of rebleeding on the 12th day after surgery. Two cases of diverticulum underwent surgical resection of diverticulum, and the prognosis was good.

CONCLUSION: The onset of gastrointestinal hemorrhage in kidney transplant patients is insidious, and the condition is acute or slow, which can cause different degrees of damage to the patient and the transplanted kidney. Active prevention, early diagnosis, timely drug treatment, if the effect is not good, decisive endoscopic titanium clip hemostasis, transvascular interventional embolization, and even surgical treatment can minimize the harm of gastrointestinal bleeding.}, } @article {pmid39396842, year = {2024}, author = {González, A and Badiola, I and Fullaondo, A and Rodríguez, J and Odriozola, A}, title = {Personalised medicine based on host genetics and microbiota applied to colorectal cancer.}, journal = {Advances in genetics}, volume = {112}, number = {}, pages = {411-485}, doi = {10.1016/bs.adgen.2024.08.004}, pmid = {39396842}, issn = {0065-2660}, mesh = {Humans ; *Colorectal Neoplasms/genetics/microbiology ; *Precision Medicine/methods ; *Gastrointestinal Microbiome/genetics ; Biomarkers, Tumor/genetics ; Prognosis ; }, abstract = {Colorectal cancer (CRC) ranks second in incidence and third in cancer mortality worldwide. This situation, together with the understanding of the heterogeneity of the disease, has highlighted the need to develop a more individualised approach to its prevention, diagnosis and treatment through personalised medicine. This approach aims to stratify patients according to risk, predict disease progression and determine the most appropriate treatment. It is essential to identify patients who may respond adequately to treatment and those who may be resistant to treatment to avoid unnecessary therapies and minimise adverse side effects. Current research is focused on identifying biomarkers such as specific mutated genes, the type of mutations and molecular profiles critical for the individualisation of CRC diagnosis, prognosis and treatment guidance. In addition, the study of the intestinal microbiota as biomarkers is being incorporated due to the growing scientific evidence supporting its influence on this disease. This article comprehensively addresses the use of current and emerging diagnostic, prognostic and predictive biomarkers in precision medicine against CRC. The effects of host genetics and gut microbiota composition on new approaches to treating this disease are discussed. How the gut microbiota could mitigate the side effects of treatment is reviewed. In addition, strategies to modulate the gut microbiota, such as dietary interventions, antibiotics, and transplantation of faecal microbiota and phages, are discussed to improve CRC prevention and treatment. These findings provide a solid foundation for future research and improving the care of CRC patients.}, } @article {pmid39396755, year = {2024}, author = {Zhang, Y and Li, P and Chen, B and Zheng, R}, title = {Therapeutic effects of fecal microbial transplantation on alcoholic liver injury in rat models.}, journal = {Clinics and research in hepatology and gastroenterology}, volume = {48}, number = {9}, pages = {102478}, doi = {10.1016/j.clinre.2024.102478}, pmid = {39396755}, issn = {2210-741X}, abstract = {OBJECTIVE: Disruption of gut microbiota is closely related to the progression of alcoholic liver disease (ALD). This study aimed to explore the therapeutic effect of fecal microbiota transplantation (FMT) in ALD rats using a combination of microbiological and metabolomic techniques.

METHODS: Three liver injury rat models were constructed using alcohol, CCL4, and alcohol combined with CCL4, and administered an FMT treatment comprising the fecal microbiota of healthy rats via the gastric route for 12 consecutive weeks. We measured the therapeutic effect of FMT treatment on liver inflammation, intestinal mucosal barrier, and bacterial translocation in ALD rats using 16S rRNA and UPLC-Q/TOF-MS technology to detect the effects of FMT on the intestinal microbiota and metabolic patterns of ALD rats.

RESULTS: FMT treatment effectively improved liver function, prolonged survival time, improved the intestinal mucosal barrier, reduced bacterial translocation, alleviated liver inflammation, and delayed the progression of liver fibrosis in three types of liver injury models. The microbiome and metabolomic results showed that FMT can effectively improve gut microbiota disorder in ALD rats and improve metabolic patterns by regulating metabolic pathways such as the arachidonic acid and retinol pathways.

CONCLUSION: FMT treatment could reverse alcohol induced liver injury by improving gut microbiota and metabolic patterns in ALD rats, and oral FMT could be an effective therapeutic approach for ALD.}, } @article {pmid39396405, year = {2024}, author = {Luo, Z and Yang, L and Zhu, T and Fan, F and Wang, X and Liu, Y and Zhan, H and Luo, D and Guo, J}, title = {Aucubin ameliorates atherosclerosis by modulating tryptophan metabolism and inhibiting endothelial-mesenchymal transitions via gut microbiota regulation.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156122}, doi = {10.1016/j.phymed.2024.156122}, pmid = {39396405}, issn = {1618-095X}, abstract = {BACKGROUND: The gut microbiota is believed to influence atherosclerosis (AS), and Aucubin (Au), a natural compound found in the traditional Chinese medicine Eucommia ulmoides Oliver, is being explored as a potential treatment for cardiovascular disease. Yet, the specific impact of Au on AS through the gut microbiota remains unclear.

PURPOSE: This study aimed to highlight the potential of Au in improving AS by influencing gut microbiota and investigating its potential mechanisms by which it and its metabolites of gut microbiota regulate lipid metabolism, inflammation and endothelial dysfunction.

METHODS: The impact of Au on AS in ApoE[-/-] mice was examined, followed by a fecal microbiota transplantation experiment to confirm the influence of Au on AS through gut microbiota. Subsequent analysis of fecal and serum samples using 16S rRNA gene sequencing and metabolomics revealed distinct features of gut microbiota and metabolites. Identified metabolites were then utilized in vivo experiments to investigate underlying mechanisms.

RESULTS: Au treatment effectively reduced dietary-induced dyslipidemia and endothelial dysfunction in a dose-dependent manner in atherosclerotic mice. It also improved vascular plaque accumulation and inflammation, increased aortic valve fibrous cap thickness, and decreased necrotic core and collagen fiber area. Subsequently, we observed a substantial increase in indole-3-acrylic acid (IAA), a microbe-derived metabolite, in cecal contents and serum, along with a significant rise in Lactobacillus abundance responsible for IAA production. Our findings demonstrated that IAA played a crucial role in alleviating AS. Furthermore, we discovered that IAA activated the Aryl hydrocarbon receptor (AhR) and suppressed the TGF-β/Smad pathway, potentially ameliorating endothelial-mesenchymal transitions in atherosclerotic mice.

CONCLUSION: These findings suggested that Au's anti-atherosclerotic effects were primarily due to elevated Lactobacillus-derived IAA, thereby potentially contributing to alleviating AS.}, } @article {pmid39395767, year = {2024}, author = {Qi, Z and Liu, J and Xu, Y and Hongguang, S and Qi, X and Cong, M and Zhang, X and Yan, Y and Liu, T}, title = {Protective effects of phenylethanol glycosides from Cistanche tubulosa against ALD through modulating gut microbiota homeostasis.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {118925}, doi = {10.1016/j.jep.2024.118925}, pmid = {39395767}, issn = {1872-7573}, abstract = {Cistanche tubulosa (Schenk) Wight, a Chinese herbal medicine (Rou Cong Rong) with Xinjiang characteristics, was recorded in many medical books in ancient China and often used as a tonic medicine. Supported by the traditional Chinese medicine theory of "homology of liver and kidney," C. tubulosa (Schenk) Wight has many clinical applications in tonifying the kidney and protecting the liver. Modern pharmacological studies have also found that the protective effects of phenylethanol glycosides from C. tubulosa (Schenk) Wight (CPhGs) play an important role in ameliorating alcoholic liver injury.

AIM OF THE STUDY: We aimed to investigate whether CPhGs can enhance the therapeutic outcome of alcoholic liver disease (ALD) by targeting the "gut-liver axis," thus contributing to the knowledge of how Chinese herbs alleviate disease by influencing the gut microbiota.

MATERIALS AND METHODS: An ALD mouse model was established using the Lieber-DeCarli alcohol liquid diet, and the effects of CPhGs on the intestinal barrier and gut microbiota of ALD mice were investigated in a pseudo-sterile mouse model and fecal microbiota transplantation (FMT) mouse model. We fed female C57BL/6N mice with Lieber-DeCarli ethanol liquid diet, according to the NIAAA model. Animal experiment of long-term, ethanol diet intervention for 6W, and short-term for 11d. The FMT experiments were also performed.

RESULTS: CPhGs significantly improved ALD manifestations. ALD mice demonstrated significant gut microbiota dysbiosis and significantly abnormal proliferation of Allobaculum compared with the control diet group in long-term NIAAA mouse model (L-Pair). In mice that received the long-term intervention, the improvement in gut barrier function in the CPhGs-treated group was accompanied by a significant decrease in the abundance of Allobaculum and a significant increase in the abundance of Akkermansia. Furthermore, compared with the mouse were gavaged fecal microbiota from the long-term NIAAA mouse donors (FMT-EtOH), the number of goblet cells, abundance of Akkermansia, and the intestinal short-chain fatty acid concentrations were significantly increased in the mouse were gavaged fecal microbiota from high (700 mg/kg) doses of CPhGs orally in long-term NIAAA model donors (FMT-EtOH-H). Network analysis and species distribution results demonstrated that Akkermansia and Allobaculum were the genera with the highest abundances in the gut microbiota and that their interaction was related to propionic acid metabolism.

CONCLUSIONS: The results suggest that CPhGs exert a protective effect against ALD by modulating the abundance and composition of Akkermansia and Allobaculum in the intestine, maintaining the intestinal mucus balance, and safeguarding intestinal barrier integrity.}, } @article {pmid39395000, year = {2024}, author = {Sayol-Altarriba, A and Aira, A and Villasante, A and Albarracín, R and Faneca, J and Casals, G and Villanueva-Cañas, JL and Casals-Pascual, C}, title = {Normalization of short-chain fatty acid concentration by bacterial count of stool samples improves discrimination between eubiotic and dysbiotic gut microbiota caused by Clostridioides difficile infection.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2415488}, doi = {10.1080/19490976.2024.2415488}, pmid = {39395000}, issn = {1949-0984}, mesh = {Humans ; *Fatty Acids, Volatile/metabolism/analysis ; *Feces/microbiology/chemistry ; *Gastrointestinal Microbiome ; *Clostridium Infections/microbiology ; *Dysbiosis/microbiology ; *Clostridioides difficile/metabolism ; *Bacterial Load ; Male ; Female ; Middle Aged ; Adult ; Aged ; Butyrates/metabolism/analysis ; Bacteria/classification/isolation & purification/metabolism/genetics ; }, abstract = {Short-chain fatty acids (SCFAs) represent a cornerstone of gut health, serving as critical mediators of immune modulation and overall host homeostasis. Patients with dysbiosis caused by Clostridioides difficile infection (CDI) typically exhibit lower SCFAs levels compared to healthy stool donors and, thus, the concentration of SCFAs has been proposed as a proxy marker of a healthy microbiota. However, there is no consistency in the methods used to quantify SCFAs in stool samples and usually, the results are normalized by the weight of the stool samples, which does not address differences in water and fiber content and ignores bacterial counts in the sample (the main component of stool that contributes to the composition of these metabolites in the sample). Here, we show that normalized SCFAs concentrations by the bacterial count improve discrimination between healthy and dysbiotic samples (patients with CDI), particularly when using acetate and propionate levels. After normalization, butyrate is the metabolite that best discriminates eubiotic and dysbiotic samples according to the area under the receiver operating characteristic (ROC) curve (AUC-ROC = 0.860, [95% CI: 0.786-0.934], p < .0001).}, } @article {pmid39394819, year = {2024}, author = {Dong, L and Luo, P and Zhang, A}, title = {Intestinal microbiota dysbiosis contributes to the liver damage in subchronic arsenic-exposed mice.}, journal = {Acta biochimica et biophysica Sinica}, volume = {}, number = {}, pages = {}, doi = {10.3724/abbs.2024131}, pmid = {39394819}, issn = {1745-7270}, abstract = {There is an extensive amount of evidence that links changes in the intestinal microbiota structure to the progression and pathophysiology of many liver diseases. However, comprehensive analysis of gut flora dysbiosis in arsenic-induced hepatotoxicity is lacking. Herein, C57BL/6 mice are exposed to arsenic (1, 2, or 4 mg/kg) for 12 weeks, after which fecal microbiota transplantation (FMT) study is conducted to confirm the roles of the intestinal microbiome in pathology. Treatment with arsenic results in pathological and histological changes in the liver, such as inflammatory cell infiltration and decreased levels of TP and CHE but increased levels of ALP, GGT, TBA, AST, and ALT. Arsenic causes an increase in the relative abundance of Escherichia-Shigella, Klebsiella and Blautia, but a decrease in the relative abundance of Muribaculum and Lactobacillus. In arsenic-exposed mice, protein expressions of Occludin, ZO-1, and MUC2 are significantly decreased, but the level of FITC in serum is increased, and FITC fluorescence is extensively dispersed in the intestinal tract. Importantly, FMT experiments show that mice gavaged with stool from arsenic-treated mice exhibit severe inflammatory cell infiltration in liver tissues. Arsenic-manipulated gut microbiota transplantation markedly facilitates gut flora dysbiosis in the recipient mice, including an up-regulation in Escherichia-Shigella and Bacteroides, and a down-regulation in Lactobacillus and Desulfovibrio. In parallel with the intestinal microbiota wreck, protein expressions of Occludin, ZO-1, and MUC2 are decreased. Our findings suggest that subchronic exposure to arsenic can affect the homeostasis of the intestinal microbiota, induce intestinal barrier dysfunction, increase intestinal permeability, and cause damage to liver tissues in mice.}, } @article {pmid39394659, year = {2024}, author = {Hachem, Y and Djouadi, LN and Raddaoui, A and Boukli-Hacene, F and Boumerdassi, H and Achour, W and Nateche, F}, title = {Phenotypic and molecular characterization of vancomycin resistant Enterococci from wild birds: First detection of a plasmid-borne vanC1 in Enterococcus faecalis.}, journal = {Letters in applied microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/lambio/ovae098}, pmid = {39394659}, issn = {1472-765X}, abstract = {Vancomycin-resistant enterococci (VRE) are a public health concern as they lead to therapeutic impasses and play a pivotal role in the dissemination of vancomycin resistance genes. As recent evidence suggests that wildlife can play a role in the dissemination of bacterial resistomes, this study explored the potential role of Algerian wild birds as a reservoir of VRE. A total of 222 cloacal and fecal samples were collected from various wild bird species and screened for VRE using a selective medium. Of the 47 isolated strains, 22 were identified as Enterococcus casseliflavus with the vanC2/C3 gene, 24 as Enterococcus gallinarum (19 carrying vanC1 and five carrying vanC2/C3), and one strain as Enterococcus faecalis with the vanC1 gene. Twenty-four (24) strains were multidrug-resistant with 61.7% resistant to rifampicin while no resistance to teicoplanin, linezolid and gentamicin was found. Additionally, 53.20% of the strains exhibited at least one virulence factor. To our knowledge, this study represents the first documentation of the vanC1 gene in E. faecalis isolated from wild birds. Furthermore, this gene was found to be carried by a conjugative plasmid, highlighting its ability to spread among bacterial populations and lead to the emergence of novel resistance phenotypes.}, } @article {pmid39393983, year = {2024}, author = {Hamilton, AM and Krout, IN and White, AC and Sampson, TR}, title = {Microbiome-based therapeutics for Parkinson's disease.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {}, number = {}, pages = {e00462}, doi = {10.1016/j.neurot.2024.e00462}, pmid = {39393983}, issn = {1878-7479}, abstract = {Recent experimental and clinical data demonstrate a significant dysregulation of the gut microbiome in individuals with Parkinson's disease (PD). With an immense influence on all aspects of physiology, this dysregulation has potential to directly or indirectly contribute to disease pathology. Experimental models have bridged these associations toward defined contributions, identifying various microbiome-dependent impacts to PD pathology. These studies have laid the foundation for human translation, examining whether certain members of the microbiome and/or whole restoration of the gut microbiome community can provide therapeutic benefit for people living with PD. Here, we review recent and ongoing clinically-focused studies that use microbiome-targeted therapies to limit the severity and progression of PD. Fecal microbiome transplants, prebiotic interventions, and probiotic supplementation are each emerging as viable methodologies to augment the gut microbiome and potentially limit PD symptoms. While still early, the data in the field to date support continued cross-talk between experimental systems and human studies to identify key microbial factors that contribute to PD pathologies.}, } @article {pmid39393976, year = {2024}, author = {Quera, R and Nuñez, P and von Muhlenbrock, C and Espinoza, R}, title = {Fecal microbiota transplantation through colonoscopy in the treatment of recurrent Clostridioides difficile: Experience at a university center.}, journal = {Revista de gastroenterologia de Mexico (English)}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.rgmxen.2024.03.004}, pmid = {39393976}, issn = {2255-534X}, abstract = {INTRODUCTION: The majority of cases of Clostridioides difficile infection (CDI) respond to antibiotic treatment. Fecal microbiota transplantation (FMT) has been accepted as an effective treatment in cases of recurrent CDI.

AIM: Our aim was to describe the clinical results of FMT performed for the treatment of recurrent CDI.

MATERIAL AND METHODS: The study was conducted on patients with recurrent CDI treated with FMT through colonoscopy, within the time frame of January 2021 and December 2023. Demographic and clinical data were collected, including pre-FMT treatment data, the FMT success rate, and clinical progression during follow-up. Telephone surveys were carried out to evaluate satisfaction.

RESULTS: Thirteen patients with a mean age of 55 years underwent FMT (including 7 patients above 65 years of age and one pregnant woman). Patients presented with a median of 3 previous episodes of CDI (range 2-4). The median time interval from first episode of CDI to FMT was 4 months (range 3-10). The effectiveness of a single FMT session was 100%. During post-FMT follow-up (median of 11 months, range 3-32), 3 patients have presented with a new CDI episode, and a successful second FMT was performed on 2 of them. No adverse events were registered, and all patients had a positive perception of FMT.

CONCLUSIONS: In the present study, despite its small size, FMT through colonoscopy was shown to be a safe, effective, and lasting therapy in cases of recurrent CDI, concurring with results from larger studies.}, } @article {pmid39393822, year = {2024}, author = {Liu, T and Fan, S and Meng, P and Ma, M and Wang, Y and Han, J and Wu, Y and Li, X and Su, X and Lu, C}, title = {Dietary Dihydroquercetin Alleviated Colitis via the Short-Chain Fatty Acids/miR-10a-5p/PI3K-Akt Signaling Pathway.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c03278}, pmid = {39393822}, issn = {1520-5118}, abstract = {Gut microbiota provides an important insight into clarifying the mechanism of active substances with low bioavailability, but its specific action mechanism varied case by case and remained unclear. Dihydroquercetin (DHQ) is a bioactive flavonoid with low bioavailability, which showed beneficial effects on colitis alleviation and gut microbiota modulation. Herein, we aimed to explore the microbiota-dependent anticolitis mechanism of DHQ in sight of gut microbiota metabolites and their interactions with microRNAs (miRNAs). Dietary supplementation of DHQ alleviated dextran sulfate sodium-induced colitis phenotypes and improved gut microbiota dysbiosis. Fecal microbiota transplantation further revealed that the anticolitis activity of DHQ was mediated by gut microbiota. To clarify how the modulated gut microbiota alleviated colitis in mice, the tandem analyses of the microbiome and targeted metabolome were performed, and altered profiles of metabolite short-chain fatty acids (SCFAs) and bile acids and their producers were observed in DHQ-treated mice. In addition, SCFA treatment showed anticolitis activity compared to that of bile acids, along with the specific inhibition on the phosphoinositide-3-kinase (PI3K)-protein kinase B (Akt) pathway. Subsequently, the colonic miRNA profile of mice receiving SCFA treatment was sequenced, and a differentially expressed miR-10a-5p was identified. Both prediction analysis and dual-luciferase reporter assay indicated that miR-10a-5p directly bind to the 3'-untranslated regions of gene pik3ca, inhibit the PI3K-Akt pathway activation, and lead to colitis alleviation. Together, we proposed that gut microbiota mediated the anticolitis activity of DHQ through the SCFAs/miR-10a-5p/PI3K-Akt axis, and it provided a novel insight into clarifying the microbiota-dependent mechanism via the interaction between metabolites and miRNAs.}, } @article {pmid39393557, year = {2024}, author = {Zhou, J and Yang, Q and Wei, W and Huo, J and Wang, W}, title = {Codonopsis pilosula polysaccharide alleviates ulcerative colitis by modulating gut microbiota and SCFA/GPR/NLRP3 pathway.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {118928}, doi = {10.1016/j.jep.2024.118928}, pmid = {39393557}, issn = {1872-7573}, abstract = {Codonopsis pilosula (Franch.) Nannf. (CP) is a Chinese herb commonly used in traditional Chinese medicine to treat ulcerative colitis (UC). C. pilosula polysaccharide (CPPS) is an important bioactive compound in CP. Polysaccharides are degraded by and interact with the gut microbiota, exerting therapeutic effects. However, the mechanism of action of CPPS in treating UC by regulating gut microbiota is unclear.

AIM OF THE STUDY: This study aimed to elucidate the therapeutic efficacy of CPPS on UC mice and its mechanism of action.

MATERIALS AND METHODS: Size-exclusion chromatography with multi-angle laser-light scattering and refractive index analysis was employed to ascertain the molecular weight of CPPS, while its monosaccharide composition was determined using ion chromatography. An experimental colitis mouse model was induced by administering 3% (dextran sulfate sodium) DSS in drinking water for five consecutive days. Three doses of CPPS were administered to evaluate their therapeutic effects on UC. CPPS was administered for seven days, and salicylazosulfapyridine was used as a positive control. Inflammatory cytokine secretion in the colon tissue was measured, and histopathological evaluation was performed on colon sections. Alterations in the abundance of the intestinal microbiota species were also analyzed. We then quantified short-chain fatty acids (SCFAs) in the cecal content and verified the G protein-coupled receptor (GPR)/nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) pathways using western blot. Furthermore, the ameliorative effect of gut microbiota on DSS-induced UC symptoms was verified using the fecal microbiota transplantation (FMT) experiment.

RESULTS: CPPS comprised of rhamnose, arabinose, galactose, glucose, and galacturonic acid. CPPS significantly alleviated DSS-induced UC. Compared to the DSS group, CPPS treatment significantly increased the ratio of the Firmicutes to the Bacteroidetes and upregulated the abundance of beneficial bacteria such as g__Ligilactobacillus, g_Akkermansia, g_Faecalibaculum, g_Odoribacter. The release of acetic acid and butyric acid were further promoted. CPPS can inhibit NLRP3 activation by binding SCFAs to GPR proteins, thereby reducing intestinal inflammation. FMT confirmed that the gut microbiota in the CPPS-trans group sufficiently mitigated DSS-induced UC symptoms.

CONCLUSIONS: CPPS ameliorates the symptoms of DSS-induced UC primarily through the gut microbiota modulation and SCFA/GPR/NLRP3 pathways, making it a promising candidate for UC treatment.}, } @article {pmid39391755, year = {2024}, author = {Fu, Y and Gu, Z and Cao, H and Zuo, C and Huang, Y and Song, Y and Jiang, Y and Wang, F}, title = {The role of the gut microbiota in neurodegenerative diseases targeting metabolism.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1432659}, pmid = {39391755}, issn = {1662-4548}, abstract = {In recent years, the incidence of neurodegenerative diseases (NDs) has gradually increased over the past decades due to the rapid aging of the global population. Traditional research has had difficulty explaining the relationship between its etiology and unhealthy lifestyle and diets. Emerging evidence had proved that the pathogenesis of neurodegenerative diseases may be related to changes of the gut microbiota's composition. Metabolism of gut microbiota has insidious and far-reaching effects on neurodegenerative diseases and provides new directions for disease intervention. Here, we delineated the basic relationship between gut microbiota and neurodegenerative diseases, highlighting the metabolism of gut microbiota in neurodegenerative diseases and also focusing on treatments for NDs based on gut microbiota. Our review may provide novel insights for neurodegeneration and approach a broadly applicable basis for the clinical therapies for neurodegenerative diseases.}, } @article {pmid39391303, year = {2024}, author = {Karimi, M and Shirsalimi, N and Hashempour, Z and Salehi Omran, H and Sedighi, E and Beigi, F and Mortezazadeh, M}, title = {Safety and efficacy of fecal microbiota transplantation (FMT) as a modern adjuvant therapy in various diseases and disorders: a comprehensive literature review.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1439176}, pmid = {39391303}, issn = {1664-3224}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Gastrointestinal Microbiome ; *Dysbiosis/therapy ; Animals ; Treatment Outcome ; }, abstract = {The human gastrointestinal (GI) tract microbiome is a complex and all-encompassing ecological system of trillions of microorganisms. It plays a vital role in digestion, disease prevention, and overall health. When this delicate balance is disrupted, it can lead to various health issues. Fecal microbiota transplantation (FMT) is an emerging therapeutic intervention used as an adjuvant therapy for many diseases, particularly those with dysbiosis as their underlying cause. Its goal is to restore this balance by transferring fecal material from healthy donors to the recipients. FMT has an impressive reported cure rate between 80% and 90% and has become a favored treatment for many diseases. While FMT may have generally mild to moderate transient adverse effects, rare severe complications underscore the importance of rigorous donor screening and standardized administration. FMT has enormous potential as a practical therapeutic approach; however, additional research is required to further determine its potential for clinical utilization, as well as its safety and efficiency in different patient populations. This comprehensive literature review offers increased confidence in the safety and effectiveness of FMT for several diseases affecting the intestines and other systems, including diabetes, obesity, inflammatory and autoimmune illness, and other conditions.}, } @article {pmid39391251, year = {2024}, author = {Zheng, J and Chen, H}, title = {Effects of intratumoral microbiota on tumorigenesis, anti-tumor immunity, and microbe-based cancer therapy.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1429722}, pmid = {39391251}, issn = {2234-943X}, abstract = {Intratumoral microbiota (IM) has emerged as a significant component of the previously thought sterile tumor microenvironment (TME), exerting diverse functions in tumorigenesis and immune modulation. This review outlines the historical background, classification, and diversity of IM, elucidating its pivotal roles in oncogenicity, cancer development, and progression, alongside its influence on anti-tumor immunity. The signaling pathways through which IM impacts tumorigenesis and immunity, including reactive oxygen species (ROS), β-catenin, stimulator of interferon genes (STING), and other pathways [NF-κB, Toll-like receptor (TLR), complement, RhoA/ROCK, PKR-like ER kinase (PERK)], are discussed comprehensively. Furthermore, we briefly introduce the clinical implications of IM, emphasizing its potential as a target for novel cancer therapies, diagnostic biomarkers, and prognostic indicators. Notably, microbe-based therapeutic strategies such as fecal microbiome transplantation (FMT), probiotics regulation, bacteriotherapy, bacteriophage therapy, and oncolytic virotherapy are highlighted. These strategies hold promise for enhancing the efficacy of current cancer treatments and warrant further exploration in clinical settings.}, } @article {pmid39389400, year = {2024}, author = {Campagnoli, LIM and Marchesi, N and Varesi, A and Morozzi, M and Mascione, L and Ricevuti, G and Esposito, C and Galeotti, N and Pascale, A}, title = {New therapeutic avenues in multiple sclerosis: is there a place for gut microbiota-based treatments?.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {107456}, doi = {10.1016/j.phrs.2024.107456}, pmid = {39389400}, issn = {1096-1186}, abstract = {The bidirectional interaction between the gut and the central nervous system (CNS), the so-called gut microbiota-brain axis, is reported to influence brain functions, thus having a potential impact on the development or the progression of several neurodegenerative disorders. Within this context, it has been documented that multiple sclerosis (MS), an autoimmune inflammatory, demyelinating, and neurodegenerative disease of the CNS, is associated with gastrointestinal symptoms, including constipation, dysphagia, and faecal incontinence. Moreover, some evidence suggests the existence of an altered gut microbiota (GM) composition in MS patients with respect to healthy individuals, as well as the potential influence of GM dysbiosis on typical MS features, including increased intestinal permeability, disruption of blood-brain barrier integrity, chronic inflammation, and altered T cells differentiation. Starting from these assumptions, the possible involvement of GM alteration in MS pathogenesis seems likely, and its restoration could represent a supplemental beneficial strategy against this disabling disease. In this regard, the present review will explore possible preventive approaches (including several dietary interventions, the administration of probiotics, prebiotics, synbiotics, and postbiotics, and the use of faecal microbiota transplantation) to be pursued as prophylaxis or in combination with pharmacological treatments with the aim of re-establishing a proper GM, thus helping to prevent the development of this disease or to manage it by alleviating symptoms or slowing down its progression.}, } @article {pmid39387234, year = {2024}, author = {Benech, N and Cassir, N and Alric, L and Barbut, F and Batista, R and Bleibtreu, A and Briot, T and Davido, B and Galperine, T and Joly, AC and Kapel, N and Melchior, C and Mosca, A and Nebbad, B and Pigneur, B and Schneider, SM and Wasiak, M and Scanzi, J and Sokol, H and , }, title = {Impact of Clinical and Pharmacological Parameters on Faecal Microbiota Transplantation Outcome in Clostridioides difficile Infections: Results of a 5-Year French National Survey.}, journal = {Alimentary pharmacology & therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/apt.18330}, pmid = {39387234}, issn = {1365-2036}, abstract = {BACKGROUND: Detailed comparative assessment of procedure-related factors associated with faecal microbiota transplantation (FMT) efficacy in Clostridioides difficile infection (CDI) is limited.

AIMS: We took advantage of the differences in procedures at the various French FMT centres to determine clinical and procedure-related factors associated with FMT success in CDI.

METHODS: We performed a nationwide retrospective multicentre cohort study. All FMTs performed within The French Faecal Transplant Group for CDI from 2018 to 2022 were included. Clinical data were collected retrospectively from recipient medical files, characteristics of stool transplant preparations were prospectively collected by each Pharmacy involved. Univariate and multivariate analyses were performed using Fisher's test and multiple logistic regression.

RESULTS: Six hundred fifty-eight FMTs were performed for 617 patients in 17 centres. The overall efficacy of FMT was 84.3% (520/617), with 0.5% of severe adverse events possibly related to FMT (3/658). Forty-seven patients were treated at the first recurrence of CDI with a similar success rate (85.1%). Severe chronic kidney disease (CKD; OR: 2.18, 95%CI [1.20-3.88]), non-severe refractory CDI (OR: 15.35, [1.94-318.2]), the use of ≥ 80% glycerol (OR: 2.52, [1.11-5.67]), insufficient bowel cleansing (OR: 5.47, [1.57-20.03]) and partial FMT retention (OR: 9.97, [2.62-48.49]) were associated with CDI recurrence within 8 weeks.

CONCLUSIONS: Conditions of transplant manufacturing, bowel cleansing, and a route of delivery tailored to the patient's characteristics are key factors in optimising FMT efficacy. FMT at first recurrence showed high success in real-life practice, whereas it had lower efficacy in severe CDI and non-severe refractory CDI.}, } @article {pmid39389184, year = {2024}, author = {Thomas, AS and Lu, Y and Campbell, M and Thompson, JA and Tan, D and Faleck, DM and Wang, Y}, title = {Immune checkpoint inhibitor induced colitis.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2024.09.034}, pmid = {39389184}, issn = {1528-0012}, } @article {pmid39387175, year = {2024}, author = {Zhang, K and Zhang, L and Jian, Y and Tang, X and Han, M and Pu, Z and Zhang, Y and Zhou, P}, title = {Early-Life Milk αS1-Casein Allergy Induces the Activation of Astrocytes in Mice and Leads to Stress Vulnerability in Adulthood.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c05425}, pmid = {39387175}, issn = {1520-5118}, abstract = {In recent years, the incidence of food allergies in children has been increasing annually, significantly affecting the quality of life for patients and their families. It has long been suspected that childhood allergies might potentially lead to behavioral and psychological issues in adulthood, but the specific connection remains unclear. In this study, we established a model of young mice allergic to milk αS1-casein, conducted behavioral tests, and employed transcriptomics, immunohistochemistry, Golgi staining, and fecal microbiota transplantation to explore the link between early life allergies and adult psychological problems. The results showed that early life milk protein allergy significantly increased intestinal epithelial permeability in mice, leading to the translocation of gut microbiota metabolites. This process subsequently activated astrocyte lysosomes via SLC15a3, making astrocytes more susceptible. This susceptibility caused mice with early life milk protein allergy to have more activated astrocytes and excessive dendritic spine phagocytosis (normal group: 5.4 ± 1.26 spines/10 μm, allergy group: 3.2 ± 0.92 spines/10 μm) under acute stress in adulthood, leading to anxiety and depressive behaviors.}, } @article {pmid39386168, year = {2024}, author = {Hao, L and Yan, Y and Huang, G and Li, H}, title = {From gut to bone: deciphering the impact of gut microbiota on osteoporosis pathogenesis and management.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1416739}, pmid = {39386168}, issn = {2235-2988}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Osteoporosis/etiology/microbiology ; *Bone Density ; *Bone and Bones/microbiology ; Animals ; Risk Factors ; }, abstract = {Osteoporosis (OP) is characterized by decreased bone mineral density (BMD) and increased fracture risk, poses a significant global health burden. Recent research has shed light on the bidirectional relationship between gut microbiota (GM) and bone health, presenting a novel avenue for understanding OP pathogenesis and developing targeted therapeutic interventions. This review provides a comprehensive overview of the GM-bone axis, exploring the impact of GM on OP development and management. We elucidate established risk factors and pathogenesis of OP, delve into the diversity and functional changes of GM in OP. Furthermore, we examine experimental evidence and clinical observations linking alterations in GM composition or function with variations in BMD and fracture risk. Mechanistic insights into microbial mediators of bone health, such as microbial metabolites and products, are discussed. Therapeutic implications, including GM-targeted interventions and dietary strategies, are also explored. Finally, we identify future research directions and challenges in translating these findings into clinical practice.}, } @article {pmid39384730, year = {2024}, author = {Liang, Y and Li, Y and Lee, C and Yu, Z and Chen, C and Liang, C}, title = {Ulcerative colitis: molecular insights and intervention therapy.}, journal = {Molecular biomedicine}, volume = {5}, number = {1}, pages = {42}, pmid = {39384730}, issn = {2662-8651}, mesh = {Humans ; *Colitis, Ulcerative/therapy/immunology ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by abdominal pain, diarrhea, rectal bleeding, and weight loss. The pathogenesis and treatment of UC remain key areas of research interest. Various factors, including genetic predisposition, immune dysregulation, and alterations in the gut microbiota, are believed to contribute to the pathogenesis of UC. Current treatments for UC include 5-aminosalicylic acids, corticosteroids, immunosuppressants, and biologics. However, study reported that the one-year clinical remission rate is only around 40%. It is necessary to prompt the exploration of new treatment modalities. Biologic therapies, such as anti-TNF-α monoclonal antibody and JAK inhibitor, primarily consist of small molecules targeting specific pathways, effectively inducing and maintaining remission. Given the significant role of the gut microbiota, research into intestinal microecologics, such as probiotics and prebiotics, and fecal microbiota transplantation (FMT) shows promising potential in UC treatment. Additionally, medicinal herbs, such as chili pepper and turmeric, used in complementary therapy have shown promising results in UC management. This article reviews recent findings on the mechanisms of UC, including genetic susceptibility, immune cell dynamics and cytokine regulation, and gut microbiota alterations. It also discusses current applications of biologic therapy, herbal therapy, microecologics, and FMT, along with their prospects and challenges.}, } @article {pmid39384149, year = {2024}, author = {Wang, H and Cai, Y and Wu, W and Zhang, M and Dai, Y and Wang, Q}, title = {Exploring the role of gut microbiome in autoimmune diseases: A comprehensive review.}, journal = {Autoimmunity reviews}, volume = {23}, number = {12}, pages = {103654}, doi = {10.1016/j.autrev.2024.103654}, pmid = {39384149}, issn = {1873-0183}, abstract = {As the industrialized society advances, there has been a gradual increase in the prevalence of autoimmune disorders. A probe into the fundamental causes has disclosed several factors in modern society that have an influence on the gut microbiome. These dramatic shifts in the gut microbiome are likely to be one of the reasons for the disarray in the immune system, and the relationship between the immune system and the gut microbiome emerging as a perennial hot topic of research. This review enumerates the findings from sequencing studies of gut microbiota on seven autoimmune diseases (ADs): Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), Ankylosing Spondylitis (AS), Systemic Sclerosis (SSc), Sjögren's Syndrome (SjS), Juvenile Idiopathic Arthritis (JIA), and Behçet's Disease (BD). It aims to identify commonalities in changes in the gut microbiome within the autoimmune disease cohort and characteristics specific to each disease. The dysregulation of the gut microbiome involves a disruption of the internal balance and the balance between the external environment and the host. This dysregulation impacts the host's immune system, potentially playing a role in the development of ADs. Damage to the gut epithelial barrier allows potential pathogens to translocate to the mucosal layer, contacting epithelial cells, disrupting tight junctions, and being recognized by antigen-presenting cells, which triggers an immune response. Primed T-cells assist B-cells in producing antibodies against pathogens; if antigen mimicry occurs, an immune response is generated in extraintestinal organs during immune cell circulation, clinically manifesting as ADs. However, current research is limited; advancements in sequencing technology, large-scale cohort studies, and fecal microbiota transplantation (FMT) research are expected to propel this field to new peaks.}, } @article {pmid39382853, year = {2024}, author = {Khanna, S}, title = {Microbiota restoration for recurrent Clostridioides difficile infection.}, journal = {Panminerva medica}, volume = {}, number = {}, pages = {}, doi = {10.23736/S0031-0808.24.05111-5}, pmid = {39382853}, issn = {1827-1898}, abstract = {Since the publication of the recent North American and European guidelines on management of Clostridioides difficile infection (CDI), new evidence describing the epidemiology, testing and treatment of CDI has emerged. Despite all advances in infection control and antibiotic stewardship, the incidence and burden of CDI in the hospitals and the community remains at a stable high. Coupled with the incidence of primary CDI, there is a stable high incidence of recurrent CDI. Testing for primary and recurrent CDI remains a clinical challenge owing to high sensitivity of the PCR (leading to false positives) and somewhat limited sensitivity of EIA for toxin. The pathophysiology of recurrent CDI involves an ongoing disruption of the microbiota owing to the infection and the treatment of CDI employed. Broad spectrum antibiotics such as vancomycin leads to further disruption of microbiota compared to fidaxomicin which has a lower disruption of the microbiota and leads to fewer recurrences. Owing to these data fidaxomicin is considered as the first line antibiotic for recurrent CDI. Intravenous bezlotoxumab is a monoclonal antibody that reduces the risk of recurrence in high-risk patients but does not restore the microbiota. Experimental fecal microbiota transplantation (FMT) has been available for more than a decade. Owing to the success of FMT, two new non-invasive donor dependent Food and Drug Administration (FDA) approved therapies have been available since late 2022. This review summarizes all these conundrums regarding CDI and provides clinical pearls to use in day-to-day practice.}, } @article {pmid39381749, year = {2024}, author = {Fu, ZP and Ying, YG and Wang, RY and Wang, YQ}, title = {Aged gut microbiota promotes arrhythmia susceptibility via oxidative stress.}, journal = {iScience}, volume = {27}, number = {10}, pages = {110888}, pmid = {39381749}, issn = {2589-0042}, abstract = {Arrhythmias and sudden cardiac death (SCD) impose a significant burden. Their prevalence rises with age and is linked to gut dysbiosis. Our study aimed to determine whether aged gut microbiota affects arrhythmogenesis. Here, we demonstrated that arrhythmia susceptibility in aged mice could be transmitted to young mice using fecal microbiota transplantation (FMT). Mechanistically, increased intestinal reactive oxygen species (ROS) in aged mice reduced ion channel protein expression and promoted arrhythmias. Gut microbiota depletion by an antibiotic cocktail reduced ROS and arrhythmia in aged mice. Interestingly, oxidative stress in heart induced by hydrogen peroxide (H2O2) increased arrhythmia. Moreover, aged gut microbiota could induce oxidative stress in young mice colon by gut microbiota metabolites transplantation. Vitexin could reduce aging and arrhythmia through OLA1-Nrf2 signaling pathway. Overall, our study demonstrated that the gut microbiota of aged mice reduced cardiac ion channel protein expression through systemic oxidative stress, thereby increased the risk of arrhythmias.}, } @article {pmid39377587, year = {2024}, author = {McMillan, AS and Zhang, G and Dougherty, MK and McGill, SK and Gulati, AS and Baker, ES and Theriot, CM}, title = {Metagenomic, metabolomic, and lipidomic shifts associated with fecal microbiota transplantation for recurrent Clostridioides difficile infection.}, journal = {mSphere}, volume = {}, number = {}, pages = {e0070624}, doi = {10.1128/msphere.00706-24}, pmid = {39377587}, issn = {2379-5042}, abstract = {Recurrent C. difficile infection (rCDI) is an urgent public health threat, for which the last resort and lifesaving treatment is a fecal microbiota transplant (FMT). However, the exact mechanisms that mediate a successful FMT are not well-understood. Here, we use longitudinal stool samples collected from patients undergoing FMT to evaluate intra-individual changes in the microbiome, metabolome, and lipidome after successful FMTs relative to their baselines pre-FMT. We show changes in the abundance of many lipids, specifically a decrease in acylcarnitines post-FMT, and a shift from conjugated bile acids pre-FMT to deconjugated secondary bile acids post-FMT. These changes correlate with a decrease in Enterobacteriaceae, which encode carnitine metabolism genes, and an increase in Lachnospiraceae, which encode bile acid altering genes such as bile salt hydrolases (BSHs) and the bile acid-inducible (bai) operon, post-FMT. We also show changes in gut microbe-encoded amino acid biosynthesis genes, of which Enterobacteriaceae was the primary contributor to amino acids C. difficile is auxotrophic for. Liquid chromatography, ion mobility spectrometry, and mass spectrometry (LC-IMS-MS) revealed a shift from microbial conjugation of primary bile acids pre-FMT to secondary bile acids post-FMT. Here, we define the structural and functional changes associated with a successful FMT and generate hypotheses that require further experimental validation. This information is meant to help guide the development of new microbiota-focused therapeutics to treat rCDI.IMPORTANCERecurrent C. difficile infection is an urgent public health threat, for which the last resort and lifesaving treatment is a fecal microbiota transplant. However, the exact mechanisms that mediate a successful FMT are not well-understood. Here, we show changes in the abundance of many lipids, specifically acylcarnitines and bile acids, in response to FMT. These changes correlate with Enterobacteriaceae pre-FMT, which encodes carnitine metabolism genes, and Lachnospiraceae post-FMT, which encodes bile salt hydrolases and baiA genes. There was also a shift from microbial conjugation of primary bile acids pre-FMT to secondary bile acids post-FMT. Here, we define the structural and functional changes associated with a successful FMT, which we hope will help aid in the development of new microbiota-focused therapeutics to treat rCDI.}, } @article {pmid39377303, year = {2024}, author = {Berrut, G and Baudron, CR and Paccalin, M and de Wazières, B and Gavazzi, G}, title = {[Clostridioides difficile infections: Update and therapeutic guidelines].}, journal = {Geriatrie et psychologie neuropsychiatrie du vieillissement}, volume = {22}, number = {3}, pages = {316-324}, doi = {10.1684/pnv.2024.1181}, pmid = {39377303}, issn = {2115-7863}, abstract = {Clostridioides difficile infection (CDI) represents a significant challenge due to its increasing incidence, severity, and treatment difficulty. Effective management requires a multifactorial approach that includes preventive strategies, prudent antibiotic use, and adapted therapeutic options. Ongoing research and innovation offer promising prospects for improving ICD management, making vigilance and informed practices essential among healthcare professionals. Two main complications of ICD are pseudomembranous colitis (PMC) and toxic megacolon. PMC involves severe colonic inflammation due to C. difficile toxins, leading to pseudomembrane formation. Diagnosis relies on clinical criteria, microbiological tests, and endoscopy. Toxic Megacolon is characterized by severe colonic dilation and systemic toxicity, requiring immediate medical intervention. ICD diagnosis combines clinical signs and microbiological tests. These tests include toxin tests, GDH antigen detection, PCR for toxin genes, and stool culture. Imaging techniques assess colonic inflammation and complications. Combined diagnostic criteria from the American Gastroenterological Association (AGA) and European guidelines emphasize integrating clinical and laboratory findings for accurate diagnosis. ICD treatment involves stopping the implicated antibiotics and starting specific antimicrobial therapy. Common treatments include mainly fidaxomicin and oral vancomycin. Fecal microbiota transplantation (TMF) is recommended for recurrent cases unresponsive to standard treatments. Bezlotoxumab, an antibody targeting C. difficile toxin B, is used to prevent recurrence in high-risk adults. ICD poses a major challenge due to its increasing incidence, severity, and difficulty in treatment. A multifactorial approach involving rigorous preventive strategies, prudent antibiotic management, and adapted therapeutic options is essential for controlling the infection. Ongoing research and innovations in treatment offer promising prospects for improving patient management. Healthcare professionals must remain vigilant and informed to ensure effective practices in combating this infection and utilizing available resources optimally.}, } @article {pmid39377231, year = {2024}, author = {Kim, DY and Lee, SY and Lee, JY and Whon, TW and Lee, JY and Jeon, CO and Bae, JW}, title = {Gut microbiome therapy: fecal microbiota transplantation vs live biotherapeutic products.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2412376}, pmid = {39377231}, issn = {1949-0984}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Gastrointestinal Microbiome ; Animals ; Clostridium Infections/therapy/microbiology ; Inflammatory Bowel Diseases/therapy/microbiology ; Biological Products/therapeutic use ; Gastrointestinal Diseases/therapy/microbiology ; }, abstract = {The human intestine hosts a complex ecosystem of various microorganisms, collectively known as the gut microbiome, which significantly impacts human health. Disruptions in the gut microbiome are linked to various disorders, including gastrointestinal diseases, such as Clostridioides difficile infection and inflammatory bowel disease, as well as metabolic, neurological, oncologic conditions. Fecal microbiota transplantation (FMT) and live biotherapeutic products (LBPs) have emerged as prospective therapeutic procedures to restore microbial and metabolic balance in the gut. This review assesses the latest advancements, challenges, and therapeutic efficacy of FMT and LBPs, highlighting the need for standardization, safety, and long-term evaluation to optimize their clinical application.}, } @article {pmid39375173, year = {2024}, author = {Rognstad, ØB and Botteri, E and Hoff, G and Bretthauer, M and Gulichsen, E and Frigstad, SO and Holme, Ø and Randel, KR}, title = {Adverse events after colonoscopy in a randomised colorectal cancer screening trial.}, journal = {BMJ open gastroenterology}, volume = {11}, number = {1}, pages = {}, pmid = {39375173}, issn = {2054-4774}, mesh = {Humans ; Male ; Female ; *Colorectal Neoplasms/diagnosis ; *Colonoscopy/adverse effects/statistics & numerical data/methods ; Middle Aged ; *Early Detection of Cancer/methods ; Aged ; Norway/epidemiology ; Cross-Sectional Studies ; Risk Factors ; Sigmoidoscopy/adverse effects/methods/statistics & numerical data ; Occult Blood ; Gastrointestinal Hemorrhage/epidemiology/diagnosis ; Abdominal Pain/etiology ; }, abstract = {OBJECTIVE: Colonoscopy-related adverse events increase the burden of colorectal cancer (CRC) screening. This cross-sectional study evaluates adverse events during and after colonoscopy in a large, randomised CRC screening trial in Norway comparing sigmoidoscopy to immunochemical testing for faecal blood.

METHODS: We included all individuals who underwent colonoscopy at two screening centres between 2012 and 2020. From medical records, we retrieved data on adverse events during and within 30 days after colonoscopy and classified them according to the American Society for Gastrointestinal Endoscopy lexicon for endoscopic adverse events. Multivariable logistic regression models were fitted to identify risk factors for adverse events.

RESULTS: Of the 10 244 included individuals, 242 (2.4%) had at least one adverse event that was possibly, probably, or definitively related to the colonoscopy. 188 (1.8%) had mild adverse events, 50 (0.49%) had moderate, 3 (0.03%) had severe, and 1 had a fatal adverse event. The most frequent adverse events were lower gastrointestinal bleeding (0.86%), abdominal pain (0.48%), vasovagal reaction (0.39%), postpolypectomy syndrome (0.20%), and perforation (0.08%). 23 (0.22%) individuals had non-gastrointestinal adverse events. Risk factors associated with adverse events were older age, female sex, screening centre, anticoagulant therapy, number of polypectomies, size of lesion removed, presence of proximal lesion, and adenocarcinoma. Adverse event rates per endoscopist ranged from 0% to 4.9%.

CONCLUSION: Adverse events after colonoscopy of screening positives occurred in about 2 out of 100 procedures. Three-quarters of events were mild. Awareness of risk factors may help endoscopists to mitigate the risk.

TRIAL REGISTRATION NUMBER: NCT01538550.}, } @article {pmid39373714, year = {2024}, author = {Chen, Y and Yang, R and Qi, B and Shan, Z}, title = {Peptidoglycan-Chi3l1 interaction shapes gut microbiota in intestinal mucus layer.}, journal = {eLife}, volume = {13}, number = {}, pages = {}, pmid = {39373714}, issn = {2050-084X}, support = {2019YFA0803100//Ministry of Science and Technology of the People's Republic of China/ ; 32071129//National Natural Science Foundation of China/ ; 32170794//National Natural Science Foundation of China/ ; 202101AT070022//Yunnan Provincial Science and Technology Department/ ; 202201AT070196//Yunnan Provincial Science and Technology Department/ ; C619300A086//Science and Technological Talent Cultivation Plan of Yunnan Province/ ; K264202230211//Science and Technological Talent Cultivation Plan of Yunnan Province/ ; 202302AP370005//Yunnan Provincial Science and Technology Project at Southwest United Graduate School/ ; 2019YFA0802100//Ministry of Science and Technology of the People's Republic of China/ ; 202001AW070006//Yunnan Provincial Science and Technology Department/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Mice ; *Peptidoglycan/metabolism ; *Intestinal Mucosa/metabolism/microbiology ; *Chitinase-3-Like Protein 1/metabolism ; Colitis/microbiology/metabolism/chemically induced ; Mice, Inbred C57BL ; Humans ; Lactobacillus/metabolism ; }, abstract = {The balanced gut microbiota in intestinal mucus layer plays an instrumental role in the health of the host. However, the mechanisms by which the host regulates microbial communities in the mucus layer remain largely unknown. Here, we discovered that the host regulates bacterial colonization in the gut mucus layer by producing a protein called Chitinase 3-like protein 1 (Chi3l1). Intestinal epithelial cells are stimulated by the gut microbiota to express Chi3l1. Once expressed, Chi3l1 is secreted into the mucus layer where it interacts with the gut microbiota, specifically through a component of bacterial cell walls called peptidoglycan. This interaction between Chi3l1 and bacteria is beneficial for the colonization of bacteria in the mucus, particularly for Gram-positive bacteria like Lactobacillus. Moreover, a deficiency of Chi3l1 leads to an imbalance in the gut microbiota, which exacerbates colitis induced by dextran sodium sulfate. By performing fecal microbiota transplantation from Villin-cre mice or replenishing Lactobacillus in IEC[∆Chil1] mice, we were able to restore their colitis to the same level as that of Villin-cre mice. In summary, this study shows a 'scaffold model' for microbiota homeostasis by interaction between intestinal Chi3l1 and bacteria cell wall interaction, and it also highlights that an unbalanced gut microbiota in the intestinal mucus contributes to the development of colitis.}, } @article {pmid39373173, year = {2024}, author = {Randel, KR and Botteri, E and de Lange, T and Schult, AL and Eskeland, SL and El-Safadi, B and Norvard, ER and Bolstad, N and Bretthauer, M and Hoff, G and Holme, Ø}, title = {Performance of Faecal Immunochemical Testing for Colorectal Cancer Screening at Varying Positivity Thresholds.}, journal = {Alimentary pharmacology & therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/apt.18314}, pmid = {39373173}, issn = {1365-2036}, support = {2015038//Helse Sør-Øst RHF/ ; //Norwegian Parliament/ ; }, abstract = {BACKGROUND: The positivity thresholds of faecal immunochemical testing (FIT) in colorectal cancer (CRC) screening vary between countries.

AIMS: To explore the trade-off between colonoscopies performed, adverse events and lesions detected at different FIT thresholds in a Norwegian CRC screening trial.

METHODS: We included first participation in biennial FIT screening for 47,265 individuals aged 50-74 years. Individuals with FIT > 15 μg Hb/g faeces were referred for colonoscopy. We estimated the number of colonoscopies, adverse events, screen-detected CRCs, advanced adenomas and serrated lesions expected at FIT thresholds currently or recently used in other European countries ranging between 20 and 150 μg/g.

RESULTS: At the 15 μg/g threshold (Norway), 3705 participants underwent colonoscopy, of whom 203 had CRC, 1119 advanced adenomas and 256 advanced serrated lesions. Using a 47 μg/g threshold, 1826 (49.3%) individuals would have undergone colonoscopy, and 154 (75.9%) would have been diagnosed with CRC, 702 (62.7%) with advanced adenoma and 128 (50.0%) with advanced serrated lesion compared to the 15 μg/g threshold. At 150 μg/g, the corresponding figures would have been 838 (22.6%) undergoing colonoscopy, 114 (56.2%) with CRC, 345 (30.8%) advanced adenoma and 54 (21.1%) advanced serrated lesions. The detection rate of stage I CRC was 0.22% at 15 μg/g and 0.11% at 150 μg/g. Post-colonoscopy bleeding rates were 0.8% and 1.7%, respectively.

CONCLUSIONS: Increasing the FIT threshold reduces colonoscopy demand, but substantially decreases lesion detection and unfavourably changes CRC stage distribution. The risk of adverse events at colonoscopy increased with FIT threshold, requiring country-specific information on adverse events.

TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01538550.}, } @article {pmid39371609, year = {2024}, author = {Yuan, Y and Li, L and Wang, J and Myagmar, BO and Gao, Y and Wang, H and Wang, Z and Zhang, C and Zhang, X}, title = {Gut microbiota-derived acetate promotes long-term recovery through angiogenesis guided by lymphatic ingrowth in older adults with stroke.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1398913}, pmid = {39371609}, issn = {1662-4548}, abstract = {INTRODUCTION: Ischemic stroke is a leading cause of morbidity and mortality in older adults. Therefore, in this study, we sought to understand the interplay between the microbiota, gut, and brain in the context of stroke in older adults.

OBJECTIVE: To determine whether gut microbiota from younger individuals promotes recovery through angiogenesis in both elderly stroke patients and aged stroke mice, we explored the changes in gut microbiota and the correlation between short-chain fatty acids (SCFAs) and angiogenesis in the aged stroke population. Then, we altered the gut microbiome in aged mice by transplanting microbiota from younger donors before inducing experimental stroke to explore the mechanism by which gut microbiota-derived SCFAs promote angiogenesis.

METHODS: Part I: We conducted a single-center, double-blind trial to compare gut microbiota diversity and SCFA levels in fecal samples from older stroke patients with those from younger stroke patients. Additionally, we measured levels of vascular endothelial growth factor (VEGF) and VEGFC levels in plasma to assess their correlation with SCFA levels. Part II: We performed fecal microbiota transplantation (FMT) 3 days before inducing ischemic stroke in aged male mice (16-18) via distal middle cerebral artery occlusion (dMCAO). The FMT was conducted using gut microbiomes from either young donors (2-3 months) or aged donors (16-18 months).

RESULTS: In older stroke patients, gut microbiota diversity was significantly reduced compared to that in younger stroke patients. Furthermore, levels of acetate, a bacterially derived SCFA, were lower and positively correlated with angiogenesis markers (VEGF and VEGF-C). In aged stroke mice, transplantation of young microbiota improved stroke outcomes by promoting angiogenesis, which was facilitated by lymphatic ingrowth into the cortex. This protective effect was linked to gut microbiota-derived acetate, which enhanced lymphangiogenesis by replenishing acetyl coenzyme A.

CONCLUSIONS: (a) Gut microbiota-derived acetate promotes angiogenesis post-stroke and (b) lymphatic ingrowth into the cerebral cortex was observed in post-dMCAO mice. These findings suggest that selectively promoting SCFA-producing bacteria, particularly acetate-producers, could be a promising therapeutic strategy to reduce functional impairments in older stroke subjects.}, } @article {pmid39371270, year = {2024}, author = {Dong, H and Li, R and Zhao, N and Dadhania, DM and Suthanthiran, M and Lee, JR and Ling, W}, title = {Antibiotic subclasses differentially perturb the gut microbiota in kidney transplant recipients.}, journal = {Frontiers in transplantation}, volume = {3}, number = {}, pages = {1400067}, pmid = {39371270}, issn = {2813-2440}, abstract = {INTRODUCTION: The impact of antibiotics on the gut microbiota in kidney transplant recipients is not well characterized. In this study, we determine the impact of different subclasses of antibiotics on the gut microbiota in a cohort of 168 kidney transplant recipients.

METHODS: Gut microbiome profiling was performed on 510 fecal specimens using 16S rRNA gene sequencing of the V4-V5 hypervariable region. We classified fecal specimens by antibiotic exposure into 5 categories: Beta-lactam, Fluoroquinolone (FQ), Beta-lactam & FQ Group, Other Antibiotics, and No Antibiotic (No Abx). Mixed-effects regression models were utilized to identify changes in microbial diversity and in the centered log-ratio (CLR) transformed abundance of genera while adjusting for important covariates.

RESULTS: Antibiotic administration was associated with a significant decrease in the Shannon alpha diversity index, a decreased abundance of 11 taxa including Eubacterium and Ruminococcus, and an increased abundance of 16 taxa including Enterococcus and Staphylococcus. Exposure to Beta-lactam antibiotics was associated with an increased abundance of 10 taxa including Enterococcus and a decreased abundance of 5 taxa including Eubacterium while exposure to FQ antibiotics was associated with an increased abundance of 3 taxa and a decreased abundance of 4 taxa including Ruminococcus.

CONCLUSIONS: Beta-lactam antibiotics and FQ antibiotics have a profound impact on the gut microbiota in kidney transplant recipients. Given the link of the gut microbiota to infectious complications, antibiotic associated changes in the microbiota may lead to an increased risk for further infections.}, } @article {pmid39371172, year = {2024}, author = {Akagbosu, CO and McCauley, KE and Namasivayam, S and Romero-Soto, HN and O'Brien, W and Bacorn, M and Bohrnsen, E and Schwarz, B and Mistry, S and Burns, AS and Perez-Chaparro, PJ and Chen, Q and LaPoint, P and Patel, A and Krausfeldt, LE and Subramanian, P and Sellers, BA and Cheung, F and Apps, R and Douagi, I and Levy, S and Nadler, EP and Hourigan, SK}, title = {Gut microbiome shifts in adolescents after sleeve gastrectomy with increased oral-associated taxa and pro-inflammatory potential.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.09.16.24313738}, pmid = {39371172}, abstract = {BACKGROUND: Bariatric surgery is highly effective in achieving weight loss in children and adolescents with severe obesity, however the underlying mechanisms are incompletely understood, and gut microbiome changes are unknown.

OBJECTIVES: 1) To comprehensively examine gut microbiome and metabolome changes after laparoscopic vertical sleeve gastrectomy (VSG) in adolescents and 2) to assess whether the microbiome/metabolome changes observed with VSG influence phenotype using germ-free murine models.

DESIGN: 1) A longitudinal observational study in adolescents undergoing VSG with serial stool samples undergoing shotgun metagenomic microbiome sequencing and metabolomics (polar metabolites, bile acids and short chain fatty acids) and 2) a human-to-mouse fecal transplant study.

RESULTS: We show adolescents exhibit significant gut microbiome and metabolome shifts several months after VSG, with increased alpha diversity and notably with enrichment of oral-associated taxa. To assess causality of the microbiome/metabolome changes in phenotype, pre-VSG and post-VSG stool was transplanted into germ-free mice. Post-VSG stool was not associated with any beneficial outcomes such as adiposity reduction compared pre-VSG stool. However, post-VSG stool exhibited an inflammatory phenotype with increased intestinal Th17 and decreased regulatory T cells. Concomitantly, we found elevated fecal calprotectin and an enrichment of proinflammatory pathways in a subset of adolescents post-VSG.

CONCLUSION: We show that in some adolescents, microbiome changes post-VSG may have inflammatory potential, which may be of importance considering the increased incidence of inflammatory bowel disease post-VSG.

Bariatric surgery is highly effective in achieving weight loss in children and adolescents with severe obesity, however the underlying mechanisms are incompletely understood, and gut microbiome changes are unknown.

WHAT THIS STUDY ADDS: Significant gut microbiome and metabolome shifts were found several months after vertical sleeve gastrectomy in adolescents, notably with enrichment of oral-associated taxa. Using human to germ-free mice fecal transplant studies, the post-surgery changes in the gut microbiome/metabolome were shown to have inflammatory potential. Furthermore, raised fecal calprotectin and inflammatory systemic pathways were seen in a subset of adolescents post-surgery.

These findings may be of importance given the growing recognition of an increased incidence of inflammatory bowel disease after bariatric surgery and warrants further investigation.}, } @article {pmid39370012, year = {2024}, author = {Wang, J and Shen, Y and Li, L and Li, L and Zhang, J and Li, M and Qiu, F}, title = {Lycopene attenuates D-galactose-induced memory and behavioral deficits by mediating microbiota-SCFAs-gut-brain axis balance in female CD-1 mice.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {109777}, doi = {10.1016/j.jnutbio.2024.109777}, pmid = {39370012}, issn = {1873-4847}, abstract = {Aging impairs cognitive function, whereas nutritional intervention can delay aging and age-related diseases. Lycopene (LYC), a naturally occurring carotenoid, posses multiple health-promoting properties, including neuroprotective function. Here, the effects of LYC on memory and behavioral deficits induced by D-galactose (D-gal) treatment and the relative contribution of LYC-derived gut microbiota in these process were investigated. Results demonstrated that LYC showed effective protection on D-gal induced cognitive deficit and neuronal damage. Moreover, LYC treatment has beneficial effects on gut barrier damage, microbiota dysbiosis and levels of SCFAs in D-gal-induced subacute aging mice. Next, fecal microbiota transplantation (FMT) experiment was performed and increased SCFAs were observed in mice received stools from D-gal+LYC group when compared with D-gal-FMT group. Thus, we added SCFAs treatment served as a control group in order to evaluated whether the alterations of gut-brain axis could be attributed to LYC-reshaped gut microbiota and SCFAs. Results showed that recipient mice received SCFAs and stools from D-gal+LYC group have similar beneficial effects in improving gut and brain function, demonstrated as: improved intestinal health via elevating antioxidant enzymes contents, increasing the expressions of tight junctions proteins and protecting gut barrier, enhanced mice working memory capacity via alleviating hippocampal neurons impairment, improving synaptic function and enhancing mitochondrial function in the intestinal pseudo-aseptic mice. In conclusion, our results demonstrated that LYC-derived microbiome played a pivotal role in the regulation of cognitive functions during aging and enhanced SCFAs formation might be an important signaling molecule connecting gut microbiome and brain.}, } @article {pmid39366468, year = {2024}, author = {Allegretti, JR and Kelly, CR and Louie, T and Fischer, M and Hota, S and Misra, B and Van Hise, NW and Yen, E and Bullock, JS and Silverman, M and Davis, I and McGill, SK and Pardi, DS and Orenstein, R and Grinspan, A and El-Nachef, N and Feuerstadt, P and Borody, TJ and Khanna S, S and Budree, S and Kassam, Z}, title = {Safety and Tolerability of CP101, a full spectrum, oral microbiome therapeutic for the prevention of recurrent C. difficile infection: A Phase 2 Randomized Controlled Trial.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2024.09.030}, pmid = {39366468}, issn = {1528-0012}, abstract = {BACKGROUND AND AIMS: Recurrent Clostridioides difficile infections (CDI) remain common. While novel microbiome therapeutics gain approval, the efficacy of a full spectrum, oral microbiome therapeutics is unknown. This study aimed to determine the safety and efficacy of CP101, an orally administered microbiome therapeutic, to restore a diverse microbiome and prevent recurrent CDI in a broad population.

METHODS: We conducted a multi-center, phase 2, double-blind, randomized, placebo-controlled trial in adults with recurrent CDI. Participants with one or more CDI recurrences and diagnosis by PCR or toxin EIA for the qualifying episode were included. Participants were randomized 1:1 to receive a single oral dose of either CP101 (∼ 6 x 10[11] CFU of lyophilized microbial cells) or placebo after standard-of-care (SOC) antibiotics. The primary efficacy endpoint was the proportion of participants without CDI recurrence through Week 8. Safety, efficacy and microbiome endpoints were evaluated through Week 8 and 24.

RESULTS: 198 participants were analyzed; CP101 (n=102) and placebo (n=96). Overall, 27.5% with a first recurrence and 62.7% diagnosed by PCR-based testing. The proportion without CDI recurrence through Week 8 was significantly higher in the CP101 group compared to placebo (74.5% [76/102] vs 61.5% [59/96], p=0.0488) with durable efficacy observed through Week 24 (73.5% [75/102] vs 59.4% [57/96], p=0.0347). Similar efficacy was observed regardless of diagnostic modality or number of CDI recurrences. Rapid and durable increase in microbiome diversity was observed in the CP101 group compared to placebo. The incidence of adverse events was similar between the two groups.

CONCLUSIONS: CP101 was superior to placebo in reducing recurrent CDI with a safety profile similar to placebo. https://clinicaltrials.gov/study/NCT03110133.}, } @article {pmid39364128, year = {2024}, author = {Guo, J and Yang, L}, title = {Regulation effect of the intestinal flora and intervention strategies targeting the intestinal flora in alleviation of pulmonary fibrosis development.}, journal = {Bioscience of microbiota, food and health}, volume = {43}, number = {4}, pages = {293-299}, pmid = {39364128}, issn = {2186-6953}, abstract = {Pulmonary fibrosis is an end-stage respiratory disease characterized by fibroblast proliferation and accumulation of extracellular matrix and collagen, which is accompanied by inflammatory damage. The disease is mainly based on pulmonary dysfunction and respiratory failure, the incidence of it is increasing year by year, and the current treatment methods for it are limited. In recent years, it has been found that gut microbes play a crucial role in the pathogenesis and development of pulmonary fibrosis. The microecological disturbance caused by changes in the composition of the intestinal flora can affect the course of pulmonary fibrosis. The regulatory network or information exchange system for gut-lung crosstalk is called the "gut-lung axis". This review focuses on the frontier research on entero-pulmonary regulation in pulmonary fibrosis and on intervention strategies for changing the gut microbiota to improve pulmonary fibrosis, including fecal microbiota transplantation, traditional Chinese medicine interventions, and supplementation with probiotics. In addition, the present problems in this field are also raised in order to provide strong theoretical and strategic support for the future exploration of regulatory mechanisms and therapeutic drug development. This paper reviews the interaction of the intestinal flora with pulmonary fibrosis, introduces the research progress for improving pulmonary fibrosis through interventions targeted at the intestinal flora, and provides new ideas for the treatment of pulmonary fibrosis.}, } @article {pmid39364121, year = {2024}, author = {Mao, Z and Zhang, J and Guo, L and Wang, X and Zhu, Z and Miao, M}, title = {Therapeutic approaches targeting the gut microbiota in ischemic stroke: current advances and future directions.}, journal = {Bioscience of microbiota, food and health}, volume = {43}, number = {4}, pages = {321-328}, pmid = {39364121}, issn = {2186-6953}, abstract = {Ischemic stroke (IS) is the predominant form of stroke pathology, and its clinical management remains constrained by therapeutic time frame. The gut microbiota (GM), comprising a multitude of bacterial and archaeal cells, surpasses the human cell count by approximately tenfold and significantly contributes to the human organism's growth, development, and overall well-being. The microbiota-gut-brain axis (MGBA) in recent years has established a strong association between gut microbes and the brain, demonstrating their intricate involvement in the progression of IS. The regulation of IS by the GM, encompassing changes in composition, abundance, and distribution, is multifaceted, involving neurological, endocrine, immunological, and metabolic mechanisms. This comprehensive understanding offers novel insights into the therapeutic approaches for IS. The objective of this paper is to examine the mechanisms of interaction between the GM and IS in recent years, assess the therapeutic effects of the GM on IS through various interventions, such as dietary modifications, probiotics, fecal microbiota transplantation, and antibiotics, and offer insights into the potential clinical application of the GM in stroke treatment.}, } @article {pmid39362719, year = {2024}, author = {Morgan, TR}, title = {Emerging Pharmacologic Treatments for Alcohol-Associated Hepatitis: Current Status and Future Landscape.}, journal = {Clinics in liver disease}, volume = {28}, number = {4}, pages = {747-760}, doi = {10.1016/j.cld.2024.06.014}, pmid = {39362719}, issn = {1557-8224}, mesh = {Humans ; *Hepatitis, Alcoholic/drug therapy/therapy ; Antioxidants/therapeutic use ; Interleukin-22 ; Acetylcysteine/therapeutic use ; Fecal Microbiota Transplantation ; Granulocyte Colony-Stimulating Factor/therapeutic use ; }, abstract = {Several treatments have shown efficacy in preliminary alcohol-associated hepatitis trials. Interleukin-22 improved Model of End-stage Liver Disease score and aminotransferases in a phase II trial. The endogenous cholesterol derivative, larsucosterol, improved outcomes in a multi-center United States or European phase II trial. The antioxidants N-acetylcysteine and metadoxine improved survival in large trials. Trials from India report improved survival with granulocyte-colony stimulating factor, as well as improved outcome among patients receiving fecal microbiota transfer. Translational studies suggest that phage treatment of cytolytic Enterococcus faecalis may reduce liver injury.}, } @article {pmid39362714, year = {2024}, author = {Yang, Y and Schnabl, B}, title = {Gut Bacteria in Alcohol-Associated Liver Disease.}, journal = {Clinics in liver disease}, volume = {28}, number = {4}, pages = {663-679}, pmid = {39362714}, issn = {1557-8224}, support = {I01 BX004594/BX/BLRD VA/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; R01 AA024726/AA/NIAAA NIH HHS/United States ; R37 AA020703/AA/NIAAA NIH HHS/United States ; P50 AA011999/AA/NIAAA NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Liver Diseases, Alcoholic/microbiology/therapy ; *Dysbiosis ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation ; Bacteriophages ; }, abstract = {Alcohol-associated liver disease (ALD) poses a significant global public health challenge, with high patient mortality rates and economic burden. The gut microbiome plays an important role in the onset and progression of alcohol-associated liver disease. Excessive alcohol consumption disrupts the intestinal barrier, facilitating the entry of harmful microbes and their products into the liver, exacerbating liver damage. Dysbiosis, marked by imbalance in gut bacteria, correlates with ALD severity. Promising microbiota-centered therapies include probiotics, phages, and fecal microbiota transplantation. Clinical trials demonstrate the potential of these interventions to improve liver function and patient outcomes, offering a new frontier in ALD treatment.}, } @article {pmid39362281, year = {2024}, author = {Headley, SA and Chapman, DJ and Germain, MJ and Evans, EE and Madsen, KL and Miele, EM and Kirton, K and Loseke, J and Cornelius, A and Martin, B and Nindl, B and Park, H and Vaziri, ND and Ikizler, TA}, title = {Effects of high amylose resistant starch on gut microbiota and uremic toxin levels in patients with stage G3a-G4 chronic kidney disease: a randomized trial.}, journal = {Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.jrn.2024.09.005}, pmid = {39362281}, issn = {1532-8503}, abstract = {OBJECTIVE: This study was designed to determine the effect of 16 weeks of supplementation with Hi-maize 260 resistant starch on the gut microbiota, uremic toxins (indoxyl sulfate and p-cresyl sulfate), markers of inflammation and oxidative stress along with vascular function in patients with stage G3a-G4 chronic kidney disease (CKD).

DESIGN: & Methods: This was a double-blind, placebo-controlled, parallel-arm, randomized controlled trial. Sixty-eight patients with stage G3a-G4 CKD were randomized to either resistant starch with usual care or placebo and usual care. Patients attended four testing sessions: two baseline visits, and follow-up visits at 8 and 16 weeks. Fasting blood samples, resting brachial and central blood pressures, along with arterial stiffness, were collected at visits (1 or 2), and weeks 8 and 16. A stool sample was collected for analysis of microbial composition at baseline and week 16. Patients were randomized after the baseline visits.

RESULTS: Patients receiving the resistant starch had a reduction in p-cresyl sulfate at week 16. This reduction was associated with a decrease in microbial α-diversity between baseline and week 16 (Chao1 p=0.014, Shannon p=0.017, PD p= 0.046, and Simpson p=0.017) as well as increases in Subdoligranulum (p=0.03) and Oscillospiraceae UCG 002 (p=0.02) and decreases in Bacteroides (p=0.009).There were no changes in microbial beta diversity and other biomarkers or markers of vascular function following the 16-week period Conclusion: Sixteen weeks of supplementation of resistant starch in patients with stage G3a-G4 CKD led to changes in microbial composition that were associated with a significant reduction in p-cresyl sulfate.}, } @article {pmid39360770, year = {2024}, author = {Verma, N and Vinod, AP and Singal, AK}, title = {The pharmacological management of alcohol-related cirrhosis: what's new?.}, journal = {Expert opinion on pharmacotherapy}, volume = {}, number = {}, pages = {1-19}, doi = {10.1080/14656566.2024.2409941}, pmid = {39360770}, issn = {1744-7666}, abstract = {INTRODUCTION: Alcohol use disorder (AUD) is present in the majority of patients with alcohol-associated liver disease (ALD), which leads to about 50% of cirrhosis-related hospitalizations and over 25% of deaths worldwide. Patients with ALD often present at an advanced stage, like cirrhosis with its complications and alcohol-associated hepatitis (AH), which has high short-term mortality. Current treatments are limited, with the limited benefit of glucocorticoids only in the short-term among patients with AH, highlighting an urgent need for novel therapies.

AREAS COVERED: This review applies the PIRO (Predisposition, Injury, Response, Organ dysfunction) concept to ALD, understanding an ongoing process of liver damage, and opportunities to address and halt the progression. We also highlight the significance of treating AUD to improve long-term outcomes in ALD.

EXPERT OPINION: Personalized therapies targeting specific genetic profiles and multiple pathogenic pathways are crucial in managing ALD. Emerging therapies like gut-liver-brain axis modulators like fecal microbiota transplant and probiotics, interleukin-22, granulocyte-colony stimulating factor (G-CSF) and stem cells, epigenetic regulators of inflammation and regeneration are encouraging with the potential of efficacy in patients with ALD. Liver transplantation (LT) is a definitive therapy for advanced cirrhosis with increasing impetus on early LT select patients with active alcohol use.}, } @article {pmid39360586, year = {2024}, author = {Cibulková, I and Řehořová, V and Wilhelm, M and Soukupová, H and Hajer, J and Duška, F and Daňková, H and Cahová, M}, title = {Evaluating Bacterial Viability in Faecal Microbiota Transplantation: A Comparative Analysis of In Vitro Cultivation and Membrane Integrity Methods.}, journal = {Journal of clinical laboratory analysis}, volume = {}, number = {}, pages = {e25105}, doi = {10.1002/jcla.25105}, pmid = {39360586}, issn = {1098-2825}, support = {IN 00023001//Institute for Clinical and Experimental medicine - IKEM/ ; //Institutional Support of FNKV University Hospital/ ; VAT No 0907206//Donatio Intensivistam Endowement fund/ ; //Cooperation Intensive Care Medicine Programme of Charles University/ ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is a developing therapy for disorders related to gut dysbiosis. Despite its growing application, standardised protocols for FMT filtrate preparation and quality assessment remain undeveloped. The viability of bacteria in the filtrate is crucial for FMT's efficacy and for validating protocol execution. We compared two methods-in vitro cultivation and membrane integrity assessment-for their accuracy, reproducibility and clinical applicability in measuring bacterial viability in frozen FMT stool filtrate.

METHODS: Bacterial viability in stool filtrate was evaluated using (i) membrane integrity through fluorescent DNA staining with SYTO9 and propidium iodide, followed by flow cytometry and (ii) culturable bacteria counts (colony-forming units, CFU) under aerobic or anaerobic conditions.

RESULTS: Using different types of samples (pure bacterial culture, stool of germ-free and conventionally bred mice, native and heat-treated human stool), we refined the bacterial DNA staining protocol integrated with flow cytometry for assessment of bacterial viability in frozen human stool samples. Both the membrane integrity-based and cultivation-based methods exhibited significant variability in bacterial viability across different FMT filtrates, without correlation. The cultivation-based method showed a mean coefficient of variance of 30.3%, ranging from 7.4% to 60.1%. Conversely, the membrane integrity approach yielded more reproducible results, with a mean coefficient of variance for viable cells of 6.4% ranging from 0.2% to 18.2%.

CONCLUSION: Bacterial viability assessment in stool filtrate using the membrane integrity method offers robust and precise data, making it a suitable option for faecal material evaluation in FMT. In contrast, the cultivation-dependent methods produce inconsistent outcomes.}, } @article {pmid39360560, year = {2024}, author = {Arzamendi, MJ and Habibyan, YB and Defaye, M and Shute, A and Baggio, CH and Chan, R and Ohland, C and Bihan, DG and Lewis, IA and Sharkey, KA and McCoy, KD and Altier, C and Geuking, MB and Nasser, Y}, title = {Sex-specific post-inflammatory dysbiosis mediates chronic visceral pain in colitis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2409207}, pmid = {39360560}, issn = {1949-0984}, mesh = {Male ; Female ; Animals ; *Dysbiosis/microbiology ; *Gastrointestinal Microbiome ; *Visceral Pain/microbiology/physiopathology/metabolism ; *Colitis/microbiology ; Mice ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Sex Factors ; Bacteria/classification/isolation & purification/genetics/metabolism ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; Dextran Sulfate ; Disease Models, Animal ; Fatty Acids, Volatile/metabolism/analysis ; Chronic Pain/microbiology/physiopathology ; Inflammation/microbiology ; Hyperalgesia/microbiology ; }, abstract = {BACKGROUND: Despite achieving endoscopic remission, over 20% of inflammatory bowel disease (IBD) patients experience chronic abdominal pain. Visceral pain and the microbiome exhibit sex-dependent interactions, while visceral pain in IBD shows a sex bias. Our aim was to evaluate whether post-inflammatory microbial perturbations contribute to visceral hypersensitivity in a sex-dependent manner.

METHODS: Males, cycling females, ovariectomized, and sham-operated females were given dextran sodium sulfate to induce colitis and allowed to recover. Germ-free recipients received sex-appropriate and cross-sex fecal microbial transplants (FMT) from post-inflammatory donor mice. Visceral sensitivity was assessed by recording visceromotor responses to colorectal distention. The composition of the microbiota was evaluated via 16S rRNA gene V4 amplicon sequencing, while the metabolome was assessed using targeted (short chain fatty acids - SCFA) and semi-targeted mass spectrometry.

RESULTS: Post-inflammatory cycling females developed visceral hyperalgesia when compared to males. This effect was reversed by ovariectomy. Both post-inflammatory males and females exhibited increased SCFA-producing species, but only males had elevated fecal SCFA content. FMT from post-inflammatory females transferred visceral hyperalgesia to both males and females, while FMT from post-inflammatory males could only transfer visceral hyperalgesia to males.

CONCLUSIONS: Female sex, hormonal status as well as the gut microbiota play a role in pain modulation. Our data highlight the importance of considering biological sex in the evaluation of visceral pain.}, } @article {pmid39358432, year = {2024}, author = {Zhi, W and Li, A and Wang, Q and Yuan, X and Qing, J and Zhang, C and Wang, Y and Li, Y}, title = {Safety and efficacy assessment of fecal microbiota transplantation as an adjunctive treatment for IgA nephropathy: an exploratory clinical trial.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {22935}, pmid = {39358432}, issn = {2045-2322}, support = {82170716//National Science Foundation of China/ ; }, mesh = {Humans ; *Glomerulonephritis, IGA/therapy ; Male ; Female ; Adult ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Gastrointestinal Microbiome ; Middle Aged ; Treatment Outcome ; Cytokines/blood/metabolism ; }, abstract = {To assess the safety and efficacy of fecal microbiota transplantation (FMT) as an adjunctive therapeutic intervention for IgA nephropathy (IgAN). Fifteen patients with IgA nephropathy were recruited based on inclusion and exclusion criteria and underwent FMT using enteric microbial capsules. Clinical indicators, intestinal microbiota and metabolomic profiles, as well as changes in serum immune cells and cytokines, were monitored before and after FMT. No severe adverse reactions were observed in the subjects. After FMT, there was a reduction in the 24-h urinary protein quantification in subjects. The relative abundances of Phocaeicola_vulgatus, Bacteroides_uniformis, Prevotella_copri, Phocaeicola_dorei, Bacteroides_ovatus, Bacteroides_xylanisolvens, Parabacteroides _distasonis, Bifidobacterium_pseudocatenulatum, Bacteroides_sp._HF-162, and Bifidobacterium_longum changed after FMT. In terms of intestinal metabolites, the levels of acylcarnitine18:0 (ACar.18:0), cotinine, N-arachidonoyl-L-serine, phosphatidylcholine (PC. (18:3e/22:6)), serotonin, and fumagillin showed significant changes. Flow cytometry analysis showed the absolute count of plasma B cells decreased in subjects, and this change correlated with alterations in the intestinal microbiota and metabolites. This study preliminarily evaluates the safety and efficacy of FMT in patients with IgAN. No significant adverse reactions were observed, and the administration of FMT alongside ACEI/ARB therapy was effective in reducing urinary protein levels in patients with IgAN, a process that may be associated with B-cell immunity.}, } @article {pmid39358252, year = {2024}, author = {Tanigawa, H and Kohara, K and Onizuka, M and Otsuka, A and Suzuki, Y and Hirohara, M}, title = {[Survey of Preventing Exposure Regarding Sweat in Patients Receiving Antineoplastic Agents at Base Hospitals for Promoting Hematopoietic Stem Cell].}, journal = {Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan}, volume = {144}, number = {10}, pages = {957-962}, doi = {10.1248/yakushi.24-00098}, pmid = {39358252}, issn = {1347-5231}, mesh = {Humans ; *Antineoplastic Agents/adverse effects ; *Occupational Exposure/prevention & control ; *Hematopoietic Stem Cell Transplantation ; Surveys and Questionnaires ; *Sweat/chemistry ; Personal Protective Equipment ; Gloves, Protective ; Guideline Adherence ; Clothing ; Practice Guidelines as Topic ; }, abstract = {This survey aimed to reveal the actual preventing exposure for handling of clothing and sweat of patients treated with anticancer drugs, following the publication of "Guideline for Preventing Occupational Exposure in Cancer Chemotherapy Drugs, 2019 Edition" (Guideline 2019). A survey was conducted among nurses working at 95 hematopoietic stem cell transplantation promotion base hospitals from September 1, 2023 to October 31, 2023. The response rate was 84.2% (80 facilities). Of the respondents, 45% wore gloves when touching patients' skin to administer anticancer drugs. Almost the nurses identified "urine" and "feces" as fluids on contaminated linen, while 14.1% also identified "sweat." For new staff, the results for preventing exposure education on "if touching the patients' skin" and "if handling clothing and linen" were 23.8% and 34.9%, respectively. This survey shows that nurses may not be following the Guideline 2019 for use of personal protective equipment and handling of clothes. Medical institutions handling anticancer drugs need to educate their staff for preventing occupational exposure.}, } @article {pmid39353099, year = {2024}, author = {Loman, BR and Alzoubi, Z and Lynch, AJ and Jaggers, RM and Jordan, K and Grant, CV and Rogers, LK and Pyter, LM and Bailey, MT}, title = {Paclitaxel chemotherapy disrupts microbiota-enterohepatic bile acid metabolism in mice.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2410475}, pmid = {39353099}, issn = {1949-0984}, mesh = {Animals ; *Bile Acids and Salts/metabolism ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Mice, Inbred C57BL ; *Liver/metabolism/drug effects ; Male ; Hepatocytes/metabolism/drug effects ; Lipopolysaccharides/metabolism ; Colon/microbiology/metabolism/drug effects/pathology ; Bacteria/classification/metabolism/genetics/isolation & purification/drug effects ; }, abstract = {Balanced interactions between the enteric microbiota and enterohepatic organs are essential to bile acid homeostasis, and thus normal gastrointestinal function. Disruption of these interactions by cancer treatment instigates bile acid malabsorption, leading to treatment delays, malnutrition, and decreased quality of life. However, the nature of chemotherapy-induced bile acid malabsorption remains poorly characterized with limited treatment options. Therefore, this study sought to characterize changes in hepatic, enteric, and microbial bile acid metabolism in a mouse model of chemotherapy-induced toxicity. Consistent with clinical bile acid malabsorption, chemotherapy increased fecal excretion of primary bile acids and water, while diminishing microbiome diversity, secondary bile acid formation, and small intestinal bile acid signaling. We identified new contributors to pathology of bile acid malabsorption in the forms of lipopolysaccharide-induced cholestasis and colonic crypt hyperplasia from reduced secondary bile acid signaling. Chemotherapy reduced markers of hepatic bile flow and bile acid synthesis, elevated markers of fibrosis and endotoxemia, and altered transcription of genes at all stages of bile acid metabolism. Primary hepatocytes exposed to lipopolysaccharide (but not chemotherapy) replicated chemotherapy-induced transcriptional differences, while gut microbial transplant into germ-free mice replicated very few differences. In the colon, chemotherapy-altered bile acid profiles (particularly higher tauromuricholic acid and lower hyodeoxycholic acid) coincided with crypt hyperplasia. Exposing primary colonoids to hyodeoxycholic acid reduced proliferation, while gut microbiota transplant enhanced proliferation. Together, these investigations reveal complex involvement of the entire microbiota-enterohepatic axis in chemotherapy-induced bile acid malabsorption. Interventions to reduce hepatic lipopolysaccharide exposure and enhance microbial bile acid metabolism represent promising co-therapies to cancer treatment.}, } @article {pmid39355844, year = {2024}, author = {Ning, S and Zhang, Z and Zhou, C and Wang, B and Liu, Z and Feng, B}, title = {Cross-talk between macrophages and gut microbiota in inflammatory bowel disease: a dynamic interplay influencing pathogenesis and therapy.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1457218}, pmid = {39355844}, issn = {2296-858X}, abstract = {Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is a group of chronic immune-mediated gastrointestinal disorders. The etiology of IBD is multifactorial, involving genetic susceptibility, environmental factors, and a complex interplay between the gut microbiota and the host's immune system. Intestinal resident macrophages play an important role in the pathogenesis and progress of IBD, as well as in maintaining intestinal homeostasis and facilitating tissue repair. This review delves into the intricate relationship between intestinal macrophages and gut microbiota, highlighting their pivotal roles in IBD pathogenesis. We discuss the impact of macrophage dysregulation and the consequent polarization of different phenotypes on intestinal inflammation. Furthermore, we explore the compositional and functional alterations in gut microbiota associated with IBD, including the emerging significance of fungal and viral components. This review also examines the effects of current therapeutic strategies, such as 5-aminosalicylic acid (5-ASA), antibiotics, steroids, immunomodulators, and biologics, on gut microbiota and macrophage function. We underscore the potential of fecal microbiota transplantation (FMT) and probiotics as innovative approaches to modulate the gut microbiome in IBD. The aim is to provide insights into the development of novel therapies targeting the gut microbiota and macrophages to improve IBD management.}, } @article {pmid39355779, year = {2024}, author = {Zhang, S and Lu, J and Jin, Z and Xu, H and Zhang, D and Chen, J and Wang, J}, title = {Gut microbiota metabolites: potential therapeutic targets for Alzheimer's disease?.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1459655}, pmid = {39355779}, issn = {1663-9812}, abstract = {BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive decline in cognitive function, which significantly increases pain and social burden. However, few therapeutic interventions are effective in preventing or mitigating the progression of AD. An increasing number of recent studies support the hypothesis that the gut microbiome and its metabolites may be associated with upstream regulators of AD pathology.

METHODS: In this review, we comprehensively explore the potential mechanisms and currently available interventions targeting the microbiome for the improvement of AD. Our discussion is structured around modern research advancements in AD, the bidirectional communication between the gut and brain, the multi-target regulatory effects of microbial metabolites on AD, and therapeutic strategies aimed at modulating gut microbiota to manage AD.

RESULTS: The gut microbiota plays a crucial role in the pathogenesis of AD through continuous bidirectional communication via the microbiota-gut-brain axis. Among these, microbial metabolites such as lipids, amino acids, bile acids and neurotransmitters, especially sphingolipids and phospholipids, may serve as central components of the gut-brain axis, regulating AD-related pathogenic mechanisms including β-amyloid metabolism, Tau protein phosphorylation, and neuroinflammation. Additionally, interventions such as probiotic administration, fecal microbiota transplantation, and antibiotic use have also provided evidence supporting the association between gut microbiota and AD. At the same time, we propose an innovative strategy for treating AD: a healthy lifestyle combined with targeted probiotics and other potential therapeutic interventions, aiming to restore intestinal ecology and microbiota balance.

CONCLUSION: Despite previous efforts, the molecular mechanisms by which gut microbes act on AD have yet to be fully described. However, intestinal microorganisms may become an essential target for connecting the gut-brain axis and improving the symptoms of AD. At the same time, it requires joint exploration by multiple centers and multiple disciplines.}, } @article {pmid39351254, year = {2024}, author = {Zhang, ZN and Sang, LX}, title = {Dual-targeted treatment for inflammatory bowel disease: Whether fecal microbiota transplantation can be an important part of it.}, journal = {World journal of gastroenterology}, volume = {30}, number = {36}, pages = {4025-4030}, pmid = {39351254}, issn = {2219-2840}, mesh = {*Fecal Microbiota Transplantation/methods/adverse effects ; Humans ; *Gastrointestinal Microbiome/drug effects ; *Inflammatory Bowel Diseases/therapy/microbiology/immunology ; Treatment Outcome ; Combined Modality Therapy/methods ; Feces/microbiology ; Biological Products/therapeutic use ; Gastrointestinal Agents/therapeutic use ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disease. With the emergence of biologics and other therapeutic methods, two biologics or one biologic combined with a novel small-molecule drug has been proposed in recent years to treat IBD. Although treatment strategies for IBD are being optimized, their efficacy and risks still warrant further consideration. This editorial explores the current risks associated with dual-targeted treatment for IBD and the great potential that fecal microbiota transplantation (FMT) may have for use in combination therapy for IBD. We are focused on addressing refractory IBD or biologically resistant IBD based on currently available dual-targeted treatment by incorporating FMT as part of this dual-targeted treatment. In this new therapy regimen, FMT represents a promising combination therapy.}, } @article {pmid39351201, year = {2024}, author = {Frith, ME and Kashyap, PC and Linden, DR and Theriault, B and Chang, EB}, title = {Microbiota-dependent early-life programming of gastrointestinal motility.}, journal = {iScience}, volume = {27}, number = {10}, pages = {110895}, pmid = {39351201}, issn = {2589-0042}, abstract = {Gastrointestinal microbes modulate peristalsis and stimulate the enteric nervous system (ENS), whose development, as in the central nervous system (CNS), continues into the murine postweaning period. Given that adult CNS function depends on stimuli received during critical periods of postnatal development, we hypothesized that adult ENS function, namely motility, depends on microbial stimuli during similar critical periods. We gave fecal microbiota transplantation (FMT) to germ-free mice at weaning or as adults and found that only the mice given FMT at weaning recovered normal transit, while those given FMT as adults showed limited improvements. RNA sequencing (RNA-seq) of colonic muscularis propria revealed enrichments in neuron developmental pathways in mice exposed to gut microbes earlier in life, while mice exposed later-or not at all-showed exaggerated expression of inflammatory pathways. These findings highlight a microbiota-dependent sensitive period in ENS development, pointing to potential roles of the early-life microbiome in later-life dysmotility.}, } @article {pmid39350740, year = {2024}, author = {Jochumsen, EA and Kragsnaes, MS and Nilsson, AC and Rasmussen, KF and Ellingsen, T and Juul, MA and Kjeldsen, J and Holm, DK}, title = {'Does this fecal microbiota transplant work?' Quality assurance of capsule based fecal microbiota transplant production.}, journal = {Scandinavian journal of gastroenterology}, volume = {}, number = {}, pages = {1-6}, doi = {10.1080/00365521.2024.2401460}, pmid = {39350740}, issn = {1502-7708}, abstract = {BACKGROUND: Fecal Microbiota Transplant (FMT) is an effective treatment for recurring Clostridioides Difficile Infections (rCDI). FMT administered via oral capsules (caFMT) offers several practical advantages to conventional liquid FMT. We began using caFMT in 2021 imported from an external institution. Based on similar production methods, we began our own caFMT production in 2022. We aimed to evaluate the quality of our caFMT.

STUDY DESIGN AND METHODS: We created a database of all FMT treatments (n = 180) provided by our institution. Quality of all FMT was evaluated by treatment success rates. We compared our caFMT to the imported caFMT.

RESULTS: Our caFMT yielded similar success rates compared to that of the imported caFMT, 65% (CI 95% 58-72%) and 72% (CI 95% 66-79%) respectively. FMT administered via colonoscopy had a significantly higher success rate, 79% (CI 95% 73-85%) than own our caFMT and other routes of administration. The combined success rate of treatments increased notably for all routes of administration when repeating FMT after prior failure.

DISCUSSION: The fact that our caFMT compared similarly to the imported caFMT was viewed as a success in terms of quality assurance. Our caFMT had a slightly lower success rates compared to da