Immunological mechanisms of fecal microbiota transplantation in recurrent Clostridioides difficile infection.

Fecal microbiota transplantation (FMT) is a successful method for treating recurrent Clostridioides difficile (C. difficile) infection (rCDI) with around 90% efficacy. Due to the relative simplicity of this approach, it is being widely used and currently, thousands of patients have been treated with FMT worldwide. Nonetheless, the mechanisms underlying its effects are just beginning to be understood. Data indicate that FMT effectiveness is due to a combination of microbiological direct mechanisms against C. difficile, but also through indirect mechanisms including the production of microbiota-derived metabolites as secondary bile acids and short chain fatty acids. Moreover, the modulation of the strong inflammatory response triggered by C. difficile after FMT seems to rely on a pivotal role of regulatory T cells, which would be responsible for the reduction of several cells and soluble inflammatory mediators, ensuing normalization of the intestinal mucosal immune system. In this minireview, we analyze recent advances in these immunological aspects associated with the efficacy of FMT.

Fecal microbiota transplantation for Carbapenem-Resistant Enterobacteriaceae: A systematic review.

The prevalence of Carbapenem-resistant Enterobacteriaceae (CRE) has increased dramatically in recent years and has become a global public health issue. Since carbapenems are considered the last drugs of choice, infections caused by these pathogens are difficult to treat and carry a high risk of mortality. Several antibiotic combination regimens have been utilized for the management of CRE infections or to eradicate colonization in CRE carriers with variable clinical responses. In addition, recent studies have explored the use of fecal microbiota transplantation (FMT) to eradicate CRE infections. Here, we conducted a systematic review of publications in which FMT was used to eliminate CRE colonization in infected individuals. We searched the PubMed, Cochrane, and Medline databases up to November 30, 2021. Ten studies (209 patients) met the inclusion criteria for this review with three articles describing retrospective cohorts (n = 53 patients) and seven reporting prospective data (n = 156 patients), including one randomized open-label clinical trial. All studies were published between 2017 and 2021 with eight studies from Europe and two from South Korea. There were substantial variations in terms of outcome measurements and study endpoint among these studies. Among the 112 FMT recipients with confirmed CRE colonization, CRE decolonization was reported in 55/90 cases at one month after FMT and at the end of the study follow-up (6-12 months), decolonization was documented in 74/94 (78.7%) patients. The predominant CRE strains reported were Klebsiella pneumoniae and Escherichia coli and the most frequently documented carbapenemases were KPC, OXA-48, and NDM. In general, FMT was well tolerated, with no severe complications reported even in immunosuppressed patients and in those with multiple underlying conditions. In conclusion, FMT appears to be safe and effective in eradicating CRE colonization, however, more studies, especially randomized trials, are needed to validate the safety and clinical utility of FMT for CRE eradication.

Fecal Microbiota Transplantation for People Living with Human Immunodeficiency Virus: A Scoping Review.

The aim of this scoping review was to determine the characteristics of studies evaluating fecal microbiota transplantation (FMT), as well as its effects and safety as a therapeutic intervention for people living with human immunodeficiency virus (HIV). We conducted a scoping review following the methodology of the Joanna Briggs Institute. We searched the following databases: PubMed, Web of Science, Scopus, Embase, Cochrane Library, and Medline until September 19, 2021. Studies that used FMT in people living with HIV and explored its effects on the health of these people were included. Two randomized and 2 uncontrolled clinical trials with a total of 55 participants were included. Participants were well-controlled HIV-infected people. Regarding microbiota changes, three studies found significant post-FMT increases in Fusobacterium, Prevotella, α-diversity, Chao index, and/or Shannon index, and/or decreases in Bacteroides. Regarding markers of intestinal damage, one study found a decrease in intestinal fatty acid binding protein post-FMT, and another study found an increase in zonulin. Other outcomes evaluated by the studies were as follows: markers of immune and inflammatory activation, markers of immunocompetence (CD4+, and CD8+ T lymphocytes), and HIV viral load; however, none showed significant changes. Clinical outcomes were not evaluated by these studies. Regarding the safety of FMT, only mild adverse events were appreciated. No serious adverse event was reported. The clinical evidence for FMT in people living with HIV is sparse. FMT appears to have good tolerability and, no serious adverse event has been reported so far. Further clinical trials and evaluation of clinically important biomedical outcomes for FMT in people living with HIV are needed.

Fecal Microbiota Transplant in a Pre-Clinical Model of Type 2 Diabetes Mellitus, Obesity and Diabetic Kidney Disease.

Diabetes mellitus (DM) burden encompasses diabetic kidney disease (DKD), the leading cause of end-stage renal disease worldwide. Despite compelling evidence indicating that pharmacological intervention curtails DKD progression, the search for non-pharmacological strategies can identify novel targets for drug development against metabolic diseases. One of those emergent strategies comprises the modulation of the intestinal microbiota through fecal transplant from healthy donors. This study sought to investigate the benefits of fecal microbiota transplant (FMT) on functional and morphological parameters in a preclinical model of type 2 DM, obesity, and DKD using BTBRob/ob mice. These animals develop hyperglycemia and albuminuria in a time-dependent manner, mimicking DKD in humans. Our main findings unveiled that FMT prevented body weight gain, reduced albuminuria and tumor necrosis factor-α (TNF-α) levels within the ileum and ascending colon, and potentially ameliorated insulin resistance in BTBRob/ob mice. Intestinal structural integrity was maintained. Notably, FMT was associated with the abundance of the succinate-consuming Odoribacteraceae bacteria family throughout the intestine. Collectively, our data pointed out the safety and efficacy of FMT in a preclinical model of type 2 DM, obesity, and DKD. These findings provide a basis for translational research on intestinal microbiota modulation and testing its therapeutic potential combined with current treatment for DM.

Fecal microbiota transplantation in inflammatory bowel disease patients: A systematic review and meta-analysis.

OBJECTIVES: Current evidence on fecal microbiota transplantation for inflammatory bowel disease is inconclusive. We conducted a systematic review to gather evidence on the efficacy and safety of fecal microbiota transplantation for inflammatory bowel disease. METHODS: Systematic searches were conducted in PubMed, Scopus, and Web of Science. Clinical remission was considered as the primary endpoint. Pairwise meta-analyses were performed for the randomized controlled studies (Mantel Haenszel, random effects model). Proportion meta-analyses, accounting for weighted pooled rates reported in the interventional studies, were conducted using the mixed effects model. Subgroup analyses considering the type of stool, donor type, and disease subtype were also performed. Cumulative meta-analyses to assess further needs of evidence were conducted. RESULTS: Sixty studies were included, from which 36 could be synthesized in the quantitative analyses. Pairwise meta-analyses of six controlled trials showed significant differences in favor of fecal microbiota transplantation compared with placebo (clinical remission: RR 1.70 [95% CI 1.12, 2.56]; clinical response: RR 1.68 [95% CI 1.04, 2.72]). An overall clinical remission of 37%, overall clinical response of 54%, and a prevalence of 29% of adverse events were found for the interventional studies. Frozen fecal material and universal donors were related to better efficacy outcomes. In addition, Crohn's disease patients seemed to benefit more from the procedure. CONCLUSIONS: The comparative analyses demonstrated that frozen fecal material from universal donors may be related to a higher rate of clinical remission, especially for Crohn's disease.

[Fecal microbiota transplantation through colonoscopy for Clostridium difficile recurrent infection. Report of eight cases]. / Experiencia del trasplante de microbiota fecal a través de colonoscopía en el tratamiento de la infección por Clostridium difficile recurrente.

BACKGROUND: Most cases of Clostridium difficile infection (CDI) respond to a standard course of antibiotics, however recurrent CDI is becoming common and alternative therapeutic strategies are needed. In this scenario, fecal microbiota transplantation (FMT) has been suggested. AIM: To describe the efficacy and safety of FMT for the treatment of recurrent CDI. PATIENTS AND METHODS: Review of medical records of all patients with recurrent CDI treated with FMT between April 2013 and April 2017. Demographic and clinical data were abstracted including details of treatment prior to FMT, rate of FMT treatment success and clinical course during follow-up period. Telephone surveys were conducted to determine patient satisfaction. RESULTS: Eight patients aged 19 to 82 years (six women) underwent FMT. They experienced a median of four previous episodes of CDI (range 3-8). The mean duration of CDI was 18 days (range 3-36) before FMT. All procedures were performed by colonoscopy. Effectiveness with one session of FMT was 100%. During the follow-up period (median 24 months, range 7-55), two patients developed CDI, one of them after using antibiotics. Adverse events were reported in three patients. Two had bloating and one patient with Crohn's disease and a history of bacteremia had an episode of Escherichia coli bacteremia. All patients would use FMT again if necessary. CONCLUSIONS: FMT through colonoscopy appears to be a safe, effective and long-lasting therapy in cases of recurrent CDI.

Experiencia del trasplante de microbiota fecal a través de colonoscopía en el tratamiento de la infección por Clostridium difficile recurrente / Fecal microbiota transplantation through colonoscopy for Clostridium difficile recurrent infection: report of eight cases

Background: Most cases of Clostridium difficile infection (CDI) respond to a standard course of antibiotics, however recurrent CDI is becoming common and alternative therapeutic strategies are needed. In this scenario, fecal microbiota transplantation (FMT) has been suggested. Aim: To describe the efficacy and safety of FMT for the treatment of recurrent CDI. Patients and Methods: Review of medical records of all patients with recurrent CDI treated with FMT between April 2013 and April 2017. Demographic and clinical data were abstracted including details of treatment prior to FMT, rate of FMT treatment success and clinical course during follow-up period. Telephone surveys were conducted to determine patient satisfaction. Results: Eight patients aged 19 to 82 years (six women) underwent FMT. They experienced a median of four previous episodes of CDI (range 3-8). The mean duration of CDI was 18 days (range 3-36) before FMT. All procedures were performed by colonoscopy. Effectiveness with one session of FMT was 100%. During the follow-up period (median 24 months, range 7-55), two patients developed CDI, one of them after using antibiotics. Adverse events were reported in three patients. Two had bloating and one patient with Crohn's disease and a history of bacteremia had an episode of Escherichia coli bacteremia. All patients would use FMT again if necessary. Conclusions: FMT through colonoscopy appears to be a safe, effective and long-lasting therapy in cases of recurrent CDI.

An Intragastric Fecal Microbiota Transplantation Program for Treatment of Recurrent Clostridium difficile in Children is Efficacious, Safe, and Inexpensive.

OBJECTIVE: To assess the safety, efficacy, and relative expense of a nurse-led fecal microbiota transplantation (FMT) program for the treatment of recurrent Clostridium difficile infection (CDI). STUDY DESIGN: Retrospective cohort study design in children aged 1-18 years with recurrent CDI. The intervention was an intragastric FMT with stool derived from a donor stool bank. Primary outcome was resolution of diarrhea at 3 months post-transplantation. A secondary analysis compared charge data associated with FMT by intragastric delivery vs administration by colonoscopy or nasoduodenal tube. RESULTS: A total of 47 intragastric FMT procedures were performed in 42 children (median age 9 years) with recurrent CDI. Response to treatment varied by disease status, with 94% success in previously healthy children, 75% in medically complex children, and 54% in children with inflammatory bowel disease (P = .04). FMT via intragastric delivery showed lower facility and professional charges by 85% and 78% compared with delivery via colonoscopy and radiology-placed nasoduodenal tube, respectively. The use of stool derived from a donor stool bank decreased charges by 49% compared with charges associated with the use of a donor who was a relative. CONCLUSION: A nurse-led intragastric FMT procedure using stool derived from a donor stool bank is a relatively inexpensive and efficacious treatment for recurrent CDI in children. Intragastric FMT success in children was attenuated by the presence of underlying disease, particularly inflammatory bowel disease.

[Practical clues for a fecal microbiota transplantation by colonoscopy for recurrent Clostridium difficile infection. Experience in a University center]. / Claves prácticas para un trasplante de microbiota fecal por colonoscopía en infección por Clostridium difficile recurrente. Experiencia en un centro universitario.

Fecal microbiota transplantation (FMT) is a highly effective therapy in recurrent Clostridium difficile. The best route to administrate the fecal matter has not been established yet. However, the lower gastrointestinal route by colonoscopy is effective and safe, presenting a higher acceptance by patients. In addition, this route allows an evaluation of colonic mucosa seeking for differential diagnostics. We present a case series of FMT performed in our institution by colonoscopy, highlighting outcomes and practical aspects for its implementation.

Claves prácticas para un trasplante de microbiota fecal por colonoscopía en infección por Clostridium difficile recurrente. Experiencia en un centro universitario / Practical clues for a fecal microbiota transplantation by colonoscopy for recurrent Clostridium difficile infection. Experience in a University center

Resumen El trasplante de microbiota fecal (TMF) constituye una terapia altamente eficaz en la infección por Clostridium difficile (ICD) recurrente. La mejor vía de administración del material fecal aún no ha sido establecida; sin embargo, la vía baja a través de colonoscopía resulta eficaz, segura y de mayor aceptación por los pacientes, permitiendo además el examen de la mucosa del colon en busca de diagnósticos diferenciales. Presentamos una serie de casos de TMF realizados en nuestra institución a través de colonoscopía, destacando los resultados y aspectos prácticos para su implementación.

Fecal microbiota transplantation (FMT) is a highly effective therapy in recurrent Clostridium difficile. The best route to administrate the fecal matter has not been established yet. However, the lower gastrointestinal route by colonoscopy is effective and safe, presenting a higher acceptance by patients. In addition, this route allows an evaluation of colonic mucosa seeking for differential diagnostics. We present a case series of FMT performed in our institution by colonoscopy, highlighting outcomes and practical aspects for its implementation.

Trasplante de microbiota fecal: indicaciones, metodología y perspectivas futuras / Faecal microbiota transplantation: indications, methodology and future prospects

La microbiota intestinal se define como el conjunto de microorganismos que habitan de forma natural en el tubo digestivo. Bacterias, hongos y virus se incluyen dentro de este ente fisiológico que va mucho más allá de ser un mero espectador pasivo de la mucosa intestinal. La microbiota interviene de forma activa en la homeostasis y su desregulación se ha relacionado con múltiples enfermedades de naturaleza infecciosa, metabólica y autoinmunitaria. El trasplante de microbiota fecal (TMF) consiste en la introducción de una solución de materia fecal debidamente procesada procedente de un donante sano en el tracto gastrointestinal de otro individuo con el fin de manipular las características de la microbiota del receptor. Aunque pueda parecer algo novedoso, los primeros casos se remontan a la época de la China Imperial; no obstante, no ha sido hasta los últimos 20 años cuando el interés y la actividad investigadora en este campo se han multiplicado de forma exponencial. Fruto de este trabajo el TMF constituye hoy en día una herramienta eficaz y validada en casos refractarios de diarrea por C. Difficile. Aunque la evidencia científica es menor, ya existen ensayos clínicos que evalúan su beneficio en la enfermedad inflamatoria intestinal y en el síndrome metabólico. Lo atractivo de su mecanismo fisiopatológico, la sencillez del procedimiento y su bajo coste lo sitúan como un tratamiento prometedor en múltiples enfermedades extradigestivas. El objetivo de esta revisión es resumir de una forma concisa, rigurosa y actualizada las indicaciones, metodología y seguridad del TMF.

The intestinal microbiota is defined as the set of organisms that live in the digestive tract. Bacteria, fungi and viruses are included in a physiological entity that goes far beyond being a passive spectator of the intestinal mucosa. The microbiota is actively involved in homeostasis and its imbalance has been linked to multiple infectious, metabolic and autoimmune diseases. Fecal microbiota transplantation (FMT) consists in the introduction of a solution made with processed stool from a healthy donor into the gastrointestinal tract of another individual in order to manipulate the characteristics of the receiver microbiota. Although it may seem new, the first cases date back to the days of Imperial China; however, it was not until the past 20 years when the interest and research in this field have grown exponentially. Nowadays, TMF is an effective and validated treatment in refractory cases of C.difficile diarrhea. Although the scientific evidence is less, there are clinical trials evaluating its benefit in inflammatory bowel disease and metabolic syndrome. The appeal of its pathophysiological mechanism, the simplicity of the procedure and its low cost place FMT as a promising treatment for multiple extraintestinal diseases. The objective of this review is to summarize in a concise, thorough and updated form its indications, methodology and safety.