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Bibliography on: Fecal Transplantation

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ESP: PubMed Auto Bibliography 16 Apr 2024 at 01:48 Created: 

Fecal Transplantation

Fecal Transplantion is a procedure in which fecal matter is collected from a tested donor, mixed with a saline or other solution, strained, and placed in a patient, by colonoscopy, endoscopy, sigmoidoscopy, or enema. The theory behind the procedure is that a normal gut microbial ecosystem is required for good health and that sometimes a benefucuial ecosystem can be destroyed, perhaps by antibiotics, allowing other bacteria, specifically Clostridium difficile to over-populate the colon, causing debilitating, sometimes fatal diarrhea. C. diff. is on the rise throughout the world. The CDC reports that approximately 347,000 people in the U.S. alone were diagnosed with this infection in 2012. Of those, at least 14,000 died. Fecal transplant has also had promising results with many other digestive or auto-immune diseases, including Irritable Bowel Syndrome, Crohn's Disease, and Ulcerative Colitis. It has also been used around the world to treat other conditions, although more research in other areas is needed. Fecal transplant was first documented in 4th century China, where the treatment was known as yellow soup.

Created with PubMed® Query: ( "(fecal OR faecal) (transplant OR transplantation)" OR "fecal microbiota transplant" ) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)


RevDate: 2024-04-15
CmpDate: 2024-04-15

Zhou Y, Zeng Y, Wang R, et al (2024)

Resveratrol Improves Hyperuricemia and Ameliorates Renal Injury by Modulating the Gut Microbiota.

Nutrients, 16(7):.

Resveratrol (RES) has been reported to prevent hyperuricemia (HUA); however, its effect on intestinal uric acid metabolism remains unclear. This study evaluated the impact of RES on intestinal uric acid metabolism in mice with HUA induced by a high-fat diet (HFD). Moreover, we revealed the underlying mechanism through metagenomics, fecal microbiota transplantation (FMT), and 16S ribosomal RNA analysis. We demonstrated that RES reduced the serum uric acid, creatinine, urea nitrogen, and urinary protein levels, and improved the glomerular atrophy, unclear renal tubule structure, fibrosis, and renal inflammation. The results also showed that RES increased intestinal uric acid degradation. RES significantly changed the intestinal flora composition of HFD-fed mice by enriching the beneficial bacteria that degrade uric acid, reducing harmful bacteria that promote inflammation, and improving microbial function via the upregulation of purine metabolism. The FMT results further showed that the intestinal microbiota is essential for the effect of RES on HUA, and that Lactobacillus may play a key role in this process. The present study demonstrated that RES alleviates HFD-induced HUA and renal injury by regulating the gut microbiota composition and the metabolism of uric acid.

RevDate: 2024-04-15
CmpDate: 2024-04-15

Byerley LO, Lorenzen B, Chang HM, et al (2024)

Gut Microbial Dysbiosis Differs in Two Distinct Cachectic Tumor-Bearing Models Consuming the Same Diet.

Nutrients, 16(7):.

The impact of cancer cachexia on the colonic microbiota is poorly characterized. This study assessed the effect of two cachectic-producing tumor types on the gut microbiota to determine if a similar dysbiosis could be found. In addition, it was determined if a diet containing an immunonutrient-rich food (walnuts) known to promote the growth of probiotic bacteria in the colon could alter the dysbiosis and slow cachexia. Male Fisher 344 rats were randomly assigned to a semi-purified diet with or without walnuts. Then, within each diet group, rats were further assigned randomly to a treatment group: tumor-bearing ad libitum fed (TB), non-tumor-bearing ad libitum fed (NTB-AL), and non-tumor-bearing group pair-fed to the TB (NTB-PF). The TB group was implanted either with the Ward colon carcinoma or MCA-induced sarcoma, both transplantable tumor lines. Fecal samples were collected after the development of cachexia, and bacteria species were identified using 16S rRNA gene analysis. Both TB groups developed cachexia but had a differently altered gut microbiome. Beta diversity was unaffected by treatment (NTB-AL, TB, and NTB-PF) regardless of tumor type but was affected by diet. Also, diet consistently changed the relative abundance of several bacteria taxa, while treatment and tumor type did not. The control diet increased the abundance of A. Anaeroplasma, while the walnut diet increased the genus Ruminococcus. There were no common fecal bacterial changes characteristic of cachexia found. Diet consistently changed the gut microbiota, but these changes were insufficient to slow the progression of cachexia, suggesting cancer cachexia is more complex than a few gut microbiota shifts.

RevDate: 2024-04-15
CmpDate: 2024-04-15

Lombardi M, Troisi J, Motta BM, et al (2024)

Gut-Liver Axis Dysregulation in Portal Hypertension: Emerging Frontiers.

Nutrients, 16(7):.

Portal hypertension (PH) is a complex clinical challenge with severe complications, including variceal bleeding, ascites, hepatic encephalopathy, and hepatorenal syndrome. The gut microbiota (GM) and its interconnectedness with human health have emerged as a captivating field of research. This review explores the intricate connections between the gut and the liver, aiming to elucidate how alterations in GM, intestinal barrier function, and gut-derived molecules impact the development and progression of PH. A systematic literature search, following PRISMA guidelines, identified 12 original articles that suggest a relationship between GM, the gut-liver axis, and PH. Mechanisms such as dysbiosis, bacterial translocation, altered microbial structure, and inflammation appear to orchestrate this relationship. One notable study highlights the pivotal role of the farnesoid X receptor axis in regulating the interplay between the gut and liver and proposes it as a promising therapeutic target. Fecal transplantation experiments further emphasize the pathogenic significance of the GM in modulating liver maladies, including PH. Recent advancements in metagenomics and metabolomics have expanded our understanding of the GM's role in human ailments. The review suggests that addressing the unmet need of identifying gut-liver axis-related metabolic and molecular pathways holds potential for elucidating pathogenesis and directing novel therapeutic interventions.

RevDate: 2024-04-12

Mullish BH, Merrick B, Quraishi MN, et al (2024)

The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

The Journal of hospital infection pii:S0195-6701(24)00080-X [Epub ahead of print].

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.

RevDate: 2024-04-12

Mullish BH, Merrick B, Quraishi MN, et al (2024)

The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

Gut pii:gutjnl-2023-331550 [Epub ahead of print].

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.

RevDate: 2024-04-12

Yang X, Zhou Y, Tan S, et al (2024)

Alterations in gut microbiota contribute to cognitive deficits induced by chronic infection of Toxoplasma gondii.

Brain, behavior, and immunity pii:S0889-1591(24)00353-2 [Epub ahead of print].

Chronic infection with Toxoplasma gondii (T. gondii) emerges as a risk factor for neurodegenerative diseases in animals and humans. However, the underlying mechanisms are largely unknown. We aimed to investigate whether gut microbiota and its metabolites play a role in T. gondii-induced cognitive deficits. We found that T. gondii infection induced cognitive deficits in mice, which was characterized by synaptic ultrastructure impairment and neuroinflammation in the hippocampus. Moreover, the infection led to gut microbiota dysbiosis, barrier integrity impairment, and inflammation in the colon. Interestingly, broad-spectrum antibiotic ablation of gut microbiota attenuated the adverse effects of the parasitic infection on the cognitive function in mice; cognitive deficits and hippocampal pathological changes were transferred from the infected mice to control mice by fecal microbiota transplantation. In addition, the abundance of butyrate-producing bacteria and the production of serum butyrate were decreased in infected mice. Interestingly, dietary supplementation of butyrate ameliorated T. gondii-induced cognitive impairment in mice. Notably, compared to the healthy controls, the decreased butyrate production was negatively correlated with the levels of anti-T. gondii IgG antibody in the serum of human subjects. Overall, this study demonstrates that gut microbiota is a key regulator of T. gondii-induced cognitive impairment.

RevDate: 2024-04-12

Bai X, Deng J, Duan Z, et al (2024)

Ginsenoside Rh4 alleviates gastrointestinal mucositis and enhances chemotherapy efficacy through modulating gut microbiota.

Phytomedicine : international journal of phytotherapy and phytopharmacology, 128:155577 pii:S0944-7113(24)00242-3 [Epub ahead of print].

BACKGROUND: Gastrointestinal mucositis stands as one of the most severe side effects of irinotecan (CPT-11). however, only palliative treatment is available at present. Therefore, there is an urgent need for adjunctive medications to alleviate the side effects of CPT-11.

PURPOSE: In this study, our objective was to explore whether ginsenoside Rh4 could serve as a modulator of the gut microbiota and an adjunctive agent for chemotherapy, thereby alleviating the side effects of CPT-11 and augmenting its anti-tumor efficacy.

STUDY DESIGN: A CPT-11-induced gastrointestinal mucositis model was used to investigate whether ginsenoside Rh4 alleviated CPT-11-induced gastrointestinal mucositis and enhanced the anti-tumor activity of CPT-11.

METHODS: In this study, we utilized CT26 cells to establish a xenograft tumor model, employing transcriptomics, genomics, and metabolomics techniques to investigate the impact of ginsenoside Rh4 on CPT-11-induced gastrointestinal mucositis and the effect on the anti-tumor activity of CPT-11. Furthermore, we explored the pivotal role of gut microbiota and their metabolites through fecal microbiota transplantation (FMT) experiments and supplementation of the key differential metabolite, hyodeoxycholic acid (HDCA).

RESULTS: The results showed that ginsenoside Rh4 repaired the impairment of intestinal barrier function and restored intestinal mucosal homeostasis in a gut microbiota-dependent manner. Ginsenoside Rh4 treatment modulated gut microbiota diversity and upregulated the abundance of beneficial bacteria, especially Lactobacillus_reuteri and Akkermansia_muciniphila, which further regulated bile acid biosynthesis, significantly promoted the production of the beneficial secondary bile acid hyodeoxycholic acid (HDCA), thereby alleviating CPT-11-induced gut microbiota dysbiosis. Subsequently, ginsenoside Rh4 further alleviated gastrointestinal mucositis through the TGR5-TLR4-NF-κB signaling pathway. On the other hand, ginsenoside Rh4 combination therapy could further reduce the weight and volume of colon tumors, promote tumor cell apoptosis, and enhance the anti-tumor activity of CPT-11 by inhibiting the PI3K-Akt signaling pathway, thus exerting a synergistic anti-tumor effect.

CONCLUSION: In summary, our findings confirm that ginsenoside Rh4 can alleviate CPT-11-induced gastrointestinal mucositis and enhance the anti-tumor activity of CPT-11 by modulating gut microbiota and its related metabolites. Our study validates the potential of ginsenoside Rh4 as a modulator of the gut microbiota and an adjunctive agent for chemotherapy, offering new therapeutic strategies for addressing chemotherapy side effects and improving chemotherapy efficacy.

RevDate: 2024-04-12

Zhang W, Ling J, Xu B, et al (2024)

Gut microbiome-mediated monocytes promote liver metastasis.

International immunopharmacology, 133:111877 pii:S1567-5769(24)00395-3 [Epub ahead of print].

The gut microbiome plays an important role in tumor growth by regulating immune cell function. However, the role of the gut microbiome-mediated monocytes in liver metastasis remains unclear. In this study, we found that fecal microbiome transplantation (FMT) from the stool of patients with liver metastasis (LM) significantly promoted liver metastasis compared with healthy donors (HD). Monocytes were upregulated in liver tissues by the CCL2/CCR2 axis in LM patients' stool transplanted mouse model. CCL2/CCR2 inhibition and monocyte depletion significantly suppress liver metastasis. FMT using LM patients' stool enhanced the plasma lipopolysaccharides (LPS) concentration. The LPS/TLR4 signaling pathway is crucial for gut microbiome-mediated liver metastasis. These results indicated that monocytes contribute to liver metastasis via the CCL2/CCR2 axis.

RevDate: 2024-04-11

Bethlehem L, Estevinho MM, Grinspan A, et al (2024)

Microbiota therapeutics for inflammatory bowel disease: the way forward.

The lancet. Gastroenterology & hepatology, 9(5):476-486.

Microbiota therapeutics that transplant faecal material from healthy donors to people with mild-to-moderate ulcerative colitis have shown the potential to induce remission in about 30% of participants in small, phase 2 clinical trials. Despite this substantial achievement, the field needs to leverage the insights gained from these trials and progress towards phase 3 clinical trials and drug approval, while identifying the distinct clinical niche for this new therapeutic modality within inflammatory bowel disease (IBD) therapeutics. We describe the lessons that can be learned from past studies of microbiota therapeutics, from full spectrum donor stool to defined products manufactured in vitro. We explore the actionable insights these lessons provide on the design of near-term studies and future trajectories for the integration of microbiota therapeutics in the treatment of IBD. If successful, microbiota therapeutics will provide a powerful orthogonal approach (complementing or in combination with existing immunomodulatory drugs) to raise the therapeutic ceiling for the many non-responders and partial responders within the IBD patient population.

RevDate: 2024-04-11

Porcari S, Fusco W, Spivak I, et al (2024)

Fine-tuning the gut ecosystem: the current landscape and outlook of artificial microbiome therapeutics.

The lancet. Gastroenterology & hepatology, 9(5):460-475.

The gut microbiome is acknowledged as a key determinant of human health, and technological progress in the past two decades has enabled the deciphering of its composition and functions and its role in human disorders. Therefore, manipulation of the gut microbiome has emerged as a promising therapeutic option for communicable and non-communicable disorders. Full exploitation of current therapeutic microbiome modulators (including probiotics, prebiotics, and faecal microbiota transplantation) is hindered by several factors, including poor precision, regulatory and safety issues, and the impossibility of providing reproducible and targeted treatments. Artificial microbiota therapeutics (which include a wide range of products, such as microbiota consortia, bacteriophages, bacterial metabolites, and engineered probiotics) have appeared as an evolution of current microbiota modulators, as they promise safe and reproducible effects, with variable levels of precision via different pathways. We describe the landscape of artificial microbiome therapeutics, from those already on the market to those still in the pipeline, and outline the major challenges for positioning these therapeutics in clinical practice.

RevDate: 2024-04-11

Xu Q, Sun L, Chen Q, et al (2024)

Gut microbiota dysbiosis contributes to depression-like behaviors via hippocampal NLRP3-mediated neuroinflammation in a postpartum depression mouse model.

Brain, behavior, and immunity, 119:220-235 pii:S0889-1591(24)00347-7 [Epub ahead of print].

Postpartum depression (PPD) is a severe mental disorder that affects approximately 10---20% of women after childbirth. The precise mechanism underlying PPD pathogenesis remains elusive, thus limiting the development of therapeutics. Gut microbiota dysbiosis is considered to contribute to major depressive disorder. However, the associations between gut microbiota and PPD remain unanswered. Here, we established a mouse PPD model by sudden ovarian steroid withdrawal after hormone-simulated pseudopregnancy-human (HSP-H) in ovariectomy (OVX) mouse. Ovarian hormone withdrawal induced depression-like and anxiety-like behaviors and an altered gut microbiota composition. Fecal microbiota transplantation (FMT) from PPD mice to antibiotic cocktail-treated mice induced depression-like and anxiety-like behaviors and neuropathological changes in the hippocampus of the recipient mice. FMT from healthy mice to PPD mice attenuated the depression-like and anxiety-like behaviors as well as the inflammation mediated by the NOD-like receptor protein (NLRP)-3/caspase-1 signaling pathway both in the gut and the hippocampus, increased fecal short-chain fatty acids (SCFAs) levels and alleviated gut dysbiosis with increased SCFA-producing bacteria and reduced Akkermansia in the PPD mice. Also, downregulation of NLRP3 in the hippocampus mitigated depression-like behaviors in PPD mice and overexpression of NLRP3 in the hippocampal dentate gyrus induced depression-like behaviors in naïve female mice. Intriguingly, FMT from healthy mice failed to alleviate depression-like behaviors in PPD mice with NLRP3 overexpression in the hippocampus. Our results highlighted the NLRP3 inflammasome as a key component within the microbiota-gut-brain axis, suggesting that targeting the gut microbiota may be a therapeutic strategy for PPD.

RevDate: 2024-04-10

Wang H, Zhou L, Zheng Q, et al (2024)

Kai-Xin-San improves cognitive impairment in D-gal and Aβ25-35 induced AD rats by regulating gut microbiota and reducing neuronal damage.

Journal of ethnopharmacology pii:S0378-8741(24)00460-4 [Epub ahead of print].

Kai-Xin-San (KXS) is a classic herbal formula for the treatment and prevention of AD (Alzheimer's disease) with definite curative effect, but its mechanism, which involves multiple components, pathways, and targets, is not yet fully understood.

AIM OF THE STUDY: To verify the effect of KXS on gut microbiota and explore its anti-AD mechanism related with gut microbiota.

MATERIALS AND METHODS: AD rat model was established and evaluated by intraperitoneal injection of D-gal and bilateral hippocampal CA1 injections of Aβ25-35. The pharmacodynamics of KXS in vivo includes general behavior, Morris water maze test, ELISA, Nissl & HE staining and immunofluorescence. Systematic analysis of gut microbiota was conducted using 16S rRNA gene sequencing technology. The potential role of gut microbiota in the anti-AD effect of KXS was validated with fecal microbiota transplantation (FMT) experiments.

RESULTS: KXS could significantly improve cognitive impairment, reduce neuronal damage and attenuate neuroinflammation and colonic inflammation in vivo in AD model rats. Nine differential intestinal bacteria associated with AD were screened, in which four bacteria (Lactobacillus murinus, Ligilactobacillus, Alloprevotella, Prevotellaceae_NK3B31_group) were very significant.

CONCLUSION: KXS can maintain the ecological balance of intestinal microbiota and exert its anti-AD effect by regulating the composition and proportion of gut microbiota in AD rats through the microbiota-gut-brain axis.

RevDate: 2024-04-11

Svačina MKR, Gao T, Sprenger-Svačina A, et al (2024)

Rejuvenating fecal microbiota transplant enhances peripheral nerve repair in aged mice by modulating endoneurial inflammation.

Experimental neurology, 376:114774 pii:S0014-4886(24)00100-6 [Epub ahead of print].

Peripheral nerve injury (PNI) resulting from trauma or neuropathies can cause significant disability, and its prognosis deteriorates with age. Emerging evidence suggests that gut dysbiosis and reduced fecal short-chain fatty acids (SCFAs) contribute to an age-related systemic hyperinflammation (inflammaging), which hinders nerve recovery after injury. This study thus aimed to evaluate the pro-regenerative effects of a rejuvenating fecal microbiota transplant (FMT) in a preclinical PNI model using aged mice. Aged C57BL/6 mice underwent bilateral crush injuries to their sciatic nerves. Subsequently, they either received FMT from young donors at three and four days after the injury or retained their aged gut microbiota. We analyzed gut microbiome composition and SCFA concentrations in fecal samples. The integrity of the ileac mucosal barrier was assessed by immunofluorescence staining of Claudin-1. Flow cytometry was utilized to examine immune cells and cytokine production in the ileum, spleen, and sciatic nerve. Various assessments, including behavioural tests, electrophysiological studies, and morphometrical analyses, were conducted to evaluate peripheral nerve function and repair following injury. Rejuvenating FMT reversed age-related gut dysbiosis by increasing Actinobacteria, especially Bifidobacteriales genera. This intervention also led to an elevation of gut SCFA levels and mitigated age-related ileac mucosal leakiness in aged recipients. Additionally, it augmented the number of T-helper 2 (Th2) and regulatory T (Treg) cells in the ileum and spleen, with the majority being positive for anti-inflammatory interleukin-10 (IL-10). In sciatic nerves, rejuvenating FMT resulted in increased M2 macrophage counts and a higher IL-10 production by IL-10[+]TNF-α[-] M2 macrophage subsets. Ultimately, restoring a youthful gut microbiome in aged mice led to improved nerve repair and enhanced functional recovery after PNI. Considering that FMT is already a clinically available technique, exploring novel translational strategies targeting the gut microbiome to enhance nerve repair in the elderly seems promising and warrants further evaluation.

RevDate: 2024-04-12
CmpDate: 2024-04-12

Sizemore N, Oliphant K, Zheng R, et al (2024)

A digital twin of the infant microbiome to predict neurodevelopmental deficits.

Science advances, 10(15):eadj0400.

Despite the recognized gut-brain axis link, natural variations in microbial profiles between patients hinder definition of normal abundance ranges, confounding the impact of dysbiosis on infant neurodevelopment. We infer a digital twin of the infant microbiome, forecasting ecosystem trajectories from a few initial observations. Using 16S ribosomal RNA profiles from 88 preterm infants (398 fecal samples and 32,942 abundance estimates for 91 microbial classes), the model (Q-net) predicts abundance dynamics with R[2] = 0.69. Contrasting the fit to Q-nets of typical versus suboptimal development, we can reliably estimate individual deficit risk (Mδ) and identify infants achieving poor future head circumference growth with ≈76% area under the receiver operator characteristic curve, 95% ± 1.8% positive predictive value at 98% specificity at 30 weeks postmenstrual age. We find that early transplantation might mitigate risk for ≈45.2% of the cohort, with potentially negative effects from incorrect supplementation. Q-nets are generative artificial intelligence models for ecosystem dynamics, with broad potential applications.

RevDate: 2024-04-09

Seida I, Al Shawaf M, N Mahroum (2024)

Fecal microbiota transplantation in autoimmune diseases - An extensive paper on a pathogenetic therapy.

Autoimmunity reviews pii:S1568-9972(24)00032-6 [Epub ahead of print].

The role of infections in the pathogenesis of autoimmune diseases has long been recognized and reported. In addition to infectious agents, the internal composition of the "friendly" living bacteria, (microbiome) and its correlation to immune balance and dysregulation have drawn the attention of researchers for decades. Nevertheless, only recently, scientific papers regarding the potential role of transferring microbiome from healthy donor subjects to patients with autoimmune diseases has been proposed. Fecal microbiota transplantation or FMT, carries the logic of transferring microorganisms responsible for immune balance from healthy donors to individuals with immune dysregulation or more accurately for our paper, autoimmune diseases. Viewing the microbiome as a pathogenetic player allows us to consider FMT as a pathogenetic-based treatment. Promising results alongside improved outcomes have been demonstrated in patients with different autoimmune diseases following FMT. Therefore, in our current extensive review, we aimed to highlight the implication of FMT in various autoimmune diseases, such as inflammatory bowel disease, autoimmune thyroid and liver diseases, systemic lupus erythematosus, and type 1 diabetes mellitus, among others. Presenting all the aspects of FMT in more than 12 autoimmune diseases in one paper, to the best of our knowledge, is the first time presented in medical literature. Viewing FMT as such could contribute to better understanding and newer application of the model in the therapy of autoimmune diseases, indeed.

RevDate: 2024-04-12
CmpDate: 2024-04-10

Bratkovič T, Zahirović A, Bizjak M, et al (2024)

New treatment approaches for Clostridioides difficile infections: alternatives to antibiotics and fecal microbiota transplantation.

Gut microbes, 16(1):2337312.

Clostridioides difficile causes a range of debilitating intestinal symptoms that may be fatal. It is particularly problematic as a hospital-acquired infection, causing significant costs to the health care system. Antibiotics, such as vancomycin and fidaxomicin, are still the drugs of choice for C. difficile infections, but their effectiveness is limited, and microbial interventions are emerging as a new treatment option. This paper focuses on alternative treatment approaches, which are currently in various stages of development and can be divided into four therapeutic strategies. Direct killing of C. difficile (i) includes beside established antibiotics, less studied bacteriophages, and their derivatives, such as endolysins and tailocins. Restoration of microbiota composition and function (ii) is achieved with fecal microbiota transplantation, which has recently been approved, with standardized defined microbial mixtures, and with probiotics, which have been administered with moderate success. Prevention of deleterious effects of antibiotics on microbiota is achieved with agents for the neutralization of antibiotics that act in the gut and are nearing regulatory approval. Neutralization of C. difficile toxins (iii) which are crucial virulence factors is achieved with antibodies/antibody fragments or alternative binding proteins. Of these, the monoclonal antibody bezlotoxumab is already in clinical use. Immunomodulation (iv) can help eliminate or prevent C. difficile infection by interfering with cytokine signaling. Small-molecule agents without bacteriolytic activity are usually selected by drug repurposing and can act via a variety of mechanisms. The multiple treatment options described in this article provide optimism for the future treatment of C. difficile infection.

RevDate: 2024-04-12
CmpDate: 2024-04-12

Straub TJ, Lombardo MJ, Bryant JA, et al (2024)

Impact of a Purified Microbiome Therapeutic on Abundance of Antimicrobial Resistance Genes in Patients With Recurrent Clostridioides difficile Infection.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 78(4):833-841.

BACKGROUND: The gastrointestinal microbiota is an important line of defense against colonization with antimicrobial resistant (AR) bacteria. In this post hoc analysis of the phase 3 ECOSPOR III trial, we assessed impact of a microbiota-based oral therapeutic (fecal microbiota spores, live; VOWST Oral Spores [VOS], formerly SER-109]; Seres Therapeutics) compared with placebo, on AR gene (ARG) abundance in patients with recurrent Clostridioides difficile infection (rCDI).

METHODS: Adults with rCDI were randomized to receive VOS or placebo orally for 3 days following standard-of-care antibiotics. ARG and taxonomic profiles were generated using whole metagenomic sequencing of stool at baseline and weeks 1, 2, 8, and 24 posttreatment.

RESULTS: Baseline (n = 151) and serial posttreatment stool samples collected through 24 weeks (total N = 472) from 182 patients (59.9% female; mean age: 65.5 years) in ECOSPOR III as well as 68 stool samples obtained at a single time point from a healthy cohort were analyzed. Baseline ARG abundance was similar between arms and significantly elevated versus the healthy cohort. By week 1, there was a greater decline in ARG abundance in VOS versus placebo (P = .003) in association with marked decline of Proteobacteria and repletion of spore-forming Firmicutes, as compared with baseline. We observed abundance of Proteobacteria and non-spore-forming Firmicutes were associated with ARG abundance, while spore-forming Firmicutes abundance was negatively associated.

CONCLUSIONS: This proof-of-concept analysis suggests that microbiome remodeling with Firmicutes spores may be a potential novel approach to reduce ARG colonization in the gastrointestinal tract.

RevDate: 2024-04-10

Maurer JJ, Cheng Y, Pedroso A, et al (2024)

Peeling back the many layers of competitive exclusion.

Frontiers in microbiology, 15:1342887.

Baby chicks administered a fecal transplant from adult chickens are resistant to Salmonella colonization by competitive exclusion. A two-pronged approach was used to investigate the mechanism of this process. First, Salmonella response to an exclusive (Salmonella competitive exclusion product, Aviguard[®]) or permissive microbial community (chicken cecal contents from colonized birds containing 7.85 Log10Salmonella genomes/gram) was assessed ex vivo using a S. typhimurium reporter strain with fluorescent YFP and CFP gene fusions to rrn and hilA operon, respectively. Second, cecal transcriptome analysis was used to assess the cecal communities' response to Salmonella in chickens with low (≤5.85 Log10 genomes/g) or high (≥6.00 Log10 genomes/g) Salmonella colonization. The ex vivo experiment revealed a reduction in Salmonella growth and hilA expression following co-culture with the exclusive community. The exclusive community also repressed Salmonella's SPI-1 virulence genes and LPS modification, while the anti-virulence/inflammatory gene avrA was upregulated. Salmonella transcriptome analysis revealed significant metabolic disparities in Salmonella grown with the two different communities. Propanediol utilization and vitamin B12 synthesis were central to Salmonella metabolism co-cultured with either community, and mutations in propanediol and vitamin B12 metabolism altered Salmonella growth in the exclusive community. There were significant differences in the cecal community's stress response to Salmonella colonization. Cecal community transcripts indicated that antimicrobials were central to the type of stress response detected in the low Salmonella abundance community, suggesting antagonism involved in Salmonella exclusion. This study indicates complex community interactions that modulate Salmonella metabolism and pathogenic behavior and reduce growth through antagonism may be key to exclusion.

RevDate: 2024-04-11

Wei N, Ju M, Su X, et al (2024)

Transplantation of gut microbiota derived from patients with schizophrenia induces schizophrenia-like behaviors and dysregulated brain transcript response in mice.

Schizophrenia (Heidelberg, Germany), 10(1):44.

Schizophrenia (SCZ), as a neurodevelopmental disorder and devastating disease, affects approximately 1% of the world population. Although numerous studies have attempted to elucidate the causes of SCZ occurrence, it is not clearly understood. Recently, the emerging roles of the gut microbiota in a range of brain disorders, including SCZ, have attracted much attention. While the molecular mechanism of gut microbiota in regulating the pathogenesis of SCZ is still lacking. Here, we first confirmed the difference of gut microbiome between SCZ patients and healthy controls, and then, we performed fecal microbiota transplantation (FMT) to clarify the roles of SCZ patients-derived microbiota in a specific pathogen free (SPF) mice model. 16 S rDNA sequencing confirmed that a significant difference of gut microbiome was present between two groups of FMT mice, which has a similar trend with the above human gut microbiome. Furthermore, we found that transplantation of fecal microbiota from SCZ patients into SPF mice was sufficient to induce schizophrenia-like (SCZ-like) symptoms, such as deficits in sociability and hyperactivity. Furthermore, the brains of mice colonized with SCZ microbiota displayed dysregulated transcript response and alternative splicing of SCZ-relevant genes. Moreover, 10 key genes were identified to be correlated with SCZ by an integrative transcriptome data analysis. Finally, 4 key genes were identified to be correlated with the 12 differential genera between two groups of FMT mice. Our results thus demonstrated that the gut microbiome might modify the transcriptomic profile in the brain, thereby modulating social behavior, and our present study can help better understand the link between gut microbiota and SCZ pathogenesis through the gut-brain axis.

RevDate: 2024-04-10
CmpDate: 2024-04-10

Dokoshi T, Chen Y, Cavagnero KJ, et al (2024)

Dermal injury drives a skin to gut axis that disrupts the intestinal microbiome and intestinal immune homeostasis in mice.

Nature communications, 15(1):3009.

The composition of the microbial community in the intestine may influence the functions of distant organs such as the brain, lung, and skin. These microbes can promote disease or have beneficial functions, leading to the hypothesis that microbes in the gut explain the co-occurrence of intestinal and skin diseases. Here, we show that the reverse can occur, and that skin directly alters the gut microbiome. Disruption of the dermis by skin wounding or the digestion of dermal hyaluronan results in increased expression in the colon of the host defense genes Reg3 and Muc2, and skin wounding changes the composition and behavior of intestinal bacteria. Enhanced expression Reg3 and Muc2 is induced in vitro by exposure to hyaluronan released by these skin interventions. The change in the colon microbiome after skin wounding is functionally important as these bacteria penetrate the intestinal epithelium and enhance colitis from dextran sodium sulfate (DSS) as seen by the ability to rescue skin associated DSS colitis with oral antibiotics, in germ-free mice, and fecal microbiome transplantation to unwounded mice from mice with skin wounds. These observations provide direct evidence of a skin-gut axis by demonstrating that damage to the skin disrupts homeostasis in intestinal host defense and alters the gut microbiome.

RevDate: 2024-04-10
CmpDate: 2024-04-10

Liu P, Liu Z, Wang J, et al (2024)

Immunoregulatory role of the gut microbiota in inflammatory depression.

Nature communications, 15(1):3003.

Inflammatory depression is a treatment-resistant subtype of depression. A causal role of the gut microbiota as a source of low-grade inflammation remains unclear. Here, as part of an observational trial, we first analyze the gut microbiota composition in the stool, inflammatory factors and short-chain fatty acids (SCFAs) in plasma, and inflammatory and permeability markers in the intestinal mucosa of patients with inflammatory depression (ChiCTR1900025175). Gut microbiota of patients with inflammatory depression exhibits higher Bacteroides and lower Clostridium, with an increase in SCFA-producing species with abnormal butanoate metabolism. We then perform fecal microbiota transplantation (FMT) and probiotic supplementation in animal experiments to determine the causal role of the gut microbiota in inflammatory depression. After FMT, the gut microbiota of the inflammatory depression group shows increased peripheral and central inflammatory factors and intestinal mucosal permeability in recipient mice with depressive and anxiety-like behaviors. Clostridium butyricum administration normalizes the gut microbiota, decreases inflammatory factors, and displays antidepressant-like effects in a mouse model of inflammatory depression. These findings suggest that inflammatory processes derived from the gut microbiota can be involved in neuroinflammation of inflammatory depression.

RevDate: 2024-04-08

Hunter C, Dia K, Boykins J, et al (2024)

An investigation for phylogenetic characterization of human Pancreatic cancer microbiome by 16SrDNA Sequencing and Bioinformatics techniques.

Research square

Pancreatic cancer is a significant public health concern, with increasing incidence rates and limited treatment options. Recent studies have highlighted the role of the human microbiome, particularly the gut microbiota, in the development and progression of this disease. Microbial dysbiosis, characterized by alterations in the composition and function of the gut microbiota, has been implicated in pancreatic carcinogenesis through mechanisms involving chronic inflammation, immune dysregulation, and metabolic disturbances. Researchers have identified specific microbial signatures associated with pancreatic cancer, offering potential biomarkers for early detection and prognostication. By leveraging advanced sequencing and bioinformatics tools, scientists have delineated differences in the gut microbiota between pancreatic cancer patients and healthy individuals, providing insights into disease pathogenesis and potential diagnostic strategies. Moreover, the microbiome holds promise as a therapeutic target in pancreatic cancer treatment. Interventions aimed at modulating the microbiome, such as probiotics, prebiotics, and fecal microbiota transplantation, have demonstrated potential in enhancing the efficacy of existing cancer therapies, including chemotherapy and immunotherapy. These approaches can influence immune responses, alter tumor microenvironments, and sensitize tumors to treatment, offering new avenues for improving patient outcomes and overcoming therapeutic resistance. Overall, understanding the complex interplay between the microbiome and pancreatic cancer is crucial for advancing our knowledge of disease mechanisms and identifying innovative therapeutic strategies. Here we report phylogenetic analysis of the 16S microbial sequences of the pancreatic cancer mice microbiome and corresponding age matched healthy mice microbiome. We successfully identified differentially abundance of microbiota in the pancreatic cancer.

RevDate: 2024-04-10

Verma A, Bhagchandani T, Rai A, et al (2024)

Short-Chain Fatty Acid (SCFA) as a Connecting Link between Microbiota and Gut-Lung Axis-A Potential Therapeutic Intervention to Improve Lung Health.

ACS omega, 9(13):14648-14671.

The microbiome is an integral part of the human gut, and it plays a crucial role in the development of the immune system and homeostasis. Apart from the gut microbiome, the airway microbial community also forms a distinct and crucial part of the human microbiota. Furthermore, several studies indicate the existence of communication between the gut microbiome and their metabolites with the lung airways, called "gut-lung axis". Perturbations in gut microbiota composition, termed dysbiosis, can have acute and chronic effects on the pathophysiology of lung diseases. Microbes and their metabolites in lung stimulate various innate immune pathways, which modulate the expression of the inflammatory genes in pulmonary leukocytes. For instance, gut microbiota-derived metabolites such as short-chain fatty acids can suppress lung inflammation through the activation of G protein-coupled receptors (free fatty acid receptors) and can also inhibit histone deacetylase, which in turn influences the severity of acute and chronic respiratory diseases. Thus, modulation of the gut microbiome composition through probiotic/prebiotic usage and fecal microbiota transplantation can lead to alterations in lung homeostasis and immunity. The resulting manipulation of immune cells function through microbiota and their key metabolites paves the way for the development of novel therapeutic strategies in improving the lung health of individuals affected with various lung diseases including SARS-CoV-2. This review will shed light upon the mechanistic aspect of immune system programming through gut and lung microbiota and exploration of the relationship between gut-lung microbiome and also highlight the therapeutic potential of gut microbiota-derived metabolites in the management of respiratory diseases.

RevDate: 2024-04-09

Biedermann L, Kreienbühl A, G Rogler (2024)

Microbiota Therapy in Inflammatory Bowel Disease.

Visceral medicine, 40(2):92-101.

BACKGROUND: In both Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel disease (IBD) the immune reaction is - at least partially - directed against components of the luminal microbiota of the gut. These immune responses as well as other factors contribute to a phenomenon frequently described as "dysbiosis" meaning an alteration of the composition of the colonic microbiota. To improve the dysbiosis and to restore the normal composition of the colonic microbiota, fecal microbiota transplantation (FMT) has been tested as a therapeutic option to induce and maintain remission in IBD patients.

SUMMARY: This review will first discuss changes in the composition of the intestinal microbiota found in IBD patients and second the therapeutic potential of microbiological interventions for the treatment of these patients. FMT has been studied in several clinical trials in both, CD and UC. Reported results and subsequent meta-analyses indicate that FMT may be effective to induce remission in UC. However, the optimal route of FMT, the necessary number of administrations and the question whether life bacteria of freshly prepared stool is more effective than frozen are still unclear. Concepts associated with an optimization of FMT such as the "super donor concept" or the "consortia-approach" will be discussed to illustrate open questions and difficulties associated with microbiota therapy in IBD.

KEY MESSAGES: The microbiota composition in IBD patients shows significant alterations compared to healthy individuals termed as "dysbiosis". FMT and other therapeutic approaches to modify the microbiota composition have been studied in clinical trials in recent years. Efficacy has been shown in UC; however, many questions with respect to the optimization of microbiota therapy remain to be answered.

RevDate: 2024-04-09

Stallhofer J, Steube A, Katzer K, et al (2024)

Microbiota-Based Therapeutics as New Standard-of-Care Treatment for Recurrent Clostridioides difficile Infection.

Visceral medicine, 40(2):82-91.

BACKGROUND: Clostridioides difficile (C. difficile) is a spore-forming bacterial species that ubiquitously exists in the environment. Colonization by C. difficile is highly prevalent in infants, while fewer than 5% of adults are asymptomatic carriers. Disruption of the microbiome, such as through antibiotic treatment, triggers the germination of bacterial spores into numerous vegetative cells. These cells then produce enterotoxins that result in watery diarrhea and colonic inflammation. If left untreated, C. difficile infection (CDI) can lead to pseudomembranous colitis with the potentially life-threatening complication of toxic megacolon.

SUMMARY: Over the past few decades, the incidence, morbidity, and mortality associated with CDIs have increased. They have emerged as the primary cause of nosocomial gastrointestinal infections in industrialized countries, posing a significant burden on healthcare systems. Despite antibiotics often being the cause of CDIs, they remain the standard treatment. However, a considerable number of patients treated with antibiotics will experience recurrent CDI (rCDI). Microbiota-based therapies targeting the core issue of CDI - antibiotic-induced dysbiosis - hold promise for rCDI treatment. While data for probiotics are insufficient, numerous studies have highlighted the effectiveness of fecal microbiota transplantation (FMT) as a safe and viable therapeutic option for rCDI. This approach is now endorsed by multiple guidelines. Nonetheless, regulatory prerequisites, such as comprehensive stool donor screening, restrict the widespread adoption of FMT beyond specialized centers. Recently, the US Food and Drug Administration has approved two commercial microbiota-based therapeutics to prevent CDI recurrence. These therapeutics are available by prescription in the USA. RBX2660 (REBYOTA™) comprises a diverse consortium of live microbes derived from human stool and is administered via enema. On the other hand, SER-109 (VOWST™) is an orally administered spore-based medication. In this review, we discuss the potential of microbiota-based treatments for rCDI against the background of medico-legal challenges associated with classical FMT.

KEY MESSAGES: FMT has emerged as a highly effective cure for rCDI. Nonetheless, regulatory prerequisites and laborious preparation procedures impede its widespread use. The establishment of ready-to-use microbiota-based therapeutics in clinical practice is necessary. In the USA, the recent approval of the first two commercial medications, including a spore-based oral preparation, marks a significant step forward.

RevDate: 2024-04-07

Chen C, Xu JL, Gu ZC, et al (2024)

Danggui Sini decoction alleviates oxaliplatin-induced peripheral neuropathy by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

Chinese medicine, 19(1):58.

BACKGROUND: Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated.

METHODS: The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation.

RESULTS: DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, L-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota.

CONCLUSION: DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

RevDate: 2024-04-06

Rook GAW (2024)

Evolution and the critical role of the microbiota in the reduced mental and physical health associated with low socioeconomic status (SES).

Neuroscience and biobehavioral reviews pii:S0149-7634(24)00122-2 [Epub ahead of print].

The evolution of the gut-microbiota-brain axis in animals reveals that microbial inputs influence metabolism, the regulation of inflammation and the development of organs, including the brain. Inflammatory, neurodegenerative and psychiatric disorders are more prevalent in people of low socioeconomic status (SES). Many aspects of low SES reduce exposure to the microbial inputs on which we are in a state of evolved dependence, whereas the lifestyle of wealthy citizens maintains these exposures. This partially explains the health deficit of low SES, so focussing on our evolutionary history and on environmental and lifestyle factors that distort microbial exposures might help to mitigate that deficit. But the human microbiota is complex and we have poor understanding of its functions at the microbial and mechanistic levels, and in the brain. Perhaps its composition is more flexible than the microbiota of animals that have restricted habitats and less diverse diets? These uncertainties are discussed in relation to the encouraging but frustrating results of attempts to treat psychiatric disorders by modulating the microbiota.

RevDate: 2024-04-05

Zeng Z, Lv B, Tang YE, et al (2024)

Effects of dietary selenized glucose on intestinal microbiota and tryptophan metabolism in rats: Assessing skatole reduction potential.

Environmental research pii:S0013-9351(24)00778-3 [Epub ahead of print].

3-Methylindole (Skatole), a degradation product of tryptophan produced by intestinal microbial activity, significantly contributes to odor nuisance. Its adverse effects on animal welfare, human health, and environmental pollution have been noted. However, it is still unclear whether the intestinal microbiota mediates the impact of selenium (Se) on skatole production and what the underlying mechanisms remain elusive. A selenized glucose (SeGlu) derivative is a novel organic selenium compound. In this study, a diverse range of dietary SeGlu-treated levels, including SeGlu-deficient (CK), SeGlu-adequate (0.15 mg Se per L), and SeGlu-supranutritional (0.4 mg Se per L) conditions, were used to investigate the complex interaction of SeGlu on intestinal microbiome and serum metabolome changes in male Sprague-Dawley (SD) rats. The study showed that SeGlu supplementation enhanced the antioxidant ability in rats, significantly manifested in the increases of the activity of catalase (CAT) and glutathione peroxidase (GSH-Px), while no change in the level of malonaldehyde (MDA). Metagenomic sequencing analysis verified that the SeGlu treatment group significantly increased the abundance of beneficial microorganisms such as Clostridium, Ruminococcus, Faecalibacterium, Lactobacillus, and Alloprevotella while reducing the abundance of opportunistic pathogens such as Bacteroides and Alistipes significantly. Further metabolomic analysis revealed phenylalanine, tyrosine, and tryptophan biosynthesis changes in the SeGlu treatment group. Notably, the biosynthesis of indole, a critical pathway, was affected by SeGlu treatment, with several crucial enzymes implicated. Correlation analysis demonstrated strong associations between specific bacterial species - Treponema, Bacteroides, and Ruminococcus, and changes in indole and derivative concentrations. Moreover, the efficacy of SeGlu-treated fecal microbiota was confirmed through fecal microbiota transplantation, leading to a decrease in the concentration of skatole in rats. Collectively, the analysis of microbiota and metabolome response to diverse SeGlu levels suggests that SeGlu is a promising dietary additive in modulating intestinal microbiota and reducing odor nuisance in the livestock and poultry industry.

RevDate: 2024-04-08
CmpDate: 2024-04-08

Lin L, Xu S, Cai M, et al (2024)

Effects of fecal microbiota transfer on blood pressure in animal models: A systematic review and meta-analysis.

PloS one, 19(4):e0300869.

BACKGROUND: Numerous recent studies have found a strong correlation between intestinal flora and the occurrence of hypertension. However, it remains unclear whether fecal microbiota transfer might affect the blood pressure of the host. This study aimed to quantify both associations.

METHODS: An electronic search was conducted in PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang database, Weipu, Embase, and SinoMed to retrieve relevant studies. The final search was completed on August 22, 2022. Two authors independently applied the inclusion criteria, extracted data, and assessed the risk of bias assessment. All data were analyzed using RevMan 5.4.

RESULTS: A total of 5 articles were selected for final inclusion. All studies were assessed as having a high risk of bias according to the SYRCLE risk of bias tool. The meta-analysis results showed that transplantation of fecal bacteria from the hypertensive model can significantly improve the host's systolic pressure (MD = 18.37, 95%CI: 9.74~26.99, P<0.001), and diastolic pressure (MD = 17.65, 95%CI: 12.37~22.93, P<0.001). Subgroup analyses revealed that the increase in systolic pressure in the hypertension model subgroup (MD = 29.56, 95%CI = 23.55-35.58, P<0.001) was more pronounced than that in the normotensive model subgroup (MD = 12.48, 95%CI = 3.51-21.45, P<0.001).

CONCLUSION: This meta-analysis suggests a relationship between gut microbiota dysbiosis and increased blood pressure, where transplantation of fecal bacteria from the hypertensive model can cause a significant increase in systolic pressure and diastolic pressure in animal models.

RevDate: 2024-04-06

Koutromanos I, Legaki E, Gazouli M, et al (2024)

Gut microbiome in alcohol use disorder: Implications for health outcomes and therapeutic strategies-a literature review.

World journal of methodology, 14(1):88519.

Alcohol use disorder (AUD) represents a major public health issue which affects millions of people globally and consist a chronic relapsing condition associated with substantial morbidity and mortality. The gut microbiome plays a crucial role in maintaining overall health and has emerged as a significant contributor to the pathophysiology of various psychiatric disorders. Recent evidence suggests that the gut microbiome is intimately linked to the development and progression of AUD, with alcohol consumption directly impacting its composition and function. This review article aims to explore the intricate relationship between the gut microbiome and AUD, focusing on the implications for mental health outcomes and potential therapeutic strategies. We discuss the bidirectional communication between the gut microbiome and the brain, highlighting the role of microbiota-derived metabolites in neuroinflammation, neurotransmission, and mood regulation. Furthermore, we examine the influence of AUD-related factors, such as alcohol-induced gut dysbiosis and increased intestinal permeability, on mental health outcomes. Finally, we explore emerging therapeutic avenues targeting the gut microbiome in the management of AUD, including prebiotics, probiotics, and fecal microbiota transplantation. Understanding the complex interplay between the gut microbiome and AUD holds promise for developing novel interventions that could improve mental health outcomes in individuals with AUD.

RevDate: 2024-04-04

Ren J, Li Y, Ni H, et al (2024)

Gut microbiota derived from fecal microbiota transplantation enhances body weight of Mimas squabs.

Animal bioscience pii:ab.23.0475 [Epub ahead of print].

OBJECTIVE: Compared to Mimas pigeons, Shiqi pigeons exhibit greater tolerance to coarse feeding because of their abundant gut microbiota. Here, to investigate the potential of utilizing intestinal flora derived from Shiqi pigeons, the intestinal flora and body indices of Mimas squabs were evaluated after fecal microbiota transplantation (FMT) from donors.

METHODS: A total of 90 one-day-old squabs were randomly divided into the control group (CON), the low-concentration group (LC) and the high-concentration group (HC): gavaged with 200 μL of bacterial solution at concentrations of 0, 0.1 and 0.2 g/15 mL, respectively.

RESULTS: The results suggested that FMT improved the body weight of Mimas squabs in the HC and LC groups (p < 0.01), and 0.1 g/15 mL was the optimal dose during FMT. After 16S rRNA sequencing was performed, compared to those in the CON group, the abundance levels of microflora, especially Lactobacillus, Muribaculaceae and Megasphaera (p < 0.05), in the FMT-treated groups were markedly greater. Random forest analysis indicated that the main functions of key microbes involve pathways associated with metabolism, further illustrating their important role in the host body.

CONCLUSION: FMT has been determined to be a viable method for augmenting the weight and intestinal microbiota of squabs, representing a unique avenue for enhancing the economic feasibility of squab breeding.

RevDate: 2024-04-04

Stevens LJ, van de Steeg E, Doppenberg JB, et al (2024)

Ex vivo Gut-Hepato-Biliary organ perfusion model to characterize oral absorption, gut-wall metabolism, pre-systemic hepatic metabolism and biliary excretion; application to midazolam.

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences pii:S0928-0987(24)00071-X [Epub ahead of print].

To date, characterization of the first-pass effect of orally administered drugs consisting of local intestinal absorption and metabolism, portal vein transport and hepatobiliary processes remains challenging. Aim of this study was to explore the applicability of a porcine ex-vivo perfusion model to study oral absorption, gut-hepatobiliary metabolism and biliary excretion of midazolam. Slaughterhouse procured porcine en bloc organs (n=4), were perfused via the aorta and portal vein. After 120min of perfusion, midazolam, atenolol, antipyrine and FD4 were dosed via the duodenum and samples were taken from the systemic- and portal vein perfusate, intestinal faecal effluent and bile to determine drug and metabolite concentrations. Stable arterial and portal vein flow was obtained and viability of the perfused organs was confirmed. After intraduodenal administration, midazolam was rapidly detected in the portal vein together with 1-OH midazolam (EG-pv of 0.16±0.1) resulting from gut wall metabolism through oxidation. In the intestinal faecal effluent, 1-OH midazolam and 1-OH midazolam glucuronide (EG-intestine 0.051±0.03) was observed resulting from local gut glucuronidation. Biliary elimination of midazolam (0.04±0.01%) and its glucuronide (0.01±0.01%) only minimally contributed to the enterohepatic circulation. More extensive hepatic metabolism (FH 0.35±0.07) over intestinal metabolism (FG 0.78±0.11) was shown, resulting in oral bioavailability of 0.27±0.05. Ex vivo perfusion demonstrated to be a novel approach to characterize pre-systemic extraction of midazolam by measuring intestinal as well as hepatic extraction. The model can generate valuable insights into the absorption and metabolism of new drugs.

RevDate: 2024-04-04

Yan G, Zhang L, Wu D, et al (2024)

Paeonol attenuates nonalcoholic steatohepatitis by regulating intestinal flora and AhR/NLRP3/Caspase-1 metabolic pathway.

Journal of ethnopharmacology pii:S0378-8741(24)00446-X [Epub ahead of print].

Non-alcoholic steatohepatitis (NASH) is a common metabolic liver injury disease that is closely associated with obesity and metabolic disorders. Paeonol, an active ingredient found in Moutan Cortex, a traditional Chinese medicine which exhibits significant therapeutic effect on liver protection, has shown promising effects in treating liver diseases, particularly NASH. However, the specific intervention mechanism of paeonol on NASH is still unknown.

AIM OF THE STUDY: Our objective is to elucidate the pharmacological mechanism of paeonol in intervening NASH at the in vivo level, focusing on the impact on intestinal flora, tryptophan-related targeted metabolome, and related Aryl hydrocarbon receptor (AhR) pathways.

MATERIALS AND METHODS: Here, we explored the intervention effect of paeonol on NASH by utilizing the NASH mouse model. The Illumina highthroughput sequencing technology was preformed to determine the differences of gut microbiota of model and paeonol treatment group. The concentration of Indoleacetic acid is determined by ELISA. The intervention effect of NASH mouse and AhR/NLRP3/Caspase-1 metabolic pathway is analyzed by HE staining, oil red O staining, Immunohistochemistry, Immunofluorescence, Western blot and qRT-PCR assays. Fecal microbiota transplantation experiment also was performed to verify the intervention effect of paeonol on NASH by affecting gut microbiota.

RESULTS: Firstly, we discovered that paeonol effectively reduced liver pathology and blood lipid levels in NASH mice, thereby intervening in the progression of NASH. Subsequently, through 16S meta-analysis, we identified that paeonol can effectively regulate the composition of intestinal flora in NASH mice, transforming it to resemble that of normal mice. Specifically, paeonol decreased the abundance of certain Gram-negative tryptophan-metabolizing bacteria. Moreover, we discovered that paeonol significantly increased the levels of metabolites Indoleacetic acid, subsequently enhancing the expression of AhR-related pathway proteins. This led to the inhibition of the NOD-like receptor protein 3 (NLRP3) inflammasome production and inflammation generation in NASH. Lastly, we verified the efficacy of paeonol in intervening NASH by conducting fecal microbiota transplantation experiments, which confirmed its role in promoting the AhR/NLRP3/cysteinyl aspartate specific proteinase (Caspase-1) pathway.

CONCLUSIONS: Our findings suggest that paeonol can increase the production of Indoleacetic acid by regulating the gut flora, and promote the AhR/NLRP3/Caspase-1 metabolic pathway to intervene NASH.

RevDate: 2024-04-04

Sottil P, Lhomme S, Saune K, et al (2024)

Evaluation of an automated platform for the detection of HEV RNA in plasma and stool.

Journal of virological methods pii:S0166-0934(24)00044-2 [Epub ahead of print].

INTRODUCTION: We evaluated the performance of the automated Altostar HEV RNA platform for detecting HEV RNA.

METHODS AND RESULTS: Clinical performance was determined by testing 81 plasma samples and 10 fecal samples manually quantified previously with the Realstar RT-PCR assay using the Magnapure instrument for extraction. The assays were concordant for 79/81 plasma samples (97.5%) and 10/10 (100%) fecal samples. The two plasma samples that tested negative with the Altostar assay had a very low HEV RNA concentration (1.6 and 1.4 log10 IU/ml). Quantitative results obtained with the automated platform and the manual workflow were highly correlated (ρ= 0.98, p<0.01). The intra-run and inter-run standard deviation were 0.09 IU/ml and 0.13 IU/ml respectively. The assay was linear from 2 to 6log IU/ml. The limit of detection determined by Probit analysis with the WHO HEV RNA standard was 7.6 [95% CI: 4.4-52.5] IU/ml.

CONCLUSIONS: The Altostar platform enables highly accurate testing for the detection of HEV RNA in stool and the quantification of HEV RNA in plasma. This allowed us to shorten turnaround times and to save time for the technical staff.

RevDate: 2024-04-04

Ren S, Feng L, Liu H, et al (2024)

Gut microbiome affects the response to immunotherapy in non-small cell lung cancer.

Thoracic cancer [Epub ahead of print].

BACKGROUND: Immunotherapy has revolutionized cancer treatment. Recent studies have suggested that the efficacy of immunotherapy can be further enhanced by the influence of gut microbiota. In this study, we aimed to investigate the impact of bacteria on the effectiveness of cancer immunotherapy by combining analysis of clinical samples with validation in animal models.

METHODS: In order to characterize the diversity and composition of microbiota and its relationship with response to immune checkpoint inhibitors (ICIs), 16S ribosomal RNA (rRNA) and GC-MS sequencing was performed on 71 stool samples from patients with advanced non-small cell lung cancer (NSCLC) prior to treatment with immune checkpoint blockade (ICB). Furthermore, fecal microbiota transplantation (FMT) was performed from different patients into mice and a subcutaneous tumor model established using the Lewis lung cancer cell line to evaluate the therapeutic effect of PD-1 on mice with varying gut microbiota.

RESULTS: The results demonstrated a significant association between elevated gut microbiota diversity and response to treatment with ICIs, p < 0.05. Faecalibacterium was markedly increased in the gut microbiota of responders (R), accompanied by increased short-chain fatty acid (SCFA) levels, especially butanoic acid, acetic acid and hexanoic acid, p < 0.05. Additionally, FMT from R and nonresponders (NR) could promote an anticancer effect and reduce the expression of Ki-67 cells in tumors in mice, p < 0.05. Moreover, R and NR FMT did not alter PD-L1 expression in the tumor tissues of mice, p > 0.05. The diversity of gut microbiota consistently correlated with an optimistic prognosis in NSCLC patients with immunotherapy, which could be functionally mediated by SCFAs.

CONCLUSION: The findings of the present study indicated that the diversity of gut microbiota and SCFAs is related to the efficacy of immunotherapy. FMT can effectively delay tumor progression, and enhance the effect of immunotherapy, thus providing evidence for improving the efficacy of immunotherapy in NSCLC patients.

RevDate: 2024-04-04

van Lingen E, Nooij S, Terveer E, et al (2024)

Fecal Microbiota Transplantation engraftment after budesonide or placebo in patients with active ulcerative colitis using pre-selected donors: a randomized pilot study.

Journal of Crohn's & colitis pii:7640395 [Epub ahead of print].

BACKGROUND: Fecal microbiota transplantation (FMT) shows some efficacy in treating patients with ulcerative colitis (UC), although variability has been observed among donors and treatment regimens. We investigated the effect of FMT using rationally selected donors after pretreatment with budesonide or placebo in active UC.

METHODS: Patients ≥ 18 years old with mild to moderate active UC were randomly assigned to three weeks budesonide (9 mg) or placebo followed by four weekly infusions of a donor feces suspension. Two donors were selected based on microbiota composition, Treg induction and SCFA production in mice. The primary endpoint was engraftment of donor microbiota after FMT. In addition, clinical efficacy was assessed.

RESULTS: In total, 24 patients were enrolled. Pretreatment with budesonide did not increase donor microbiota engraftment (p=0.56) nor clinical response, and engraftment was not associated with clinical response. At week 14, 10/24 (42%) of patients achieved (partial) remission. Remarkably, patients treated with FMT suspensions from one donor were associated with clinical response (80% of responders, p<0.05) but had lower overall engraftment of donor microbiota. Furthermore, differences in the taxonomic composition of the donors and the engraftment of certain taxa were associated with clinical response.

CONCLUSION: In this small study, pretreatment with budesonide did not significantly influence engraftment or clinical response after FMT. However, clinical response appeared donor-dependent. Response to FMT may be related to transfer of specific strains instead of overall engraftment, demonstrating the need to characterize mechanisms of actions of strains that maximize therapeutic benefit in ulcerative colitis.

RevDate: 2024-04-05

Al Naser Y, AlGashami M, L Aljashaami (2024)

Clostridioides difficile infection: a changing treatment paradigm.

Przeglad gastroenterologiczny, 19(1):1-5.

Clostridioides difficile infection (CDI) poses a persistent challenge in healthcare, with substantial morbidity and mortality implications. This comprehensive review explores current CDI management, emphasising guidelines from IDSA, SHEA, and ESCMID. Additionally, this study spotlights recent drug developments that have the potential to reshape CDI treatment paradigms. Within the current treatment landscape, fidaxomicin, vancomycin, bezlotoxumab, and faecal microbiota transplantation offer varied options, each with its unique strengths and limitations. Fidaxomicin, effective yet resource-constrained, presents a dilemma, with vancomycin emerging as a pragmatic alternative. Bezlotoxumab, though augmenting antibiotics, grapples with cost and safety concerns. Meanwhile, faecal microbiota transplantation, highly efficacious, confronts evolving safety considerations. The horizon of CDI treatment also features promising therapies such as SER-109 and Rebyota, epitomising the evolving paradigm. As CDI management advances, the critical role of standardised microbiome restoration therapies becomes evident, ensuring long-term safety and diversifying treatment strategies.

RevDate: 2024-04-03

Menozzi E, AHV Schapira (2024)

The Gut Microbiota in Parkinson Disease: Interactions with Drugs and Potential for Therapeutic Applications.

CNS drugs [Epub ahead of print].

The concept of a 'microbiota-gut-brain axis' has recently emerged as an important player in the pathophysiology of Parkinson disease (PD), not least because of the reciprocal interaction between gut bacteria and medications. The gut microbiota can influence levodopa kinetics, and conversely, drugs administered for PD can influence gut microbiota composition. Through a two-step enzymatic pathway, gut microbes can decarboxylate levodopa to dopamine in the small intestine and then dehydroxylate it to m-tyramine, thus reducing availability. Inhibition of bacterial decarboxylation pathways could therefore represent a strategy to increase levodopa absorption. Other bacterial perturbations common in PD, such as small intestinal bacterial overgrowth and Helicobacter pylori infection, can also modulate levodopa metabolism, and eradication therapies may improve levodopa absorption. Interventions targeting the gut microbiota offer a novel opportunity to manage disabling motor complications and dopa-unresponsive symptoms. Mediterranean diet-induced changes in gut microbiota composition might improve a range of non-motor symptoms. Prebiotics can increase levels of short-chain fatty acid-producing bacteria and decrease pro-inflammatory species, with positive effects on clinical symptoms and levodopa kinetics. Different formulations of probiotics showed beneficial outcomes on constipation, with some of them improving dopamine levels; however, the most effective dosage and duration and long-term effects of these treatments remain unknown. Data from faecal microbiota transplantation studies are preliminary, but show encouraging trends towards improvement in both motor and non-motor outcomes.This article summarises the most up-to-date knowledge in pharmacomicrobiomics in PD, and discusses how the manipulation of gut microbiota represents a potential new therapeutic avenue for PD.

RevDate: 2024-04-04

Hopper AL, Hudson CL, Klair D, et al (2024)

Rain splash-mediated dispersal of Escherichia coli from fecal deposits to field-grown lettuce in the mid- and south Atlantic U.S. regions is affected by mulch type.

Frontiers in plant science, 15:1370495.

INTRODUCTION: Wildlife feces can contaminate vegetables when enteric bacteria are released by rain and splashed onto crops. Regulations require growers to identify and not harvest produce that is likely contaminated, but U.S. federal standards do not define dimensions for no-harvest zones. Moreover, mulching, used to retain soil moisture and maximize crop yield may impact rain-mediated bacterial dispersal from feces.

METHODS: To assess Escherichia coli dissemination from a fecal point source to lettuce grown on various mulches, lettuce cv. 'Magenta' was transplanted into raised beds with plastic, biodegradable plastic, straw, or left uncovered at field sites in Maryland and Georgia. Eleven days post-transplant, 10 g of rabbit manure spiked with ~8 log CFU g[-1] E. coli were deposited in each bed. One day following natural or simulated rain events, lettuce was sampled along 1.5 m transects on either side of fecal deposits. Lettuce-associated E. coli was semi-quantified with an MPN assay and dependence on fecal age (stale or fresh), lettuce age (baby leaf or mature head), distance from point source, mulch and post-rain days were statistically evaluated.

RESULTS: Distance (p<0.001), fecal age (p<0.001) and mulch (p<0.01) were factors for E. coli transfer from point source to lettuce. The highest and lowest E. coli estimates were measured from lettuce grown on biodegradable plastic and straw, respectively, with a 2-log MPN difference (p<0.001). Mulch and distance were also significant factors in E. coli recovery 3 days post-rain (both p<0.001), where plastic mulches differed from bare ground and straw (p<0.01). For all treatments, fewer E. coli were retrieved from lettuce at 0.3 m, 3 days post-rain compared to 1 day (p<0.001). Fitting the data to a Weibull Model predicated that a 7-log reduction in E. coli from fecal levels would be achieved at 1.2-1.4 m from the point source on plastic mulches, 0.75 m on bare soil (p<0.05) and 0.43 m on straw (p<0.01).

DISCUSSION: Straw and bare ground limited rain-mediated E. coli dispersal from feces to lettuce compared to plastic mulches. Fecal age was negatively associated with E. coli dispersal. These findings can inform harvesting recommendations for measures related to animal intrusion in vegetable production areas.

RevDate: 2024-04-04
CmpDate: 2024-04-04

Boussamet L, Montassier E, Mathé C, et al (2024)

Investigating the metabolite signature of an altered oral microbiota as a discriminant factor for multiple sclerosis: a pilot study.

Scientific reports, 14(1):7786.

In multiple sclerosis (MS), alterations of the gut microbiota lead to inflammation. However, the role of other microbiomes in the body in MS has not been fully elucidated. In a pilot case-controlled study, we carried out simultaneous characterization of faecal and oral microbiota and conducted an in-depth analysis of bacterial alterations associated with MS. Using 16S rRNA sequencing and metabolic inference tools, we compared the oral/faecal microbiota and bacterial metabolism pathways in French MS patients (n = 14) and healthy volunteers (HV, n = 21). A classification model based on metabolite flux balance was established and validated in an independent German cohort (MS n = 12, HV n = 38). Our analysis revealed decreases in diversity indices and oral/faecal compartmentalization, the depletion of commensal bacteria (Aggregatibacter and Streptococcus in saliva and Coprobacter and Roseburia in faeces) and enrichment of inflammation-associated bacteria in MS patients (Leptotrichia and Fusobacterium in saliva and Enterobacteriaceae and Actinomyces in faeces). Several microbial pathways were also altered (the polyamine pathway and remodelling of bacterial surface antigens and energetic metabolism) while flux balance analysis revealed associated alterations in metabolite production in MS (nitrogen and nucleoside). Based on this analysis, we identified a specific oral metabolite signature in MS patients, that could discriminate MS patients from HV and rheumatoid arthritis patients. This signature allowed us to create and validate a discrimination model on an independent cohort, which reached a specificity of 92%. Overall, the oral and faecal microbiomes were altered in MS patients. This pilot study highlights the need to study the oral microbiota and oral health implications in patients with autoimmune diseases on a larger scale and suggests that knowledge of the salivary microbiome could help guide the identification of new pathogenic mechanisms associated with the microbiota in MS patients.

RevDate: 2024-04-04
CmpDate: 2024-04-04

Yang H, Wu X, Li X, et al (2024)

A commensal protozoan attenuates Clostridioides difficile pathogenesis in mice via arginine-ornithine metabolism and host intestinal immune response.

Nature communications, 15(1):2842.

Antibiotic-induced dysbiosis is a major risk factor for Clostridioides difficile infection (CDI), and fecal microbiota transplantation (FMT) is recommended for treating CDI. However, the underlying mechanisms remain unclear. Here, we show that Tritrichomonas musculis (, an integral member of the mouse gut commensal microbiota, reduces CDI-induced intestinal damage by inhibiting neutrophil recruitment and IL-1β secretion, while promoting Th1 cell differentiation and IFN-γ secretion, which in turn enhances goblet cell production and mucin secretion to protect the intestinal mucosa. can actively metabolize arginine, not only influencing the host's arginine-ornithine metabolic pathway, but also shaping the metabolic environment for the microbial community in the host's intestinal lumen. This leads to a relatively low ornithine state in the intestinal lumen in C. difficile-infected mice. These changes modulate C. difficile's virulence and the host intestinal immune response, and thus collectively alleviating CDI. These findings strongly suggest interactions between an intestinal commensal eukaryote, a pathogenic bacterium, and the host immune system via inter-related arginine-ornithine metabolism in the regulation of pathogenesis and provide further insights for treating CDI.

RevDate: 2024-04-02

Zhang L, Yin Z, Liu X, et al (2024)

Dietary emulsifier polysorbate 80 exposure accelerates age-related cognitive decline.

Brain, behavior, and immunity pii:S0889-1591(24)00333-7 [Epub ahead of print].

Gut microbial homeostasis is crucial for the health of cognition in elderly. Previous study revealed that polysorbate 80 (P80) as a widely used emulsifier in food industries and pharmaceutical formulations could directly alter the human gut microbiota compositions. However, whether long-term exposure to P80 could accelerate age-related cognitive decline via gut-brain axis is still unknown. Accordingly, in this study, we used the senescence accelerated mouse prone 8 (SAMP8) mouse model to investigate the effects of the emulsifier P80 intake (1 % P80 in drinking water for 12 weeks) on gut microbiota and cognitive function. Our results indicated that P80 intake significantly exacerbated cognitive decline in SAMP8 mice, along with increased brain pathological proteins deposition, disruption of the blood-brain barrier and activation of microglia and neurotoxic astrocytes. Besides, P80 intake could also induce gut microbiota dysbiosis, especially the increased abundance of secondary bile acids producing bacteria, such as Ruminococcaceae, Lachnospiraceae, and Clostridium scindens. Moreover, fecal microbiota transplantation from P80 mice into 16-week-old SAMP8 mice could also exacerbated cognitive decline, microglia activation and intestinal barrier impairment. Intriguingly, the alterations of gut microbial composition significantly affected bile acid metabolism profiles after P80 exposure, with markedly elevated levels of deoxycholic acid (DCA) in serum and brain tissue. Mechanically, DCA could activate microglial and promote senescence-associated secretory phenotype production through adenosine triphosphate-binding cassette transporter A1 (ABCA1) importing lysosomal cholesterol. Altogether, the emulsifier P80 accelerated cognitive decline of aging mice by inducing gut dysbiosis, bile acid metabolism alteration, intestinal barrier and blood brain barrier disruption as well as neuroinflammation. This study provides strong evidence that dietary-induced gut microbiota dysbiosis may be a risk factor for age-related cognitive decline.

RevDate: 2024-04-03

Quan YX, Lao YD, Wu HY, et al (2024)

Beneficial effects of the first case of washed microbiota transplantation for postorgasmic illness syndrome: a case report.

Sexual medicine, 12(2):qfae015.

INTRODUCTION: Postorgasmic illness syndrome (POIS) is characterized by allergic symptoms and flu-like illness after ejaculation. There are still no effective treatments for POIS.

AIM: To report the first case of washed microbiota transplantation (WMT) to treat patient with POIS.

METHODS: Data were collected from a patient with POIS who had received 3 courses of WMT: self-rating scale of POIS symptoms, Self-rating Anxiety Scale, Self-rating Depression Scale, and Symptom Checklist 90. The patient's stool samples for 16sDNA sequencing were collected 1 month after WMT.

RESULTS: POIS symptoms improved after WMT. Scores decreased from baseline after WMT: self-rating scale of POIS symptoms (before WMT, 16; after first, 16; after second, 8; after third, 9), Self-rating Anxiety Scale (45, 42.5, 37.5, 45), Self-rating Depression Scale (63.75, 58.75, 47.5, 50), and Symptom Checklist 90 (143, 140, 109, 149). Characteristics of the patient's gut microbiota changed. At the genus level, the relative abundance of beneficial bacteria increased, and some opportunistic pathogenic bacteria decreased.

CONCLUSION: WMT may be an effective and safe choice for the treatment of patients with POIS by changing the gut microbiota of the host.

RevDate: 2024-04-03

Lee KE, Tu VY, AS Faye (2024)

Optimal Management of Refractory Crohn's Disease: Current Landscape and Future Direction.

Clinical and experimental gastroenterology, 17:75-86.

Refractory Crohn's disease, defined as ongoing inflammation despite the trial of multiple advanced therapies, impacts a number of individuals with Crohn's disease, and leads to significant burden in quality of life and cost. Interventions such as early implementation of advanced therapies, optimization of current therapies prior to switching to an alternative, as well as understanding the overlapping pathophysiology between immune-mediated disorders, however, can help shift the current landscape and reduce the number of patients with refractory disease. As such, in this review we summarize the key takeaways of the latest research in the management of moderate-to-severe Crohn's disease, focusing on maximization of our currently available medications, while also exploring topics such as combination advanced therapies. We also describe evidence for emerging and alternative therapeutic modalities, including fecal microbiota transplant, exclusive enteral feeding, hyperbaric oxygen, stem cell therapy, bone marrow transplant, and posaconazole, with a focus on both the potential impact and specific indications for each.

RevDate: 2024-04-01

Bolia R, Goel A, N Thapar (2024)

Transanal irrigation in children with functional constipation: A systematic review and meta-analysis.

Journal of pediatric gastroenterology and nutrition [Epub ahead of print].

OBJECTIVES: Refractory functional constipation is a challenging condition to manage in children. The use of transanal irrigation (TAI) is well reported in children with neurological disorders as well as anorectal malformations but less so in children with functional disorders of defecation. The objective of our study was to evaluate the effectiveness, safety and outcomes of TAI in children with functional constipation.

METHODS: PubMed, Scopus and Google Scholar were searched for publications related to the use of TAI in functional constipation. Data regarding the study design, sample size, patient characteristics, investigator-reported response to TAI and adverse effects were extracted from studies that met the selection criteria. The inverse variance heterogeneity model was used for ascertaining the summary effect in this meta-analysis.

RESULTS: The search strategy yielded 279 articles of which five studies were included in the final review. The studies were from the United Kingdom (n = 2), Netherlands (n = 2) and Denmark (n = 1). These studies included 192 children with a median age ranging from 7 to 12.2 years old. The TAI systems used in these studies were: Peristeen (n = 2), Peristeen or Qufora (n = 1), Alterna (n = 1) and Navina (n = 1). The follow-up duration ranged from 5.5 months to 3 years. Eleven (5.7%) children did not tolerate TAI and withdrew from treatment soon after initiation. The pooled investigator-reported success of TAI was 62% (95% CI: 52%-71%). The most common adverse event was pain which was experienced by 21.7% of children. A total of 27 (14%) were successfully weaned off TAI at the last follow-up.

CONCLUSIONS: TAI is reported to be successful in 62% of children with refractory functional constipation. There is a need for well-designed prospective trials to evaluate this treatment option in children with refractory functional constipation.

RevDate: 2024-03-31

Vega-Abellaneda S, Dopazo C, Yañez F, et al (2024)

Microbiome Composition Recovery after Liver Transplantation Correlates with Initial Liver Disease Severity and Antibiotics Treatment.

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons pii:S1600-6135(24)00248-X [Epub ahead of print].

Liver transplantation (LT) is crucial for end-stage liver disease, but it is linked to infection risks. Pathobionts, microorganisms potentially harmful under specific conditions, can cause complications post-transplant. Monitoring such pathogens in fecal samples can be challenging and therefore remains underexplored post-LT. This study aimed to analyze the gut microbiome before and after LT, tracking pathobionts and correlating clinical data. The study involved 17 liver transplant recipients, 17 healthy relatives (spouses), and 13 donors. Gut samples collected pre- and post-transplantation underwent bacterial and fungal profiling through DNA sequencing. Quantitative PCR was used to assess microbial load. Statistical analyses included alpha and beta diversity measures, differential abundance analysis, and correlation tests between microbiome and clinical parameters. Microbiome analysis revealed dynamic changes in diversity post-transplant. Notably, high-severity patients showed persistent and greater dysbiosis during the first months post-LT compared to low-severity patients, partly due to an antibiotic treatment pre-LT. The analysis identified a higher proportion of pathogens such as Escherichia coli/Shigella flexneri in high-severity cases post-transplant. Furthermore, butyrate producers including Roseburia intestinalis, Anaerostipes hadrus and Eubacterium coprostanoligenes were positively correlated with levels of albumin. This study offers valuable insights into post-LT microbiome changes, shedding light on the need for tailored prophylactic treatment post-LT.

RevDate: 2024-03-31

Tu Y, Luo L, Zhou Q, et al (2024)

Fecal Microbiota Transplantation Repairs Radiation Enteritis Through Modulating the Gut Microbiota-Mediated Tryptophan Metabolism.

Radiation research pii:499674 [Epub ahead of print].

Radiation enteritis is a common complication of abdominal and pelvic radiotherapy. Several previous studies showed that fecal microbiota transplantation (FMT) could alleviate radiation enteritis. In this study, we investigated the efficacy of FMT in alleviating radiation enteritis and explored the mechanisms by multi-omics approaches. Briefly, C57BL/6J mice were subjected to 9 Gy irradiation to the localized abdominal field, and randomized received FMT from healthy donor mice or saline. H&E staining of harvested small intestine showed FMT decreased epithelial injury. Radiation-induced microbiota dysbiosis, characterized by a decrease in beneficial bacteria Lactobacillaceae and Lachnospiraceae, while these bacteria were restored by FMT. Fecal metabolomics analysis revealed that FMT modulated metabolic dysregulation. Two tryptophan pathway metabolites, indole-3-acetaldehyde and N-Acetyl-5-hydroxytryptamine were decreased after irradiation, whereas these metabolites showed a pronounced recovery in mice receiving FMT. Proteomics analysis of small intestine indicated that radiation enteritis triggered immune-inflammatory responses, which were potentially mitigated by FMT. In 21 patients receiving pelvic radiotherapy for cervical cancer, those who developed enteritis (n = 15) had higher abundance in Lachnospiraceae. Moreover, Indole-3-acetaldehyde was reduced after irradiation. These findings provide insights into the therapeutic effects of FMT in radiation enteritis and highlight Lachnospiraceae and the tryptophan metabolite, Indole-3-acetaldehyde may protect against radiation enteritis.

RevDate: 2024-04-02
CmpDate: 2024-04-01

Heston SM, Young RR, Jenkins K, et al (2024)

The effects of antibiotic exposures on the gut resistome during hematopoietic cell transplantation in children.

Gut microbes, 16(1):2333748.

Antibiotic resistance is a global threat driven primarily by antibiotic use. We evaluated the effects of antibiotic exposures on the gut microbiomes and resistomes of children at high risk of colonization by antibiotic-resistant bacteria. We performed shotgun metagenomic sequencing of 691 serially collected fecal samples from 80 children (<18 years) undergoing hematopoietic cell transplantation. We evaluated the effects of aerobic (cefepime, vancomycin, fluoroquinolones, aminoglycosides, macrolides, and trimethoprim-sulfamethoxazole) and anaerobic (piperacillin-tazobactam, carbapenems, metronidazole, and clindamycin) antibiotic exposures on the diversity and composition of the gut microbiome and resistome. We identified 372 unique antibiotic resistance genes (ARGs); the most frequent ARGs identified encode resistance to tetracyclines (n = 88), beta-lactams (n = 84), and fluoroquinolones (n = 79). Both aerobic and anaerobic antibiotic exposures were associated with a decrease in the number of bacterial species (aerobic, β = 0.71, 95% CI: 0.64, 0.79; anaerobic, β = 0.66, 95% CI: 0.53, 0.82) and the number of unique ARGs (aerobic, β = 0.81, 95% CI: 0.74, 0.90; anaerobic, β = 0.73, 95% CI: 0.61, 0.88) within the gut metagenome. However, only antibiotic regimens that included anaerobic activity were associated with an increase in acquisition of new ARGs (anaerobic, β = 1.50; 95% CI: 1.12, 2.01) and an increase in the relative abundance of ARGs in the gut resistome (anaerobic, β = 1.62; 95% CI: 1.15, 2.27). Specific antibiotic exposures were associated with distinct changes in the number and abundance of ARGs for individual antibiotic classes. Our findings detail the impact of antibiotics on the gut microbiome and resistome and demonstrate that anaerobic antibiotics are particularly likely to promote acquisition and expansion of antibiotic-resistant bacteria.

RevDate: 2024-04-02
CmpDate: 2024-04-01

Dörner PJ, Anandakumar H, Röwekamp I, et al (2024)

Clinically used broad-spectrum antibiotics compromise inflammatory monocyte-dependent antibacterial defense in the lung.

Nature communications, 15(1):2788.

Hospital-acquired pneumonia (HAP) is associated with high mortality and costs, and frequently caused by multidrug-resistant (MDR) bacteria. Although prior antimicrobial therapy is a major risk factor for HAP, the underlying mechanism remains incompletely understood. Here, we demonstrate that antibiotic therapy in hospitalized patients is associated with decreased diversity of the gut microbiome and depletion of short-chain fatty acid (SCFA) producers. Infection experiments with mice transplanted with patient fecal material reveal that these antibiotic-induced microbiota perturbations impair pulmonary defense against MDR Klebsiella pneumoniae. This is dependent on inflammatory monocytes (IMs), whose fatty acid receptor (FFAR)2/3-controlled and phagolysosome-dependent antibacterial activity is compromized in mice transplanted with antibiotic-associated patient microbiota. Collectively, we characterize how clinically relevant antibiotics affect antimicrobial defense in the context of human microbiota, and reveal a critical impairment of IM´s antimicrobial activity. Our study provides additional arguments for the rational use of antibiotics and offers mechanistic insights for the development of novel prophylactic strategies to protect high-risk patients from HAP.

RevDate: 2024-04-01
CmpDate: 2024-04-01

Paraschiv AC, Vacaras V, Nistor C, et al (2024)

Dysbiosis in Multiple Sclerosis: Can Immunoglobulin Y Supplements Help?.

Journal of gastrointestinal and liver diseases : JGLD, 33(1):115-122.

The role of gut microbiota in autoimmune disorders like multiple sclerosis is gaining attention. Multiple sclerosis is characterized by inflammation, demyelination, and neurodegeneration in the central nervous system. Alterations in gut microbiota have been linked to multiple sclerosis development, with decreased beneficial bacteria and increased harmful species. The gut-brain axis is a complex interface influencing bidirectional interactions between the gut and the brain. Dysbiosis, an imbalance in gut microbiota, has been associated with autoimmune diseases. The influence of gut microbiota in multiple sclerosis is reversible, making it a potential therapeutic target. Probiotics, prebiotics, and fecal microbiota transplantation have shown promise in multiple sclerosis treatment, with positive effects on inflammation and immune regulation. Immunoglobulin Y (IgY) supplements derived from chicken egg yolk have potential as nutraceuticals or dietary supplements. IgY technology has been effective against various infections, and studies have highlighted its role in modulating gut microbiota and immune responses. Clinical trials using IgY supplements in multiple sclerosis are limited but have shown positive outcomes, including reduced symptoms, and altered immune responses. Future research directions involve understanding the mechanisms of IgY's interaction with gut microbiota, optimal dosage determination, and long-term safety assessments. Combining IgY therapy with other interventions and investigating correlations between microbiota changes and clinical outcomes are potential avenues for advancing multiple sclerosis treatment with IgY supplements.

RevDate: 2024-04-02
CmpDate: 2024-04-02

Blair HA (2024)

SER-109 (VOWST[™]): A Review in the Prevention of Recurrent Clostridioides difficile Infection.

Drugs, 84(3):329-336.

SER-109 (VOWST[™]; fecal microbiota spores, live-brpk) is a live biotherapeutic product indicated to prevent the recurrence of Clostridioides difficile infection (CDI) in patients 18 years of age and older following standard of care (SOC) antibacterial treatment for recurrent CDI. It is a purified bacterial spore suspension sourced from healthy donors. As the first oral faecal microbiota product approved for prevention of recurrent CDI, SER-109 is administered as four capsules once daily for three consecutive days. In a well-designed, placebo-controlled, phase III trial (ECOSPOR III), SER-109 significantly reduced the risk of recurrent CDI at 8 weeks post-treatment, with a durable response seen at 6 months post-treatment. Treatment with SER-109 was also associated with rapid and steady improvement in health-related quality of life compared with placebo. SER-109 was generally well tolerated, with a safety profile similar to that of placebo. The most common adverse events were of mild to moderate severity and generally gastrointestinal in nature. Thus, with the convenience of oral administration and lack of necessity for cold storage, SER-109 is a valuable option for preventing further CDI recurrence in adults following antibacterial treatment for recurrent CDI.

RevDate: 2024-03-30

Zhu X, Zhou Z, X Pan (2024)

Research reviews and prospects of gut microbiota in liver cirrhosis: a bibliometric analysis (2001-2023).

Frontiers in microbiology, 15:1342356.

INTRODUCTION: The gut-liver axis has emerged as a focal point in chronic liver disorders, prompting more research into the role of the gut microbiota in liver cirrhosis. In individuals with liver cirrhosis, changes in the structure and function of the gut microbiota are closely tied to clinical prognosis. However, there is a scarcity of bibliometric evaluations conducted in this particular field.

METHODS: This study is aiming to conduct a complete analysis of the knowledge structure and centers pertaining to gut microbiota in liver cirrhosis using bibliometric methods. Publications on gut microbiota and liver cirrhosis from 2001 to 2023 are sourced from the Web of Science Core Collection. For the bibliometric analysis, we employ VOSviewer, CiteSpace, and the R package "bibliometrix".

RESULTS: Our study encompasses a comprehensive collection of 3109 articles originating from 96 countries, with notable contributions from leading nations such as the United States and China. The quantity of publications concerning the gut microbiota of liver cirrhosis rises annually. The University of California San Diego, Virginia Commonwealth University, Zhejiang University are the primary research institutions. World Journal of Gastroenterology publishes the most papers in this field, while hepatology is the most frequently co-cited journal. These publications come from a total of 15,965 authors, and the most prolific authors are Bajaj Jasmohan S., Schnabl Bernd and Gillevet Patrick M., while the most co-cited authors are Bajaj Jasmohan S., Younossi Zobair M., and Reiner Wiest. In addition, "dysbiosis", "gut microbiota", "intestinal barrier", "fecal microbiota transplantation", and "complement-system" are the primary keywords of research trends in recent years.

DISCUSSION: This study offering a comprehensive insight into the research dynamics surrounding gut microbiota in patients with liver cirrhosis. It delineates the current research frontiers and hotspots, serving as a valuable guide for scholars.

RevDate: 2024-03-31

Jiang L, Ye Y, Han Y, et al (2024)

Microplastics dampen the self-renewal of hematopoietic stem cells by disrupting the gut microbiota-hypoxanthine-Wnt axis.

Cell discovery, 10(1):35.

Microplastics (MPs) are contaminants ubiquitously found in the global biosphere that enter the body through inhalation or ingestion, posing significant risks to human health. Recent studies emerge that MPs are present in the bone marrow and damage the hematopoietic system. However, it remains largely elusive about the specific mechanisms by which MPs affect hematopoietic stem cells (HSCs) and their clinical relevance in HSC transplantation (HSCT). Here, we established a long-term MPs intake mouse model and found that MPs caused severe damage to the hematopoietic system. Oral gavage administration of MPs or fecal transplantation of microbiota from MPs-treated mice markedly undermined the self-renewal and reconstitution capacities of HSCs. Mechanistically, MPs did not directly kill HSCs but disrupted gut structure and permeability, which eventually ameliorated the abundance of Rikenellaceae and hypoxanthine in the intestine and inactivated the HPRT-Wnt signaling in bone marrow HSCs. Furthermore, administration of Rikenellaceae or hypoxanthine in mice as well as treatment of WNT10A in the culture system substantially rescued the MPs-induced HSC defects. Finally, we validated in a cohort of human patients receiving allogenic HSCT from healthy donors, and revealed that the survival time of patients was negatively correlated with levels of MPs, while positively with the abundance of Rikenellaceae, and hypoxanthine in the HSC donors' feces and blood. Overall, our study unleashes the detrimental roles and mechanisms of MPs in HSCs, which provides potential strategies to prevent hematopoietic damage from MPs and serves as a fundamental critique for selecting suitable donors for HSCT in clinical practice.

RevDate: 2024-04-01
CmpDate: 2024-04-01

Singh J, Ibrahim B, SH Han (2024)

Nontraditional Treatment of Hepatic Encephalopathy.

Clinics in liver disease, 28(2):297-315.

The pathophysiology of hepatic encephalopathy (HE) is complex, with hyperammonemia playing a central role in its development. Traditional therapies for HE have targeted ammonia and include medications such as lactulose and rifaximin. Although these agents are considered standard of care, nontraditional treatments seek to affect other factors in the pathogenesis of HE. Finally, procedural therapies include albumin dialysis, shunt closure, and the ultimate cure for HE, which is liver transplant. The treatments discussed provide alternative options for patients who have failed standard of care. However, more high-quality studies are needed to routinely recommend many of these agents.

RevDate: 2024-03-28

Khalessi A, NT Pyrsopoulos (2024)

Pharmacologic Management of Hepatic Encephalopathy.

Clinics in liver disease, 28(2):287-296.

Hepatic encephalopathy is a common cause of morbidity and mortality among patients with decompensated liver cirrhosis. In this article, we review the history, mechanism, and evidence for first-line pharmacologic therapies for hepatic encephalopathy including nonabsorbable disaccharides, antibiotics, and electrolyte management. We also review newer, second-line therapies including polyethylene glycol, albumin, branched-chain amino acids, probiotics and fecal microbiota transplant, zinc, and l-ornithine-l-aspartate.

RevDate: 2024-03-28

Yousefi Y, Baines KJ, S Maleki Vareki (2024)

Microbiome bacterial influencers of host immunity and response to immunotherapy.

Cell reports. Medicine pii:S2666-3791(24)00133-2 [Epub ahead of print].

The gut microbiota influences anti-tumor immunity and can induce or inhibit response to immune checkpoint inhibitors (ICIs). Therefore, microbiome features are being studied as predictive/prognostic biomarkers of patient response to ICIs, and microbiome-based interventions are attractive adjuvant treatments in combination with ICIs. Specific gut-resident bacteria can influence the effectiveness of immunotherapy; however, the mechanism of action on how these bacteria affect anti-tumor immunity and response to ICIs is not fully understood. Nevertheless, early bacterial-based therapeutic strategies have demonstrated that targeting the gut microbiome through various methods can enhance the effectiveness of ICIs, resulting in improved clinical responses in patients with a diverse range of cancers. Therefore, understanding the microbiota-driven mechanisms of response to immunotherapy can augment the success of these interventions, particularly in patients with treatment-refractory cancers.

RevDate: 2024-03-28

Pötgens SA, Havelange V, Lecop S, et al (2024)

Gut microbiome alterations at acute myeloid leukemia diagnosis are associated with muscle weakness and anorexia.

Haematologica [Epub ahead of print].

The gut microbiota makes critical contributions to host homeostasis, and its role in the treatment of acute myeloid leukaemia (AML) has attracted attention. We investigated whether the gut microbiome is affected by AML, and whether such changes are associated with cachectic hallmarks. Biological samples and clinical data were collected from 30 antibiotic-free AML patients at diagnosis and matched volunteers (1:1) in a multicenter cross-sectional prospective study. The composition and functional potential of the faecal microbiota were analyzed using shotgun metagenomics. Faecal, blood, and urine metabolomics analyses were performed. AML patients displayed muscle weakness, anorexia, signs of altered gut function, and glycaemic disorders. The composition of the faecal microbiota differed between patients with AML and control subjects, with an increase in oral bacteria. Alterations in bacterial functions and faecal metabolome support an altered redox status in the gut microbiota, which may contribute to the altered redox status observed in patients with AML. Eubacterium eligens, reduced 3-fold in AML patients, was strongly correlated with muscle strength and citrulline, a marker of enterocyte mass and function. Blautia and Parabacteroides, increased in patients with AML, were correlated with anorexia. Several bacterial taxa and metabolites (e.g. Blautia, Prevotella, phenylacetate, and hippurate) previously associated with glycaemic disorders were altered. Our work revealed important perturbations in the gut microbiome of AML patients at diagnosis, which are associated with muscle strength, altered redox status, and anorexia. These findings pave the way for future mechanistic work to explore the function and therapeutic potential of the bacteria identified in this study.

RevDate: 2024-03-28

Pettit NN, Shaeer KM, EB Chahine (2024)

Live Biotherapeutic Products for the Prevention of Recurrent Clostridioides difficile Infection.

The Annals of pharmacotherapy [Epub ahead of print].

OBJECTIVE: To review the efficacy, safety, and role of live biotherapeutic products (LBPs) in the prevention of recurrent Clostridioides difficile infection (rCDI).

DATA SOURCES: A literature search was performed using PubMed and Google Scholar (through February 2024) with search terms RBX2660, SER-109, and fecal microbiota. Other resources included abstracts presented at recent conferences, national clinical practice guidelines, and manufacturers' websites.

All relevant studies, trial updates, conference abstracts, and guidelines in the English language were included.

DATA SYNTHESIS: Two LBPs were recently approved by the Food and Drug Administration for the prevention of recurrence in adults following antibiotic treatment for rCDI. Fecal microbiota, live-jslm is administered rectally as a retention enema, whereas fecal microbiota spores, live-brpk is given orally after bowel preparation. Several phase 2 and phase 3 clinical trials have established the safety and efficacy of these LBPs in reducing rates of rCDI compared with placebo. Patients with severe immunosuppression and those with inflammatory bowel disease were largely excluded from these trials.

Live biotherapeutic products offer a similar mechanism to conventional fecal microbiota transplant (FMT) in preventing rCDI through microbiota restoration. The primary advantages of LBPs over FMT are their standardized composition and donor stool screening processes for transmissible pathogens. Bezlotoxumab is also available for the prevention of Clostridioides difficile infection; however, there are no clinical data available to compare the efficacy of LBPs with bezlotoxumab, and the benefit of simultaneous use of these preventative therapies is unclear.

CONCLUSIONS: Live biotherapeutic products provide a safe and effective option for the prevention of rCDI and represent an improvement over conventional FMT. Additional studies are needed to further determine their place in therapy relative to bezlotoxumab and in the setting of immunosuppression and inflammatory bowel disease.

RevDate: 2024-03-29

Patel RK, Cardeiro M, Frankel L, et al (2024)

Incidence of Colorectal Cancer After Intestinal Infection Due to Clostridioides difficile.

World journal of oncology, 15(2):279-286.

BACKGROUND: Clostridioides difficile (C. difficile or C. diff) is a toxin-producing bacteria that is notorious for causing life-threatening diarrhea. Recent literature has investigated various effects of Clostridioides difficile infection (CDI) in cancer patients, but research into the impact of CDI on the development of cancer and its effects on the microbiome is limited. CDI predominately affects the colon, which urges consideration into the sequalae of infection. This study investigated the correlation between CDI and the incidence of colorectal carcinoma (CRC).

METHODS: A retrospective study (2010 - 2020) was conducted using a Health Insurance Portability and Accountability Act (HIPAA) compliant national database. The International Classification of Disease ninth and 10th Codes (ICD-9, ICD-10), Current Procedural Terminology (CPT), and National Drug Codes were used to identify CRC diagnosis, CDI, and matching or control parameters. Patients were matched for age, sex, Charlson Comorbidity Index (CCI), region of residence, and CDI treatment. An additional, but separate, query was executed to include obese patients with and without CDI, who were similarly matched and assessed for CRC. Statistical analyses were implemented to assess significance and estimate odds ratios (ORs).

RESULTS: CDI was associated with a decreased incidence of CRC (OR = 0.59, 95% confidence interval (CI): 0.55 - 0.63), and the difference was statistically significant (P < 2.2 × 10[-16]). CDI treatment, including appropriate antibiotics and fecal microbiota transplant (FMT), was controlled for in both infected and noninfected populations. Patients with a prior CDI who received relevant treatment were compared to patients with no history of CDI and received analogous treatment. Both populations subsequently developed CRC. Results remained statistically significant (P < 2.2 × 10[-16]) with a relative risk (RR) of 0.57 (95% CI: 0.54 - 0.60). Obesity was explored as a controlled variable in relation to CRC development in patients with and without prior CDI. Obese patients without a history of CDI were found to have a decreased risk of developing CRC. Results were statistically significant (P < 4.3 × 10[-13]) with an OR of 0.70 (95% CI: 0.63 - 0.77).

CONCLUSIONS: This study shows a statistically significant correlation between CDI and decreased incidence of CRC. Additionally, there is a statistically significant correlation between obese patients with CDI and an increased incidence of CRC. Further research is needed to explore the mechanism of this striking relationship and the implications of CDIs on the microbiome.

RevDate: 2024-03-29

Marshall DA, MacDonald KV, Kao D, et al (2024)

Patient preferences for active ulcerative colitis treatments and fecal microbiota transplantation.

Therapeutic advances in chronic disease, 15:20406223241239168.

BACKGROUND: Fecal microbiota transplantation (FMT) is a promising treatment for active ulcerative colitis (UC). Understanding patient preferences can identify treatment features that may impact treatment decisions, improve shared decision-making, and contribute to patient-centered care, which is especially important in the context of novel treatments like FMT.

OBJECTIVES: We aimed to quantify preferences for active UC treatments, specifically FMT and biologics, and identify patient characteristics associated with different preference patterns.

DESIGN: This is a cross-sectional survey study.

METHODS: We administered a discrete choice experiment (DCE) survey to elicit preferences in a sample of Canadian adults with UC. DCE data were analyzed using a main-effects mixed logit model and used to predict uptake of hypothetical scenarios reflecting alternative combinations of treatment features. Latent class modeling identified heterogeneity in patient preference patterns.

RESULTS: Participants' (n = 201) mean age was 47.1 years (SD: 14.5 years), 58% were female, and most (84%) had at least some post-secondary education. Almost half were willing to undergo FMT. When considering treatments for active UC, the most important attributes were chance of remission and severity of rare unknown side effects. All else equal, participants were most likely to uptake treatment that involves oral capsules/pills. Participants in the class with the highest utility for chance of remission were younger, had more severe disease, and 58% indicated that they would be willing to undergo FMT.

CONCLUSION: We identified characteristics of UC patients who are more likely to be interested in FMT using preference elicitation methods. Patient-centered care can be enhanced by knowing which patients are more likely to be interested in FMT, potentially improving satisfaction with and adherence to treatments for active UC to maximize the effectiveness of treatment while considering heterogeneity in patient preferences.

RevDate: 2024-03-28

Soukupova H, Rehorova V, Cibulkova I, et al (2024)

Assessment of Faecal Microbiota Transplant Stability in Deep-Freeze Conditions: A 12-Month Ex Vivo Viability Analysis.

Journal of clinical laboratory analysis [Epub ahead of print].

BACKGROUND: Faecal microbiota transplantation (FMT) is an established treatment for Clostridioides difficile infection and is under investigation for other conditions. The availability of suitable donors and the logistics of fresh stool preparation present challenges, making frozen, biobanked stools an attractive alternative.

AIMS: This study aimed to evaluate the long-term viability of bacterial populations in faecal samples stored at -80°C for up to 12 months, supporting the feasibility of using frozen grafts for FMT.

METHODS: Fifteen faecal samples from nine healthy donors were processed, mixed with cryoprotectants and stored at -80°C. Samples were assessed at baseline and after 3, 6 and 12 months using quantitative culturing methods to determine the concentration of live bacteria.

RESULTS: Quantitative analysis showed no significant decrease in bacterial viability over the 12-month period for both aerobic and anaerobic cultures (p = 0.09). At all timepoints, the coefficients of variability in colony-forming unit (CFU) counts were greater between samples (102 ± 21% and 100 ± 13% for aerobic and anaerobic cultures, respectively) than the variability between measurements of the same sample (30 ± 22% and 30 ± 19%).

CONCLUSIONS: The study confirmed that faecal microbiota can be preserved with high viability in deep-freeze storage for up to a year, making allogenic FMT from biobanked samples a viable and safer option for patients. However, a multidonor approach may be beneficial to mitigate the risk of viability loss in any single donor sample.

RevDate: 2024-03-28

Yadav D, Sainatham C, Filippov E, et al (2024)

Gut Microbiome-Colorectal Cancer Relationship.

Microorganisms, 12(3): pii:microorganisms12030484.

Traditionally, the role of gut dysbiosis was thought to be limited to pathologies like Clostridioides difficile infection, but studies have shown its role in other intestinal and extraintestinal pathologies. Similarly, recent studies have surfaced showing the strong potential role of the gut microbiome in colorectal cancer, which was traditionally attributed mainly to sporadic or germline mutations. Given that it is the third most common cancer and the second most common cause of cancer-related mortality, 78 grants totaling more than USD 28 million have been granted to improve colon cancer management since 2019. Concerted efforts by several of these studies have identified specific bacterial consortia inducing a proinflammatory environment and promoting genotoxin production, causing the induction or progression of colorectal cancer. In addition, changes in the gut microbiome have also been shown to alter the response to cancer chemotherapy and immunotherapy, thus changing cancer prognosis. Certain bacteria have been identified as biomarkers to predict the efficacy of antineoplastic medications. Given these discoveries, efforts have been made to alter the gut microbiome to promote a favorable diversity to improve cancer progression and the response to therapy. In this review, we expand on the gut microbiome, its association with colorectal cancer, and antineoplastic medications. We also discuss the evolving paradigm of fecal microbiota transplantation in the context of colorectal cancer management.

RevDate: 2024-03-28

Shi Y, Chen J, Qu D, et al (2024)

Ginsenoside Rg5 Activates the LKB1/AMPK/mTOR Signaling Pathway and Modifies the Gut Microbiota to Alleviate Nonalcoholic Fatty Liver Disease Induced by a High-Fat Diet.

Nutrients, 16(6): pii:nu16060842.

The primary objective of this investigation was to elucidate the manner in which ginsenoside Rg5 (Rg5) ameliorates nonalcoholic fatty liver disease (NAFLD) via the modulation of the gut microbiota milieu. We administered either a standard diet (ND) or a high-fat diet (HFD), coupled with 12-week treatment employing two distinct doses of Rg5 (50 and 100 mg/kg/d), to male C57BL/6J mice. In comparison to the HFD cohort, the Rg5-treated group demonstrated significant enhancements in biochemical parameters, exemplified by a substantial decrease in lipid concentrations, as well as the reduced expression of markers indicative of oxidative stress and liver injury. This signifies a mitigation of hepatic dysfunction induced by an HFD. Simultaneously, Rg5 demonstrates the capacity to activate the LKB1/AMPK/mTOR signaling pathway, instigating energy metabolism and consequently hindering the progression of NAFLD. Furthermore, we underscored the role of Rg5 in the treatment of NAFLD within the gut-microbiota-liver axis. Analysis via 16S rRNA sequencing unveiled that Rg5 intervention induced alterations in gut microbiota composition, fostering an increase in beneficial bacteria, such as Bacteroides and Akkermansia, while concurrently reducing the relative abundance of detrimental bacteria, exemplified by Olsenella. Furthermore, employing fecal microbiota transplantation (FMT) experiments, we observed analogous outcomes in mice subjected to fecal bacterial transplants, providing additional verification of the capacity of Rg5 to mitigate NAFLD in mice by actively participating in the restoration of gut microbiota via FMT. Drawing from these data, the regulation of the gut microbiota is recognized as an innovative strategy for treating or preventing NAFLD and metabolic syndrome. Consequently, these research findings suggest that Rg5 holds promise as a potential therapeutic agent for NAFLD management.

RevDate: 2024-03-28

Choi SY, JH Choi (2024)

Ovarian Cancer and the Microbiome: Connecting the Dots for Early Diagnosis and Therapeutic Innovations-A Review.

Medicina (Kaunas, Lithuania), 60(3): pii:medicina60030516.

Ovarian cancer, which ranks eighth among global female cancers and fifth in fatality, poses a significant health challenge owing to its asymptomatic early stages. Understanding the pathogenesis requires extensive research. Recent studies have emphasized the role of the gut and cervicovaginal microbiota in ovarian cancer. This review explores the current understanding of the relationship between the microbiome and ovarian cancer, considering the potential of biomarkers in the serum and various tissues. Insights into the influence of the microbiome on treatments, including surgery and chemotherapy, open doors to innovative approaches, such as fecal microbiome transplantation. This synthesis of recent findings provides crucial insights into the intricate interplay between the microbiome and ovarian cancer, thereby shaping diagnostic and treatment strategies.

RevDate: 2024-03-27

Jessop E, Li L, Renaud DL, et al (2024)

Neonatal Calf Diarrhea and Gastrointestinal Microbiota: Etiologic Agents and Microbiota Manipulation for Treatment and Prevention of Diarrhea.

Veterinary sciences, 11(3): pii:vetsci11030108.

Neonatal calf diarrhea is the leading cause of neonatal morbidity and mortality globally. The changes associated with the gastrointestinal microbiota in neonatal calves experiencing diarrhea and its etiology are not fully understood or completely defined in the literature. Several studies have demonstrated that the fecal microbiota of calves that experience diarrhea substantially deviates from that of healthy age-matched calves. However, one key question remains: whether the changes observed in the bacterial communities (also known as dysbiosis) are a predisposing factor for, or the consequence of, gastrointestinal inflammation caused by the pathogens associated with calf diarrhea. The first objective of this literature review is to present the current information regarding the changes in the fecal microbiota of diarrheic calves and the impact of the pathogens associated with diarrhea on fecal microbiota. Modulation of the gastrointestinal microbiota using pre- and probiotics, colostrum feeding, and fecal microbiota transplantation (FMT) has been used to treat and prevent gastrointestinal diseases in humans and dogs. Although information regarding the use of probiotics for the prevention of diarrhea is available in cattle, little information is available regarding the use of these strategies for treating calf diarrhea and the use of prebiotics or FMT to prevent diarrhea. The second objective of this literature review is to summarize the current knowledge regarding the impact of prebiotics, probiotics, synbiotics, colostrum feeding, and FMT for the treatment and prevention of calf diarrhea.

RevDate: 2024-03-27

Clarke LM, JR Allegretti (2024)

The epidemiology and management of Clostridioides difficile infection-A clinical update.

Alimentary pharmacology & therapeutics [Epub ahead of print].

BACKGROUND: Clostridioides difficile is the most common cause of healthcare-associated infection, and severe cases can result in significant complications. While anti-microbial therapy is central to infection management, adjunctive therapies may be utilised as preventative strategies.

AIM: This article aims to review updates in the epidemiology, diagnosis, and management, including treatment and prevention, of C. difficile infections.

METHODS: A narrative review was performed to evaluate the current literature between 1986 and 2023.

RESULTS: The incidence of C. difficile infection remains significantly high in both hospital and community settings, though with an overall decline in recent years and similar surveillance estimates globally. Vancomycin and fidaxomicin remain the first line antibiotics for treatment of non-severe C. difficile infection, though due to lower recurrence rates, infectious disease society guidelines now favour use of fidaxomicin. Faecal microbiota transplantation should still be considered to prevent recurrent C. difficile infection. However, in the past year the field has had a significant advancement with the approval of the first two live biotherapeutic products-faecal microbiota spores-live brpk, an oral capsule preparation, and faecal microbiota live-jslm-both indicated for the prevention of recurrent C. difficile infection, with additional therapies on the horizon.

CONCLUSION: Although the prevalence of C. difficile infection remains high, there have been significant advances in the development of novel therapeutics and preventative measures following changes in recent practice guidelines, and will continue to evolve in the future.

RevDate: 2024-03-27

Cui J, Wang S, Zhai Z, et al (2024)

Induction of autism-related behavior in male mice by early-life vitamin D deficiency: association with disruption of the gut microbial composition and homeostasis.

Food & function [Epub ahead of print].

Vitamin D deficiency (VDD) during early life emerges as a potential risk factor for autism spectrum disorder (ASD). Individuals with autism commonly exhibit lower vitamin D (VD) levels compared to the general population, and VD deficiency is prevalent during pregnancy and lactation. Moreover, gastrointestinal comorbidity, prevalent in ASD patients, correlates closely with disruptions in the gut microbiota and altered intestinal permeability. Therefore, it is fascinating and significant to explore the effects of maternal VD deficiency during pregnancy and lactation on the maturation of the gut microbiota of the offspring and its relevance to autism spectrum disorders. In this study, we established maternal pregnancy and lactation VD-deficient mouse models, employed shotgun macrogenomic sequencing to unveil alterations in the gut microbiome of offspring mice, and observed autism-related behaviours. Furthermore, fecal microbial transplantation (FMT) reversed repetitive and anxious behaviours and alleviated social deficits in offspring mice by modulating the gut microbiota and increasing short-chain fatty acid levels in the cecum, along with influencing the concentrations of claudin-1 and occludin in the colon. Our findings confirm that VDD during pregnancy and lactation is a risk factor for autism in the offspring, with disturbances in the structure and function of the offspring's gut microbiota contributing at least part of the effect. The study emphasises the importance of nutrition and gut health early in life. Simultaneously, this study further demonstrates the effect of VDD on ASD and provides potential ideas for early prevention and intervention of ASD.

RevDate: 2024-03-28
CmpDate: 2024-03-28

Sheikh IA, Bianchi-Smak J, Laubitz D, et al (2024)

Transplant of microbiota from Crohn's disease patients to germ-free mice results in colitis.

Gut microbes, 16(1):2333483.

Although the role of the intestinal microbiota in the pathogenesis of inflammatory bowel disease (IBD) is beyond debate, attempts to verify the causative role of IBD-associated dysbiosis have been limited to reports of promoting the disease in genetically susceptible mice or in chemically induced colitis. We aimed to further test the host response to fecal microbiome transplantation (FMT) from Crohn's disease patients on mucosal homeostasis in ex-germ-free (xGF) mice. We characterized and transferred fecal microbiota from healthy patients and patients with defined Crohn's ileocolitis (CD_L3) to germ-free mice and analyzed the resulting microbial and mucosal homeostasis by 16S profiling, shotgun metagenomics, histology, immunofluorescence (IF) and RNAseq analysis. We observed a markedly reduced engraftment of CD_L3 microbiome compared to healthy control microbiota. FMT from CD_L3 patients did not lead to ileitis but resulted in colitis with features consistent with CD: a discontinued pattern of colitis, more proximal colonic localization, enlarged isolated lymphoid follicles and/or tertiary lymphoid organ neogenesis, and a transcriptomic pattern consistent with epithelial reprograming and promotion of the Paneth cell-like signature in the proximal colon and immune dysregulation characteristic of CD. The observed inflammatory response was associated with persistently increased abundance of Ruminococcus gnavus, Erysipelatoclostridium ramosum, Faecalimonas umbilicate, Blautia hominis, Clostridium butyricum, and C. paraputrificum and unexpected growth of toxigenic C. difficile, which was below the detection level in the community used for inoculation. Our study provides the first evidence that the transfer of a dysbiotic community from CD patients can lead to spontaneous inflammatory changes in the colon of xGF mice and identifies a signature microbial community capable of promoting colonization of pathogenic and conditionally pathogenic bacteria.

RevDate: 2024-03-27

Chang M, Chang KT, F Chang (2024)

Just a gut feeling: Faecal microbiota transplant for treatment of depression - A mini-review.

Journal of psychopharmacology (Oxford, England) [Epub ahead of print].

BACKGROUND: The microbiota-gut-brain axis (MGBA) allows bidirectional crosstalk between the brain and gut microbiota (GM) and is believed to contribute to regulating mood/cognition/behaviour/metabolism/health and homeostasis. Manipulation of GM through faecal microbiota transplant (FMT) is a new, exciting and promising treatment for major depressive disorder (MDD).

AIMS: This mini-review examines current research into GM and FMT as a therapy for depression.

METHODS: Original research articles published in Medline/Cochrane Library/PubMed/EMBASE/PsycINFO databases/National Institute of Health website were searched. Full articles included in reference lists were evaluated. We summarise current data on GM and depression and discuss communication through the MGBA and the interaction of antidepressants and GM through this. We review compositions of dysbiosis in depressed cohorts, focusing on future directions in the treatment of MDD.

RESULTS: Studies have demonstrated significant gut dysbiosis in depressed patients compared to healthy cohorts, with overgrowth of pro-inflammatory microbiota, reduction in anti-inflammatory species and reduced overall stability and taxonomic richness. FMT allows the introduction of healthy microbiota into the gastrointestinal tract, facilitating the restoration of eubiosis.

CONCLUSION: The GM plays an integral role in human health and disease through its communication with the rest of the body via the MGBA. FMT may provide a means to transfer the healthy phenotype into the recipient and this concept in humans is attracting enormous attention as a prospective treatment for psychopathologies, such as MDD, in the future. It may be possible to manipulate the GM in a number of ways, but further research is needed to determine the exact likelihood and profiles involved in the development and amelioration of MDD in humans, as well as the long-term effects and potential risks of this procedure.

RevDate: 2024-03-28
CmpDate: 2024-03-28

Luu LDW, Pandey A, Paramsothy S, et al (2024)

Profiling the colonic mucosal response to fecal microbiota transplantation identifies a role for GBP5 in colitis in humans and mice.

Nature communications, 15(1):2645.

Host molecular responses to fecal microbiota transplantation (FMT) in ulcerative colitis are not well understood. Here, we profile the human colonic mucosal transcriptome prior to and following FMT or placebo to identify molecules regulated during disease remission. FMT alters the transcriptome above the effect of placebo (n = 75 vs 3 genes, q < 0.05), including modulation of structural, metabolic and inflammatory pathways. This response is attributed to responders with no consistency observed in non-responders. Regulated pathways in responders include tight junctions, calcium signalling and xenobiotic metabolism. Genes significantly regulated longitudinally in responders post-FMT could discriminate them from responders and non-responders at baseline and non-responders post-FMT, with GBP5 and IRF4 downregulation being associated with remission. Female mice with a deletion of GBP5 are more resistant to developing colitis than their wild-type littermates, showing higher colonic IRF4 phosphorylation. The colonic mucosal response discriminates UC remission following FMT, with GBP5 playing a detrimental role in colitis.

RevDate: 2024-03-26

Yu H, Yang WM, Chen YH, et al (2024)

The gut microbiome from middle-aged women with depression modulates depressive-like behaviors and plasma fatty acid metabolism in female middle-aged mice.

Journal of psychiatric research, 173:139-150 pii:S0022-3956(24)00165-1 [Epub ahead of print].

BACKGROUND: Intestinal dysbacteriosis has frequently been involved in the context of depression. Nonetheless, only scant information is available about the features and functional changes of gut microbiota in female middle-aged depression (MAD).

OBJECTIVE: This study aims to explore whether there are characteristic changes in the gut microbes of female MAD and whether these changes are associated with depressive-like behaviors. Meanwhile, this study observed alterations in the lipid metabolism function of gut microbes and further examined changes in plasma medium- and long-chain fatty acids (MLCFAs) in mice that underwent fecal microbiota transplantation (FMT).

METHODS: Stool samples obtained from 31 MAD, along with 24 healthy individuals (HC) were analyzed by 16 S rRNA gene sequencing. Meanwhile, 14-month-old female C57BL/6J mice received antibiotic cocktails and then oral gavage of the microbiota suspension of MAD or HC for 3 weeks to reconstruct gut microbiota. The subsequent depressive-like behaviors, the composition of gut microbiota, as well as MLCFAs in the plasma were evaluated.

RESULTS: A noteworthy disruption in gut microbial composition in MAD individuals compared to HC was observed. Several distinct bacterial taxa, including Dorea, Butyricicoccus, and Blautia, demonstrated associations with the demographic variables. A particular microbial panel encompassing 49 genera effectively differentiated MAD patients from HC (AUC = 0.82). Fecal microbiome transplantation from MAD subjects led to depressive-like behaviors and dysfunction of plasma MLCFAs in mice.

CONCLUSIONS: These findings suggest that microbial dysbiosis is linked to the pathogenesis of MAD, and its role may be associated with the regulation of MLCFAs metabolism.

RevDate: 2024-03-26

Gurung M, Schlegel BT, Rajasundaram D, et al (2024)

Microbiota from human infants consuming secretors or non-secretors mothers' milk impacts the gut and immune system in mice.

mSystems [Epub ahead of print].

UNLABELLED: Maternal secretor status is one of the determinants of human milk oligosaccharides (HMOs) composition, which, in turn, influences the gut microbiota composition of infants. To understand if this change in gut microbiota impacts immune cell composition, intestinal morphology, and gene expression, 21-day-old germ-free C57BL/6 mice were transplanted with fecal microbiota from infants whose mothers were either secretors (SMM) or non-secretors (NSM) or from infants consuming dairy-based formula (MFM). For each group, one set of mice was supplemented with HMOs. HMO supplementation did not significantly impact the microbiota diversity; however, SMM mice had a higher abundance of genus Bacteroides, Bifidobacterium, and Blautia, whereas, in the NSM group, there was a higher abundance of Akkermansia, Enterocloster, and Klebsiella. In MFM, gut microbiota was represented mainly by Parabacteroides, Ruminococcaceae_unclassified, and Clostrodium_sensu_stricto. In mesenteric lymph node, Foxp3+ T cells and innate lymphoid cells type 2 were increased in MFM mice supplemented with HMOs, while in the spleen, they were increased in SMM + HMOs mice. Similarly, serum immunoglobulin A was also elevated in MFM + HMOs group. Distinct global gene expression of the gut was observed in each microbiota group, which was enhanced with HMOs supplementation. Overall, our data show that distinct infant gut microbiota due to maternal secretor status or consumption of dairy-based formula and HMO supplementation impacts immune cell composition, antibody response, and intestinal gene expression in a mouse model.

IMPORTANCE: Early life factors like neonatal diet modulate gut microbiota, which is important for the optimal gut and immune function. One such factor, human milk oligosaccharides (HMOs), the composition of which is determined by maternal secretor status, has a profound effect on infant gut microbiota. However, how the infant gut microbiota composition determined by maternal secretor status or consumption of infant formula devoid of HMOs impacts infant intestinal ammorphology, gene expression, and immune signature is not well explored. This study provides insights into the differential establishment of infant microbiota derived from infants fed by secretor or non-secretor mothers milk or those consuming infant formula and demonstrates that the secretor status of mothers promotes Bifidobacteria and Bacteroides sps. establishment. This study also shows that supplementation of pooled HMOs in mice changed immune cell composition in the spleen and mesenteric lymph nodes and immunoglobulins in circulation. Hence, this study highlights that maternal secretor status has a role in infant gut microbiota composition, and this, in turn, can impact host gut and immune system.

RevDate: 2024-03-27
CmpDate: 2024-03-27

Yang Y, Ma Q, Wang Q, et al (2024)

Mannose enhances intestinal immune barrier function and dextran sulfate sodium salt-induced colitis in mice by regulating intestinal microbiota.

Frontiers in immunology, 15:1365457.

BACKGROUND: Inflammatory bowel disease (IBD) greatly affects human quality of life. Mannose has been reported to be used to treat IBD, but the mechanism is currently unknown.

METHODS: C57/BL mice were used as research subjects, and the mouse acute colitis model was induced using dextran sulfate sodium salt (DSS). After oral administration of mannose, the body weights and disease activity index (DAI) scores of the mice were observed. The colon lengths, histopathological sections, fecal content microbial sequencing, colon epithelial inflammatory genes, and tight junction protein Occludin-1 expression levels were measured. We further used the feces of mice that had been orally administered mannose to perform fecal bacterial transplantation on the mice with DSS-induced colitis and detected the colitis-related indicators.

RESULTS: Oral administration of mannose increased body weights and colon lengths and reduced DAI scores in mice with DSS-induced colitis. In addition, it reduced the expression of colon inflammatory genes and the levels of serum inflammatory factors (TNF-α, IL-6, and IL-1β), further enhancing the expression level of the colonic Occludin-1 protein and alleviating the toxic response of DSS to the intestinal epithelium of the mice. In addition, gut microbial sequencing revealed that mannose increased the abundance and diversity of intestinal flora. Additionally, after using the feces of the mannose-treated mice to perform fecal bacterial transplantation on the mice with DSS-induced colitis, they showed the same phenotype as the mannose-treated mice, and both of them alleviated the intestinal toxic reaction induced by the DSS. It also reduced the expression of intestinal inflammatory genes (TNF-α, IL-6, and IL-1β) and enhanced the expression level of the colonic Occludin-1 protein.

CONCLUSION: Mannose can treat DSS-induced colitis in mice, possibly by regulating intestinal microorganisms to enhance the intestinal immune barrier function and reduce the intestinal inflammatory response.

RevDate: 2024-03-27
CmpDate: 2024-03-27

Yu F, Hu X, Ren H, et al (2024)

Protective effect of synbiotic combination of Lactobacillus plantarum SC-5 and olive oil extract tyrosol in a murine model of ulcerative colitis.

Journal of translational medicine, 22(1):308.

BACKGROUND: Ulcerative colitisis (UC) classified as a form of inflammatory bowel diseases (IBD) characterized by chronic, nonspecific, and recurrent symptoms with a poor prognosis. Common clinical manifestations of UC include diarrhea, fecal bleeding, and abdominal pain. Even though anti-inflammatory drugs can help alleviate symptoms of IBD, their long-term use is limited due to potential side effects. Therefore, alternative approaches for the treatment and prevention of inflammation in UC are crucial.

METHODS: This study investigated the synergistic mechanism of Lactobacillus plantarum SC-5 (SC-5) and tyrosol (TY) combination (TS) in murine colitis, specifically exploring their regulatory activity on the dextran sulfate sodium (DSS)-induced inflammatory pathways (NF-κB and MAPK) and key molecular targets (tight junction protein). The effectiveness of 1 week of treatment with SC-5, TY, or TS was evaluated in a DSS-induced colitis mice model by assessing colitis morbidity and colonic mucosal injury (n = 9). To validate these findings, fecal microbiota transplantation (FMT) was performed by inoculating DSS-treated mice with the microbiota of TS-administered mice (n = 9).

RESULTS: The results demonstrated that all three treatments effectively reduced colitis morbidity and protected against DSS-induced UC. The combination treatment, TS, exhibited inhibitory effects on the DSS-induced activation of mitogen-activated protein kinase (MAPK) and negatively regulated NF-κB. Furthermore, TS maintained the integrity of the tight junction (TJ) structure by regulating the expression of zona-occludin-1 (ZO-1), Occludin, and Claudin-3 (p < 0.05). Analysis of the intestinal microbiota revealed significant differences, including a decrease in Proteus and an increase in Lactobacillus, Bifidobacterium, and Akkermansia, which supported the protective effect of TS (p < 0.05). An increase in the number of Aspergillus bacteria can cause inflammation in the intestines and lead to the formation of ulcers. Bifidobacterium and Lactobacillus can regulate the micro-ecological balance of the intestinal tract, replenish normal physiological bacteria and inhibit harmful intestinal bacteria, which can alleviate the symptoms of UC. The relative abundance of Akkermansia has been shown to be negatively associated with IBD. The FMT group exhibited alleviated colitis, excellent anti-inflammatory effects, improved colonic barrier integrity, and enrichment of bacteria such as Akkermansia (p < 0.05). These results further supported the gut microbiota-dependent mechanism of TS in ameliorating colonic inflammation.

CONCLUSION: In conclusion, the TS demonstrated a remission of colitis and amelioration of colonic inflammation in a gut microbiota-dependent manner. The findings suggest that TS could be a potential natural medicine for the protection of UC health. The above results suggest that TS can be used as a potential therapeutic agent for the clinical regulation of UC.

RevDate: 2024-03-25

Costa DVS, Pham NV, Loureiro AV, et al (2024)

Clostridioides difficile infection promotes gastrointestinal dysfunction in human and mice post-acute phase of the disease.

Anaerobe pii:S1075-9964(24)00020-9 [Epub ahead of print].

OBJECTIVES: In the US, Clostridioides difficile (C. difficile) infection (CDI) is the 8th leading cause for hospital readmission and 7th for mortality among all gastrointestinal (GI) disorders. Here, we investigated GI dysfunction post-CDI in human and mice post-acute infection.

MATERIALS AND METHODS: From March 2020 to July 2021, we reviewed the clinical records of 67 patients referred to the UVA Complicated C. difficile clinic for fecal microbiota transplantation (FMT) eligibility. In vivo, C57BL/6 mice were infected with C. difficile and clinical scores were determined daily. Stool samples from mice were collected to measure the shedding of C. difficile and myeloperoxidase (MPO) levels. On day 21 post-infection, Evans's blue and FITC-70kDa method were performed to evaluate GI motility in mice.

RESULTS: Of the 67 patients evaluated at the C. difficile clinic, 40 patients (59.7%) were confirmed to have CDI, and 22 patients (32.8%) with post-CDI IBS (diarrhea-type, constipation-type, and mixed-type). In infected mice, levels of MPO in stools and clinical score were higher on day 3. On day 21, mice have recovered from body weight loss induced by CDI, and fecal MPO was undetectable. The total GI transit time (TGITT) and FITC-70kDa levels on proximal colon were increased in infected mice (p = 0.002), suggesting a constipation phenotype post-acute phase of CDI. A positive correlation on intestinal inflammation on day 3 and TGITT on day 21 was observed.

CONCLUSION: In conclusion, post-infection intestinal dysfunction occurs in humans and mice post-CDI. Importantly, we have validated in the mouse model that CDI causes abnormal GI transit in the recovery phase of the disease, indicating the potential utility of the model in exploring the underlying mechanisms of post-infectious IBS in humans.

RevDate: 2024-03-25

Maccauro V, Fianchi F, Gasbarrini A, et al (2024)


Digestive diseases (Basel, Switzerland) pii:000538493 [Epub ahead of print].

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease of unknown etiology characterized by biliary inflammation and periductal fibrosis. The gut microbiota plays a crucial role in the pathogenesis of PSC by regulating bile acids metabolism, inflammation and immune response. On the other hand, liver disease progression affects the composition of the gut microbiota, fostering these mechanisms in a mutual detrimental way.

SUMMARY: Recent evidences described a specific pro-inflammatory microbial signature in PSC patients, with an overall reduced bacterial diversity and the loss of beneficial metabolites such as short-chain fatty acids. As effective therapies for PSC are still lacking, targeting the gut microbiota offers a new perspective in the management of this disease. To date, antibiotics, fecal microbiota transplantation and probiotics are the most studied gut microbiota-targeted intervention in PSC, but new potential strategies such as vaccines and bacteriophages represent possible future therapeutic horizons.

KEY MESSAGES: In this review, we focus on the role of the gut microbiota in PSC, considering its pathogenetic and prognostic role, and the therapeutic implications.

RevDate: 2024-03-27
CmpDate: 2024-03-27

Fletcher KA, DB Johnson (2024)

Investigational Approaches for Treatment of Melanoma Patients Progressing After Standard of Care.

Cancer journal (Sudbury, Mass.), 30(2):126-131.

The advent of effective immunotherapy, specifically cytotoxic T-lymphocyte associated protein 4 and programmed cell death 1 inhibitors, as well as targeted therapy including BRAF/MEK inhibitors, has dramatically changed the prognosis for metastatic melanoma patients. Up to 50% of patients may experience long-term survival currently. Despite these advances in melanoma treatment, many patients still progress and die of their disease. As such, there are many studies aimed at providing new treatment options for this population. Therapies currently under investigation include, but are not limited to, novel immunotherapies, targeted therapies, tumor-infiltrating lymphocytes and other cellular therapies, oncolytic viral therapy and other injectables, and fecal microbiota transplant. In this review, we discuss the emerging treatment options for metastatic melanoma patients who have progressed on standard of care treatments.

RevDate: 2024-03-26

D'Amico F, Rinaldi M, Pascale R, et al (2024)

Gut microbiome dynamics and Enterobacterales infection in liver transplant recipients: A prospective observational study.

JHEP reports : innovation in hepatology, 6(4):101039.

BACKGROUND & AIMS: The aim of this study was to investigate gut microbiome (GM) dynamics in relation to carbapenem-resistant Enterobacterales (CRE) colonization, CRE infection, and non-CRE infection development within 2 months after liver transplant (LT).

METHODS: A single-center, prospective study was performed in patients undergoing LT from November 2018 to January 2020. The GM was profiled through 16S rRNA amplicon sequencing of a rectal swab taken on the day of transplantation, and fecal samples were collected weekly until 1 month after LT. A subset of samples was subjected to shotgun metagenomics, including resistome dynamics. The primary endpoint was to explore changes in the GM in the following groups: (1) CRE carriers developing CRE infection (CRE_I); (2) CRE carriers not developing infection (CRE_UI); (3) non-CRE carriers developing microbial infection (INF); and (4) non-CRE carriers not developing infection (NEG).

RESULTS: Overall, 97 patients were enrolled, and 91 provided fecal samples. Of these, five, nine, 22, and 55 patients were classified as CRE_I, CRE_UI, INF, and NEG, respectively. CRE_I patients showed an immediate and sustained post-LT decrease in alpha diversity, with depletion of the GM structure and gradual over-representation of Klebsiella and Enterococcus. The proportions of Klebsiella were significantly higher in CRE_I patients than in NEG patients even before LT, serving as an early marker of subsequent CRE infection. CRE_UI patients had a more stable and diverse GM, whose compositional dynamics tended to overlap with those of NEG patients.

CONCLUSIONS: GM profiling before LT could improve patient stratification and risk prediction and guide early GM-based intervention strategies to reduce infectious complications and improve overall prognosis.

IMPACT AND IMPLICATIONS: Little is known about the temporal dynamics of gut microbiome (GM) in liver transplant recipients associated with carbapenem-resistant Enterobacterales (CRE) colonization and infection. The GM structure and functionality of patients colonized with CRE and developing infection appeared to be distinct compared with CRE carriers without infection or patients with other microbial infection or no infection and CRE colonization. Higher proportions of antimicrobial-resistant pathogens and poor representation of bacteria and metabolic pathways capable of promoting overall host health were observed in CRE carriers who developed infection, even before liver transplant. Therefore, pretransplant GM profiling could improve patient stratification and risk prediction and guide early GM-based intervention strategies to reduce infectious complications and improve overall prognosis.

RevDate: 2024-03-23

Wan L, Qian C, Yang C, et al (2024)

Ginseng polysaccharides ameliorate ulcerative colitis via regulating gut microbiota and tryptophan metabolism.

International journal of biological macromolecules pii:S0141-8130(24)01626-X [Epub ahead of print].

Ulcerative colitis (UC) is regarded as a recurring inflammatory disorder of the gastrointestinal tract, for which treatment approaches remain notably limited. In this study, we demonstrated that ginseng polysaccharides (GPs) could alleviate the development of dextran sulfate sodium (DSS)-induced UC as reflected by the ameliorated pathological lesions in the colon. GPs strikingly suppressed the expression levels of multiple inflammatory cytokines, as well as significantly inhibited the infiltration of inflammatory cells. Microbiota-dependent investigations by virtue of 16S rRNA gene sequencing, antibiotic treatment and fecal microbiota transplantation illustrated that GPs treatment prominently restored intestinal microbial balance predominantly through modulating the relative abundance of Lactobacillus. Additionally, GPs remarkably influenced the levels of microbial tryptophan metabolites, diminished the intestinal permeability and strengthened intestinal barrier integrity via inhibiting the 5-HT/HTR3A signaling pathway. Taken together, the promising therapeutic potential of GPs on the development of UC predominantly hinges on the capacity to suppress the expression of inflammatory cytokines as well as to influence Lactobacillus and microbial tryptophan metabolites.

RevDate: 2024-03-23

Moreau GB, Naz F, WA Petri (Jr) (2024)

Fecal microbiota transplantation stimulates type 2 and tolerogenic immune responses in a mouse model.

Anaerobe pii:S1075-9964(24)00024-6 [Epub ahead of print].

OBJECTIVES: Clostridioides difficile infection (CDI) is the leading hospital-acquired infection in North America. While previous work on fecal microbiota transplantation (FMT), a highly effective treatment for CDI, has focused on colonization resistance mounted against C. difficile by FMT-delivered commensals, the effects of FMT on host gene expression are relatively unexplored. This study aims to identify transcriptional changes associated with FMT, particularly changes associated with protective immune responses.

METHODS: Gene expression was assessed on day 2 and day 7 after FMT in mice after antibiotic-induced dysbiosis. Flow cytometry was also performed on colon and mesenteric lymph nodes at day 7 to investigate changes in immune cell populations.

RESULTS: FMT administration after antibiotic-induced dysbiosis successfully restored microbial alpha diversity to levels of donor mice by day 7 post-FMT. Bulk RNA sequencing of cecal tissue at day 2 identified immune genes, including both pro-inflammatory and Type 2 immune pathways as upregulated after FMT. RNA sequencing was repeated on day 7 post-FMT, and expression of these immune genes was decreased along with upregulation of genes associated with restoration of intestinal homeostasis. Immunoprofiling on day 7 identified increased colonic CD45[+] immune cells that exhibited dampened Type 1 and heightened regulatory and Type 2 responses. These include an increased abundance of eosinophils, alternatively activated macrophages, Th2, and T regulatory cell populations.

CONCLUSION: These results highlight the impact of FMT on host gene expression, providing evidence that FMT restores intestinal homeostasis after antibiotic treatment and facilitates tolerogenic and Type 2 immune responses.

RevDate: 2024-03-23

Stone CB, Rudinsky AJ, Urion RJ, et al (2024)

Gastrointestinal release site for delayed release and gelatin capsules in healthy dogs.

Journal of veterinary pharmacology and therapeutics [Epub ahead of print].

Gelatin capsules deliver their contents to the stomach, while delayed-release (DR) capsules are designed to allow delivery to the small intestine. This study evaluated the gastrointestinal release site of DR capsules in six healthy adult dogs compared to gelatin capsules. Both gelatin and DR capsules were filled with barium-impregnated polyethylene spheres (BIPS™), and following enteral administration, release site was assessed using abdominal radiographs at baseline, immediately after ingestion, 15 min post-ingestion, 30 min post-ingestion, and then every 30 min thereafter. The evaluated phases included fasted conditions (phase 1, n = 6), increased meal size (phase 2, n = 2), double encapsulation (phase 3, n = 2), and altered capsule size (phase 4, n = 1). The released site was the stomach in all phases for both capsule types. In phase 1, DR capsules had a significantly prolonged time (median 60 min, range 60-90) to release BIPS™ compared to gelatin capsules (15 min, range 15-30; p = .03). In phase 2 (full meal size), 3 (double encapsulation), and 4 (smaller capsule size) pilot studies, release time was prolonged but still occurred in the stomach. This is similar to the release site for gelatin capsules but differs from the release site for DR capsules in people. This has implications for pharmacologic outcomes for products that are affected by gastric physiology (e.g. fecal microbiota transplantation). Based on this pilot data, clinicians and researchers should not assume DR capsules will allow for intestinal delivery of contents in dogs. Future studies should be conducted on larger and varied populations of dogs.

RevDate: 2024-03-22

Zhang HJ, Fu J, Yu H, et al (2024)

Berberine promotes the degradation of phenylacetic acid to prevent thrombosis by modulating gut microbiota.

Phytomedicine : international journal of phytotherapy and phytopharmacology, 128:155517 pii:S0944-7113(24)00181-8 [Epub ahead of print].

BACKGROUND: Berberine is the main bioactive constituent of Coptis chinensis, a quaternary ammonium alkaloid. While berberine's cardiovascular benefits are well-documented, its impact on thrombosis remains not fully understood.

PURPOSE: This study investigates the potential of intestinal microbiota as a novel target for preventing thrombosis, with a focus on berberine, a natural compound known for its effectiveness in managing cardiovascular conditions.

METHODS: Intraperitoneal injection of carrageenan induces the secretion of chemical mediators such as histamine and serotonin from mast cells to promote thrombosis. This model can directly and visually observe the progression of thrombosis in a time-dependent manner. Thrombosis was induced by intravenous injection of 1 % carrageenan solution (20 mg/kg) to all mice except the vehicle control group. Quantitative analysis of gut microbiota metabolites through LC/MS. Then, the gut microbiota of mice was analyzed using 16S rRNA sequencing to assess the changes. Finally, the effects of gut microbiota on thrombosis were explored by fecal microbiota transplantation.

RESULTS: Our research shows that berberine inhibits thrombosis by altering intestinal microbiota composition and related metabolites. Notably, berberine curtails the biosynthesis of phenylacetylglycine, a thrombosis-promoting coproduct of the host-intestinal microbiota, by promoting phenylacetic acid degradation. This research underscores the significance of phenylacetylglycine as a thrombosis-promoting risk factor, as evidenced by the ability of intraperitoneal phenylacetylglycine injection to reverse berberine's efficacy. Fecal microbiota transplantation experiment confirms the crucial role of intestinal microbiota in thrombus formation.

CONCLUSION: Initiating our investigation from the perspective of the gut microbiota, we have, for the first time, unveiled that berberine inhibits thrombus formation by promoting the degradation of phenylacetic acid, consequently suppressing the biosynthesis of PAG. This discovery further substantiates the intricate interplay between the gut microbiota and thrombosis. Our study advances the understanding that intestinal microbiota plays a crucial role in thrombosis development and highlights berberine-mediated intestinal microbiota modulation as a promising therapeutic approach for thrombosis prevention.

RevDate: 2024-03-22

Belotserkovsky I, Stabryla LM, Hunter M, et al (2024)

Standards for fecal microbiota transplant: Tools and therapeutic advances.

Biologicals : journal of the International Association of Biological Standardization, 86:101758 pii:S1045-1056(24)00015-0 [Epub ahead of print].

Fecal microbiota transplantation (FMT) has been demonstrated to be efficacious in preventing recurrent Clostridioides difficile (C. difficile) infections, and is being investigated for treatment of several other diseases including inflammatory bowel disease, cancer, obesity, liver disease, and diabetes. To speed up the translation of FMT into clinical practice as a safe and standardized therapeutic intervention, additional evidence-based technical and regulatory guidance is needed. To this end in May of 2022, the International Alliance for Biological Standardization (IABS) and the BIOASTER Microbiology Technology Institute hosted a second webinar to discuss key issues still impeding the advancement and standardization of FMT. The goal of this two-day webinar was to provide a forum for scientific experts to share and discuss data and key challenges with one another. Discussion included a focus on the evaluation of safety, efficacy, clinical trial design, reproducibility and accuracy in obtained microbiome measurements and data reporting, and the potential for standardization across these areas. It also focused on increasing the application potential and visibility of FMT beyond treating C. difficile infections.

RevDate: 2024-03-22

Dong S, Zeng Q, He W, et al (2024)

Effect of Lactobacillus plantarum BFS1243 on a female frailty model induced by fecal microbiota transplantation in germ-free mice.

Food & function [Epub ahead of print].

Frailty, a complex geriatric syndrome, significantly impedes the goal of achieving 'healthy aging'. Increasing evidence suggests a connection between gut microbiota, systemic inflammation, and disease. However, it remains to be determined whether interventions targeting the intestinal flora can effectively ameliorate frailty. Our research involved fecal microbiota transplantation (FMT) experiments on germ-free (GF) mice, dividing these mice into three groups: a group receiving transplants from healthy elderly individuals (HF group), a group of frailty patients (FF group), and the FF group supplemented with Lactobacillus plantarum BFS1243 (FFL group). Our findings indicated a significant shift in the gut microbiota of the FF group, in contrast to the HF group, characterized by decreased Akkermansia and increased Enterocloster, Parabacteroides, and Eisenbergiella. Concurrently, there was a reduction in amino acids and SCFAs, with BFS1243 partially mitigating these changes. The FF group exhibited an upregulation of inflammatory markers, including PGE2, CRP, and TNF-α, and a downregulation of irisin, all of which were moderated by BFS1243 treatment. Furthermore, BFS1243 improved intestinal barrier integrity and physical endurance in the FF mice. Correlation analysis revealed a negative association between SCFA-producing species and metabolites like lysine and butyric acid with pro-inflammatory factors. In conclusion, our study conclusively demonstrated that alterations in the gut microbiota of elderly individuals can lead to physical frailty, likely due to detrimental effects on the intestinal barrier and a pro-inflammatory state. These findings underscore the potential of gut microbiome modulation as a clinical strategy for treating frailty.

RevDate: 2024-03-23

Vidal-Gallardo A, Méndez Benítez JE, Flores Rios L, et al (2024)

The Role of Gut Microbiome in the Pathogenesis and the Treatment of Inflammatory Bowel Diseases.

Cureus, 16(2):e54569.

Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, is a chronic condition characterized by inflammation of the gastrointestinal tract. Its exact cause is unknown, but it's thought to result from a dysregulated immune response influenced by various factors, including changes in the intestinal microbiota, diet, lifestyle, and genetics. The gut microbiome, consisting of diverse microorganisms, plays a crucial role in maintaining physiological balance, with its disruption leading to inflammatory responses typical of IBD. Treatments primarily aim at symptom control, employing immunomodulators, corticosteroids, and newer approaches like probiotics, prebiotics, fecal transplants, and dietary modifications, all focusing on leveraging the microbiota's potential in disease management. These strategies aim to restore the delicate balance of the gut microbiome, typically altered in IBD, marked by a decrease in beneficial bacteria and an increase in harmful pathogens. This review underscores the importance of the gut microbiome in the pathogenesis and treatment of IBD, highlighting the shift towards personalized medicine and the necessity for further research in understanding the complex interactions between the gut microbiota, immune system, and genetics in IBD. It points to the potential of emerging treatments and the importance of a multifaceted approach in managing this complex and challenging disease.

RevDate: 2024-03-23

Caputi V, Hill L, Figueiredo M, et al (2024)

Functional contribution of the intestinal microbiome in autism spectrum disorder, attention deficit hyperactivity disorder, and Rett syndrome: a systematic review of pediatric and adult studies.

Frontiers in neuroscience, 18:1341656.

INTRODUCTION: Critical phases of neurodevelopment and gut microbiota diversification occur in early life and both processes are impacted by genetic and environmental factors. Recent studies have shown the presence of gut microbiota alterations in neurodevelopmental disorders. Here we performed a systematic review of alterations of the intestinal microbiota composition and function in pediatric and adult patients affected by autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and Rett syndrome (RETT).

METHODS: We searched selected keywords in the online databases of PubMed, Cochrane, and OVID (January 1980 to December 2021) with secondary review of references of eligible articles. Two reviewers independently performed critical appraisals on the included articles using the Critical Appraisal Skills Program for each study design.

RESULTS: Our systematic review identified 18, 7, and 3 original articles describing intestinal microbiota profiles in ASD, ADHD, and RETT, respectively. Decreased Firmicutes and increased Bacteroidetes were observed in the gut microbiota of individuals affected by ASD and ADHD. Proinflammatory cytokines, short-chain fatty acids and neurotransmitter levels were altered in ASD and RETT. Constipation and visceral pain were related to changes in the gut microbiota in patients affected by ASD and RETT. Hyperactivity and impulsivity were negatively correlated with Faecalibacterium (phylum Firmicutes) and positively correlated with Bacteroides sp. (phylum Bacteroidetes) in ADHD subjects. Five studies explored microbiota-or diet-targeted interventions in ASD and ADHD. Probiotic treatments with Lactobacillus sp. and fecal microbiota transplantation from healthy donors reduced constipation and ameliorated ASD symptoms in affected children. Perinatal administration of Lactobacillus sp. prevented the onset of Asperger and ADHD symptoms in adolescence. Micronutrient supplementation improved disease symptomatology in ADHD without causing significant changes in microbiota communities' composition.

DISCUSSION: Several discrepancies were found among the included studies, primarily due to sample size, variations in dietary practices, and a high prevalence of functional gastrointestinal symptoms. Further studies employing longitudinal study designs, larger sample sizes and multi-omics technologies are warranted to identify the functional contribution of the intestinal microbiota in developmental trajectories of the human brain and neurobehavior., CRD42020158734.

RevDate: 2024-03-23

Qiu XX, Cheng SL, Liu YH, et al (2024)

Fecal microbiota transplantation for treatment of non-alcoholic fatty liver disease: Mechanism, clinical evidence, and prospect.

World journal of gastroenterology, 30(8):833-842.

The population of non-alcoholic fatty liver disease (NAFLD) patients along with relevant advanced liver disease is projected to continue growing, because currently no medications are approved for treatment. Fecal microbiota transplantation (FMT) is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease. There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment, however, existing findings diverge on its effects. Herein, we briefly summarized the mechanism of FMT for NAFLD treatment, reviewed randomized controlled trials for evaluating its efficacy in NAFLD, and proposed the prospect of future trials on FMT.

RevDate: 2024-03-21

Xu J, Lu L, Jiang S, et al (2024)

Paeoniflorin ameliorates oxaliplatin-induced peripheral neuropathy via inhibiting neuroinflammation through influence on gut microbiota.

European journal of pharmacology pii:S0014-2999(24)00204-8 [Epub ahead of print].

Oxaliplatin (OXA)-induced peripheral neuropathy (OIPN) is a severe side effect that greatly limits OXA clinical use and threatens patients' life and health. Paeoniflorin exhibits extensive anti-inflammatory and neuroprotective effects, but whether it can protect against OIPN and the underlying mechanisms remain unclear. This study aimed to investigate the effects of paeoniflorin on OIPN and probe into the underlying mechanisms. The OIPN model was established through oxaliplatin injection in rats. The ameliorative effects of paeoniflorin on OIPN was assessed by nociceptive hypersensitivities through pain behavioral methods. Neuroinflammation were examined by measuring the levels of inflammatory cytokines and immune cells infiltration. The signaling pathway of TLR4/MyD88/NF-κB was evaluated by Western blotting. Gut microbial changes were detected by 16S rDNA sequencing technology. In addition, antibiotics-induced microbiota eradication and fecal microbial transplantation (FMT) were applied for exploring the function of gut microbiota in the protective effects of paeoniflorin. The results revealed that paeoniflorin significantly alleviated mechanical and cold hypersensitivity, mitigated neuroinflammation and influenced gut microbial composition in OIPN rats. Fecal microbiota transplantation further verified that gut microbiota was required for paeoniflorin ameliorating OIPN and that the underlying mechanism involved downregulation of TLR4/MyD88/NF-κB signaling. Specifically, Akkermansia, Dubosiella and Corynebacterium might serve as crucial genera regulated by paeoniflorin in the treatment of OIPN. In summary, our investigations delineate paeoniflorin's ameliorative effects on OIPN by alleviating neuroinflammation through regulations of gut microbiota. This suggests that paeoniflorin may serve as a new potential strategy for treatment of OIPN in clinical practice.

RevDate: 2024-03-21

Liu D, Hu L, Yang Y, et al (2024)

Saccharomyces boulardii alleviates allergic asthma by restoring gut microbiota and metabolic homeostasis via up-regulation of METTL3 in an m6A-dependent manner.

Immunology letters pii:S0165-2478(24)00027-0 [Epub ahead of print].

BACKGROUND: Allergic asthma is a heterogeneous disease and new strategies are needed to prevent or treat this disease. Studies have shown that probiotic interventions are effective in preventing asthma. Here, we investigated the impact of Saccharomyces boulardii (S. boulardii) on ovalbumin (OVA)-induced allergic asthma in mice, as well as the underlying mechanisms.

METHODS: First, we constructed a mouse asthma model using OVA and given S. boulardii intervention. Next, we measured N6-methyladenosine (m6A) levels in lung injury tissues. 16s rRNA was employed to identify different gut microbiota in fecal samples. The analysis of differential metabolites in feces was performed by non-targeted metabolomics. Pearson correlation coefficient was utilized to analyze correlation between gut microbiota, metabolites and methyltransferase-like 3 (METTL3). Finally, we collected mouse feces treated by OVA and S. boulardii intervention for fecal microbiota transplantation (FMT) and interfered with METTL3.

RESULTS: S. boulardii improved inflammation and oxidative stress and alleviated lung damage in asthmatic mice. In addition, S. boulardii regulated m6A modification levels in asthmatic mice. 16s rRNA sequencing showed that S. boulardii remodeled gut microbiota homeostasis in asthmatic mice. Non-targeted metabolomics analysis showed S. boulardii restored metabolic homeostasis in asthmatic mice. There was a correlation between gut microbiota, differential metabolites, and METTL3 analyzed by Pearson correlation. Additionally, through FMT and interference of METTL3, we found that gut microbiota mediated the up-regulation of METTL3 by S. boulardii improved inflammation and oxidative stress in asthmatic mice, and alleviated lung injury.

CONCLUSIONS: S. boulardii alleviated allergic asthma by restoring gut microbiota and metabolic homeostasis via up-regulation of METTL3 in an m6A-dependent manner.

RevDate: 2024-03-21

Zhu X, Huang X, Hu M, et al (2024)

A specific enterotype derived from gut microbiome of older individuals enables favorable responses to immune checkpoint blockade therapy.

Cell host & microbe pii:S1931-3128(24)00075-1 [Epub ahead of print].

Immunotherapy has revolutionized cancer treatment, but inconsistent responses persist. Our study delves into the intriguing phenomenon of enhanced immunotherapy sensitivity in older individuals with cancers. Through a meta-analysis encompassing 25 small-to-mid-sized trials of immune checkpoint blockade (ICB), we demonstrate that older individuals exhibit heightened responsiveness to ICB therapy. To understand the underlying mechanism, we reanalyze single-cell RNA sequencing (scRNA-seq) data from multiple studies and unveil distinct upregulation of exhausted and cytotoxic T cell markers within the tumor microenvironment (TME) of older patients. Recognizing the potential role of gut microbiota in modulating the efficacy of immunotherapy, we identify an aging-enriched enterotype linked to improved immunotherapy outcomes in older patients. Fecal microbiota transplantation experiments in mice confirm the therapeutic potential of the aging-enriched enterotype, enhancing treatment sensitivity and reshaping the TME. Our discoveries confront the prevailing paradox and provide encouraging paths for tailoring cancer immunotherapy strategies according to an individual's gut microbiome profile.

RevDate: 2024-03-21

Benedé-Ubieto R, Cubero FJ, YA Nevzorova (2024)

Breaking the barriers: the role of gut homeostasis in Metabolic-Associated Steatotic Liver Disease (MASLD).

Gut microbes, 16(1):2331460.

Obesity, insulin resistance (IR), and the gut microbiome intricately interplay in Metabolic-associated Steatotic Liver Disease (MASLD), previously known as Non-Alcoholic Fatty Liver Disease (NAFLD), a growing health concern. The complex progression of MASLD extends beyond the liver, driven by "gut-liver axis," where diet, genetics, and gut-liver interactions influence disease development. The pathophysiology of MASLD involves excessive liver fat accumulation, hepatocyte dysfunction, inflammation, and fibrosis, with subsequent risk of hepatocellular carcinoma (HCC). The gut, a tripartite barrier, with mechanical, immune, and microbial components, engages in a constant communication with the liver. Recent evidence links dysbiosis and disrupted barriers to systemic inflammation and disease progression. Toll-like receptors (TLRs) mediate immunological crosstalk between the gut and liver, recognizing microbial structures and triggering immune responses. The "multiple hit model" of MASLD development involves factors like fat accumulation, insulin resistance, gut dysbiosis, and genetics/environmental elements disrupting the gut-liver axis, leading to impaired intestinal barrier function and increased gut permeability. Clinical management strategies encompass dietary interventions, physical exercise, pharmacotherapy targeting bile acid (BA) metabolism, and microbiome modulation approaches through prebiotics, probiotics, symbiotics, and fecal microbiota transplantation (FMT). This review underscores the complex interactions between diet, metabolism, microbiome, and their impact on MASLD pathophysiology and therapeutic prospects.

RevDate: 2024-03-22
CmpDate: 2024-03-22

Faraci M, Bonaretti C, Dell'Orso G, et al (2024)

Association between oral and fecal microbiome dysbiosis and treatment complications in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.

Scientific reports, 14(1):6708.

The oral and gastrointestinal mucosae represent the main targets of the toxic effect of chemo and/or radiotherapy administered during the conditioning regimen before hematopoietic stem cell transplant (HSCT). These harmful consequences and the immunological complications that may occur after the transplant (such as Graft versus Host Disease, GvHD) are responsible for the clinical symptoms associated with mucositis during the aplasia phase, like pain, nausea, vomiting, and diarrhea. These toxicities could play a critical role in the oral and gastrointestinal microbiomes during the post-transplant phase, and the degree of microbial dysbiosis and dysregulation among different bacterial species could also be crucial in intestinal mucosa homeostasis, altering the host's innate and adaptive immune responses and favoring abnormal immune responses responsible for the occurrence of GvHD. This prospective pediatric study aims to analyze longitudinally oral and gut microbiomes in 17 pediatric patients who received allogeneic HSCT for malignant and non-malignant diseases. The oral mucositis was mainly associated with an increased relative abundance of Fusobacteria, and Prevotella species, while Streptococcus descendants showed a negative correlation. The fecal microbiome of subjects affected by cutaneous acute GvHD (aGvHD) correlated with Proteobacteria. Oral mucosal microbiota undergoes changes after HSCT, Fusobacteria, and Prevotella represent bacterial species associated with mucositis and they could be the target for future therapeutic approaches, while fecal microbiome in patients with acute GvHD (aGvHD) revealed an increase of different class of Proteobacteria (Alphaproteobacteria and Deltaproteobacteria) and a negative correlation with the class of Gammaproteobacteria.

RevDate: 2024-03-22
CmpDate: 2024-03-22

Fu Y, Chen YS, Xia DY, et al (2024)

Lactobacillus rhamnosus GG ameliorates hyperuricemia in a novel model.

NPJ biofilms and microbiomes, 10(1):25.

Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.

RevDate: 2024-03-20

Tao S, Fan J, Li J, et al (2024)

Extracellular vesicles derived from Lactobacillus johnsonii promote gut barrier homeostasis by enhancing M2 macrophage polarization.

Journal of advanced research pii:S2090-1232(24)00111-5 [Epub ahead of print].

INTRODUCTION: Diarrheic disease is a common intestinal health problem worldwide, causing great suffering to humans and animals. Precise manipulation strategies based on probiotics to combat diarrheic diseases have not been fully developed.

OBJECTIVES: The aim of this study was to investigate the molecular mechanisms by which probiotics manipulate macrophage against diarrheic disease.

METHODS: Metagenome reveals gut microbiome profiles of healthy and diarrheic piglets. Fecal microbial transplantation (FMT) was employed to explore the causal relationship between gut microbes and diarrhea. The protective role of probiotics and their derived extracellular vesicles (EVs) was investigated in ETEC K88-infected mice. Macrophage depletion was performed to assess the role of macrophages in EVs against diarrhea. Execution of in vitro cell co-culture and transcriptome analyses elucidated the molecular mechanisms by which EVs modulate the macrophage and intestinal epithelial barrier.

RESULTS: Escherichia coli was enriched in weaned diarrheic piglets, while Lactobacillus johnsonii (L. john) showed a negative correlation with Escherichia coli. The transmission of diarrheic illness symptoms was achieved by transferring fecal microbiota, but not metabolites, from diarrheic pigs to germ-free (GF) mice. L. john's intervention prevented the transmission of disease phenotypes from diarrheic piglets to GF mice. L. john also reduces the gut inflammation induced by ETEC K88. The EVs secreted by L. john demonstrated enhanced efficacy in mitigating the adverse impacts induced by ETEC K88 through the modulation of macrophage phenotype. In vitro experiments have revealed that EVs activate M2 macrophages in a manner that shuts down ERK, thereby inhibiting NLRP3 activation in intestinal epithelial cells.

CONCLUSION: Our results reveal that intestinal microbiota drives the onset of diarrheic disease and that probiotic-derived EVs ameliorate diarrheic disease symptoms by modulating macrophage phenotypes. These findings can enhance the advancement of innovative therapeutic approaches for diarrheic conditions based on probiotic-derived EVs.

RevDate: 2024-03-20

Cymbal M, Chatterjee A, Baggott B, et al (2024)

Management of Clostridioides difficile infection: Diagnosis, Treatment, and Future Perspectives.

The American journal of medicine pii:S0002-9343(24)00167-0 [Epub ahead of print].

Clostridioides difficile infection is the most common healthcare-associated infection in the United States, with potential life-threatening complications and significant impact in the costs of care. Antibiotic stewardship as well as discontinuation of chronic acid suppressive therapy are key for its prevention and treatment. Effective infection management requires appropriate interpretation of diagnostic tests, as well as the use of vancomycin and fidaxomicin as first-line treatment. Novel treatments as Bezlotoxumab, fecal microbiota transplant and live biotherapeutic products are proven effective in recurrent C. difficile infection and addresses dysbiosis.

RevDate: 2024-03-21
CmpDate: 2024-03-21

Rojo Gutiérrez MI, Ballesteros González D, AK Ortiz Durán (2023)

[Non-IgE-mediated food allergy].

Revista alergia Mexico (Tecamachalco, Puebla, Mexico : 1993), 70(4):269-279.

Food allergy is an immune response to proteins in food. It usually affects 8% of children and 2% of adults in Western countries. Non-IgE-mediated food allergy mainly affects the gastrointestinal tract. Gastrointestinal food allergies are classified, by their underlying pathogenesis, as: IgE-mediated, non-IgE-mediated, or mixed. The symptoms of patients with food protein-induced allergic proctocolitis originate from local inflammation of the distal colon, which causes hematochezia in neonates. It can affect the entire gastrointestinal tract and cause symptoms of intractable emesis, with subsequent metabolic disorders and hypovolemic shock. Food protein-induced enterocolitis syndrome is a non-IgE-mediated allergy that usually appears in childhood, with prolonged repetitive vomiting, starting 1 to 4 hours after ingestion of food. The manifestation in adults is usually triggered by the consumption of shellfish. Atopic diseases affect 40-60% of patients with food protein- induced enterocolitis syndrome, including 40-50% of those with food protein-induced enteropathy and proctocolitis. Probiotics (Lactobacillus GG) can alleviate the symptoms of allergic proctocolitis induced by food proteins, by altering the composition of the intestinal microbiota. Fecal microbiota transplantation (FMT) can change intestinal microecology efficiently compared to food or probiotics.

RevDate: 2024-03-20

Böttger TW, Turina M, Ensle F, et al (2024)

Episodic Abdominal Pain-An Unexpected Cause for a Common Clinical Problem.

Journal of general internal medicine [Epub ahead of print].

A previously healthy 55-year-old male patient presented repeatedly to the emergency department with severe episodic periumbilical abdominal pain. After an extensive diagnostic work-up and subsequent clinical deterioration, appendiceal diverticulitis was diagnosed. We identified a correlation of white blood cell counts and possibly faecal calprotectin with the clinical presentation. We suggest that appendiceal diverticulitis should be considered in middle-aged patients with recurrent episodes of abdominal pain that correlate with laboratory markers of inflammation.

RevDate: 2024-03-19

Xu B, Fu Y, Yin N, et al (2024)

Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii served as key components of fecal microbiota transplantation to alleviate colitis.

American journal of physiology. Gastrointestinal and liver physiology [Epub ahead of print].

Fecal microbiota transplantation (FMT) is a promising therapy for inflammatory bowel disease (IBD) via rectifying gut microbiota. The aim of this study was to identify a mechanism of how specific bacteria-associated immune response contributes to alleviated colitis. 40 donors were divided into high (donor-H) and low (donor-L) groups according to diversity and the abundance of Bacteroides and Faecalibacterium by 16S rRNA sequencing. FMT was performed on dextran sulfate sodium (DSS)-induced colitis in mice. Mice with colitis showed significant improvement in intestinal injury and immune imbalance after FMT with group donor-H (p <0.05). Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii were identified as targeted strains in donor feces by real-time PCR and droplet digital PCR. Mice with colitis were treated with mono- or dual-bacterial gavage therapy. Dual-bacterial therapy significantly ameliorated intestinal injury compared with mono-bacterial therapy (p <0.05). Dual-bacterial therapy increased the M2/M1 macrophage polarization and improved the Th17/Treg imbalance and elevated IL-10 production by Tregs compared with the DSS group (p <0.05). Metabolomics showed increased abundance of lecithin in the glycerophospholipid metabolism pathway. In conclusion, B. thetaiotaomicron and F. prausnitzii, as the key bacteria in donor feces, alleviate colitis in mice. The mechanism may involve increasing lecithin and regulating IL-10 production of intestinal Tregs.

RevDate: 2024-03-21
CmpDate: 2024-03-20

Tan Z, Wang Z, Zeng Q, et al (2024)

Natural intestinal metabolite xylitol reduces BRD4 levels to mitigate renal fibrosis.

Clinical and translational science, 17(3):e13770.

Renal fibrosis is a typical pathological change from chronic kidney disease (CKD) to end-stage renal failure, which presents significant challenges in prevention and treatment. The progression of renal fibrosis is closely associated with the "gut-kidney axis," therefore, although clinical intervention to modulate the "gut-kidney axis" imbalance associated with renal fibrosis brings hope for its treatment. In this study, we first identified the close relationship between renal fibrosis development and the intestinal microenvironment through fecal microtransplantation and non-absorbable antibiotics experiments. Then, we analyzed the specific connection between the intestinal microenvironment and renal fibrosis using microbiomics and metabolomics, screening for the differential intestinal metabolite. Potential metabolite action targets were initially identified through network simulation of molecular docking and further verified by molecular biology experiment. We used flow cytometry, TUNEL apoptosis staining, immunohistochemistry, and Western blotting to assess renal injury and fibrosis extent, exploring the potential role of gut microbial metabolite in renal fibrosis development. We discovered that CKD-triggered alterations in the intestinal microenvironment exacerbate renal injury and fibrosis. When metabolomic analysis was combined with experiments in vivo, we found that the differential metabolite xylitol delays renal injury and fibrosis development. We further validated this hypothesis at the cellular level. Mechanically, bromodomain-containing protein 4 (BRD4) protein exhibits strong binding with xylitol, and xylitol alleviates renal fibrosis by inhibiting BRD4 and its downstream transforming growth factor-β (TGF-β) pathway. In summary, our findings suggest that the natural intestinal metabolite xylitol mitigates renal fibrosis by inhibiting the BRD4-regulated TGF-β pathway.

RevDate: 2024-03-20

Allegretti JR, Axelrad J, Dalal RS, et al (2024)

Outcomes after Fecal Microbiota Transplantation in combination with Bezlotoxumab for Inflammatory Bowel Disease and Recurrent C . difficile Infection.

The American journal of gastroenterology pii:00000434-990000000-01081 [Epub ahead of print].

Fecal microbiota transplantation (FMT) prevents recurrent C. difficile infections (rCDI) in IBD. Patients. Bezlotoxumab is also indicated to prevent rCDI. We assess the impact of FMT in combination with bezlotoxumab in patients with IBD and rCDI. We conducted a multicenter randomized placebo-controlled trial. All received a single colonoscopic FMT. Patients were randomized 1:1 to receive bezlotoxumab or placebo. Sixty-one patients were enrolled (30 received treatment and 31 placebo. Overall, 5 participants (8%) experienced a CDI recurrence; 4 in the treatment arm, 1 in placebo (13% vs 3%, p=0.15). There was no clear benefit to the combination approach compared to FMT alone.


ESP Quick Facts

ESP Origins

In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

ESP Support

In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.

ESP Rationale

Although the methods of molecular biology can seem almost magical to the uninitiated, the original techniques of classical genetics are readily appreciated by one and all: cross individuals that differ in some inherited trait, collect all of the progeny, score their attributes, and propose mechanisms to explain the patterns of inheritance observed.

ESP Goal

In reading the early works of classical genetics, one is drawn, almost inexorably, into ever more complex models, until molecular explanations begin to seem both necessary and natural. At that point, the tools for understanding genome research are at hand. Assisting readers reach this point was the original goal of The Electronic Scholarly Publishing Project.

ESP Usage

Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.

ESP Content

When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.

ESP Help

Early support from the DOE component of the Human Genome Project was critically important for getting the ESP project on a firm foundation. Since that funding ended (nearly 20 years ago), the project has been operated as a purely volunteer effort. Anyone wishing to assist in these efforts should send an email to Robbins.

ESP Plans

With the development of methods for adding typeset side notes to PDF files, the ESP project now plans to add annotated versions of some classical papers to its holdings. We also plan to add new reference and pedagogical material. We have already started providing regularly updated, comprehensive bibliographies to the ESP.ORG site.

Electronic Scholarly Publishing
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Bellingham, WA 98226

E-mail: RJR8222 @

Papers in Classical Genetics

The ESP began as an effort to share a handful of key papers from the early days of classical genetics. Now the collection has grown to include hundreds of papers, in full-text format.

Digital Books

Along with papers on classical genetics, ESP offers a collection of full-text digital books, including many works by Darwin and even a collection of poetry — Chicago Poems by Carl Sandburg.


ESP now offers a large collection of user-selected side-by-side timelines (e.g., all science vs. all other categories, or arts and culture vs. world history), designed to provide a comparative context for appreciating world events.


Biographical information about many key scientists (e.g., Walter Sutton).

Selected Bibliographies

Bibliographies on several topics of potential interest to the ESP community are automatically maintained and generated on the ESP site.

ESP Picks from Around the Web (updated 07 JUL 2018 )