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Bibliography on: Fecal Transplantation

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ESP: PubMed Auto Bibliography 08 Mar 2021 at 01:33 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®)

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RevDate: 2021-03-06

Verdier C, Denis S, Gasc C, et al (2021)

An Oral FMT Capsule as Efficient as an Enema for Microbiota Reconstruction Following Disruption by Antibiotics, as Assessed in an In Vitro Human Gut Model.

Microorganisms, 9(2): pii:microorganisms9020358.

Fecal microbiota transplantation (FMT) is an innovative therapy already used in humans to treat Clostridioides difficile infections associated with massive use of antibiotics. Clinical studies are obviously the gold standard to evaluate FMT efficiency but remain limited by regulatory, ethics, and cost constraints. In the present study, an in vitro model of the human colon reproducing medically relevant perturbation of the colonic ecosystem by antibiotherapy was used to compare the efficiency of traditional FMT enema formulations and a new oral capsule in restoring gut microbiota composition and activity. Loss of microbial diversity, shift in bacterial populations, and sharp decrease in fermentation activities induced in vivo by antibiotherapy were efficiently reproduced in the in vitro model, while capturing inter-individual variability of gut microbiome. Oral capsule was as efficient as enema to decrease the number of disturbed days and bacterial load had no effect on enema performance. This study shows the relevance of human colon models as an alternative approach to in vivo assays during preclinical studies for evaluating FMT efficiency. The potential of this in vitro approach could be extended to FMT testing in the management of many digestive or extra-intestinal pathologies where gut microbial dysbiosis has been evidenced such as inflammatory bowel diseases, obesity or cancers.

RevDate: 2021-03-06

Shabbir U, Arshad MS, Sameen A, et al (2021)

Crosstalk between Gut and Brain in Alzheimer's Disease: The Role of Gut Microbiota Modulation Strategies.

Nutrients, 13(2): pii:nu13020690.

The gut microbiota (GM) represents a diverse and dynamic population of microorganisms and about 100 trillion symbiotic microbial cells that dwell in the gastrointestinal tract. Studies suggest that the GM can influence the health of the host, and several factors can modify the GM composition, such as diet, drug intake, lifestyle, and geographical locations. Gut dysbiosis can affect brain immune homeostasis through the microbiota-gut-brain axis and can play a key role in the pathogenesis of neurodegenerative diseases, including dementia and Alzheimer's disease (AD). The relationship between gut dysbiosis and AD is still elusive, but emerging evidence suggests that it can enhance the secretion of lipopolysaccharides and amyloids that may disturb intestinal permeability and the blood-brain barrier. In addition, it can promote the hallmarks of AD, such as oxidative stress, neuroinflammation, amyloid-beta formation, insulin resistance, and ultimately the causation of neural death. Poor dietary habits and aging, along with inflammatory responses due to dysbiosis, may contribute to the pathogenesis of AD. Thus, GM modulation through diet, probiotics, or fecal microbiota transplantation could represent potential therapeutics in AD. In this review, we discuss the role of GM dysbiosis in AD and potential therapeutic strategies to modulate GM in AD.

RevDate: 2021-03-06

Giampaolino P, Foreste V, Di Filippo C, et al (2021)

Microbiome and PCOS: State-of-Art and Future Aspects.

International journal of molecular sciences, 22(4): pii:ijms22042048.

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease. The hypothesis that alterations in the microbiome are involved in the genesis of PCOS has been postulated. Aim of this review is to summarize the available literature data about the relationship between microbiome and PCOS. A search on PubMed and Medline databases was performed from inception to November 20Most of evidence has focused on the connection of intestinal bacteria with sex hormones and insulin-resistance: while in the first case, a relationship with hyperandrogenism has been described, although it is still unclear, in the second one, chronic low-grade inflammation by activating the immune system, with increased production of proinflammatory cytokines which interfere with insulin receptor function, causing IR (Insulin Resistance)/hyperinsulinemia has been described, as well as the role of gastrointestinal hormones like Ghrelin and peptide YY (PYY), bile acids, interleukin-22 and Bacteroides vulgatus have been highlighted. The lower genital tract microbiome would be affected by changes in PCOS patients too. The therapeutic opportunities include probiotic, prebiotics and synbiotics, as well as fecal microbiota transplantation and the use of IL-22, to date only in animal models, as a possible future drug. Current evidence has shown the involvement of the gut microbiome in PCOS, seen how humanized mice receiving a fecal transplant from women with PCOS develop ovarian dysfunction, immune changes and insulin resistance and how it is capable of disrupting the secondary bile acid biosynthesis. A future therapeutic approach for PCOS may involve the human administration of IL-22 and bile acid glycodeoxycholic acid.

RevDate: 2021-03-06

Ciernikova S, Mego M, M Chovanec (2021)

Exploring the Potential Role of the Gut Microbiome in Chemotherapy-Induced Neurocognitive Disorders and Cardiovascular Toxicity.

Cancers, 13(4): pii:cancers13040782.

Chemotherapy, targeting not only malignant but also healthy cells, causes many undesirable side effects in cancer patients. Due to this fact, long-term cancer survivors often suffer from late effects, including cognitive impairment and cardiovascular toxicity. Chemotherapy damages the intestinal mucosa and heavily disrupts the gut ecosystem, leading to gastrointestinal toxicity. Animal models and clinical studies have revealed the associations between intestinal dysbiosis and depression, anxiety, pain, impaired cognitive functions, and cardiovascular diseases. Recently, a possible link between chemotherapy-induced gut microbiota disruption and late effects in cancer survivors has been proposed. In this review, we summarize the current understanding of preclinical and clinical findings regarding the emerging role of the microbiome and the microbiota-gut-brain axis in chemotherapy-related late effects affecting the central nervous system (CNS) and heart functions. Importantly, we provide an overview of clinical trials evaluating the relationship between the gut microbiome and cancer survivorship. Moreover, the beneficial effects of probiotics in experimental models and non-cancer patients with neurocognitive disorders and cardiovascular diseases as well as several studies on microbiota modulations via probiotics or fecal microbiota transplantation in cancer patients are discussed.

RevDate: 2021-03-05

Ranallo RT, Clifford McDonald L, Laufer Halpin A, et al (2021)

The State of Microbiome Science at the Intersection of Infectious Diseases and Antimicrobial Resistance.

The Journal of infectious diseases pii:6154668 [Epub ahead of print].

Along with the rise in modern chronic diseases, ranging from diabetes to asthma, lay the challenges posed by increasing antibiotic resistance resulting in difficult to treat infections, as well as sepsis. An emerging and unifying theme in the pathogenesis of these diverse public health threats is changes in the microbial communities that inhabit multiple body sites. Although there is great promise in exploring the role of these microbial communities in chronic disease pathogenesis, the shorter timeframe of most infectious disease pathogenesis may allow early translation of our basic scientific understanding of microbial ecology and host-microbiota-pathogen interactions. Likely translation avenues include development of preventive strategies, diagnostics, and therapeutics. For example, as basic research related to microbial pathogenesis continues to progress, Clostridioides difficile infection (CDI) is already being addressed clinically through at least two of these three avenues: targeted antibiotic stewardship and treatment of recurrent disease through fecal microbiota transplantation (FMT).

RevDate: 2021-03-05

El-Salhy M, Patcharatrakul T, S Gonlachanvit (2021)

The role of diet in the pathophysiology and management of irritable bowel syndrome.

Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology [Epub ahead of print].

Irritable bowel syndrome (IBS) is a chronic gastrointestinal (GI) disorder that reportedly affects 5% to 20% of the world population. The etiology of IBS is not completely understood, but diet appears to play an important role in its pathophysiology. Asian diets differ considerably from those in Western countries, which might explain differences in the prevalence, sex, and clinical presentation seen between patients with IBS in Asian and Western countries. Dietary regimes such as a low-fermentable oligo-, di-, monosaccharides, and polyols (FODMAP) diet and the modified National Institute for Health and Care Excellence (NICE) diet improve both symptoms and the quality of life in a considerable proportion of IBS patients. It has been speculated that diet is a prebiotic for the intestinal microbiota and favors the growth of certain bacteria. These bacteria ferment the dietary components, and the products of fermentation act upon intestinal stem cells to influence their differentiation into enteroendocrine cells. The resulting low density of enteroendocrine cells accompanied by low levels of certain hormones gives rise to intestinal dysmotility, visceral hypersensitivity, and abnormal secretion. This hypothesis is supported by the finding that changing to a low-FODMAP diet restores the density of GI cells to the levels in healthy subjects. These changes in gut endocrine cells caused by low-FODMAP diet are also accompanied by improvements in symptoms and the quality of life.

RevDate: 2021-03-05

Kopper JJ, Alexander TL, Kogan CJ, et al (2021)

In Vitro Evaluation of the Effect of Storage at -20°C and Proximal Gastrointestinal Conditions on Viability of Equine Fecal Microbiota Transplant.

Journal of equine veterinary science, 98:103360.

Fecal microbiota transplant (FMT), a technique used to restore normal intestinal microbial communities, has been successful in treating humans with Clostridioides difficile colitis. Subsequently, FMT is being used in veterinary patients with suspected intestinal dysbiosis. Unfortunately, little data are available regarding best practices for FMT in horses. The objective of this study was to evaluate the effects of storing manure prepared for equine FMT (MP-FMT) at -20°C for up to 4 weeks and passage through a simulated proximal gastrointestinal (GI) tract on the viability of MP-FMT. The results of this study indicate that storage at -20°C for greater than 1 week and exposure to conditions consistent with the proximal GI tract significantly decreased viability of the microbial population, with gram-negative enteric bacteria most significantly impacted. This preliminary evaluation indicates that further work is necessary to determine best practices to preserve the viability MP-FMT in horses.

RevDate: 2021-03-01

Fecal Microbiota Transplantation-standardization Study Group (2020)

Nanjing consensus on methodology of washed microbiota transplantation.

Chinese medical journal, 133(19):2330-2332.

RevDate: 2021-03-04

Xu JY, Liu MT, Tao T, et al (2021)

The role of gut microbiota in tumorigenesis and treatment.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 138:111444 pii:S0753-3322(21)00229-8 [Epub ahead of print].

A large number of microbial communities exist in normal human intestinal tracts, which maintain a relatively stable dynamic balance under certain conditions. Gut microbiota are closely connected with human health and the occurrence of tumors. The colonization of certain intestinal bacteria on specific sites, gut microbiota disturbance and intestinal immune disorders can induce the occurrence of tumors. Meanwhile, gut microbiota can also play a role in tumor therapy by participating in immune regulation, influencing the efficacy of anti-tumor drugs, targeted therapy of engineered probiotics and fecal microbiota transplantation. This article reviews the role of gut microbiota in the occurrence, development, diagnosis and treatment of tumors. A better understanding of how gut microbiota affect tumors will help us find more therapies to treat the disease.

RevDate: 2021-03-04

Mikolašević I, Hauser G, Abram M, et al (2021)

Fecal microbiota transplantation - where are we?.

Croatian medical journal, 62(1):52-58.

RevDate: 2021-03-04

Khurana S, Kahl A, Yu K, et al (2020)

Recent advances in the treatment of Clostridioides difficile infection: the ever-changing guidelines.

Faculty reviews, 9:13.

Clostridioides difficile infection (CDI), formerly known as Clostridium difficile, continues to be the most common healthcare-associated infection worldwide. With the shifting epidemiology towards higher a incidence of community-acquired CDI and the continued burden on the healthcare system posed by high rates of CDI recurrence, there has been an impetus to advance the diagnostic testing and treatment strategies. Recent advancements over the past decade have led to rapidly changing guidelines issued by the Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases. With our comprehensive review, we aim to summarize the latest advances in diagnosing and treating CDI and thus attempt to help readers guide best practices for patient care. This article also focusses on cost-effectiveness of various therapies currently available on the market and provides an analysis of the current evidence on a relatively new monoclonal antibody therapy, Bezlotoxumab, to treat recurrent CDI.

RevDate: 2021-03-04

Тикунов АЮ, Морозов ВВ, Швалов АН, et al (2020)

[Fecal microbiome change in patients with ulcerative colitis after fecal microbiota transplantation].

Vavilovskii zhurnal genetiki i selektsii, 24(2):168-175.

Intestinal human microbiota is a dynamic system that is under the pressures of its host organism and external factors. Microbiota disruption caused by these factors can lead to severe diseases including inflammatory and oncological diseases of the gastrointestinal tract. One of the possible approaches in managing the intestinal microbiota is fecal microbiota transplantation (FT) - transfer of the microbiota from the stool of a healthy donor to the intestinal tract of a recipient patient. Currently, this procedure is recognized as an efficacious method to normalize the intestinal microbiota mainly in inflammatory diseases of the gastrointestinal tract. In Russia, pilot studies of the effectiveness of FT in patients with ulcerative colitis have been conducted for several years, and these studies were started in Novosibirsk. The aim of this study was to assess the change of intestinal microbiome in 20 patients with ulcerative colitis after a single FT procedure. The main method is a comparative analysis of 16S ribosomal RNA sequence libraries constructed using fecal samples obtained from patients with ulcerative colitis before and after FT and sequenced on the Illumina MiSeq platform. The obtained results showed that FT led to an increase in average biodiversity in samples after FT compared to samples before FT; however, the difference was not significant. In the samples studied, the proportion of Firmicutes sequences, the major gastrointestinal microbiota of healthy people, was decreased (~32 % vs. >70 %), while the proportion of Proteobacteria sequences was increased (>9 % vs. <5 %). In some samples collected before FT, sequences of pathogenic Firmicutes and Proteobacteria were detected, including Acinetobacter spp., Enterococcus spp., Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus aureus, Stenotrophomonas maltophylia, Streptococcus spp. In most cases, the proportion of such sequences after FT substantially decreased in appropriate samples. The exception was the Clostridium difficile sequences, which accounted for <0.5 % of the sequences in samples from almost half of the patients and after FT, the share of such C. difficile sequences was significantly reduced only in samples from three patients. It should be noted that the proportion of Lactobacillus spp. increased ten-fold and their species composition significantly expanded. According to the obtained results, a preliminary conclusion can be made that even a single FT procedure can lead to an increase in the biodiversity of the gastrointestinal microbiota in patients and to the optimization of the taxonomic composition of the microbiota.

RevDate: 2021-03-04

Huang J, Shan W, Li F, et al (2021)

Fecal microbiota transplantation mitigates vaginal atrophy in ovariectomized mice.

Aging, 13: pii:202627 [Epub ahead of print].

Vulvovaginal atrophy (VVA) is a common menopause-related symptom affecting more than 50% of midlife and older women and cancer patients whose ovarian function are lost or damaged. Regardless of estrogen deficiency, whether other factors such as the gut microbiota play role in VVA have not been thoroughly investigated. To this end, we performed ovariectomy on 12-weeks' old mice and follow-up at 4 weeks after ovariectomy, and observed atrophied vagina and an altered gut microbiota in ovariectomized mice.. We further performed fecal microbiota transplantation with feces from another cohort of ovary-intact fecund female mice to the ovariectomized ones, and found that the vaginal epithelial atrophy was significantly alleviated as well as the gut microbiota was pointedly changed. All these results suggest that ovarian activity has some influence on the gut microbiota, and the latter from the ovary-intact female mice can somehow make the vagina of mice deficient in ovarian function healthier maybe by up-expressing ESR1 in vaginal cells and enhancing regeneration in vagina. This kind of association between gut microbiota and vaginal health need further exploration such that it may provide an alternative treatment by modulating gut microbiota in patients suffering from VVA but may be reluctant to hormone therapy.

RevDate: 2021-03-04
CmpDate: 2021-03-04

Kang M, Choe D, Kim K, et al (2020)

Synthetic Biology Approaches in The Development of Engineered Therapeutic Microbes.

International journal of molecular sciences, 21(22):.

Since the intimate relationship between microbes and human health has been uncovered, microbes have been in the spotlight as therapeutic targets for several diseases. Microbes contribute to a wide range of diseases, such as gastrointestinal disorders, diabetes and cancer. However, as host-microbiome interactions have not been fully elucidated, treatments such as probiotic administration and fecal transplantations that are used to modulate the microbial community often cause nonspecific results with serious safety concerns. As an alternative, synthetic biology can be used to rewire microbial networks such that the microbes can function as therapeutic agents. Genetic sensors can be transformed to detect biomarkers associated with disease occurrence and progression. Moreover, microbes can be reprogrammed to produce various therapeutic molecules from the host and bacterial proteins, such as cytokines, enzymes and signaling molecules, in response to a disturbed physiological state of the host. These therapeutic treatment systems are composed of several genetic parts, either identified in bacterial endogenous regulation systems or developed through synthetic design. Such genetic components are connected to form complex genetic logic circuits for sophisticated therapy. In this review, we discussed the synthetic biology strategies that can be used to construct engineered therapeutic microbes for improved microbiome-based treatment.

RevDate: 2021-03-03

Liao C, Taylor BP, Ceccarani C, et al (2021)

Compilation of longitudinal microbiota data and hospitalome from hematopoietic cell transplantation patients.

Scientific data, 8(1):71.

The impact of the gut microbiota in human health is affected by several factors including its composition, drug administrations, therapeutic interventions and underlying diseases. Unfortunately, many human microbiota datasets available publicly were collected to study the impact of single variables, and typically consist of outpatients in cross-sectional studies, have small sample numbers and/or lack metadata to account for confounders. These limitations can complicate reusing the data for questions outside their original focus. Here, we provide comprehensive longitudinal patient dataset that overcomes those limitations: a collection of fecal microbiota compositions (>10,000 microbiota samples from >1,000 patients) and a rich description of the "hospitalome" experienced by the hosts, i.e., their drug exposures and other metadata from patients with cancer, hospitalized to receive allogeneic hematopoietic cell transplantation (allo-HCT) at a large cancer center in the United States. We present five examples of how to apply these data to address clinical and scientific questions on host-associated microbial communities.

RevDate: 2021-03-03

Dalal RS, JR Allegretti (2021)

Diagnosis and management of Clostridioides difficile infection in patients with inflammatory bowel disease.

Current opinion in gastroenterology pii:00001574-900000000-99052 [Epub ahead of print].

PURPOSE OF REVIEW: Clostridioides difficile infection (CDI) may complicate the course of ulcerative colitis and Crohn's disease. The clinical presentation of CDI in this population is often atypical, and patients may experience exacerbations of their underlying inflammatory bowel disease (IBD) secondary to C. difficile. In this review, we aim to review the risk factors, diagnosis, and management of CDI in the context of IBD.

RECENT FINDINGS: Patients with colonic involvement of their IBD are at higher risk for CDI and colonization may be more common than in the general population. Therefore, CDI is confirmed using a two-step approach to stool testing. Oral vancomycin or fidaxomicin are the preferred agents for nonfulminant disease, and oral metronidazole is no longer recommended as first-line therapy. For all patients with CDI recurrence, fecal microbiota transplant (FMT) should be considered, as this has been shown to be safe and effective. Among those who have worsening of their underlying IBD, retrospective research suggest that outcomes are improved for those who undergo escalation of immunosuppression with appropriate antimicrobial treatment of C. difficile, however prospective data are needed.

SUMMARY: CDI may complicate the course of IBD, however the presentation may not be typical. Therefore, all patients with worsening gastrointestinal symptoms should be evaluated for both CDI and IBD exacerbation. Providers should consider FMT for all patients with recurrent CDI as well as escalation of immunosuppression for patients who fail to improve with appropriate antimicrobial therapy.

RevDate: 2021-03-03

Grajeda-Iglesias C, Durand S, Daillère R, et al (2021)

Oral administration of Akkermansia muciniphila elevates systemic antiaging and anticancer metabolites.

Aging, 13: pii:202739 [Epub ahead of print].

The presence of Akkermansia muciniphila (Akk) in the human gut is associated with good health, leanness and fitness. Mouse experimentation has demonstrated positive effects for Akk, which counteracts aging, mediates antiobesity and antidiabetic effects, dampens inflammation and improves anticancer immunosurveillance. Clinical trials have confirmed antidiabetic effects for Akk. Here, we investigated the time-dependent effects of oral administration of Akk (which was live or pasteurized) and other bacteria to mice on the metabolome of the ileum, colon, liver and blood plasma. Metabolomics was performed by a combination of chromatographic and mass spectrometric methods, yielding a total of 1.637.227 measurements. Akk had major effects on metabolism, causing an increase in spermidine and other polyamines in the gut and in the liver. Pasteurized Akk (Akk-past) was more efficient than live Akk in elevating the intestinal concentrations of polyamines, short-chain fatty acids, 2-hydroxybutyrate, as well multiple bile acids, which also increased in the circulation. All these metabolites have previously been associated with human health, providing a biochemical basis for the beneficial effects of Akk.

RevDate: 2021-03-03

Khor B, Snow M, Herrman E, et al (2021)

Interconnections Between the Oral and Gut Microbiomes: Reversal of Microbial Dysbiosis and the Balance Between Systemic Health and Disease.

Microorganisms, 9(3): pii:microorganisms9030496.

The human microbiota represents a complex array of microbial species that influence the balance between the health and pathology of their surrounding environment. These microorganisms impart important biological benefits to their host, such as immune regulation and resistance to pathogen colonization. Dysbiosis of microbial communities in the gut and mouth precede many oral and systemic diseases such as cancer, autoimmune-related conditions, and inflammatory states, and can involve the breakdown of innate barriers, immune dysregulation, pro-inflammatory signaling, and molecular mimicry. Emerging evidence suggests that periodontitis-associated pathogens can translocate to distant sites to elicit severe local and systemic pathologies, which necessitates research into future therapies. Fecal microbiota transplantation, probiotics, prebiotics, and synbiotics represent current modes of treatment to reverse microbial dysbiosis through the introduction of health-related bacterial species and substrates. Furthermore, the emerging field of precision medicine has been shown to be an effective method in modulating host immune response through targeting molecular biomarkers and inflammatory mediators. Although connections between the human microbiome, immune system, and systemic disease are becoming more apparent, the complex interplay and future innovations in treatment modalities will become elucidated through continued research and cross-disciplinary collaboration.

RevDate: 2021-03-02

Yang S, Hu T, Liu H, et al (2021)

Akebia saponin D ameliorates metabolic syndrome (MetS) via remodeling gut microbiota and attenuating intestinal barrier injury.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 138:111441 pii:S0753-3322(21)00226-2 [Epub ahead of print].

Metabolic syndrome (MetS) is a complex, multifactorial disease which lead to an increased risk of cardiovascular disease, type 2 diabetes, and stroke. However, selective, and potent drugs for the treatment of MetS are still lacking. Previous studies have found that Akebia saponin D (ASD) has beneficial effects on metabolic diseases such as obesity, atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). Therefore, our study was designed to determine the effect and mechanism of action of ASD against MetS in a high-fat diet (HFD) induced mouse model. ASD significantly decreased plasma lipid and insulin resistance in these mice, and a targeted approach using metabolomic analyses of plasma and feces indicated that glucose and lipids in these mice crossed the damaged intestinal barrier into circulation. Furthermore, ASD was able to increase lipid excretion and inhibit intestinal epithelial lipid absorption. Results for gut microbiota composition showed that ASD significantly reduced HFD-associated Alistipes, Prevotella, and enhanced the proportions of Butyricimonas, Ruminococcus, and Bifidobacterium. After 14 weeks of ASD/fecal microbiota transplantation (FMT) interventions the developed gut barrier dysfunction was restored. Additionally, RNA-seq revealed that ASD reduced the lipid-induced tight junction (TJ) damage in intestinal epithelial cells via down-regulation of the PPAR-γ-FABP4 pathway in vitro and that use of the PPAR-γ inhibitor (T0070907) was able to partially block the effects of ASD, indicating that the PPAR-γ/FABP4 pathway is a critical mediator involved in the improvement of MetS. Our results demonstrated that ASD not only modifies the gut microbiome but also ameliorates the HFD-induced gut barrier disruption via down-regulation of the PPAR-γ-FABP4 pathway. These findings suggest a promising, and novel therapeutic strategy for gut protection against MetS.

RevDate: 2021-03-02

Ghorbani Y, Schwenger KJP, JP Allard (2021)

Manipulation of intestinal microbiome as potential treatment for insulin resistance and type 2 diabetes.

European journal of nutrition [Epub ahead of print].

PURPOSE: Increasing evidence suggests that the intestinal microbiome (IM) and bacterial metabolites may influence glucose homeostasis, energy expenditure and the intestinal barrier integrity and lead to the presence of systemic low-grade inflammation, all of which can contribute to insulin resistance (IR) and type 2 diabetes (T2D). The purpose of this review is to explore the role of the IM and bacterial metabolites in the pathogenesis and treatment of these conditions.

RESULTS: This review summarizes research focused on how to modulate the IM through diet, prebiotics, probiotics, synbiotics and fecal microbiota transplant in order to treat IR and T2D.

CONCLUSION: There is an abundance of evidence suggesting a role for IM in the pathogenesis of IR and T2D based on reviewed studies using various methods to modulate IM and metabolites. However, the results are inconsistent. Future research should further assess this relationship.

RevDate: 2021-02-28

Al-Bakri AG, Akour AA, WK Al-Delaimy (2021)

Knowledge, attitudes, ethical and social perspectives towards fecal microbiota transplantation (FMT) among Jordanian healthcare providers.

BMC medical ethics, 22(1):19.

BACKGROUND: Fecal microbiota transplant (FMT) is a treatment modality that involves the introduction of stool from a healthy pre-screened donor into the gastrointestinal tract of a patient. It exerts its therapeutic effects by remodeling the gut microbiota and treating microbial dysbiosis-imbalance. FMT is not regulated in Jordan, and regulatory effort for FMT therapy in Jordan, an Islamic conservative country, might be faced with unique cultural, social, religious, and ethical challenges. We aimed to assess knowledge, attitudes, and perceptions of ethical and social issues of FMT use among Jordanian healthcare professionals.

METHODS: An observational, cross-sectional study design was used to assess knowledge, attitudes, and perceptions of ethical and social issues of FMT among 300 Jordanian healthcare professionals.

RESULTS: A large proportion (39 %) thought that the safety and efficacy of this technique are limited and 29.3 % thought there is no evidence to support its use. Almost all (95 %) responded that they would only perform it in certain cases, if ethically justified, and 48.3 % would use it due to treatment failure of other approaches. When reporting about reasons for not using it, 40 % reported that they would not perform it due to concerns about medical litigation, fear of infections (38 %), and lack of knowledge of long safety and efficacy (31.3 %). Interestingly, all practitioners said they would perform this procedure through the lower rather than upper gastrointestinal tract modality and the majority will protect the patient's confidentiality via double-blinding (43.3 %). For a subset of participants (n = 100), the cultural constraints that might affect the choice of performing FMT were mainly due to donor's religion, followed by dietary intake, and alcohol consumption.

CONCLUSIONS: Our healthcare practitioners are generally reluctant to use the FMT modality due to religious and ethical reasons but would consider it if there was a failure of other treatment and after taking into consideration many legislative, social, ethical and practice-based challenges including safety, efficacy and absence of guidelines.

RevDate: 2021-02-28

Afecto E, Ponte A, Fernandes S, et al (2021)

Fecal microbiota transplantation in hepatic encephalopathy : a review of the current evidence and future perspectives.

Acta gastro-enterologica Belgica, 84(1):87-90.

Hepatic encephalopathy (HE) is a leading cause of hospitalization and morbimortality in advanced cirrhosis with limited therapeutic options available. Given the paramount role of gut microbiota in HE, and the efficacy of fecal microbiota transplantation (FMT) in other diseases, this review intends to summarize the evidence supporting the safety, efficacy and future perspectives of FMT in HE. Current evidence, despite being scarce, points towards FMT being a safe, effective and tolerable procedure in HE. Some unanswered questions remain about the optimal dose, the administration route, the long term effects and the selection of the optimal donor. Future trials, some of which are already underway, will provide us additional evidence and hopefully the necessary answers.

RevDate: 2021-03-01
CmpDate: 2021-03-01

Schluter J, Peled JU, Taylor BP, et al (2020)

The gut microbiota is associated with immune cell dynamics in humans.

Nature, 588(7837):303-307.

The gut microbiota influences development1-3 and homeostasis4-7 of the mammalian immune system, and is associated with human inflammatory8 and immune diseases9,10 as well as responses to immunotherapy11-14. Nevertheless, our understanding of how gut bacteria modulate the immune system remains limited, particularly in humans, where the difficulty of direct experimentation makes inference challenging. Here we study hundreds of hospitalized-and closely monitored-patients with cancer receiving haematopoietic cell transplantation as they recover from chemotherapy and stem-cell engraftment. This aggressive treatment causes large shifts in both circulatory immune cell and microbiota populations, enabling the relationships between the two to be studied simultaneously. Analysis of observed daily changes in circulating neutrophil, lymphocyte and monocyte counts and more than 10,000 longitudinal microbiota samples revealed consistent associations between gut bacteria and immune cell dynamics. High-resolution clinical metadata and Bayesian inference allowed us to compare the effects of bacterial genera in relation to those of immunomodulatory medications, revealing a considerable influence of the gut microbiota-together and over time-on systemic immune cell dynamics. Our analysis establishes and quantifies the link between the gut microbiota and the human immune system, with implications for microbiota-driven modulation of immunity.

RevDate: 2021-03-01
CmpDate: 2021-03-01

Wang H, Yang F, Xin R, et al (2020)

The gut microbiota attenuate neuroinflammation in manganese exposure by inhibiting cerebral NLRP3 inflammasome.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 129:110449.

Manganese (Mn) exposure has been reported to cause neurodegenerative disorders. β-Amyloid (Aβ) induced Tau pathology in an NLRP3-dependent manner is at the heart of Alzheimer's and Parkinson's diseases. The gut microbiota plays a crucial role in the bidirectional gut-brain axis that integrates the gut and central nervous system (CNS) activities. In this study, we found that Mn exposure increases Aβ1-40 and Tau production in brain, and causes hippocampal degeneration and necrosis. Meanwhile, Mn exposure can stimulate neurotoxicity by increasing inflammation either in peripheral blood and CNS. Importantly, we found that transplantation of gut microbiota from normal rats into Mn exposure rats reduced Aβ and Tau expression, and the cerebral expression of NLRP3 was downregulated, and the expression of neuroinflammatory factors was also downregulated. Therefore, improving the composition of gut microbiota in Mn exposure rats can attenuate neuroinflammation, which is considered as a novel therapeutic strategy for Mn exposure by remodelling the gut microbiota.

RevDate: 2021-02-27

Kelly CR, Wu GD, LA Laine (2021)

Response to: Olesen SW, "Fecal microbiota transplantation "donor effects" are not clinically relevant for Clostridioides difficile infection.".

RevDate: 2021-02-26

Staley C, Halaweish H, Graiziger C, et al (2021)

Lower endoscopic delivery of freeze-dried intestinal microbiota results in more rapid and efficient engraftment than oral administration.

Scientific reports, 11(1):4519.

Fecal microbiota transplantation (FMT) is a highly effective treatment for recurrent Clostridioides difficile infection (rCDI). However, standardization of FMT products is essential for its broad implementation into clinical practice. We have developed an oral preparation of freeze-dried, encapsulated microbiota, which is ~ 80% clinically effective, but results in delayed engraftment of donor bacteria relative to administration via colonoscopy. Our objective was to measure the engraftment potential of freeze-dried microbiota without the complexity of variables associated with oral administration. We compared engraftment of identical preparations and doses of freeze-dried microbiota following colonoscopic (9 patients) versus oral administration (18 patients). Microbiota were characterized by sequencing of the 16S rRNA gene, and engraftment was determined using the SourceTracker algorithm. Oligotyping analysis was done to provide high-resolution patterns of microbiota engraftment. Colonoscopic FMT was associated with greater levels of donor engraftment within days following the procedure (ANOVA P = 0.035) and specific increases in the relative abundances of donor Lachnospiraceae, Bacteroidaceae, and Porphyromonadaceae (P ≤ 0.033). Lower relative abundances of Bacteroidaceae, Lachnospiraceae, and Ruminococcaceae families were associated with clinical failures. These results suggest that further optimization of oral capsule FMT may improve its engraftment efficiency and clinical efficacy.

RevDate: 2021-02-25

Du D, Tang W, Zhou C, et al (2021)

Fecal Microbiota Transplantation Is a Promising Method to Restore Gut Microbiota Dysbiosis and Relieve Neurological Deficits after Traumatic Brain Injury.

Oxidative medicine and cellular longevity, 2021:5816837.

Background: Traumatic brain injury (TBI) can induce persistent fluctuation in the gut microbiota makeup and abundance. The present study is aimed at determining whether fecal microbiota transplantation (FMT) can rescue microbiota changes and ameliorate neurological deficits after TBI in rats.

Methods: A controlled cortical impact (CCI) model was used to simulate TBI in male Sprague-Dawley rats, and FMT was performed for 7 consecutive days. 16S ribosomal RNA (rRNA) sequencing of fecal samples was performed to analyze the effects of FMT on gut microbiota. Modified neurological severity score and Morris water maze were used to evaluate neurobehavioral functions. Metabolomics was used to screen differential metabolites from the rat serum and ipsilateral brains. The oxidative stress indices were measured in the brain.

Results: TBI induced significance changes in the gut microbiome, including the alpha- and beta-bacterial diversity, as well as the microbiome composition at 8 days after TBI. On the other hand, FMT could rescue these changes and relieve neurological deficits after TBI. Metabolomics results showed that the level of trimethylamine (TMA) in feces and the level of trimethylamine N-oxide (TMAO) in the ipsilateral brain and serum was increased after TBI, while FMT decreased TMA levels in the feces, and TMAO levels in the ipsilateral brain and serum. Antioxidant enzyme methionine sulfoxide reductase A (MsrA) in the ipsilateral hippocampus was decreased after TBI but increased after FMT. In addition, FMT elevated SOD and CAT activities and GSH/GSSG ratio and diminished ROS, GSSG, and MDA levels in the ipsilateral hippocampus after TBI.

Conclusions: FMT can restore gut microbiota dysbiosis and relieve neurological deficits possibly through the TMA-TMAO-MsrA signaling pathway after TBI.

RevDate: 2021-02-24
CmpDate: 2021-02-24

Johnson D, Letchumanan V, Thurairajasingam S, et al (2020)

A Revolutionizing Approach to Autism Spectrum Disorder Using the Microbiome.

Nutrients, 12(7):.

The study of human microbiota and health has emerged as one of the ubiquitous research pursuits in recent decades which certainly warrants the attention of both researchers and clinicians. Many health conditions have been linked to the gut microbiota which is the largest reservoir of microbes in the human body. Autism spectrum disorder (ASD) is one of the neurodevelopmental disorders which has been extensively explored in relation to gut microbiome. The utilization of microbial knowledge promises a more integrative perspective in understanding this disorder, albeit being an emerging field in research. More interestingly, oral and vaginal microbiomes, indicating possible maternal influence, have equally drawn the attention of researchers to study their potential roles in the etiopathology of ASD. Therefore, this review attempts to integrate the knowledge of microbiome and its significance in relation to ASD including the hypothetical aetiology of ASD and its commonly associated comorbidities. The microbiota-based interventions including diet, prebiotics, probiotics, antibiotics, and faecal microbial transplant (FMT) have also been explored in relation to ASD. Of these, diet and probiotics are seemingly promising breakthrough interventions in the context of ASD for lesser known side effects, feasibility and easier administration, although more studies are needed to ascertain the actual clinical efficacy of these interventions. The existing knowledge and research gaps call for a more expanded and resolute research efforts in establishing the relationship between autism and microbiomes.

RevDate: 2021-02-24

Wang J, Li X, Wu X, et al (2021)

Gut microbiota alterations associated with antibody-mediated rejection after kidney transplantation.

Applied microbiology and biotechnology [Epub ahead of print].

Antibody-mediated rejection (AMR) has become the major challenge for kidney transplantation, and the efficacy of existing therapies was limited to prevent AMR. Increasing evidences have demonstrated the link between gut microbiota alterations and allograft outcome. However, there has been no comprehensive analysis to profile the gut microbiota associated with AMR after kidney transplantation. We performed this study to characterize the gut microbiota possibly associated with AMR. Fecal specimens were collected from 24 kidney transplantation recipients with AMR and 29 controls. DNA extracted from the specimens was processed for 16S rRNA gene sequencing using Illumina MiSeq. Gut microbial community of recipients with AMR was significantly different from that of controls based on unweighted (P = 0.001) and weighted (P = 0.02) UniFrac distances, and the bacterial richness (observed species: P = 0.0448; Chao1 index: P = 0.0450; ACE index: P = 0.0331) significantly decreased in the AMR group. LEfSe showed that 1 phylum, 5 classes, 7 families, and 10 genera were increased, whereas 1 class, 2 order, 3 families, and 4 genera were decreased in the AMR group. Specific taxa such as Clostridiales could be potentially used as biomarkers to distinguish the recipients with AMR from the controls (AUC = 0.77). PICRUSt analysis illustrated that 16 functional pathways were with significantly different abundances in the AMR and control groups. Our findings provide a foundation for further investigation on the role of gut microbiota in AMR after kidney transplantation, and potentially support novel diagnostic biomarkers and therapeutic options for AMR. KEY POINTS: • Gut microbial community of kidney recipients with AMR was different from that of controls. • Clostridiales is a potential marker to distinguish recipients with AMR from controls.

RevDate: 2021-02-24

Berland M, Cadiou J, Levenez F, et al (2021)

High engraftment capacity of frozen ready-to-use human fecal microbiota transplants assessed in germ-free mice.

Scientific reports, 11(1):4365.

The number of indications for fecal microbiota transplantation is expected to rise, thus increasing the needs for production of readily available frozen or freeze-dried transplants. Using shotgun metagenomics, we investigated the capacity of two novel human fecal microbiota transplants prepared in maltodextrin-trehalose solutions (abbreviated MD and TR for maltodextrin:trehalose, 3:1, w/w, and trehalose:maltodextrin 3:1, w/w, respectively), to colonize a germ-free born mouse model. Gavage with frozen-thawed MD or TR suspensions gave the taxonomic profiles of mouse feces that best resembled those obtained with the fresh inoculum (Spearman correlations based on relative abundances of metagenomic species around 0.80 and 0.75 for MD and TR respectively), while engraftment capacity of defrosted NaCl transplants most diverged (Spearman correlations around 0.63). Engraftment of members of the family Lachnospiraceae and Ruminoccocaceae was the most challenging in all groups of mice, being improved with MD and TR transplants compared to NaCl, but still lower than with the fresh preparation. Improvement of engraftment of this important group in maintaining health represents a challenge that could benefit from further research on fecal microbiota transplant manufacturing.

RevDate: 2021-02-23

Sheh A (2021)

The Gastrointestinal Microbiota of the Common Marmoset (Callithrix jacchus).

ILAR journal pii:6146828 [Epub ahead of print].

The microbiota is heavily involved in both health and disease pathogenesis, but defining a normal, healthy microbiota in the common marmoset has been challenging. The aim of this review was to systematically review recent literature involving the gastrointestinal microbiome of common marmosets in health and disease. Twelve sources were included in this review. The gut microbiome composition was reviewed across institutions worldwide, and taxonomic shifts between healthy individuals were described. Unlike the human gut microbiome, which is dominated by Firmicutes and Bacteroidetes, the marmoset gut microbiome shows great plasticity across institutions, with 5 different phyla described as dominant in different healthy cohorts. Genera shared across institutions include Anaerobiospirillum, Bacteroides, Bifidobacterium, Collinsella, Fusobacterium, Megamonas, Megasphaera, Phascolarctobacterium, and Prevotella. Shifts in the abundance of Prevotella or Bifidobacterium or invasion by pathogens like Clostridium perfringens may be associated with disease. Changes in microbial composition have been described in healthy and diseased marmosets, but factors influencing the severe changes in microbial composition have not been established. Multi-institutional, prospective, and longitudinal studies that utilize multiple testing methodologies are required to determine sources of variability in the reporting of marmoset microbiomes. Furthermore, methods of microbial manipulation, whether by diet, enrichment, fecal microbiome transplantation, etc, need to be established to modulate and maintain robust and resilient microbiome communities in marmoset colonies and reduce the incidence of idiopathic gastrointestinal disease.

RevDate: 2021-02-22

Rungue M, Melo V, Martins D, et al (2021)

NLRP6-associated host microbiota composition impacts in the intestinal barrier to systemic dissemination of Brucella abortus.

PLoS neglected tropical diseases, 15(2):e0009171 pii:PNTD-D-20-01646 [Epub ahead of print].

Brucella abortus is a Gram-negative bacterium responsible for a worldwide zoonotic infection-Brucellosis, which has been associated with high morbidity rate in humans and severe economic losses in infected livestock. The natural route of infection is through oral and nasal mucosa but the invasion process through host gut mucosa is yet to be understood. Studies have examined the role of NLRP6 (NOD-like receptor family pyrin domain-containing-6 protein) in gut homeostasis and defense against pathogens. Here, we investigated the impact of gut microbiota and NLRP6 in a murine model of Ba oral infection. Nlrp6-/- and wild-type (WT) mice were infected by oral gavage with Ba and tissues samples were collected at different time points. Our results suggest that Ba oral infection leads to significant alterations in gut microbiota. Moreover, Nlrp6-/- mice were more resistant to infection, with decreased CFU in the liver and reduction in gut permeability when compared to the control group. Fecal microbiota transplantation from WT and Nlrp6-/- into germ-free mice reflected the gut permeability phenotype from the donors. Additionally, depletion of gut microbiota by broad-spectrum-antibiotic treatment prevented Ba replication in WT while favoring bacterial growth in Nlrp6-/-. Finally, we observed higher eosinophils in the gut and leukocytes in the blood of infected Nlrp6-/- compared to WT-infected mice, which might be associated to the Nlrp6-/- resistance phenotype. Altogether, these results indicated that gut microbiota composition is the major factor involved in the initial stages of pathogen host replication and partially also by the resistance phenotype observed in Nlrp6 -/- mice regulating host inflammation against Ba infection.

RevDate: 2021-02-22

Henson MA (2021)

Computational modeling of the gut microbiota reveals putative metabolic mechanisms of recurrent Clostridioides difficile infection.

PLoS computational biology, 17(2):e1008782 pii:PCOMPBIOL-D-20-00965 [Epub ahead of print].

Approximately 30% of patients who have Clostridioides difficile infection (CDI) will suffer at least one incident of reinfection. While the underlying causes of CDI recurrence are poorly understood, interactions between C. difficile and commensal gut bacteria are thought to play an important role. In this study, an in silico pipeline was used to process 16S rRNA gene amplicon sequence data of 225 stool samples from 93 CDI patients into sample-specific models of bacterial community metabolism. Clustered metabolite production rates generated from post-diagnosis samples generated a high Enterobacteriaceae abundance cluster containing disproportionately large numbers of recurrent samples and patients. This cluster was predicted to have significantly reduced capabilities for secondary bile acid synthesis but elevated capabilities for aromatic amino acid catabolism. When applied to 16S sequence data of 40 samples from fecal microbiota transplantation (FMT) patients suffering from recurrent CDI and their stool donors, the community modeling method generated a high Enterobacteriaceae abundance cluster with a disproportionate large number of pre-FMT samples. This cluster also was predicted to exhibit reduced secondary bile acid synthesis and elevated aromatic amino acid catabolism. Collectively, these in silico predictions suggest that Enterobacteriaceae may create a gut environment favorable for C. difficile spore germination and/or toxin synthesis.

RevDate: 2021-02-22

Pham VT, Fehlbaum S, Seifert N, et al (2021)

Effects of colon-targeted vitamins on the composition and metabolic activity of the human gut microbiome- a pilot study.

Gut microbes, 13(1):1-20.

An increasing body of evidence has shown that gut microbiota imbalances are linked to diseases. Currently, the possibility of regulating gut microbiota to reverse these perturbations by developing novel therapeutic and preventive strategies is being extensively investigated. The modulatory effect of vitamins on the gut microbiome and related host health benefits remain largely unclear. We investigated the effects of colon-delivered vitamins A, B2, C, D, and E on the gut microbiota using a human clinical study and batch fermentation experiments, in combination with cell models for the assessment of barrier and immune functions. Vitamins C, B2, and D may modulate the human gut microbiome in terms of metabolic activity and bacterial composition. The most distinct effect was that of vitamin C, which significantly increased microbial alpha diversity and fecal short-chain fatty acids compared to the placebo. The remaining vitamins tested showed similar effects on microbial diversity, composition, and/or metabolic activity in vitro, but in varying degrees. Here, we showed that vitamins may modulate the human gut microbiome. Follow-up studies investigating targeted delivery of vitamins to the colon may help clarify the clinical significance of this novel concept for treating and preventing dysbiotic microbiota-related human diseases. Trial registration: ClinicalTrials.gov, NCT03668964. Registered 13 September 2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03668964.

RevDate: 2021-02-22

Qi R, Zhang Z, Wang J, et al (2021)

Introduction of Colonic and Fecal Microbiota From an Adult Pig Differently Affects the Growth, Gut Health, Intestinal Microbiota and Blood Metabolome of Newborn Piglets.

Frontiers in microbiology, 12:623673.

Microbiota transplantation is a rapid and effective method for changing and reshaping the intestinal microbiota and metabolic profile in humans and animals. This study compared the different influences of the introduction of fecal microbes and colonic microbes from a fat, adult pig in newborn pigs. Both colonic microbiota transplantation (CMT) and fecal microbiota transplantation (FMT) promoted growth and improved gut functions in suckling pigs up to weaning. FMT was more beneficial for body weight gain and body fat deposition in piglets, while CMT was more beneficial for intestinal health and mucosal immunity. 16S rDNA sequence analysis indicated that both CMT and FMT significantly increased the abundances of beneficial or functional bacteria, such as Lactobacillus and Prevotella_2 genera, in the piglets, and reduced the abundances of harmful bacteria, such as Escherichia-Shigella. Blood metabolome analysis showed that transplantation, especially FMT, enhanced lipid metabolism in piglets. In addition, while CMT also changed amino acid metabolism and increased anti-inflammatory metabolites such as 3-indoleacetic acid and 3-indolepropionic acid in piglets, FMT did not. Of note, FMT damaged the intestinal barrier of piglets to a certain extent and increased the levels of inflammatory factors in the blood that are potentially harmful to the health of pigs. Taken together, these results suggested that intestinal and fecal microbiota transplantations elicited similar but different physiological effects on young animals, so the application of microbiota transplantation in animal production requires the careful selection and evaluation of source bacteria.

RevDate: 2021-02-22
CmpDate: 2021-02-22

Khoruts A, Staley C, MJ Sadowsky (2021)

Faecal microbiota transplantation for Clostridioides difficile: mechanisms and pharmacology.

Nature reviews. Gastroenterology & hepatology, 18(1):67-80.

Faecal microbiota transplantation (FMT) has emerged as a remarkably successful treatment for recurrent Clostridioides difficile infection that cannot be cured with antibiotics alone. Understanding the complex biology and pathogenesis of C. difficile infection, which we discuss in this Perspective, is essential for understanding the potential mechanisms by which FMT cures this disease. Although FMT has already entered clinical practice, different microbiota-based products are currently in clinical trials and are vying for regulatory approval. However, all these therapeutics belong to an entirely new class of agents that require the development of a new branch of pharmacology. Characterization of microbiota therapeutics uses novel and rapidly evolving technologies and requires incorporation of microbial ecology concepts. Here, we consider FMT within a pharmacological framework, including its essential elements: formulation, pharmacokinetics and pharmacodynamics. From this viewpoint, multiple gaps in knowledge become apparent, identifying areas that require systematic research. This knowledge is needed to help clinical providers use microbiota therapeutics appropriately and to facilitate development of next-generation microbiota products with improved safety and efficacy. The discussion here is limited to FMT as a representative of microbiota therapeutics and recurrent C. difficile as the indication; however, consideration of the intrinsic basic principles is relevant to this entire class of microbiota-based therapeutics.

RevDate: 2021-02-20

Gunaratnam S, Millette M, McFarland LV, et al (2021)

Potential role of probiotics in reducing Clostridioides difficile virulence: Interference with quorum sensing systems.

Microbial pathogenesis pii:S0882-4010(21)00070-X [Epub ahead of print].

Opportunistic pathogenic bacteria may cause disease after the normally protective microbiome is disrupted (typically by antibiotic exposure). Clostridioides difficile is one such pathogen having a severe impact on healthcare facilities and increasing costs of medical care. The search for new therapeutic strategies that are not reliant on additional antibiotic exposures are currently being explored. One such strategy is to disrupt the production of C. difficile virulence factors by interfering with quorum sensing (QS) systems. QS has been well studied in other bacteria, but our understanding in C. difficile is not so well understood. Some probiotic strains or combinations of strains have been shown to be effective in the treatment or primary prevention of C. difficile infections and may possess multiple mechanisms of action. One mechanism of probiotics might be the inhibition of QS, but their role has not been clearly defined yet. A literature search was conducted using standard databases (PubMed, Google Scholar) from database inception to August 2020. The objective of this paper is to update our understanding of how QS leads to toxin production by C. difficile, which is important in pathogenesis, and how QS inhibitors or probiotics may disrupt this pathway. We found two main QS systems for C. difficile (Agr and Lux systems) that are involved in C. difficile pathogenesis by regulating toxin production, motility and adherence. Probiotics and other QS inhibitors targeting QS systems may represent important new directions of therapy and prevention of CDI.

RevDate: 2021-02-20

Barrow F, Khan S, Fredrickson G, et al (2021)

Microbiota-Driven Activation of Intrahepatic B Cells Aggravates Nonalcoholic Steatohepatitis through Innate and Adaptive Signaling.

Hepatology (Baltimore, Md.) [Epub ahead of print].

BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) is rapidly becoming the leading cause of liver failure and indication for liver transplantation. Hepatic inflammation is a key feature of NASH but the immune pathways involved in this process are poorly understood. B lymphocytes are cells of the adaptive immune system that are critical regulators of immune responses. However, the role of B cells in the pathogenesis of NASH and the potential mechanisms leading to their activation in the liver are unclear.

APPROACH AND RESULTS: In this study, we report that NASH livers accumulate B cells with elevated pro-inflammatory cytokine secretion and antigen-presentation ability. Single-cell and bulk RNA sequencing of intrahepatic B cells from mice with NASH unveiled a transcriptional landscape that reflects their pro-inflammatory function. Accordingly, B cell-deficiency ameliorated NASH progression and adoptively transferring B cells from NASH livers recapitulates the disease. Mechanistically, B cell activation during NASH involves signaling through the innate adaptor myeloid differentiation primary response protein 88 (MyD88) as B cell-specific deletion of MyD88 reduced hepatic T cell-mediated inflammation and fibrosis, but not steatosis. In addition, activation of intrahepatic B cells implicates B cell receptor signaling, delineating a synergy between innate and adaptive mechanisms of antigen recognition. Furthermore, fecal microbiota transplantation of human NAFLD gut microbiotas into recipient mice promoted the progression of NASH by increasing the accumulation and activation of intrahepatic B cells, suggesting that gut microbial factors drive the pathogenic function of B cells during NASH.

CONCLUSION: Our findings reveal that a gut microbiota-driven activation of intrahepatic B cells leads to hepatic inflammation and fibrosis during the progression of NASH via innate and adaptive immune mechanisms.

RevDate: 2021-02-20

Kazemian N, Ramezankhani M, Sehgal A, et al (2021)

Author Correction: The trans-kingdom battle between donor and recipient gut microbiome influences fecal microbiota transplantation outcome.

Scientific reports, 11(1):4546 pii:10.1038/s41598-021-82644-z.

RevDate: 2021-02-19

Wang B, Zhu S, Liu Z, et al (2021)

Increased Expression of Colonic Mucosal Melatonin in Patients with Irritable Bowel Syndrome Correlated with Gut Dysbiosis.

Genomics, proteomics & bioinformatics pii:S1672-0229(21)00018-8 [Epub ahead of print].

Dysregulation of the gut microbiota/gut hormone axis contributes to the pathogenesis of irritable bowel syndrome (IBS). Melatonin plays a beneficial role in gut motility and immunity. However, altered expression of local mucosal melatonin in IBS and its relationship with the gut microbiota remain unclear. Therefore, we aimed to detect the colonic melatonin levels and microbiota profiles in patients with diarrhea-predominant IBS (IBS-D) and explore their relationship in germ-free (GF) rats and BON-1 cells. Thirty-two IBS-D patients and twenty-eight healthy controls (HC) were recruited. Fecal specimens from IBS-D patients and HC were separately transplanted into GF rats by gavage. The levels of colon mucosal melatonin were assessed by immunohistochemical methods, and fecal microbiota communities were analyzed using 16S rDNA sequencing. The effect of butyrate on melatonin synthesis in BON-1 cells was evaluated by ELISA. Melatonin levels were significantly increased and negatively correlated with visceral sensitivity in IBS-D patients. GF rats inoculated with fecal microbiota from IBS-D patients had high colonic melatonin levels. Butyrate-producing Clostridium cluster XIVa species, such as Roseburia species and Lachnospira species, were positively related to colonic mucosal melatonin expression. Butyrate significantly increased melatonin secretion in BON-1 cells. Increased melatonin expression may be an adaptive protective mechanism in the development of IBS-D. Moreover, some Clostridium cluster XIVa species could increase melatonin expression via butyrate production. Modulation of the gut hormone/gut microbiota axis offers a promising target of interest for IBS in the future.

RevDate: 2021-02-19

Gupta S, Mullish BH, JR Allegretti (2021)

Fecal Microbiota Transplantation: The Evolving Risk Landscape.

The American journal of gastroenterology [Epub ahead of print].

Fecal microbiota transplantation (FMT) has been recommended in clinical guidelines for the treatment of recurrent Clostridioides difficile infection (CDI). However, it is considered investigational by most regulatory agencies. As the adoption of FMT has increased from a small group of CDI experts alone to more widespread use, there has been a corresponding increase in concern regarding potential risk. FMT is largely considered a safe procedure although risks described range from mild gastrointestinal symptoms to serious infection. Currently, there is variability in how "FMT" is characterized specifically regarding testing approach, which, in turn, impacts the risk profile. This has been highlighted by the rare cases of multidrug-resistant organisms, Shiga toxin-producing Escherichia and enteropathogenic E. coli, recently reported, where these organisms were not screened. These cases have prompted additional screening mandates from the US Food and Drug Administration (FDA), which has maintained its policy of enforcement discretion for the use of FMT for CDI not responding to standard therapy. Here, we examine the evolving risk landscape of FMT.

RevDate: 2021-02-19

Zhang LT, Westblade LF, Iqbal F, et al (2021)

Gut microbiota profiles and fecal beta-glucuronidase activity in kidney transplant recipients with and without post-transplant diarrhea.

Clinical transplantation [Epub ahead of print].

Post-transplant diarrhea is a common complication after solid organ transplantation and is frequently attributed to the widely prescribed immunosuppressant mycophenolate mofetil (MMF). Given recent work identifying the relationship between MMF toxicity and gut bacterial β-glucuronidase activity, we evaluated the relationship between gut microbiota composition, fecal β-glucuronidase activity, and post-transplant diarrhea. We recruited 97 kidney transplant recipients and profiled the gut microbiota in 273 fecal specimens using 16S rRNA gene sequencing. We further characterized fecal β-glucuronidase activity in a subset of this cohort. Kidney transplant recipients with post-transplant diarrhea had decreased gut microbial diversity and decreased relative gut abundances of 12 genera when compared to those without post-transplant diarrhea (adjusted P value<0.15, Wilcoxon rank sum test). Among the kidney transplant recipients with post-transplant diarrhea, those with higher fecal β-glucuronidase activity had a more prolonged course of diarrhea (≥7 days) compared to patients with lower fecal β-glucuronidase activity (91% vs 40%, P=0.02, Fisher's exact test). Our data reveal post-transplant diarrhea as a complex phenomenon with decreased gut microbial diversity and commensal gut organisms. This study further links commensal bacterial metabolism with an important clinical outcome measure, suggesting fecal β-glucuronidase activity could be a novel biomarker for gastrointestinal-related MMF toxicity.

RevDate: 2021-02-19

Serrano-Villar S, Talavera-Rodríguez A, Gosalbes MJ, et al (2021)

Fecal microbiota transplantation in HIV: A pilot placebo-controlled study.

Nature communications, 12(1):1139.

Changes in the microbiota have been linked to persistent inflammation during treated HIV infection. In this pilot double-blind study, we study 30 HIV-infected subjects on antiretroviral therapy (ART) with a CD4/CD8 ratio < 1 randomized to either weekly fecal microbiota capsules or placebo for 8 weeks. Stool donors were rationally selected based on their microbiota signatures. We report that fecal microbiota transplantation (FMT) is safe, not related to severe adverse events, and attenuates HIV-associated dysbiosis. FMT elicits changes in gut microbiota structure, including significant increases in alpha diversity, and a mild and transient engraftment of donor's microbiota during the treatment period. The greater engraftment seems to be achieved by recent antibiotic use before FMT. The Lachnospiraceae and Ruminococcaceae families, which are typically depleted in people with HIV, are the taxa more robustly engrafted across time-points. In exploratory analyses, we describe a significant amelioration in the FMT group in intestinal fatty acid-binding protein (IFABP), a biomarker of intestinal damage that independently predicts mortality. Gut microbiota manipulation using a non-invasive and safe strategy of FMT delivery is feasible and deserves further investigation. Trial number: NCT03008941.

RevDate: 2021-02-19

Hua H, Zhang Y, Zhao F, et al (2021)

Celastrol inhibits intestinal lipid absorption by reprofiling the gut microbiota to attenuate high-fat diet-induced obesity.

iScience, 24(2):102077.

Celastrol, a compound extracted from traditional Chinese medicine, has been reported as a potent anti-obesity agent with controversial mechanisms. Here both C57BL/6J and leptin-deficient (ob/ob) mice fed a high-fat diet (HFD) displayed body weight loss after celastrol therapy, opposing the previous viewpoint that celastrol improves obesity by sensitizing leptin signaling. More importantly, celastrol downregulated lipid transporters in the intestine, increased lipid excretion in feces, and reduced body weight gain in HFD mice. Meanwhile, analysis of gut microbiota revealed that celastrol altered the gut microbiota composition in HFD-fed mice, and modulating gut microbiota by antibiotics or fecal microbiota transplantation blocked the celastrol effect on intestinal lipid transport and body weight gain, suggesting a critical role of the gut microbiota composition in mediating the anti-obesity role of celastrol under HFD. Together, the findings revealed that celastrol reduces intestinal lipid absorption to antagonize obesity by resetting the gut microbiota profile under HFD feeding.

RevDate: 2021-02-19

Zeng J, Peng L, Zheng W, et al (2021)

Fecal microbiota transplantation for rheumatoid arthritis: A case report.

Clinical case reports, 9(2):906-909.

No previous case of using fecal microbiota transplantation (FMT) to treat rheumatoid arthritis (RA) has been reported. We report a case of a patient with refractory RA successfully treated with FMT indicating that FMT may have a good therapeutic effect on RA.

RevDate: 2021-02-18
CmpDate: 2021-02-18

SahBandar IN, Chew GM, Corley MJ, et al (2020)

Changes in gastrointestinal microbial communities influence HIV-specific CD8+ T-cell responsiveness to immune checkpoint blockade.

AIDS (London, England), 34(10):1451-1460.

OBJECTIVES: The aim of this study was to examine the relationship between gut microbial communities in HIV-infected individuals on suppressive antiretroviral therapy (cART), and the peripheral HIV-Gag-specific CD8 T-cell responses before and after ex-vivo immune checkpoint blockade (ICB).

DESIGN: Thirty-four HIV-seropositive, 10 HIV-seronegative and 12 HIV-seropositive receiving faecal microbiota transplant (FMT) participants were included. Gut microbial communities, peripheral and gut associated negative checkpoint receptors (NCRs) and peripheral effector functions were assessed.

METHODS: Bacterial 16s rRNA sequencing for gut microbiome study and flow-based assays for peripheral and gut NCR and their cognate ligand expression, including peripheral HIV-Gag-specific CD8 T-cell responses before and after ex-vivo anti-PD-L1 and anti-TIGIT ICB were performed.

RESULTS: Fusobacteria abundance was significantly higher in HIV-infected donors compared to uninfected controls. In HIV-infected participants receiving Fusobacteria-free FMT, Fusobacteria persisted up to 24 weeks in stool post FMT. PD-1 TIGIT and their ligands were expanded in mucosal vs. peripheral T cells and dendritic cells, respectively. PD-L1 and TIGIT blockade significantly increased the magnitude of peripheral anti-HIV-Gag-specific CD8 T-cell responses. Higher gut Fusobacteria abundance was associated with lower magnitude of peripheral IFN-γ+ HIV-Gag-specific CD8 T-cell responses following ICB.

CONCLUSION: The gut colonization of Fusobacteria in HIV infection is persistent and may influence anti-HIV T-cell immunity to PD-1 or TIGIT blockade. Strategies modulating Fusobacteria colonization may elicit a favourable mucosal immune landscape to enhance the efficacy of ICB for HIV cure.

RevDate: 2021-02-19
CmpDate: 2021-02-19

Rogala AR, Oka A, RB Sartor (2020)

Strategies to Dissect Host-Microbial Immune Interactions That Determine Mucosal Homeostasis vs. Intestinal Inflammation in Gnotobiotic Mice.

Frontiers in immunology, 11:214.

When identifying the key immunologic-microbial interactions leading to either mucosal homeostasis in normal hosts or intestinal inflammatory responses in genetically susceptible individuals, it is important to not only identify microbial community correlations but to also define the functional pathways involved. Gnotobiotic rodents are a very effective tool for this purpose as they provide a highly controlled environment in which to identify the function of complex intestinal microbiota, their individual components, and metabolic products. Herein we review specific strategies using gnotobiotic mice to functionally evaluate the role of various intestinal microbiota in host responses. These studies include basic comparisons between host responses in germ-free (GF), specific-pathogen-free or conventionally raised wild-type mice or those with underlying genetic susceptibilities to intestinal inflammation. We also discuss what can be learned from studies in which GF mice are colonized with single wild-type or genetically-modified microbial isolates to examine the functions of individual bacteria and their targeted bacterial genes, or colonized by multiple defined isolates to determine interactions between members of defined consortia. Additionally, we discuss studies to identify functions of complex microbial communities from healthy or diseased human or murine hosts via fecal transplant into GF mice. Finally, we conclude by suggesting ways to improve studies of immune-microbial interactions using gnotobiotic mice.

RevDate: 2021-02-17

Shivaji S (2021)

A systematic review of gut microbiome and ocular inflammatory diseases: Are they associated?.

Indian journal of ophthalmology, 69(3):535-542.

The primary focus of this review was to establish the possible association of dysbiotic changes in the gut bacterial microbiomes with both intestinal and extra-intestinal diseases with emphasis on ocular diseases such as bacterial keratitis, fungal keratitis, uveitis, age-related macular degeneration, and ocular mucosal diseases. For this particular purpose, a systematic search was conducted using PubMed and Google Scholar for publications related to gut microbiome and human health (using the keywords: gut microbiome, ocular disease, dysbiosis, keratitis, uveitis, and AMD). The predictions are that microbiome studies would help to unravel dysbiotic changes in the gut bacterial microbiome at the taxonomic and functional level and thus form the basis to mitigate inflammatory diseases of the eye by using nutritional supplements or fecal microbiota transplantation.

RevDate: 2021-02-17

Li S, Guo H, Xu X, et al (2021)

Therapeutic Methods for Gut Microbiota Modification in Lipopolysaccharide-Associated Encephalopathy.

Shock (Augusta, Ga.) pii:00024382-900000000-97293 [Epub ahead of print].

OBJECTIVE: To compare the efficacy of four therapeutic methods to modify gut microbiota dysbiosis and brain dysfunction in septic rats.

METHODS: Rats were treated with fecal microbiota transplantation, prebiotics, probiotics, and synbiotics after exposure to lipopolysaccharide. The diversity and composition of gut microbiota, electroencephalogram values, and the concentrations of TNF-α, IL-1β, and IL-6 in the cortex were analyzed.

RESULTS: Fecal microbiota transplantation was the most efficacious method to restore intestinal microbial diversity and exert the best corrective effects in modulating microbial composition in septic rats. More interestingly, fecal microbiota transplantation exerted the best protective effects in brain dysfunction in septic rats.

CONCLUSION: Among the four methods, fecal microbiota transplantation was the most useful method to modify the dysbiosis of intestinal microbiota and improve brain function in septic rats. These findings reveal the protective consequence of microbiota modification, and the findings suggest opportunities to improve brain function in sepsis.

RevDate: 2021-02-17

Langdon A, Schwartz DJ, Bulow C, et al (2021)

Microbiota restoration reduces antibiotic-resistant bacteria gut colonization in patients with recurrent Clostridioides difficile infection from the open-label PUNCH CD study.

Genome medicine, 13(1):28.

BACKGROUND: Once antibiotic-resistant bacteria become established within the gut microbiota, they can cause infections in the host and be transmitted to other people and the environment. Currently, there are no effective modalities for decreasing or preventing colonization by antibiotic-resistant bacteria. Intestinal microbiota restoration can prevent Clostridioides difficile infection (CDI) recurrences. Another potential application of microbiota restoration is suppression of non-C. difficile multidrug-resistant bacteria and overall decrease in the abundance of antibiotic resistance genes (the resistome) within the gut microbiota. This study characterizes the effects of RBX2660, a microbiota-based investigational therapeutic, on the composition and abundance of the gut microbiota and resistome, as well as multidrug-resistant organism carriage, after delivery to patients suffering from recurrent CDI.

METHODS: An open-label, multi-center clinical trial in 11 centers in the USA for the safety and efficacy of RBX2660 on recurrent CDI was conducted. Fecal specimens from 29 of these subjects with recurrent CDI who received either one (N = 16) or two doses of RBX2660 (N = 13) were analyzed secondarily. Stool samples were collected prior to and at intervals up to 6 months post-therapy and analyzed in three ways: (1) 16S rRNA gene sequencing for microbiota taxonomic composition, (2) whole metagenome shotgun sequencing for functional pathways and antibiotic resistome content, and (3) selective and differential bacterial culturing followed by isolate genome sequencing to longitudinally track multidrug-resistant organisms.

RESULTS: Successful prevention of CDI recurrence with RBX2660 correlated with taxonomic convergence of patient microbiota to the donor microbiota as measured by weighted UniFrac distance. RBX2660 dramatically reduced the abundance of antibiotic-resistant Enterobacteriaceae in the 2 months after administration. Fecal antibiotic resistance gene carriage decreased in direct relationship to the degree to which donor microbiota engrafted.

CONCLUSIONS: Microbiota-based therapeutics reduce resistance gene abundance and resistant organisms in the recipient gut microbiome. This approach could potentially reduce the risk of infections caused by resistant organisms within the patient and the transfer of resistance genes or pathogens to others.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT01925417 ; registered on August 19, 2013.

RevDate: 2021-02-17

Moshkelgosha S, Verhasselt HL, Masetti G, et al (2021)

Modulating gut microbiota in a mouse model of Graves' orbitopathy and its impact on induced disease.

Microbiome, 9(1):45.

BACKGROUND: Graves' disease (GD) is an autoimmune condition in which autoantibodies to the thyrotropin receptor (TSHR) cause hyperthyroidism. About 50% of GD patients also have Graves' orbitopathy (GO), an intractable disease in which expansion of the orbital contents causes diplopia, proptosis and even blindness. Murine models of GD/GO, developed in different centres, demonstrated significant variation in gut microbiota composition which correlated with TSHR-induced disease heterogeneity. To investigate whether correlation indicates causation, we modified the gut microbiota to determine whether it has a role in thyroid autoimmunity. Female BALB/c mice were treated with either vancomycin, probiotic bacteria, human fecal material transfer (hFMT) from patients with severe GO or ddH2O from birth to immunization with TSHR-A subunit or beta-galactosidase (βgal; age ~ 6 weeks). Incidence and severity of GD (TSHR autoantibodies, thyroid histology, thyroxine level) and GO (orbital fat and muscle histology), lymphocyte phenotype, cytokine profile and gut microbiota were analysed at sacrifice (~ 22 weeks).

RESULTS: In ddH2O-TSHR mice, 84% had pathological autoantibodies, 67% elevated thyroxine, 77% hyperplastic thyroids and 70% orbital pathology. Firmicutes were increased, and Bacteroidetes reduced relative to ddH2O-βgal; CCL5 was increased. The random forest algorithm at the genus level predicted vancomycin treatment with 100% accuracy but 74% and 70% for hFMT and probiotic, respectively. Vancomycin significantly reduced gut microbiota richness and diversity compared with all other groups; the incidence and severity of both GD and GO also decreased; reduced orbital pathology correlated positively with Akkermansia spp. whilst IL-4 levels increased. Mice receiving hFMT initially inherited their GO donors' microbiota, and the severity of induced GD increased, as did the orbital brown adipose tissue volume in TSHR mice. Furthermore, genus Bacteroides, which is reduced in GD patients, was significantly increased by vancomycin but reduced in hFMT-treated mice. Probiotic treatment significantly increased CD25+ Treg cells in orbital draining lymph nodes but exacerbated induced autoimmune hyperthyroidism and GO.

CONCLUSIONS: These results strongly support a role for the gut microbiota in TSHR-induced disease. Whilst changes to the gut microbiota have a profound effect on quantifiable GD endocrine and immune factors, the impact on GO cellular changes is more nuanced. The findings have translational potential for novel, improved treatments. Video abstract.

RevDate: 2021-02-16
CmpDate: 2021-02-16

Olsson LM, Poitou C, Tremaroli V, et al (2020)

Gut microbiota of obese subjects with Prader-Willi syndrome is linked to metabolic health.

Gut, 69(7):1229-1238.

OBJECTIVE: The gut microbiota has been implicated in the aetiology of obesity and associated comorbidities. Patients with Prader-Willi syndrome (PWS) are obese but partly protected against insulin resistance. We hypothesised that the gut microbiota of PWS patients differs from that of non-genetically obese controls and correlate to metabolic health. Therefore, here we used PWS as a model to study the role of gut microbiota in the prevention of metabolic complications linked to obesity.

DESIGN: We conducted a case-control study with 17 adult PWS patients and 17 obese subjects matched for body fat mass index, gender and age. The subjects were metabolically characterised and faecal microbiota was profiled by 16S ribosomal RNA gene sequencing. The patients' parents were used as a non-obese control group. Stool samples from two PWS patients and two obese controls were used for faecal microbiota transplantations in germ-free mice to examine the impact of the microbiota on glucose metabolism.

RESULTS: The composition of the faecal microbiota in patients with PWS differed from that of obese controls, and was characterised by higher phylogenetic diversity and increased abundance of several taxa such as Akkermansia, Desulfovibrio and Archaea, and decreased abundance of Dorea. Microbial taxa prevalent in the PWS microbiota were associated with markers of insulin sensitivity. Improved insulin resistance of PWS was partly transmitted by faecal microbiota transplantations into germ-free mice.

CONCLUSION: The gut microbiota of PWS patients is similar to that of their non-obese parents and might play a role for the protection of PWS patients from metabolic complications.

RevDate: 2021-01-15

Marcella C, Cui B, Kelly CR, et al (2021)

Systematic review: the global incidence of faecal microbiota transplantation-related adverse events from 2000 to 2020.

Alimentary pharmacology & therapeutics, 53(1):33-42.

BACKGROUND: Faecal microbiota transplantation (FMT) is an effective treatment in C. difficile infection (CDI) and is currently being investigated in other diseases. There is concern around the safety of FMT and that side effects or complications may be under-reported in the medical literature.

AIM: To evaluate the safety of FMT by summarising the overall reported Adverse Events (AEs) over a 20-year period METHODS: We searched EMBASE, MEDLINE, and Cochrane Library databases, and CNKI and Wanfang Data from January 2000 to April 2020. All original studies reporting FMT-related AEs were considered for inclusion. FMT-related AEs were further classified as delivery-related or microbiota-related.

RESULTS: Based on the inclusion criteria, 129 studies, which included 4241 patients (5688 FMT courses), were finally eligible. The most common indication for FMT was CDI. Overall, FMT-related AEs were observed in 19% of FMT procedures. The most frequently reported FMT-related AEs were diarrhoea (10%) and abdominal discomfort/pain/cramping (7%). FMT-related serious adverse events (SAEs), including infections and deaths, have been reported in 1.4% of patients who underwent FMT (0.99% microbiota-related SAEs). Four of five FMT-related deaths were reported in patients receiving FMT via the upper gastrointestinal route. Importantly, all reported FMT-related SAEs were in patients with mucosal barrier injury.

CONCLUSION: Most FMT-related AEs were mild or moderate and self-limiting. Although FMT appears to be highly safe, its methodology should be improved to reduce both delivery-related AEs and, microbiota-related AEs.

RevDate: 2020-10-01

Benech N, Leboucher G, Monard C, et al (2020)

Septic shock due to refractory severe clostridioides difficile colitis rapidly resolving after faecal microbiota transplantation.

BMJ case reports, 13(9): pii:13/9/e234329.

RevDate: 2020-09-03

Costello SP, Day A, Yao CK, et al (2020)

Faecal microbiota transplantation (FMT) with dietary therapy for acute severe ulcerative colitis.

BMJ case reports, 13(8):.

A 19-year-old man presented with acute severe ulcerative colitis. He was taking azathioprine (therapeutic metabolites) and sulphasalazine as well as infliximab with a therapeutic drug level. On day 3 of hydrocortisone therapy, he met day Oxford criteria with >8 bloody stools per day and was given faecal microbiota transplantation and subsequently commenced on dietary therapy combining several strategies-(1) increased intake of fermentable fibres, (2) reduced intake of overall and sulfur-containing protein and (3) restriction of sulfate and sulfite food additives. At week 8 assessment, he was in clinical and endoscopic remission and remained in clinical and endoscopic remission at 12 months.

RevDate: 2020-09-16

Jiménez-Jorge S, Labrador-Herrera G, Rosso-Fernández CM, et al (2020)

Assessing the impact on intestinal microbiome and clinical outcomes of antibiotherapy optimisation strategies in haematopoietic stem cell transplant recipients: study protocol for the prospective multicentre OptimBioma study.

BMJ open, 10(7):e034570.

INTRODUCTION: Haematopoietic stem cell transplantation (HSCT) is a life-saving treatment for a number of haematological diseases. Graft versus host disease (GVHD) is its main complication and hampers survival. There is strong evidence that intestinal microbiota diversity of the recipient may increase the risk of GVHD worsening survival. Antibiotic regimens used during the early phase of the transplant may influence clinical outcomes by reducing intestinal microbiota diversity. Present guidelines of European Conference on Infections in Leukaemia exhort to optimising antibiotic use in haematological patients including HSCT recipients. The present study aims to investigate if, in HSCT recipients, the optimisation of antibacterial use may preserve intestinal microbiota composition reducing the incidence and severity of acute GVHD and improving relevant clinical outcomes.

METHODS AND ANALYSIS: This is a prospective longitudinal observational study of two cohorts of HSCT recipients: (1) the intervention cohort includes patients treated in centres in which a predefined strategy of antibiotherapy optimisation is implemented, with the objective of optimising and reducing antibiotic administration according to clinical criteria and (2) the control cohort includes patients treated in centres in which a classic permissive strategy of antibiotic prophylaxis and treatment is used. Adult patient receiving a first HSCT as a treatment for any haematological condition are included. Clinical variables are prospectively recorded and up to five faecal samples are collected for microbiota characterisation at prestablished peritransplant time points. Patients are followed since the preconditioning phase throughout 1-year post-transplant and four follow-up visits are scheduled. Faecal microbiota composition and diversity will be compared between both cohorts along with acute GVHD incidence and severity, severe infections rate, mortality and overall and disease-free survival.

ETHICS AND DISSEMINATION: The study was approved between 2017 and 2018 by the Ethical Committees of participant centres. Study results will be disseminated through peer-reviewed journals and national and international scientific conferences.

TRIAL REGISTRATION NUMBER: NCT03727113.

RevDate: 2021-02-05

Aron-Wisnewsky J, Warmbrunn MV, Nieuwdorp M, et al (2020)

Nonalcoholic Fatty Liver Disease: Modulating Gut Microbiota to Improve Severity?.

Gastroenterology, 158(7):1881-1898.

Gut microbiota plays a role in the pathophysiology of metabolic diseases, which include nonalcoholic fatty liver diseases, through the gut-liver axis. To date, clinical guidelines recommend a weight loss goal of 7%-10% to improve features of nonalcoholic fatty liver diseases. Because this target is not easily achieved by all patients, alternative therapeutic options are currently being evaluated. This review focuses on therapeutics that aim to modulate the gut microbiota and the gut-liver axis. We discuss how probiotics, prebiotics, synbiotic, fecal microbiota transfer, polyphenols, specific diets, and exercise interventions have been found to modify gut microbiota signatures; improve nonalcoholic fatty liver disease outcomes; and detail, when available, the different mechanisms by which these beneficial outcomes might occur. Apart from probiotics that have already been tested in human randomized controlled trials, most of these potential therapeutics have been studied in animals. Their efficacy still warrants confirmation in humans using appropriate design.

RevDate: 2021-02-10

Park HK, Choi Y, Lee DH, et al (2020)

Altered gut microbiota by azithromycin attenuates airway inflammation in allergic asthma.

The Journal of allergy and clinical immunology, 145(5):1466-1469.e8.

RevDate: 2021-02-13

Wilmes L, Collins JM, O'Riordan KJ, et al (2021)

Of bowels, brain and behavior: A role for the gut microbiota in psychiatric comorbidities in irritable bowel syndrome.

Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society [Epub ahead of print].

BACKGROUND: The gastrointestinal microbiota has emerged as a key regulator of gut-brain axis signalling with important implications for neurogastroenterology. There is continuous bidirectional communication between the gut and the brain facilitated by neuronal, endocrine, metabolic, and immune pathways. The microbiota influences these signalling pathways via several mechanisms. Studies have shown compositional and functional alterations in the gut microbiota in stress-related psychiatric disorders. Gut microbiota reconfigurations are also a feature of irritable bowel syndrome (IBS), a gut-brain axis disorder sharing high levels of psychiatric comorbidity including both anxiety and depression. It remains unclear how the gut microbiota alterations in IBS align with both core symptoms and these psychiatric comorbidities.

METHODS: In this review, we highlight common and disparate features of these microbial signatures as well as the associated gut-brain axis signalling pathways. Studies suggest that patients with either IBS, depression or anxiety, alone or comorbid, present with alterations in gut microbiota composition and harbor immune, endocrine, and serotonergic system alterations relevant to the common pathophysiology of these comorbid conditions.

KEY RESULTS: Research has illustrated the utility of fecal microbiota transplantation in animal models, expanding the evidence base for a potential causal role of disorder-specific gut microbiota compositions in symptom set expression. Moreover, an exciting study by Constante and colleagues in this issue highlights the possibility of counteracting this microbiota-associated aberrant behavioral phenotype with a probiotic yeast, Saccharomyces boulardii CNCM I-745.

CONCLUSIONS AND INFERENCES: Such data highlights the potential for therapeutic targeting of the gut microbiota as a valuable strategy for the management of comorbid psychiatric symptoms in IBS.

RevDate: 2021-02-13

Golonka RM, M Vijay-Kumar (2021)

Atypical immunometabolism and metabolic reprogramming in liver cancer: Deciphering the role of gut microbiome.

Advances in cancer research, 149:171-255.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality worldwide. Much recent research has delved into understanding the underlying molecular mechanisms of HCC pathogenesis, which has revealed to be heterogenous and complex. Two major hallmarks of HCC include: (i) a hijacked immunometabolism and (ii) a reprogramming in metabolic processes. We posit that the gut microbiota is a third component in an entanglement triangle contributing to HCC progression. Besides metagenomic studies highlighting the diagnostic potential in the gut microbiota profile, recent research is pinpointing the gut microbiota as an instigator, not just a mere bystander, in HCC. In this chapter, we discuss mechanistic insights on atypical immunometabolism and metabolic reprogramming in HCC, including the examination of tumor-associated macrophages and neutrophils, tumor-infiltrating lymphocytes (e.g., T-cell exhaustion, regulatory T-cells, natural killer T-cells), the Warburg effect, rewiring of the tricarboxylic acid cycle, and glutamine addiction. We further discuss the potential involvement of the gut microbiota in these characteristics of hepatocarcinogenesis. An immediate highlight is that microbiota metabolites (e.g., short chain fatty acids, secondary bile acids) can impair anti-tumor responses, which aggravates HCC. Lastly, we describe the rising 'new era' of immunotherapies (e.g., immune checkpoint inhibitors, adoptive T-cell transfer) and discuss for the potential incorporation of gut microbiota targeted therapeutics (e.g., probiotics, fecal microbiota transplantation) to alleviate HCC. Altogether, this chapter invigorates for continuous research to decipher the role of gut microbiome in HCC from its influence on immunometabolism and metabolic reprogramming.

RevDate: 2021-02-13

Lee JJ, Yong D, Suk KT, et al (2021)

Alteration of Gut Microbiota in Carbapenem-Resistant Enterobacteriaceae Carriers during Fecal Microbiota Transplantation According to Decolonization Periods.

Microorganisms, 9(2): pii:microorganisms9020352.

Fecal microbiota transplantation (FMT) has been suggested as an alternative therapeutic option to decolonize carbapenem-resistant Enterobacteriaceae (CRE). However, the analysis of gut microbiota alteration in CRE carriers during FMT is still limited. Here, gut microbiota changes in CRE carriers were evaluated during FMT according to decolonization periods. The decolonization of 10 CRE carriers was evaluated after FMT, using serial consecutive rectal swab cultures. Alterations of gut microbiota before and after FMT (56 serial samples) were analyzed using high-throughput sequencing. The decolonization rates of CRE carriers were 40%, 50%, and 90% within 1, 3 and 5 months after initial FMT, respectively. Gut microbiota significantly changed after FMT (p = 0.003). Microbiota alteration was different between the early decolonization carriers (EDC) and late decolonization carriers (LDC). Microbiota convergence in carriers to donors was detected in EDC within 4 weeks, and keystone genera within the Bacteroidetes were found in the gut microbiota of EDC before FMT. The relative abundance of Klebsiella was lower in EDC than in LDC, before and after FMT. Our results indicate that FMT is a potential option for CRE decolonization. The gut microbiota of CRE carriers could be used to predict decolonization timing after FMT, and determine repeated FMT necessity.

RevDate: 2021-02-13

Heo G, Lee Y, E Im (2021)

Interplay between the Gut Microbiota and Inflammatory Mediators in the Development of Colorectal Cancer.

Cancers, 13(4): pii:cancers13040734.

Inflammatory mediators modulate inflammatory pathways during the development of colorectal cancer. Inflammatory mediators secreted by both immune and tumor cells can influence carcinogenesis, progression, and tumor metastasis. The gut microbiota, which colonize the entire intestinal tract, especially the colon, are closely linked to colorectal cancer through an association with inflammatory mediators such as tumor necrosis factor, nuclear factor kappa B, interleukins, and interferons. This association may be a potential therapeutic target, since therapeutic interventions targeting the gut microbiota have been actively investigated in both the laboratory and in clinics and include fecal microbiota transplantation and probiotics.

RevDate: 2021-02-12

Fujimoto K, Kimura Y, Allegretti JR, et al (2021)

Functional Restoration of Bacteriomes and Viromes by Fecal Microbiota Transplantation.

Gastroenterology pii:S0016-5085(21)00400-5 [Epub ahead of print].

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI). However, the overall mechanisms underlying FMT success await comprehensive elucidation, and the safety of FMT has recently become a serious concern because of the occurrence of drug-resistant bacteremia transmitted by FMT. We investigated whether functional restoration of the bacteriomes and viromes by FMT could be an indicator of successful FMT.

METHODS: The human intestinal bacteriomes and viromes from nine patients with rCDI who had undergone successful FMT and their donors were analyzed. Prophage-based and CRISPR spacer-based host bacteria-phage associations in samples from recipients before and after FMT and in donor samples were examined. The gene functions of intestinal microorganisms affected by FMT were evaluated.

RESULTS: Metagenomic sequencing of both the viromes and bacteriomes revealed that FMT does change the characteristics of intestinal bacteriomes and viromes in recipients after FMT compared with those before FMT. In particular, many Proteobacteria, the fecal abundance of which was high before FMT, were eliminated, and the proportion of Microviridae increased in recipients. Most temperate phages also behaved in parallel with the host bacteria that were altered by FMT. Furthermore, the identification of bacterial and viral gene functions before and after FMT revealed that some distinctive pathways, including fluorobenzoate degradation and secondary bile acid biosynthesis, were significantly represented.

CONCLUSIONS: The coordinated action of phages and their host bacteria restored the recipients' intestinal flora. These findings show that the restoration of intestinal microflora functions reflects the success of FMT.

RevDate: 2021-02-13

Saha S, S Khanna (2021)

Stool banking for fecal microbiota transplantation: ready for prime time?.

Hepatobiliary surgery and nutrition, 10(1):110-112.

RevDate: 2021-02-13

Sheng L, Jena PK, Hu Y, et al (2021)

Age-specific microbiota in altering host inflammatory and metabolic signaling as well as metabolome based on the sex.

Hepatobiliary surgery and nutrition, 10(1):31-48.

Background: Metabolism is sex-different, and the direct link between gut microbiota and aging-associated metabolic changes needs to be established in both sexes.

Methods: Gene expression, metabolic and inflammatory signaling, gut microbiota profile, and metabolome were studied during aging and after fecal microbiota transplantation (FMT) in mice of both sexes.

Results: Our data revealed young female mice and aged male mice were the most insulin sensitive and resistant group, respectively. In addition, aging reduced sex difference in insulin sensitivity. Such age- and sex-dependent metabolic phenotypes were accompanied by shifted gut microbiota profile and altered abundance of bacterial genes that produce butyrate, propionate, and bile acids. After receiving feces from the aged males (AFMT), the most insulin-resistant group, recipients of both sexes had increased hepatic inflammation and serum endotoxin. However, AFMT only increased insulin resistance in female mice and abolished sex difference in insulin sensitivity. Additionally, such changes were accompanied by narrowed sex difference in metabolome. Metabolomics data revealed that age-associated insulin resistance in males was accompanied by increased sugar alcohols and dicarboxylic acids as well as reduced aromatic and branched-chain amino acids. Further, receiving feces from the young females (YFMT), the most insulin-sensitive group, reduced body weight and fasting blood glucose in male recipients and improved insulin sensitivity in females, leading to enhanced sex differences in insulin sensitivity and metabolome.

Conclusions: Aging systemically affected inflammatory and metabolic signaling based on the sex. Gut microbiome is age and sex-specific, which affects inflammation and metabolism in a sex-dependent manner.

RevDate: 2021-02-12

Ciernikova S, Kasperova B, Drgona L, et al (2020)

Targeting the gut microbiome: An emerging trend in hematopoietic stem cell transplantation.

Blood reviews pii:S0268-960X(20)30140-5 [Epub ahead of print].

Mounting evidence has demonstrated the critical role of the gut microbiome in different cancer treatment modalities showing intensive crosstalk between microbiota and the host immune system. In cancer patients receiving hematopoietic stem cell transplantation (HSCT), conditioning regimens including chemotherapy, radiotherapy, and immunosuppressive therapy, as well as antimicrobial prophylaxis, result in intestinal barrier disruption and massive changes in microbiota composition. According to clinical studies, a drastic loss of microbial diversity during HSCT is associated with enhanced pro-inflammatory immune response and an increased risk of transplant-related complications such as graft-versus-host disease (GvHD) and mortality. In this review, we outline the current understanding of the role of microbiota diversity in the patient response to cancer therapies and highlight the impact of changes in the gut microbiome on clinical outcomes in post-HSCT patients. Moreover, the therapeutic implications of microbiota modulation by probiotics, prebiotics, and fecal microbiota transplantation (FMT) in hematologic cancer patients receiving HSCT are discussed.

RevDate: 2021-02-11

Ianiro G, Mullish BH, Hvas CL, et al (2021)

SARS-CoV-2 vaccines and donor recruitment for FMT.

RevDate: 2021-02-11

Rebeck ON, Dantas G, DJ Schwartz (2021)

Improving ICI outcomes with a little help from my microbial friends.

Cell host & microbe, 29(2):155-157.

Gut microbiome composition correlates with responsiveness to immune checkpoint inhibitor therapy. In a recent study in Science, Baruch et al. manipulated gut microbiome composition in patients with refractory metastatic melanoma using fecal microbiota transplants. Fecal microbiota transplant was safe and partially effective in inducing remission in refractory patients.

RevDate: 2021-02-11

Huang Y, Yang Q, Mi X, et al (2021)

Ripened Pu-erh Tea Extract Promotes Gut Microbiota Resilience against Dextran Sulfate Sodium Induced Colitis.

Journal of agricultural and food chemistry [Epub ahead of print].

Ripened Pu-erh tea (RPT) has been shown to be an effective natural ingredient to defend against experimentally induced colitis. We hypothesized that RPT would alleviate dextran sulfate sodium (DSS) induced colitis via modulating intestinal microbiota. The effect of RPT on mice gut microbiota was evaluated using 16S rRNA gene amplicon sequencing, broad-spectrum antibiotic (ABX) treatment, and fecal microbiota transplantation (FMT). Pretreatment with RPT enhanced intestinal barrier function, reduced colonic and serum proinflammatory cytokine and macrophage infiltration, and preserved the resilience of gut microbiota in mice during a DSS challenge. Administration of either RPT-regulated or healthy control-derived gut microbiota showed similar protection against colitis, and such protection could not be recapitulated with fecal microbiota from ABX-treated mice, suggesting a key role of protective consortium in the disease protection. Mechanistically, cecal contents of short-chain fatty acids (SCFAs) and colonic peroxisome proliferator activated receptor-γ (PPAR-γ) expression in colitis mice increased significantly by RPT intervention. Collectively, RPT treatment improved DSS-induced colitis by partially reversing the dysbiosis state of gut microbiota, which might be associated with an increase in SCFA level and PPAR-γ expression.

RevDate: 2021-02-11

Wada A, Higashiyama M, Kurihara C, et al (2021)

Protective Effect of Luminal Uric Acid Against Indomethacin-Induced Enteropathy: Role of Antioxidant Effect and Gut Microbiota.

Digestive diseases and sciences [Epub ahead of print].

BACKGROUND: Uric acid (UA) has anti- and pro-inflammatory properties. We previously revealed that elevated serum UA levels provide protection against murine small intestinal injury probably via luminal UA secreted in the small intestine. Luminal UA may act as an antioxidant, preventing microbiota vulnerability to oxidative stress. However, whether luminal UA is increased under hyperuricemia and plays a protective role in a dose-dependent manner as well as the mechanism by which luminal UA exerts its protective effects on enteropathy remains unknown.

METHODS: Inosinic acid (IMP) (1000 mg/kg, i.p.) was administered to obtain high serum UA (HUA) and moderate serum UA (500 mg/kg IMP, i.p.) mice. UA concentrations and levels of oxidative stress markers in the serum and intestine were measured. Mice received indomethacin (20 mg/kg, i.p.) to evaluate the effects of UA on indomethacin-induced enteropathy. Reactive oxygen species (ROS) on the ileal mucosa were analyzed. The fecal microbiota of HUA mice was transplanted to investigate its effect on indomethacin-induced enteropathy.

RESULTS: IMP increased luminal UA dose-dependently, with higher levels of luminal antioxidant markers. Indomethacin-induced enteropathy was significantly ameliorated in both UA-elevated groups, with decreased indomethacin-induced luminal ROS. The microbiota of HUA mice showed a significant increase in α-diversity and a significant difference in β-diversity from the control. Fecal microbiota transplantation from HUA mice ameliorated indomethacin-induced enteropathy.

CONCLUSIONS: The protective role of luminal UA in intestinal injury is likely exerted via oxidative stress elimination and microbiota composition modulation, preferably for gut immunity. Therefore, enhancing anaerobic conditions using antioxidants is a potential therapeutic target.

RevDate: 2021-02-10

Janket SJ, Conte HA, EP Diamandis (2021)

Inappropriate extrapolations abound in fecal microbiota research.

RevDate: 2021-02-11

Gouveia C, Palos C, Pereira P, et al (2020)

Fecal Microbiota Transplant in a Patient Infected with Multidrug-Resistant Bacteria: A Case Report.

GE Portuguese journal of gastroenterology, 28(1):56-61.

Introduction: There has been a growing interest in fecal microbiota transplantation (FMT) as a way to manipulate gut microbiota, with potential benefit in patients infected with multidrug-resistant (MDR) bacteria.

Case Presentation: We present the case of an 87-year-old male with recurrent ascending cholangitis due to biliary atony and impaired biliary drainage after multiple biliary sphincterotomies and two papillary balloon dilations. In this context, a choledochoduodenostomy was performed, but the patient kept on having repeated episodes of acute cholangitis, resulting in multiple hospitalizations, every other week, with need of multiple broad-spectrum antibiotic courses, which led to bacteremias with MDR microorganisms. Several therapeutic strategies such as prophylactic antibiotics (including rifaximin), pre- and probiotics, prokinetics, and ursodeoxycholic acid were unsuccessfully attempted. After multidisciplinary case discussion, an FMT was proposed, with the aim of manipulating gut microbiota and decreasing MDR bacteremias. We first performed FMT via colonoscopy in September 2018, after which the patient still had 3 more hospitalizations for acute cholangitis, but isolated bacteria in blood cultures were resistant only to amoxicillin and clavulanic acid. Considering this apparent change in the microbial resistance profile, we performed a second FMT in January 2019 via the upper gastrointestinal route. During the next 4 months, the patient remained well. In April 2019, the patient relapsed again with three more episodes of cholangitis, for which we repeated the FMT via upper gastrointestinal endoscopy. No readmissions were observed during the next 4 months. All three FMTs were performed without complications.

Discussion and Conclusion: FMT seems to be a safe procedure and was effective in decreasing hospital admissions and changing the profile of MDR bacteria previously isolated from blood cultures.

RevDate: 2021-02-11

Chen H, Chen Z, Shen L, et al (2020)

Fecal microbiota transplantation from patients with autoimmune encephalitis modulates Th17 response and relevant behaviors in mice.

Cell death discovery, 6(1):75.

The significance of the microbiota-gut-brain axis has been increasingly recognized as a major modulator of autoimmunity. Here, we aim to characterize the gut microbiota of a large cohort of treatment-naïve anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis patients relative to that of healthy controls (HCs). Relative to HCs, anti-NMDAR encephalitis patients had a decreased microbiome alpha-diversity index, marked disturbances of gut microbial composition and intestinal permeability damage. Disturbed microbiota in anti-NMDAR encephalitis patients might be linked with different clinical characteristics. Imputed KEGG analysis revealed perturbations of functional modules in the gut microbiomes of anti-NMDAR encephalitis. Compared to HCs, microbiota-depleted mice receiving fecal microbiota transplantation (FMT) from anti-NMDAR encephalitis patients had hypersensitivity and cognitive impairment. Furthermore, anti-NMDAR encephalitis FMT mice showed altered T cells in the spleen and small intestine lamina propria with an increased Th17 cells. Overall, this study first suggests that the anti-NMDAR encephalitis microbiome itself can influence neurologic, Th17 response and behavioral function. The gut microbiota is a potential therapeutic target for anti-NMDAR encephalitis.

RevDate: 2021-02-09

Zhang JD, Liu J, Zhu SW, et al (2021)

Berberine alleviates visceral hypersensitivity in rats by altering gut microbiome and suppressing spinal microglial activation.

Acta pharmacologica Sinica [Epub ahead of print].

Accumulating evidence shows that agents targeting gut dysbiosis are effective for improving symptoms of irritable bowel syndrome (IBS). However, the potential mechanisms remain unclear. In this study we investigated the effects of berberine on the microbiota-gut-brain axis in two rat models of visceral hypersensitivity, i.e., specific pathogen-free SD rats subjected to chronic water avoidance stress (WAS) and treated with berberine (200 mg· kg-1 ·d-1, ig, for 10 days) as well as germ-free (GF) rats subjected to fecal microbiota transplantation (FMT) from a patient with IBS (designated IBS-FMT) and treated with berberine (200 mg· kg-1 ·d-1, ig, for 2 weeks). Before the rats were sacrificed, visceral sensation and depressive behaviors were evaluated. Then colonic tryptase was measured and microglial activation in the dorsal lumbar spinal cord was assessed. The fecal microbiota was profiled using 16S rRNA sequencing, and short chain fatty acids (SCFAs) were measured. We showed that berberine treatment significantly alleviated chronic WAS-induced visceral hypersensitivity and activation of colonic mast cells and microglia in the dorsal lumbar spinal cord. Transfer of fecal samples from berberine-treated stressed donors to GF rats protected against acute WAS. FMT from a patient with IBS induced visceral hypersensitivity and pro-inflammatory phenotype in microglia, while berberine treatment reversed the microglial activation and altered microbial composition and function and SCFA profiles in stools of IBS-FMT rats. We demonstrated that berberine did not directly influence LPS-induced microglial activation in vitro. In both models, several SCFA-producing genera were enriched by berberine treatment, and positively correlated to the morphological parameters of microglia. In conclusion, activation of microglia in the dorsal lumbar spinal cord was involved in the pathogenesis of IBS caused by dysregulation of the microbiota-gut-brain axis, and the berberine-altered gut microbiome mediated the modulatory effects of the agent on microglial activation and visceral hypersensitivity, providing a potential option for the treatment of IBS.

RevDate: 2021-02-12

Liu F, Ye S, Zhu X, et al (2021)

Gastrointestinal disturbance and effect of fecal microbiota transplantation in discharged COVID-19 patients.

Journal of medical case reports, 15(1):60.

BACKGROUND: To investigate the potential beneficial effect of fecal microbiota transplantation (FMT) on gastrointestinal symptoms, gut dysbiosis and immune status in discharged COVID-19 patients.

CASE PRESENTATION: A total of 11 COVID-19 patients were recruited in April, 2020, about one month on average after they were discharged from the hospital. All subjects received FMT for 4 consecutive days by oral capsule administrations with 10 capsules for each day. In total, 5 out of 11 patients reported to be suffered from gastrointestinal symptoms, which were improved after FMT. After FMT, alterations of B cells were observed, which was characterized as decreased naive B cell (P = 0.012) and increased memory B cells (P = 0.001) and non-switched B cells (P = 0.012).The microbial community richness indicated by operational taxonomic units number, observed species and Chao1 estimator was marginally increased after FMT. Gut microbiome composition of discharged COVID-19 patients differed from that of the general population at both phylum and genera level, which was characterized with a lower proportion of Firmicutes (41.0%) and Actinobacteria (4.0%), higher proportion of Bacteroidetes (42.9%) and Proteobacteria (9.2%). FMT can partially restore the gut dysbiosis by increasing the relative abundance of Actinobacteria (15.0%) and reducing Proteobacteria (2.8%) at the phylum level. At the genera level, Bifidobacterium and Faecalibacterium had significantly increased after FMT.

CONCLUSIONS: After FMT, altered peripheral lymphocyte subset, restored gut microbiota and alleviated gastrointestinal disorders were observe, suggesting that FMT may serve as a potential therapeutic and rehabilitative intervention for the COVID-19.

RevDate: 2021-02-09

Pession A, Zama D, Muratore E, et al (2021)

Fecal Microbiota Transplantation in Allogeneic Hematopoietic Stem Cell Transplantation Recipients: A Systematic Review.

Journal of personalized medicine, 11(2): pii:jpm11020100.

The disruption of gut microbiota eubiosis has been linked to major complications in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Various strategies have been developed to reduce dysbiosis and related complications. Fecal microbiota transplantation (FMT) consists of the infusion of fecal matter from a healthy donor to restore impaired intestinal homeostasis, and could be applied in the allo-HSCT setting. We conducted a systematic review of studies addressing the use of FMT in allo-HSCT patients. In the 23 papers included in the qualitative synthesis, FMT was used for the treatment of recurrent Clostridioides difficile infections or as a therapeutic strategy for steroid-resistant gut aGvHD. FMT was also performed with a preventive aim (e.g., to decolonize from antibiotic-resistant bacteria). Additional knowledge on the biological mechanisms underlying clinical findings is needed in order to employ FMT in clinical practice. There is also concern regarding the administration of microbial consortia in immune-compromised patients with altered gut permeability. Therefore, the safety profile and efficacy of the procedure must be determined to better assess the role of FMT in allo-HSCT recipients.

RevDate: 2021-02-12

Wu L, Yan Q, Chen F, et al (2021)

Bupleuri radix extract ameliorates impaired lipid metabolism in high-fat diet-induced obese mice via gut microbia-mediated regulation of FGF21 signaling pathway.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 135:111187 pii:S0753-3322(20)31380-9 [Epub ahead of print].

BACKGROUND: Obesity and its comorbidities are associated with abnormal lipid metabolism and gut microbiota dysbiosis. Bupleuri Radix is a medicinal plant used in traditional Chinese medicine with the prevention and treatment of obesity-related diseases. In this study, we aim to validate the regulation of Bupleuri Radix Extract (BupE) on lipid metabolism in obese mice, and try to find out the potential active components and reveal the underlying mechanisms.

METHODS: Ingredients in BupE, their circulating metabolites in mice and fecal biotransformation products were analyzed by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS). Western blotting, RT-PCR and ELISA were used for tests of objective genes and proteins. 16 s rRNA sequencing was performed to examine intestinal bacteria composition and microbes' functional changes were predicted with PICRUSt software. An absolute quantification method was set up via the construction of recombinant plasmid for the assays of intestinal flora. Specific microbial strains were cultured in anaerobic conditions and oral administrated to mice for intestinal mono-colonization.

RESULTS: BupE attenuated obesity, liver steatosis, and dyslipidemia in HFD-fed mice by up-regulating the expression of FGF21 in liver and white adipose tissue (WAT) as well as the downstream proteins of FGF21 signal pathway including β-klotho, GLUT1 and PGC-1α, etc. UPLC/Q-TOF-MS fingerprints showed no compounds from BupE or their metabolites or biotransformation products were detected in rodent serum samples. High-throughput pyrosequencing data indicated that BupE reversed obesity-induced constructional and functional alterations of intestinal flora. Two bacterial strains, Bacteroides acidifaciens (B. acidifaciens) and Ruminococcus gnavus (R. gnavus), were separated and identified from the feces of obese mice and by intestinal mono-colonization they were verified to intervene in the anti-obesity effects of BupE on mice.

CONCLUSION: These data suggest that BupE protects against diet-induced obesity and counteracts metabolic syndrome features consistent with a mechanism involving the gut-liver axis that boosts hepatic FGF21 secretion and consequent down-stream proteins expression relating to lipid metabolism. And in this gut-liver axis, intestinal microbes such as B.acidifaciens and R.gnavus play an indispensable role.

RevDate: 2021-02-08

Jung HJ, Sorbara MT, EG Pamer (2021)

TAM mediates adaptation of carbapenem-resistant Klebsiella pneumoniae to antimicrobial stress during host colonization and infection.

PLoS pathogens, 17(2):e1009309 pii:PPATHOGENS-D-20-02079 [Epub ahead of print].

Gram-negative pathogens, such as Klebsiella pneumoniae, remodel their outer membrane (OM) in response to stress to maintain its integrity as an effective barrier and thus to promote their survival in the host. The emergence of carbapenem-resistant K. pneumoniae (CR-Kp) strains that are resistant to virtually all antibiotics is an increasing clinical problem and OM impermeability has limited development of antimicrobial agents because higher molecular weight antibiotics cannot access sites of activity. Here, we demonstrate that TAM (translocation and assembly module) deletion increases CR-Kp OM permeability under stress conditions and enhances sensitivity to high-molecular weight antimicrobials. SILAC-based proteomic analyses revealed mis-localization of membrane proteins in the TAM deficient strain. Stress-induced sensitization enhances clearance of TAM-deficient CR-Kp from the gut lumen following fecal microbiota transplantation and from infection sites following pulmonary or systemic infection. Our study suggests that TAM, as a regulator of OM permeability, represents a potential target for development of agents that enhance the effectiveness of existing antibiotics.

RevDate: 2021-02-08

Sofi MH, Wu Y, Ticer T, et al (2021)

A single strain of Bacteroides fragilis protects gut integrity and reduces GVHD.

JCI insight, 6(3): pii:136841.

Graft-versus-host disease (GVHD) is a pathological process caused by an exaggerated donor lymphocyte response to host antigens after allogeneic hematopoietic cell transplantation (allo-HCT). Donor T cells undergo extensive clonal expansion and differentiation, which culminate in damage to recipient target organs. Damage to the gastrointestinal tract is a main contributor to morbidity and mortality. The loss of diversity among intestinal bacteria caused by pretransplant conditioning regimens leads to an outgrowth of opportunistic pathogens and exacerbated GVHD after allo-HCT. Using murine models of allo-HCT, we found that an increase of Bacteroides in the intestinal microbiota of the recipients was associated with reduced GVHD in mice given fecal microbial transplantation. Administration of Bacteroides fragilis through oral gavage increased gut microbiota diversity and beneficial commensal bacteria and significantly ameliorated acute and chronic GVHD development. Preservation of gut integrity following B. fragilis exposure was likely attributed to increased short chain fatty acids, IL-22, and regulatory T cells, which in turn improved gut tight junction integrity and reduced inflammatory cytokine production of pathogenic T cells. The current study provides a proof of concept that a single strain of commensal bacteria can be a safe and effective means to protect gut integrity and ameliorate GVHD after allo-HCT.

RevDate: 2021-02-10

Jeevarathinam AS, Guo F, Williams T, et al (2021)

Enzyme functionalized microgels enable precise regulation of dissolved oxygen and anaerobe culture.

Materials today. Bio, 9:100092.

Anaerobes are a major constituent of the gut microbiome and profoundly influence the overall health of humans. However, the lack of a simple, cost-effective, and scalable system that mimics the anaerobic conditions of the human gut is hindering research on the gut microbiome and the development of therapeutics. Here, we address this gap by using glucose oxidase and catalase containing gelatin microparticles (GOx-CAT-GMPs) to precisely regulate dissolved oxygen concentration [O2] via GOx-mediated consumption of oxygen. Fluorescence images generated using conjugated polymer afterglow nanoparticles showed that [O2] can be tuned from 257.9 ​± ​6.2 to 0.0 ​± ​4.0 ​μM using GOx-CAT-GMPs. Moreover, when the obligate anaerobe Bacteroides thetaiotaomicron was inoculated in media containing GOx-CAT-GMPs, bacterial growth under ambient oxygen was comparable to control conditions in an anaerobic chamber (5.4 ​× ​105 and 8.8 ​× ​105 colony forming units mL-1, respectively). Finally, incorporating GOx-CAT-GMPs into a bioreactor that permitted continuous radial diffusion of oxygen and glucose generated a gut-mimetic [O2] gradient of 132.4 ​± ​2.6 ​μM in the outer ring of the reactor to 7.9 ​± ​1.7 ​μM at the core. Collectively, these results indicate that GOx-CAT-GMPs are highly effective oxygen-regulating materials. These materials can potentially be leveraged to advance gut microbiome research and fecal microbiota transplantation, particularly in low-resource settings.

RevDate: 2021-02-10

Bajaj JS, Shamsaddini A, Fagan A, et al (2021)

Fecal Microbiota Transplant in Cirrhosis Reduces Gut Microbial Antibiotic Resistance Genes: Analysis of Two Trials.

Hepatology communications, 5(2):258-271.

Antibiotic resistance leads to poor outcomes in cirrhosis. Fecal microbiota transplant (FMT) is associated with reduction in antibiotic resistance gene (ARG) burden in patients without cirrhosis; however, the impact in cirrhosis is unclear. We aimed to study the effect of capsule and enema FMT on ARG abundance in fecal samples, which were collected during two published FMT trials in patients with cirrhosis on rifaximin, lactulose, and proton pump inhibitors. ARGs were identified using metagenomics and mapped against the Comprehensive Antibiotic Resistance Database. Changes in ARG abundance were studied within/between groups. The capsule FMT trial involved a one-time FMT or placebo capsule administration with stool collection at baseline and week 4 postintervention. Antibiotics+enema FMT included preprocedure antibiotics followed by FMT enema versus standard-of-care (SOC). Stool was collected at baseline, postantibiotics, and day 7/15 postintervention. Both trials included 20 patients each. There was no safety/infection signal linked to FMT. In the capsule trial, beta-lactamase (OXY/LEN) expression decreased post-FMT versus baseline. Compared to placebo, patients who were post-FMT had lower abundance of vancomycin (VanH), beta-lactamase (ACT), and rifamycin ARGs; the latter was associated with cognitive improvement. No changes were seen within patients treated with placebo. In the antibiotics+enema trial for postantibiotics at day 7 versus baseline, there was an increase in vancomycin and beta-lactamase ARGs, which decreased at day 15. However, quinolone resistance increased at day 15 versus baseline. Between SOC and FMT, day 7 had largely lower ARG (CfxA beta-lactamase, VanW, and VanX) that continued at day 15 (cepA beta-lactamase, VanW). No changes were seen within the SOC group. Conclusion: Despite differences in routes of administration and preintervention antibiotics, we found that ARG abundance is largely reduced after FMT compared to pre-FMT baseline and non-FMT groups in decompensated cirrhosis.

RevDate: 2021-02-10

Mohammadi SO, Yadegar A, Kargar M, et al (2020)

The impact of Helicobacter pylori infection on gut microbiota-endocrine system axis; modulation of metabolic hormone levels and energy homeostasis.

Journal of diabetes and metabolic disorders, 19(2):1855-1861.

The gut microbiota is a complex ecosystem that is involved in the development and preservation of the immune system, energy homeostasis and nutritional status of the host. The crosstalk between gut microbiota and the host cells modulates host physiology and metabolism through different mechanisms. Helicobacter pylori (H. pylori) is known to reside in the gastric mucosa, induce inflammation, and alter both gastric and intestinal microbiota resulting in a broad spectrum of diseases, in particular metabolic syndrome-related disorders. Infection with H. pylori have been shown to affect production level and physiological regulation of the gut metabolic hormones such as ghrelin and leptin which are involved in food intake, energy expenditure and body mass. In this study, we reviewed and discussed data from the literature and follow-up investigations that links H. pylori infection to alterations of the gut microbiota and metabolic hormone levels, which can exert broad influences on host metabolism, energy homeostasis, behavior, appetite, growth, reproduction and immunity. Also, we discussed the strong potential of fecal microbiota transplantation (FMT) as an innovative and promising investigational treatment option for homeostasis of metabolic hormone levels to overcome H. pylori-associated metabolic syndrome-related disorders.

RevDate: 2021-02-12

Strati F, Pujolassos M, Burrello C, et al (2021)

Antibiotic-associated dysbiosis affects the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in experimental colitis models.

Microbiome, 9(1):39.

BACKGROUND: The gut microbiota plays a central role in host physiology and in several pathological mechanisms in humans. Antibiotics compromise the composition and functions of the gut microbiota inducing long-lasting detrimental effects on the host. Recent studies suggest that the efficacy of different clinical therapies depends on the action of the gut microbiota. Here, we investigated how different antibiotic treatments affect the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in an experimental colitis model and in ex vivo experiments with human intestinal biopsies.

RESULTS: Murine fecal donors were pre-treated with different antibiotics, i.e., vancomycin, streptomycin, and metronidazole before FMT administration to colitic animals. The analysis of the gut microbiome, fecal metabolome, and the immunophenotyping of colonic lamina propria immune cells revealed that antibiotic pre-treatment significantly influences the capability of the microbiota to control intestinal inflammation. Streptomycin and vancomycin-treated microbiota failed to control intestinal inflammation and were characterized by the blooming of pathobionts previously associated with IBD as well as with metabolites related to the presence of oxidative stress and metabolism of simple sugars. On the contrary, the metronidazole-treated microbiota retained its ability to control inflammation co-occurring with the enrichment of Lactobacillus and of innate immune responses involving iNKT cells. Furthermore, ex vivo cultures of human intestinal lamina propria mononuclear cells and iNKT cell clones from IBD patients with vancomycin pre-treated sterile fecal water showed a Th1/Th17 skewing in CD4+ T-cell populations; metronidazole, on the other hand, induced the polarization of iNKT cells toward the production of IL10.

CONCLUSIONS: Diverse antibiotic regimens affect the ability of the gut microbiota to control intestinal inflammation in experimental colitis by altering the microbial community structure and microbiota-derived metabolites. Video Abstract.

RevDate: 2021-02-11

Xu F, Li N, Wang C, et al (2021)

Clinical efficacy of fecal microbiota transplantation for patients with small intestinal bacterial overgrowth: a randomized, placebo-controlled clinic study.

BMC gastroenterology, 21(1):54.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is characterized by the condition that bacteria overgrowth in the small intestine. Fecal microbiota transplantation (FMT) has been applied as an effective tool for reestablishing the structure of gut microbiota. However, whether FMT could be applied as a routine SIBO treatment has not been investigated.

METHODS: In this trial, 55 SIBO patients were enrolled. All participants were randomized in two groups, and were given FMT capsule or placebo capsules once a week for 4 consecutive weeks. Measurements including the lactulose hydrogen breath test gastrointestinal symptoms, as well as fecal microbiota diversity were assessed before and after FMT therapy.

RESULTS: Gastrointestinal symptoms significantly improved in SIBO patients after treatment with FMT compared to participants in placebo group. The gut microbiota diversity of FMT group had a significant increase, while placebo group showed none.

CONCLUSIONS: This study suggests that applying FMT for patients with SIBO can alleviate gastrointestinal symptoms, indicating that FMT may be a promising and novel therapeutic regimen for SIBO. Trial registry This study was retrospectively registered with the Chinese Clinical Trial registry on 2019.7.10 (ID: ChiCTR1900024409, http://www.chictr.org.cn).

RevDate: 2021-02-08

Parker KD, Maurya AK, Ibrahim H, et al (2021)

Dietary Rice Bran-Modified Human Gut Microbial Consortia Confers Protection against Colon Carcinogenesis Following Fecal Transfaunation.

Biomedicines, 9(2): pii:biomedicines9020144.

Rice bran, removed from whole grain rice for white rice milling, has demonstrated efficacy for the control and suppression of colitis and colon cancer in multiple animal models. Dietary rice bran intake was shown to modify human stool metabolites as a result of modifications to metabolism by gut microbiota. In this study, human stool microbiota from colorectal cancer (CRC) survivors that consumed rice bran daily was examined by fecal microbiota transplantation (FMT) for protection from azoxymethane and dextran sodium sulfate (AOM/DSS) induced colon carcinogenesis in germ-free mice. Mice transfaunated with rice bran-modified microbiota communities (RMC) harbored fewer neoplastic lesions in the colon and displayed distinct enrichment of Flavonifractor and Oscillibacter associated with colon health, and the depletion of Parabacteroides distasonis correlated with increased tumor burden. Two anti-cancer metabolites, myristoylcarnitine and palmitoylcarnitine were increased in the colon of RMC transplanted mice. Trimethylamine-N-oxide (TMAO) and tartarate that are implicated in CRC development were reduced in murine colon tissue after FMT with rice bran-modified human microbiota. Findings from this study show that rice bran modified gut microbiota from humans confers protection from colon carcinogenesis in mice and suggests integrated dietary-FMT intervention strategies should be tested for colorectal cancer control, treatment, and prevention.

RevDate: 2021-02-08

Plaza-Díaz J, Solis-Urra P, Aragón-Vela J, et al (2021)

Insights into the Impact of Microbiota in the Treatment of NAFLD/NASH and Its Potential as a Biomarker for Prognosis and Diagnosis.

Biomedicines, 9(2): pii:biomedicines9020145.

Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver illness associated with obesity and metabolic disorders, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. A more severe type of NAFLD, non-alcoholic steatohepatitis (NASH), is considered an ongoing global health threat and dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma. Several reports have demonstrated that liver steatosis is associated with the elevation of certain clinical and biochemical markers but with low predictive potential. In addition, current imaging methods are inaccurate and inadequate for quantification of liver steatosis and do not distinguish clearly between the microvesicular and the macrovesicular types. On the other hand, an unhealthy status usually presents an altered gut microbiota, associated with the loss of its functions. Indeed, NAFLD pathophysiology has been linked to lower microbial diversity and a weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defense and inflammation via toll-like receptor signaling. Moreover, this activation of inflammation in hepatocytes induces progression from simple steatosis to NASH. In the present review, we aim to: (a) summarize studies on both human and animals addressed to determine the impact of alterations in gut microbiota in NASH; (b) evaluate the potential role of such alterations as biomarkers for prognosis and diagnosis of this disorder; and (c) discuss the involvement of microbiota in the current treatment for NAFLD/NASH (i.e., bariatric surgery, physical exercise and lifestyle, diet, probiotics and prebiotics, and fecal microbiota transplantation).

RevDate: 2021-02-08

Davar D, Dzutsev AK, McCulloch JA, et al (2021)

Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients.

Science (New York, N.Y.), 371(6529):595-602.

Anti-programmed cell death protein 1 (PD-1) therapy provides long-term clinical benefits to patients with advanced melanoma. The composition of the gut microbiota correlates with anti-PD-1 efficacy in preclinical models and cancer patients. To investigate whether resistance to anti-PD-1 can be overcome by changing the gut microbiota, this clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti-PD-1 in patients with PD-1-refractory melanoma. This combination was well tolerated, provided clinical benefit in 6 of 15 patients, and induced rapid and durable microbiota perturbation. Responders exhibited increased abundance of taxa that were previously shown to be associated with response to anti-PD-1, increased CD8+ T cell activation, and decreased frequency of interleukin-8-expressing myeloid cells. Responders had distinct proteomic and metabolomic signatures, and transkingdom network analyses confirmed that the gut microbiome regulated these changes. Collectively, our findings show that FMT and anti-PD-1 changed the gut microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti-PD-1 in a subset of PD-1 advanced melanoma.

RevDate: 2021-02-09
CmpDate: 2021-02-09

Woelk CH, A Snyder (2021)

Modulating gut microbiota to treat cancer.

Science (New York, N.Y.), 371(6529):573-574.

RevDate: 2021-02-04

Kim M, Huda MN, BJ Bennett (2021)

Sequence Meets Function-Microbiota And Cardiovascular Disease.

Cardiovascular research pii:6127468 [Epub ahead of print].

The discovery that gut-microbiota plays a profound role in human health has opened a new avenues of basic and clinical research. Application of ecological approaches where the Bacterial 16S rRNA gene is queried has provided a number of candidate bacteria associated with coronary artery disease and hypertension. We examine the associations between gut microbiota and a variety of CVD including atherosclerosis, coronary artery disease and blood pressure. These approaches are associative in nature and there is now increasing interest in identifying the mechanisms underlying these associations. We discuss three potential mechanisms including: gut permeability and endotoxemia, increased immune system activation, and microbial derived metabolites. In addition to discussing these potential mechanisms we highlight current studies manipulating the gut microbiota or microbial metabolites to move beyond sequenced based association studies. The goal of these mechanistic studies is to determine the mode of action by which the gut microbiota may affect disease susceptibility and severity. Importantly, the gut microbiota appears to have a significant effect on host metabolism and CVD by producing metabolites entering the host circulatory system such as short chain fatty acids (SCFAs) and trimethylamine N-Oxide (TMAO). Therefore, the intersection of metabolomics and microbiota research may yield novel targets to reduce disease susceptibility. Finally, we discuss approaches to demonstrate causality such as specific diet changes, inhibition of microbial pathways and fecal microbiota transplant.

RevDate: 2021-02-06

Gill T, JT Rosenbaum (2020)

Putative Pathobionts in HLA-B27-Associated Spondyloarthropathy.

Frontiers in immunology, 11:586494.

Spondyloarthritis (SpA) is a group of immune mediated inflammatory diseases with a strong association to the major histocompatibility (MHC) class I molecule, HLA-B27. Although the association between HLA-B27 and AS has been known for almost 50 years, the mechanisms underlying disease pathogenesis are elusive. Over the years, three hypotheses have been proposed to explain HLA-B27 and disease association: 1) HLA B27 presents arthritogenic peptides and thus creates a pathological immune response; 2) HLA-B27 misfolding causes endoplasmic reticulum (ER) stress which activates the unfolded protein response (UPR); 3) HLA-B27 dimerizes on the cell surface and acts as a target for natural killer (NK) cells. None of these hypotheses explains SpA pathogenesis completely. Evidence supports the hypothesis that HLA-B27-related diseases have a microbial pathogenesis. In animal models of various SpAs, a germ-free environment abrogates disease development and colonizing these animals with gut commensal microbes can restore disease manifestations. The depth of microbial influence on SpA development has been realized due to our ability to characterize microbial communities in the gut using next-generation sequencing approaches. In this review, we will discuss various putative pathobionts in the pathogenesis of HLA-B27-associated diseases. We pursue whether a single pathobiont or a disruption of microbial community and function is associated with HLA-B27-related diseases. Furthermore, rather than a specific pathobiont, metabolic functions of various disease-associated microbes might be key. While the use of germ-free models of SpA have facilitated understanding the role of microbes in disease development, future studies with animal models that mimic diverse microbial communities instead of mono-colonization are indispensable. We discuss the causal mechanisms underlying disease pathogenesis including the role of these pathobionts on mucin degradation, mucosal adherence, and gut epithelial barrier disruption and inflammation. Finally, we review the various uses of microbes as therapeutic modalities including pre/probiotics, diet, microbial metabolites and fecal microbiota transplant. Unravelling these complex host-microbe interactions will lead to the development of new targets/therapies for alleviation of SpA and other HLA-B27 associated diseases.

RevDate: 2021-02-04

Seo HS, Chin HS, Kim YH, et al (2021)

Laboratory Aspects of Donor Screening for Fecal Microbiota Transplantation at a Korean Fecal Microbiota Bank.

Annals of laboratory medicine, 41(4):424-428.

Fecal microbiota transplantation (FMT) is a widely accepted alternative therapy for Clostridioides difficile infection and other gastrointestinal disorders. Thorough donor screening is required as a safety control measure to minimize transmission of infectious agents in FMT. We report the donor screening process and outcomes at a fecal microbiota bank in Korea. From August 2017 to June 2020, the qualification of 62 individuals as FMT donors was evaluated using clinical assessment and laboratory tests. Forty-six (74%) candidates were excluded after clinical assessment; high body mass index (>25) was the most common reason for exclusion, followed by atopy, asthma, and allergy history. Four of the remaining 16 (25%) candidates failed to meet laboratory test criteria, resulting in a 19% qualification rate. FMT donor re-qualification was conducted monthly as an additional safety control measure, and only three (5%) candidates were eligible for repeated donation. As high prevalence of multidrug-resistant organisms (55%) and Helicobacter pylori (44%) were detected in qualified donors during the screening, a urea breath test was added to the existing protocol. The present results emphasize the importance of implementing a donor re-qualification system to minimize risk factors not identified during initial donor screening.

RevDate: 2021-02-04

Parisi A, Porzio G, Pulcini F, et al (2021)

What Is Known about Theragnostic Strategies in Colorectal Cancer.

Biomedicines, 9(2): pii:biomedicines9020140.

Despite the paradigmatic shift occurred in recent years for defined molecular subtypes in the metastatic setting treatment, colorectal cancer (CRC) still remains an incurable disease in most of the cases. Therefore, there is an urgent need for new tools and biomarkers for both early tumor diagnosis and to improve personalized treatment. Thus, liquid biopsy has emerged as a minimally invasive tool that is capable of detecting genomic alterations from primary or metastatic tumors, allowing the prognostic stratification of patients, the detection of the minimal residual disease after surgical or systemic treatments, the monitoring of therapeutic response, and the development of resistance, establishing an opportunity for early intervention before imaging detection or worsening of clinical symptoms. On the other hand, preclinical and clinical evidence demonstrated the role of gut microbiota dysbiosis in promoting inflammatory responses and cancer initiation. Altered gut microbiota is associated with resistance to chemo drugs and immune checkpoint inhibitors, whereas the use of microbe-targeted therapies including antibiotics, pre-probiotics, and fecal microbiota transplantation can restore response to anticancer drugs, promote immune response, and therefore support current treatment strategies in CRC. In this review, we aim to summarize preclinical and clinical evidence for the utilization of liquid biopsy and gut microbiota in CRC.

RevDate: 2021-02-03

Ruan W, R Kellermayer (2021)

Alternative Diagnoses in Pediatric Fecal Microbiota Transplant Referral Patients.

Journal of pediatric gastroenterology and nutrition pii:00005176-900000000-95775 [Epub ahead of print].

ABSTRACT: The incidence of Clostridioides difficile infection (CDI) has been increasing in the United States. About 10-20% recur after initial treatment, with increasing recurrence following subsequent treatment courses. This sequence can lead to recurrent CDI (rCDI), refractory to conventional therapeutics resulting in the most common indication for fecal microbiota transplantation (FMT). FMT is the most effective microbial therapeutic to date and can cure rCDI in 80-90% of cases. There is growing concern, however, for pathogen transmission through FMT, underscoring the importance of careful recipient selection. In adults referred for FMT with a tentative diagnosis of rCDI, alternative diagnoses were recognized in 25% of patients, but such observation in children is lacking. In this single-center retrospective study, alternative diagnoses (for example constipation/overflow diarrhea, inflammatory bowel disease) were found in 13 (22.4%) of 58 children who were referred for FMT evaluation for rCDI. Of the patients who were diagnosed with rCDI, 16 (27.6%) did not require FMT.

RevDate: 2021-02-04

Durham SH, Le P, AT Cassano (2020)

Navigating changes in Clostridioides difficile prevention and treatment.

Journal of managed care & specialty pharmacy, 26(12-a Suppl):S3-S23.

Clostridioides difficile (C. difficile, previously known as Clostridium difficile) infections are a major health care concern. The Centers for Disease Control and Prevention (CDC) estimates that C. difficile causes almost half a million illnesses in the United States yearly, and approximately 1 in 5 patients with a C. difficile infection (CDI) will experience 1 or more recurrent infections. The incidence of infection has risen dramatically in recent years, and infection severity has increased due to the emergence of hypervirulent strains. There have been noteworthy advances in the development of CDI prevention and treatment, including a growth in the understanding of the role a patient's gut microbiome plays. The 2017 Infectious Diseases Society of America (IDSA) guidelines made a significant change in treatment recommendations for first time CDI episodes by recommending the use of oral vancomycin or fidaxomicin in place of metronidazole as a first-line treatment. The guidelines also included detailed recommendations on the use of fecal microbiota transplant (FMT) in those patients who experience 3 or more recurrent CDI episodes. A number of novel therapies for the treatment of CDI are in various stages of development. Treatments currently in phase 3 trials include the antibiotic ridinilazole, the microbiome products SER-109 and RBX2660, and a vaccine. All of these agents have shown promise in phase 1 and 2 trials. Additionally, several other antibiotic and microbiome candidates are currently in phase 1 or phase 2 trials. A qualitative review and evaluation of the literature on the cost-effectiveness of treatments for CDI in the U.S. setting was conducted, and the summary provided herein. Due to the higher cost of newer agents, cost-effectiveness evaluations will continue to be critical in clinical decision making for CDI. This paper reviews the updated CDI guidelines for prevention and treatment, the role of the microbiome in new and recurrent infections, pipeline medications, and comparative effectiveness research (CER) data on these treatments. DISCLOSURES: Durham and Le have nothing to disclose. Cassano reports consulting fees from Baxter Healthcare. Peer reviewers Drs. Ami Gopalan and Mark Rubin and Ms. Kathleen Jarvis have nothing to disclose. Planners Dr. Christine L. Cooper and Ms. Susan Yarbrough have nothing to disclose.

RevDate: 2021-02-06

Shin W, Ambrosini YM, Shin YC, et al (2020)

Robust Formation of an Epithelial Layer of Human Intestinal Organoids in a Polydimethylsiloxane-Based Gut-on-a-Chip Microdevice.

Frontiers in medical technology, 2:.

Polydimethylsiloxane (PDMS) is a silicone polymer that has been predominantly used in a human organ-on-a-chip microphysiological system. The hydrophobic surface of a microfluidic channel made of PDMS often results in poor adhesion of the extracellular matrix (ECM) as well as cell attachment. The surface modification by plasma or UV/ozone treatment in a PDMS-based device produces a hydrophilic surface that allows robust ECM coating and the reproducible attachment of human intestinal immortalized cell lines. However, these surface-activating methods have not been successful in forming a monolayer of the biopsy-derived primary organoid epithelium. Several existing protocols to grow human intestinal organoid cells in a PDMS microchannel are not always reproducibly operative due to the limited information. Here, we report an optimized methodology that enables robust and reproducible attachment of the intestinal organoid epithelium in a PDMS-based gut-on-a-chip. Among several reported protocols, we optimized a method by performing polyethyleneimine-based surface functionalization followed by the glutaraldehyde cross linking to activate the PDMS surface. Moreover, we discovered that the post-functionalization step contributes to provide uniform ECM deposition that allows to produce a robust attachment of the dissociated intestinal organoid epithelium in a PDMS-based microdevice. We envision that our optimized protocol may disseminate an enabling methodology to advance the integration of human organotypic cultures in a human organ-on-a-chip for patient-specific disease modeling.

RevDate: 2021-02-12

Littmann ER, Lee JJ, Denny JE, et al (2021)

Host immunity modulates the efficacy of microbiota transplantation for treatment of Clostridioides difficile infection.

Nature communications, 12(1):755.

Fecal microbiota transplantation (FMT) is a successful therapeutic strategy for treating recurrent Clostridioides difficile infection. Despite remarkable efficacy, implementation of FMT therapy is limited and the mechanism of action remains poorly understood. Here, we demonstrate a critical role for the immune system in supporting FMT using a murine C. difficile infection system. Following FMT, Rag1 heterozygote mice resolve C. difficile while littermate Rag1-/- mice fail to clear the infection. Targeted ablation of adaptive immune cell subsets reveal a necessary role for CD4+ Foxp3+ T-regulatory cells, but not B cells or CD8+ T cells, in FMT-mediated resolution of C. difficile infection. FMT non-responsive mice exhibit exacerbated inflammation, impaired engraftment of the FMT bacterial community and failed restoration of commensal bacteria-derived secondary bile acid metabolites in the large intestine. These data demonstrate that the host's inflammatory immune status can limit the efficacy of microbiota-based therapeutics to treat C. difficile infection.

RevDate: 2021-02-12

Haifer C, Paramsothy S, Borody TJ, et al (2021)

Long-Term Bacterial and Fungal Dynamics following Oral Lyophilized Fecal Microbiota Transplantation in Clostridioides difficile Infection.

mSystems, 6(1):.

Oral lyophilized fecal microbiota transplantation (FMT) is effective in recurrent Clostridioides difficile infection (CDI); however, limited data exist on its efficacy in primary CDI and long-term microbial engraftment. Patients with primary or recurrent CDI were prospectively enrolled to receive oral FMT. Changes in the bacterial and fungal communities were characterized prior to and up to 6 months following treatment. A total of 37 patients with CDI (15 primary, 22 recurrent) were treated with 6 capsules each containing 0.35-g lyophilized stool extract. A total of 33 patients (89%) had sustained CDI cure, of whom 3 required a second course. There were no safety signals identified. FMT significantly increased bacterial diversity and shifted composition toward donor profiles in responders but not in nonresponders, with robust donor contribution observed to 6 months following FMT (P < 0.001). Responders showed consistent decreases in Enterobacteriaceae and increases in Faecalibacterium sp. to levels seen in donors. Mycobiome profiling revealed an association with FMT failure and increases in one Penicillium taxon, as well as coexclusion relationships between Candida sp. and bacterial taxa enriched in both donors and responders. Primary CDI was associated with more robust changes in the bacterial community than those with recurrent disease. Oral FMT leads to durable microbial engraftment in patients with primary and recurrent CDI, with several microbial taxa being associated with therapy outcome. Novel coexclusion relationships between bacterial and fungal species support the clinical relevance of transkingdom dynamics.IMPORTANCEClostridioides difficile infection (CDI) is a substantial health concern worldwide, complicated by patterns of increasing antibiotic resistance that may impact primary treatment. Orally administered fecal microbiota transplantation (FMT) is efficacious in the management of recurrent CDI, with specific bacterial species known to influence clinical outcomes. To date, little is known about the efficacy of FMT in primary CDI and the impact of the mycobiome on therapeutic outcomes. We performed matched bacterial and fungal sequencing on longitudinal samples from a cohort of patients treated with oral FMT for primary and recurrent CDI. We validated many bacterial signatures following oral therapy, confirmed engraftment of donor microbiome out to 6 months following therapy, and demonstrated coexclusion relationships between Candida albicans and two bacterial species in the gut microbiota, which has potential significance beyond CDI, including in the control of gut colonization by this fungal species.

RevDate: 2021-02-05

Subba R, Sandhir R, Singh SP, et al (2021)

Pathophysiology linking Depression and Type 2 Diabetes: Psychotherapy, Physical Exercise and Fecal Microbiome Transplantation as damage control.

The European journal of neuroscience [Epub ahead of print].

Diabetes increases the likelihood of developing depression and vice versa. Research on this bidirectional association has somewhat managed to delineate the interplay among implicated physiological processes. Still, further exploration is required in this context. This review addresses the comorbidity by investigating suspected common pathophysiological mechanisms. One such factor is psychological stress which disturbs the hypothalamic-pituitary-adrenal axis causing hormonal imbalance. This includes elevated cortisol levels, a common biomarker of both depression and diabetes. Disrupted insulin signaling drives the hampered neurotransmission of serotonin, dopamine, and norepinephrine. Also, adipokine hormones such as adiponectin, leptin, and resistin, and the orexigenic hormone, ghrelin, are involved in both depression and T2DM. This disarray further interferes with physiological processes encompassing sleep, the gut-brain axis, metabolism, and mood stability. Behavioral coping mechanisms, such as unhealthy eating, mediate disturbed glucose homeostasis, and neuroinflammation. This is intricately linked to oxidative stress, redox imbalance, and mitochondrial dysfunction. However, interventions such as psychotherapy, physical exercise, fecal microbiota transplantation, and insulin-sensitizing agents can help to manage the distressing condition. The possibility of Glucagon-like peptide 1 possessing a therapeutic role has also been discussed. Nonetheless, there stands an urgent need for unraveling new correlating targets and biological markers for efficient treatment.

RevDate: 2021-02-02

Liu Y, Tran DQ, Lindsey JW, et al (2021)

The Association of Gut Microbiota and Treg Dysfunction in Autoimmune Diseases.

Advances in experimental medicine and biology, 1278:191-203.

Autoimmune conditions affect 23 million Americans or 7% of the US population. There are more than 100 autoimmune disorders, affecting every major organ system in humans. This chapter aims to further explain Treg dysfunction autoimmune disorders, including monogenic primary immune deficiency such as immune dysregulation polyendocrinopathy, enteropathy, X-linked inheritance (IPEX) syndrome, and polygenic autoimmune diseases with Treg dysfunction such as multiple sclerosis (MS), inflammatory bowel disease (IBD), and food allergy. These conditions are associated with an abnormal small intestinal and colonic microbiome. Some disorders clearly improve with therapies aimed at microbial modification, including probiotics and fecal microbiota transplantation (FMT). Approaches to prevent and treat these disorders will need to focus on the acquisition and maintenance of a healthy colonic microbiota, in addition to more focused approaches at immune suppression during acute disease exacerbations.

RevDate: 2021-02-02

Zheng L, XL Wen (2021)

Gut microbiota and inflammatory bowel disease: The current status and perspectives.

World journal of clinical cases, 9(2):321-333.

Inflammatory bowel disease (IBD) is a chronic immune-mediated disease that affects the gastrointestinal tract. It is argued that environment, microbiome, and immune-mediated factors interact in a genetically susceptible host to trigger IBD. Recently, there has been increased interest in the development, progression, and treatment of IBD because of our understanding of the microbiome. Researchers have proved that some factors can alter the microbiome and the pathogenesis of IBD. As a result, there has been increasing interest in the application of probiotics, prebiotics, antibiotics, fecal microbiota transplantation, and gene manipulation in treating IBD because of the possible curative effect of microbiome-modulating interventions. In this review, we summarize the findings from human and animal studies and discuss the effect of the gut microbiome in treating patients with IBD.

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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.

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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).

Timelines

ESP now offers a much improved and expanded collection of timelines, designed to give the user choice over subject matter and dates.

Biographies

Biographical information about many key scientists.

Selected Bibliographies

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

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