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1.
World J Gastroenterol ; 30(16): 2179-2183, 2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38690018

ABSTRACT

In this editorial we comment on the article published in the recent issue of the World journal of Gastroenterology. We focus specifically on the mechanisms un-derlying the effects of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS), the factors which affect the outcomes of FMT in IBS patients, and challenges. FMT has emerged as a efficacious intervention for clostridium difficile infection and holds promise as a therapeutic modality for IBS. The utilization of FMT in the treatment of IBS has undergone scrutiny in numerous randomized controlled trials, yielding divergent outcomes. The current frontier in this field seeks to elucidate these variations, underscore the existing knowledge gaps that necessitate exploration, and provide a guideline for successful FMT imple-mentation in IBS patients. At the same time, the application of FMT as a treatment for IBS confronts several challenges.


Subject(s)
Fecal Microbiota Transplantation , Gastrointestinal Microbiome , Irritable Bowel Syndrome , Irritable Bowel Syndrome/therapy , Irritable Bowel Syndrome/microbiology , Fecal Microbiota Transplantation/methods , Humans , Treatment Outcome , Feces/microbiology , Randomized Controlled Trials as Topic , Clostridioides difficile/pathogenicity , Clostridium Infections/therapy , Clostridium Infections/microbiology
2.
Dtsch Med Wochenschr ; 149(12): 709-713, 2024 Jun.
Article in German | MEDLINE | ID: mdl-38781994

ABSTRACT

Gastrointestinal infections are still responsible for around 60% of the infectious diseases that must be reported in Germany and are probably among the most common gastroenterological diseases. The main therapy for gastrointestinal infections remains oral fluid replacement. The recommendations for Clostridioides difficile infections (CDI) have been adapted according to the current data and based on international guidelines; vancomycin or, especially if there is an increased risk of recurrence, fidaxomicin should now be used primarily in CDI. In the case of febrile diarrhea and/or bloody diarrhea, malaria diagnosis should be carried out immediately.


Subject(s)
Gastrointestinal Diseases , Practice Guidelines as Topic , Humans , Gastrointestinal Diseases/therapy , Gastrointestinal Diseases/diagnosis , Germany , Clostridium Infections/diagnosis , Clostridium Infections/therapy , Anti-Bacterial Agents/therapeutic use
3.
J Prim Care Community Health ; 15: 21501319241249645, 2024.
Article in English | MEDLINE | ID: mdl-38726585

ABSTRACT

Clostridioides difficile infection (CDI) is one of the most common and severe nosocomial infections worldwide. It can also affect healthy individuals in the community. The incidence of CDI has been on the rise globally for the past decade, necessitating a proactive approach to combat its spread; new strategies are being developed to enhance diagnostic accuracy and optimize treatment outcomes. Implementing the 2-step testing has increased diagnostic specificity, reducing the usage of CD-specific antibiotics with no concomitant increase in surgical complication rates. In 2021, the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) shifted its preference for initial treatment to fidaxomicin over vancomycin and metronidazole due to its lower recurrence rate. It also prioritized fidaxomicin for the treatment of recurrent CDI. There are new developments on the frontiers of fecal microbiota therapies, with RBX2660 and SER-109 approved recently by the FDA for prevention, with other microbiome-based therapies in various development and clinical trials. This review offers providers an updated and practical guide for CDI management.


Subject(s)
Anti-Bacterial Agents , Clostridioides difficile , Clostridium Infections , Humans , Clostridium Infections/prevention & control , Clostridium Infections/diagnosis , Clostridium Infections/therapy , Anti-Bacterial Agents/therapeutic use , Fecal Microbiota Transplantation , Cross Infection/prevention & control , Practice Guidelines as Topic , Fidaxomicin/therapeutic use , Metronidazole/therapeutic use
4.
Nat Commun ; 15(1): 2842, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38565558

ABSTRACT

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


Subject(s)
Clostridioides difficile , Clostridium Infections , Animals , Mice , Arginine , Ornithine , Intestines/microbiology , Fecal Microbiota Transplantation , Clostridium Infections/therapy , Clostridium Infections/microbiology
5.
Appl Environ Microbiol ; 90(5): e0001624, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38651930

ABSTRACT

Growing evidence demonstrates the key role of the gut microbiota in human health and disease. The recent success of microbiotherapy products to treat recurrent Clostridioides difficile infection has shed light on its potential in conditions associated with gut dysbiosis, such as acute graft-versus-host disease, intestinal bowel diseases, neurodegenerative diseases, or even cancer. However, the difficulty in defining a "good" donor as well as the intrinsic variability of donor-derived products' taxonomic composition limits the translatability and reproducibility of these studies. Thus, the pooling of donors' feces has been proposed to homogenize product composition and achieve higher taxonomic richness and diversity. In this study, we compared the metagenomic profile of pooled products to corresponding single donor-derived products. We demonstrated that pooled products are more homogeneous, diverse, and enriched in beneficial bacteria known to produce anti-inflammatory short chain fatty acids compared to single donor-derived products. We then evaluated pooled products' efficacy compared to corresponding single donor-derived products in Salmonella and C. difficile infectious mouse models. We were able to demonstrate that pooled products decreased pathogenicity by inducing a structural change in the intestinal microbiota composition. Single donor-derived product efficacy was variable, with some products failing to control disease progression. We further performed in vitro growth inhibition assays of two extremely drug-resistant bacteria, Enterococcus faecium vanA and Klebsiella pneumoniae oxa48, supporting the use of pooled microbiotherapies. Altogether, these results demonstrate that the heterogeneity of donor-derived products is corrected by pooled fecal microbiotherapies in several infectious preclinical models.IMPORTANCEGrowing evidence demonstrates the key role of the gut microbiota in human health and disease. Recent Food and Drug Administration approval of fecal microbiotherapy products to treat recurrent Clostridioides difficile infection has shed light on their potential to treat pathological conditions associated with gut dysbiosis. In this study, we combined metagenomic analysis with in vitro and in vivo studies to compare the efficacy of pooled microbiotherapy products to corresponding single donor-derived products. We demonstrate that pooled products are more homogeneous, diverse, and enriched in beneficial bacteria compared to single donor-derived products. We further reveal that pooled products decreased Salmonella and Clostridioides difficile pathogenicity in mice, while single donor-derived product efficacy was variable, with some products failing to control disease progression. Altogether, these findings support the development of pooled microbiotherapies to overcome donor-dependent treatment efficacy.


Subject(s)
Clostridioides difficile , Clostridium Infections , Disease Models, Animal , Fecal Microbiota Transplantation , Feces , Gastrointestinal Microbiome , Animals , Mice , Clostridium Infections/therapy , Clostridium Infections/microbiology , Feces/microbiology , Bacteria/classification , Bacteria/genetics , Humans , Mice, Inbred C57BL , Female
6.
Surg Clin North Am ; 104(3): 545-556, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38677819

ABSTRACT

Clostridioides difficile colitis is an important source of hospital-acquired diarrhea associated with antibiotic use. Symptoms are profuse watery diarrhea, typically following a course of antibiotics; however, some cases of fulminant disease may manifest with shock, ileus, or megacolon. Nonfulminant colitis is treated with oral fidaxomicin. C difficile colitis has a high potential for recurrence, and recurrent episodes are also treated with fidaxomicin. Bezlotoxumab is another medication that may be used in populations at high risk for further recurrence. Fulminant disease is treated with maximal medical therapy and early surgical consultation. Antibiotic stewardship is critical to preventing C difficile colitis.


Subject(s)
Anti-Bacterial Agents , Clostridioides difficile , Clostridium Infections , Colitis , Humans , Clostridium Infections/diagnosis , Clostridium Infections/therapy , Anti-Bacterial Agents/therapeutic use , Colitis/microbiology , Colitis/diagnosis , Colitis/therapy , Fidaxomicin/therapeutic use
7.
Surg Clin North Am ; 104(3): 647-656, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38677827

ABSTRACT

The gut microbiome is defined as the microorganisms that reside within the gastrointestinal tract and produce a variety of metabolites that impact human health. These microbes play an intricate role in human health, and an imbalance in the gut microbiome, termed gut dysbiosis, has been implicated in the development of varying diseases. The purpose of this review is to highlight what is known about the microbiome and its impact on colorectal cancer, inflammatory bowel disease, constipation, Clostridioides difficile infection, the impact of bowel prep, and anastomotic leaks.


Subject(s)
Colorectal Neoplasms , Gastrointestinal Microbiome , Humans , Gastrointestinal Microbiome/physiology , Colorectal Neoplasms/microbiology , Dysbiosis/microbiology , Inflammatory Bowel Diseases/microbiology , Clostridium Infections/therapy , Clostridium Infections/microbiology , Constipation/microbiology , Constipation/etiology , Anastomotic Leak/microbiology , Anastomotic Leak/etiology
8.
J Hosp Infect ; 148: 189-219, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38609760

ABSTRACT

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


Subject(s)
Clostridium Infections , Fecal Microbiota Transplantation , Fecal Microbiota Transplantation/methods , Humans , Clostridium Infections/therapy , United Kingdom , Clostridioides difficile , COVID-19/therapy , Recurrence , Gastroenterology/standards , Gastroenterology/methods , SARS-CoV-2 , Societies, Medical
9.
Expert Rev Anti Infect Ther ; 22(5): 297-306, 2024 May.
Article in English | MEDLINE | ID: mdl-38676422

ABSTRACT

INTRODUCTION: Strong clinical data demonstrate that inflammatory bowel disease (IBD) is an independent risk factor for Clostridiodes difficile infection (CDI) and suggest a globally increased prevalence and severity of C. difficile coinfection in IBD patients (CDI-IBD). In addition to elderly individuals, children are also at higher risk of CDI-IBD. Rapid diagnosis is essential since the clinical manifestations of active IBD and CDI-IBD are indistinguishable. Antibiotics have been well established in the treatment of CDI-IBD, but they do not prevent recurrence. AREAS COVERED: Herein, the authors focus on reviewing recent research advances on the new therapies of CDI-IBD. The novel therapies include gut microbiota restoration therapies (such as prebiotics, probiotics and FMT), immunotherapy (such as vaccines and monoclonal antibodies) and diet strategies (such as groningen anti-inflammatory diet and mediterranean diet). Future extensive prospective and placebo-controlled studies are required to evaluate their efficacy and long-term safety. EXPERT OPINION: Available studies show that the prevalence of CDI-IBD is not optimistic. Currently, potential treatment options for CDI-IBD include a number of probiotics and novel antibiotics. This review updates the knowledge on the management of CDI in IBD patients, which is timely and important for GI doctors and scientists.


Subject(s)
Anti-Bacterial Agents , Clostridium Infections , Inflammatory Bowel Diseases , Probiotics , Humans , Clostridium Infections/therapy , Clostridium Infections/microbiology , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/therapy , Inflammatory Bowel Diseases/microbiology , Probiotics/administration & dosage , Anti-Bacterial Agents/administration & dosage , Risk Factors , Fecal Microbiota Transplantation , Clostridioides difficile/isolation & purification , Gastrointestinal Microbiome , Prebiotics/administration & dosage , Coinfection , Immunotherapy/methods , Child , Prevalence , Severity of Illness Index , Age Factors , Aged
10.
Microbiol Spectr ; 12(5): e0378423, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38511948

ABSTRACT

Clostridium perfringens is a prevalent bacterial pathogen in poultry, and due to the spread of antimicrobial resistance, alternative treatments are needed to prevent and treat infection. Bacteriophages (phages), viruses that kill bacteria, offer a viable option and can be used therapeutically to treat C. perfringens infections. The aim of this study was to isolate phages against C. perfringens strains currently circulating on farms across the world and establish their virulence and development potential using host range screening, virulence assays, and larva infection studies. We isolated 32 phages of which 19 lysed 80%-92% of our global C. perfringens poultry strain collection (n = 97). The virulence of these individual phages and 32 different phage combinations was quantified in liquid culture at multiple doses. We then developed a multi-strain C. perfringens larva infection model, to mimic an effective poultry model used by the industry. We tested the efficacy of 16/32 phage cocktails in the larva model. From this, we identified that our phage cocktail consisting of phages CPLM2, CPLM15, and CPLS41 was the most effective at reducing C. perfringens colonization in infected larvae when administered before bacterial challenge. These data suggest that phages do have significant potential to prevent and treat C. perfringens infection in poultry. IMPORTANCE: Clostridium perfringens causes foodborne illness worldwide, and 95% of human infections are linked to the consumption of contaminated meat, including chicken products. In poultry, C. perfringens infection causes necrotic enteritis, and associated mortality rates can be up to 50%. However, treating infections is difficult as the bacterium is becoming antibiotic-resistant. Furthermore, the poultry industry is striving toward reduced antibiotic usage. Bacteriophages (phages) offer a promising alternative, and to progress this approach, robust suitable phages and laboratory models that mimic C. perfringens infections in poultry are required. In our study, we isolated phages targeting C. perfringens and found that many lyse C. perfringens strains isolated from chickens worldwide. Consistent with other published studies, in the model systems we assayed here, when some phages were combined as cocktails, the infection was cleared most effectively compared to individual phage use.


Subject(s)
Bacteriophages , Clostridium Infections , Clostridium perfringens , Host Specificity , Poultry Diseases , Clostridium perfringens/virology , Animals , Bacteriophages/physiology , Clostridium Infections/microbiology , Clostridium Infections/therapy , Clostridium Infections/veterinary , Poultry Diseases/microbiology , Poultry Diseases/virology , Virulence , Chickens , Poultry/microbiology , Phage Therapy/methods , Larva/microbiology , Larva/virology , Disease Models, Animal
11.
Res Vet Sci ; 172: 105241, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38555776

ABSTRACT

Necrotic enteritis caused by Clostridium perfringens (CP), is a common enteric disease of poultry that has been previously controlled by in-feed antibiotics. However, due to the rapid emergence of antimicrobial resistance, alternatives to antibiotics such as probiotics have received considerable attention because of their immunomodulatory and intestinal health benefits. The present study investigated the effects of probiotic lactobacilli on gut histomorphology and intestinal innate responses in chickens. Day-old male broiler chickens were treated with 1 × 107 or 1 × 108 colony-forming units (CFU) of a lactobacilli cocktail on days 1, 7, 14, and 20 post-hatch, while control groups were not treated with lactobacilli. On day 21, birds in all groups (except the negative control) were challenged with 3 × 108 CFU of CP for 3 days. Intestinal tissue samples were collected before and after the CP challenge to assess gene expression and for histomorphological analysis. Lactobacilli treatment at a dose of 1 × 108 CFU conferred partial protection against NE by lowering lesion scores, increasing villus height in the ileum and reducing crypt depth in the jejunum. In addition, 1 × 108 CFU of lactobacilli enhanced the expression of Toll-like receptor (TLR) 2, interferon-gamma (IFN-γ), interleukin (IL)-10, IL-12, and IL-13 in both the jejunum and ileum at different timepoints and subsequently decreased the expression of transforming growth factor beta (TGF-ß) and IL-1ß post-CP challenge. In conclusion, the results indicate that treatment with lactobacilli mitigated NE in a dose-dependent manner via improvement of intestinal morphology and modulation of innate immune response in chickens.


Subject(s)
Chickens , Clostridium Infections , Clostridium perfringens , Immunity, Innate , Lactobacillus , Poultry Diseases , Probiotics , Animals , Chickens/immunology , Chickens/microbiology , Clostridium perfringens/physiology , Male , Clostridium Infections/veterinary , Clostridium Infections/immunology , Clostridium Infections/therapy , Clostridium Infections/microbiology , Poultry Diseases/microbiology , Poultry Diseases/immunology , Probiotics/administration & dosage , Probiotics/pharmacology , Intestines/microbiology , Enteritis/veterinary , Enteritis/microbiology , Enteritis/immunology
12.
Aliment Pharmacol Ther ; 59(11): 1335-1349, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38534216

ABSTRACT

BACKGROUND: Clostridioides difficile is the most common cause of healthcare-associated infection, and severe cases can result in significant complications. While anti-microbial therapy is central to infection management, adjunctive therapies may be utilised as preventative strategies. AIM: This article aims to review updates in the epidemiology, diagnosis, and management, including treatment and prevention, of C. difficile infections. METHODS: A narrative review was performed to evaluate the current literature between 1986 and 2023. RESULTS: The incidence of C. difficile infection remains significantly high in both hospital and community settings, though with an overall decline in recent years and similar surveillance estimates globally. Vancomycin and fidaxomicin remain the first line antibiotics for treatment of non-severe C. difficile infection, though due to lower recurrence rates, infectious disease society guidelines now favour use of fidaxomicin. Faecal microbiota transplantation should still be considered to prevent recurrent C. difficile infection. However, in the past year the field has had a significant advancement with the approval of the first two live biotherapeutic products-faecal microbiota spores-live brpk, an oral capsule preparation, and faecal microbiota live-jslm-both indicated for the prevention of recurrent C. difficile infection, with additional therapies on the horizon. CONCLUSION: Although the prevalence of C. difficile infection remains high, there have been significant advances in the development of novel therapeutics and preventative measures following changes in recent practice guidelines, and will continue to evolve in the future.


Subject(s)
Anti-Bacterial Agents , Clostridioides difficile , Clostridium Infections , Fecal Microbiota Transplantation , Humans , Clostridium Infections/epidemiology , Clostridium Infections/drug therapy , Clostridium Infections/therapy , Clostridium Infections/prevention & control , Anti-Bacterial Agents/therapeutic use , Cross Infection/epidemiology , Cross Infection/drug therapy , Cross Infection/prevention & control , Fidaxomicin/therapeutic use , Incidence , Vancomycin/therapeutic use
13.
Dig Dis Sci ; 69(5): 1778-1784, 2024 May.
Article in English | MEDLINE | ID: mdl-38457115

ABSTRACT

BACKGROUND: Fecal microbiota transplants can be administered orally in encapsulated form or require invasive procedures to administer liquid formulations. There is a need for an oral liquid formulation of fecal microbiota for patients who are unable to swallow capsules, especially if they require multiple, repeated administrations. AIMS: These studies were conducted to develop a protocol to manufacture an organoleptically acceptable powdered fecal microbiota formulation that can be suspended in a liquid carrier and used for fecal microbiota transplantation. METHODS: Several processing steps were investigated, including extra washes of microbiota prior to lyophilization and an addition of a flavoring agent. The viability of bacteria in the transplant formulation was tested using live/dead microscopy staining and engraftment into antibiotic-treated mice. After development of a clinical protocol for suspension of the powdered microbiota, the new formulation was tested in three elderly patients with recurrent Clostridioides difficile infections and who have difficulties in swallowing capsules. Changes in the microbial community structure in one of the patients were characterized using 16S rRNA gene profiling and engraftment analysis. RESULTS: The processing steps used to produce an organoleptically acceptable suspension of powdered fecal microbiota did not result in loss of its viability. The powder could be easily suspended in a liquid carrier. The use of the new formulation was associated with abrogation of the cycle of C. difficile infection recurrences in the three patients. CONCLUSION: We developed a novel organoleptically acceptable liquid formulation of fecal microbiota that is suitable for use in clinical trials for patients with difficulties in swallowing capsules.


Subject(s)
Fecal Microbiota Transplantation , Fecal Microbiota Transplantation/methods , Humans , Animals , Administration, Oral , Clostridium Infections/therapy , Clostridium Infections/microbiology , Mice , Aged , Feces/microbiology , Clostridioides difficile/isolation & purification , Recurrence , Male , Female , Gastrointestinal Microbiome/drug effects , Powders , Treatment Outcome , Aged, 80 and over
14.
J Affect Disord ; 354: 309-317, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38499070

ABSTRACT

BACKGROUND: The gut-brain-axis has a role in mental health disorders. In people with generalized anxiety disorder, GAD,1 normal flora Escherichia-Shigella, are significantly elevated. Fecal microbiota transplant, FMT,2 has been used to alter the gut composition in unhealthy individuals. There may be a role for FMT in the treatment of GAD to improve the gut-brain-axis. METHODS: A systematic review of literature was conducted on articles published in PubMed, CINAHL Plus, Scopus, Cochrane Library, and Wed of Science from 2000 to 2022 that analyzed FMT as a modality to alter the gut microbiome in which Escherichia-Shigella levels were quantified and reported. RESULTS: Of 1916 studies identified, 14 fit criteria and were included. Recipients undergoing FMT procedures had at least one enteric diagnosis and increased percentages of Escherichia-Shigella pre-FMT. Five studies on recurrent Clostridioides difficile infection, three irritable bowel syndrome, two ulcerative colitis, one ulcerative colitis and recurrent Clostridioides difficile infection, one acute intestinal and chronic graft-vs-host disease, one pouchitis, and one slow transit constipation. 10 articles (71.4 %) showed decreased levels of Escherichia-Shigella post-FMT compared to pre-FMT. Four studies claimed the results were significant (40 %). LIMITATIONS: Limitations include potential bias in study selection, study methods of analysis, and generalization of results. CONCLUSIONS: The gut-brain-axis has a role in GAD. Those with GAD have significantly higher Escherichia-Shigella compared to those without GAD. FMT has the potential to decrease Escherichia-Shigella in patients with GAD to positively alter the gut-brain-axis as a potential for future GAD treatment.


Subject(s)
Clostridium Infections , Colitis, Ulcerative , Humans , Fecal Microbiota Transplantation/methods , Feces , Anxiety Disorders/therapy , Clostridium Infections/therapy , Treatment Outcome
15.
Anaerobe ; 86: 102841, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38521227

ABSTRACT

OBJECTIVES: Clostridioides difficile infection (CDI) is the leading hospital-acquired infection in North America. While previous work on fecal microbiota transplantation (FMT), a highly effective treatment for CDI, has focused on colonization resistance mounted against C. difficile by FMT-delivered commensals, the effects of FMT on host gene expression are relatively unexplored. This study aims to identify transcriptional changes associated with FMT, particularly changes associated with protective immune responses. METHODS: Gene expression was assessed on day 2 and day 7 after FMT in mice after antibiotic-induced dysbiosis. Flow cytometry was also performed on colon and mesenteric lymph nodes at day 7 to investigate changes in immune cell populations. RESULTS: FMT administration after antibiotic-induced dysbiosis successfully restored microbial alpha diversity to levels of donor mice by day 7 post-FMT. Bulk RNA sequencing of cecal tissue at day 2 identified immune genes, including both pro-inflammatory and Type 2 immune pathways as upregulated after FMT. RNA sequencing was repeated on day 7 post-FMT, and expression of these immune genes was decreased along with upregulation of genes associated with restoration of intestinal homeostasis. Immunoprofiling on day 7 identified increased colonic CD45+ immune cells that exhibited dampened Type 1 and heightened regulatory and Type 2 responses. These include an increased abundance of eosinophils, alternatively activated macrophages, Th2, and T regulatory cell populations. CONCLUSION: These results highlight the impact of FMT on host gene expression, providing evidence that FMT restores intestinal homeostasis after antibiotic treatment and facilitates tolerogenic and Type 2 immune responses.


Subject(s)
Clostridium Infections , Disease Models, Animal , Fecal Microbiota Transplantation , Animals , Fecal Microbiota Transplantation/methods , Mice , Clostridium Infections/therapy , Clostridium Infections/immunology , Clostridium Infections/microbiology , Gastrointestinal Microbiome , Dysbiosis/therapy , Clostridioides difficile/immunology , Immune Tolerance , Mice, Inbred C57BL
16.
Genome Med ; 16(1): 37, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38419010

ABSTRACT

BACKGROUND: Multidrug-resistant (MDR) bacteria are a growing global threat, especially in healthcare facilities. Faecal microbiota transplantation (FMT) is an effective prevention strategy for recurrences of Clostridioides difficile infections and can also be useful for other microbiota-related diseases. METHODS: We study the effect of FMT in patients with multiple recurrent C. difficile infections on colonisation with MDR bacteria and antibiotic resistance genes (ARG) on the short (3 weeks) and long term (1-3 years), combining culture methods and faecal metagenomics. RESULTS: Based on MDR culture (n = 87 patients), we notice a decrease of 11.5% in the colonisation rate of MDR bacteria after FMT (20/87 before FMT = 23%, 10/87 3 weeks after FMT). Metagenomic sequencing of patient stool samples (n = 63) shows a reduction in relative abundances of ARGs in faeces, while the number of different resistance genes in patients remained higher compared to stools of their corresponding healthy donors (n = 11). Furthermore, plasmid predictions in metagenomic data indicate that patients harboured increased levels of resistance plasmids, which appear unaffected by FMT. In the long term (n = 22 patients), the recipients' resistomes are still donor-like, suggesting the effect of FMT may last for years. CONCLUSIONS: Taken together, we hypothesise that FMT restores the gut microbiota to a composition that is closer to the composition of healthy donors, and potential pathogens are either lost or decreased to very low abundances. This process, however, does not end in the days following FMT. It may take months for the gut microbiome to re-establish a balanced state. Even though a reservoir of resistance genes remains, a notable part of which on plasmids, FMT decreases the total load of resistance genes.


Subject(s)
Clostridioides difficile , Clostridium Infections , Microbiota , Humans , Fecal Microbiota Transplantation/methods , Clostridioides difficile/genetics , Feces/microbiology , Clostridium Infections/therapy , Clostridium Infections/microbiology , Treatment Outcome
17.
Gastroenterology ; 166(3): 409-434, 2024 03.
Article in English | MEDLINE | ID: mdl-38395525

ABSTRACT

BACKGROUND & AIMS: Fecal microbiota-based therapies include conventional fecal microbiota transplant and US Food and Drug Administration-approved therapies, fecal microbiota live-jslm and fecal microbiota spores live-brpk. The American Gastroenterological Association (AGA) developed this guideline to provide recommendations on the use of fecal microbiota-based therapies in adults with recurrent Clostridioides difficile infection; severe to fulminant C difficile infection; inflammatory bowel diseases, including pouchitis; and irritable bowel syndrome. METHODS: The guideline was developed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis. The guideline panel used the Evidence-to-Decision framework to develop recommendations for the use of fecal microbiota-based therapies in the specified gastrointestinal conditions and provided implementation considerations for clinical practice. RESULTS: The guideline panel made 7 recommendations. In immunocompetent adults with recurrent C difficile infection, the AGA suggests select use of fecal microbiota-based therapies on completion of standard of care antibiotics to prevent recurrence. In mildly or moderately immunocompromised adults with recurrent C difficile infection, the AGA suggests select use of conventional fecal microbiota transplant. In severely immunocompromised adults, the AGA suggests against the use of any fecal microbiota-based therapies to prevent recurrent C difficile. In adults hospitalized with severe or fulminant C difficile not responding to standard of care antibiotics, the AGA suggests select use of conventional fecal microbiota transplant. The AGA suggests against the use of conventional fecal microbiota transplant as treatment for inflammatory bowel diseases or irritable bowel syndrome, except in the context of clinical trials. CONCLUSIONS: Fecal microbiota-based therapies are effective therapy to prevent recurrent C difficile in select patients. Conventional fecal microbiota transplant is an adjuvant treatment for select adults hospitalized with severe or fulminant C difficile infection not responding to standard of care antibiotics. Fecal microbiota transplant cannot yet be recommended in other gastrointestinal conditions.


Subject(s)
Clostridioides difficile , Clostridium Infections , Gastrointestinal Diseases , Inflammatory Bowel Diseases , Irritable Bowel Syndrome , Microbiota , Adult , Humans , Irritable Bowel Syndrome/drug therapy , Treatment Outcome , Gastrointestinal Diseases/therapy , Gastrointestinal Diseases/drug therapy , Fecal Microbiota Transplantation/adverse effects , Inflammatory Bowel Diseases/drug therapy , Clostridium Infections/therapy , Clostridium Infections/drug therapy , Anti-Bacterial Agents/therapeutic use , Recurrence
18.
Indian J Gastroenterol ; 43(1): 129-144, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38334893

ABSTRACT

Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic modality within the domain of inflammatory bowel disease (IBD). While FMT has secured approval and demonstrated efficacy in addressing recurrent and refractory Clostridioides difficile infection, its application in IBD remains an area of active exploration and research. The current status of FMT in IBD reflects a nuanced landscape, with ongoing investigations delving into its effectiveness, safety and optimal implementation. Early-stage clinical trials and observational studies have provided insights into the potential of FMT to modulate the dysbiotic gut microbiota associated with IBD, aiming to mitigate inflammation and promote mucosal healing. However, considerable complexities persist, including variations in donor selection, treatment protocols and outcome assessments. Challenges in standardizing FMT protocols for IBD treatment are compounded by the dynamic nature of the gut microbiome and the heterogeneity of IBD itself. Despite these challenges, enthusiasm for FMT in IBD emanates from its capacity to address gut microbial dysbiosis, signifying a paradigm shift towards more comprehensive approaches in IBD management. As ongoing research progresses, an enhanced understanding of FMT's role in IBD therapy is anticipated. This article synthesizes the current status of FMT in IBD, elucidating the attendant challenges and aspiring towards the refinement of its application for improved patient outcomes.


Subject(s)
Clostridium Infections , Inflammatory Bowel Diseases , Humans , Fecal Microbiota Transplantation/methods , Inflammatory Bowel Diseases/therapy , Inflammatory Bowel Diseases/complications , Clostridium Infections/therapy , Clostridium Infections/complications , Longitudinal Studies , Inflammation/complications , Dysbiosis/therapy , Treatment Outcome
19.
Trends Mol Med ; 30(3): 209-222, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38195358

ABSTRACT

Fecal microbiota transplantation (FMT) has emerged as an alternative or adjunct experimental therapy for microbiome-associated diseases following its success in the treatment of recurrent Clostridioides difficile infections (rCDIs). However, the mechanisms of action involved remain relatively unknown. The term 'dysbiosis' has been used to describe microbial imbalances in relation to disease, but this traditional definition fails to consider the complex cross-feeding networks that define the stability of the microbiome. Emerging research transitions toward the targeted restoration of microbial functional networks in treating different diseases. In this review, we explore potential mechanisms responsible for the efficacy of FMT and future therapeutic applications, while revisiting definitions of 'dysbiosis' in favor of functional network restoration in rCDI, inflammatory bowel diseases (IBDs), metabolic diseases, and cancer.


Subject(s)
Clostridioides difficile , Clostridium Infections , Gastrointestinal Microbiome , Microbiota , Humans , Fecal Microbiota Transplantation , Clostridium Infections/therapy , Treatment Outcome
20.
Br J Nurs ; 33(1): 8-14, 2024 Jan 11.
Article in English | MEDLINE | ID: mdl-38194333

ABSTRACT

BACKGROUND: Faecal microbiota transplantation (FMT) has mainly been studied in quantitative research to investigate effect rates. However, there is a lack of qualitative studies to explore patient perspectives. AIM: To explore perceptions of quality of life in older patients with Clostridioides difficile infection (CDI) at least 1 week after receiving FMT. METHOD: A qualitative study examining quality of life for patients treated with FMT. FINDINGS: Patients with a permanent or transient treatment effect experienced an increase in quality of life in the physical, psychological and social domains. However, patients who did not respond to the treatment experienced negative impacts on their psychological, physical, and social domains. Although patients found the content unappealing, none had reservations about receiving the treatment. CONCLUSION: This study highlights the importance of considering the psychological, social and physical wellbeing of patients when assessing the efficacy of FMT as a treatment option for patients with CDI. It further emphasises the importance of health professionals identifying patients' individual ways of handling the disease and everyday life to improve their quality of life.


Subject(s)
Clostridium Infections , Quality of Life , Humans , Aged , Fecal Microbiota Transplantation , Clostridium Infections/therapy , Health Personnel , Patients
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