Host immunity modulates the efficacy of microbiota transplantation for treatment of Clostridioides difficile infection.
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ABSTRACT:
SUBMITTER: Littmann ER
PROVIDER: S-EPMC7854624 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Abstarct In fecal microbiota transplantation (FMT) against recurrent Clostridioides difficile infection (CDI), clinical outcomes are usually determined after 8 weeks. We hypothesized that the intestinal microbiota changes earlier than this timepoint, and analyzed fecal samples obtained 1 week after treatment from 64 patients diagnosed with recurrent CDI and included in a randomized clinical trial, where the infection was treated with either vancomycin-preceded FMT (N = 24), vancomycin (N = 16) or fidaxomicin (N = 24). In comparison with non-responders, patients with sustained resolution after FMT had increased microbial alpha diversity, enrichment of Ruminococcaceae and Lachnospiraceae, depletion of Enterobacteriaceae, more pronounced donor microbiota engraftment, and resolution of gut microbiota dysbiosis. We found that a constructed index, based on markers for the identified genera Escherichia and Blautia, successfully predicted clinical outcomes at Week 8, which exemplifies a way to utilize clinically feasible methods to predict treatment failure. Microbiota changes were restricted to patients who received FMT rather than antibiotic monotherapy, indicating that FMT confers treatment response in a different way than antibiotics. We suggest that early identification of microbial community structures after FMT is of clinical value to predict response to the treatment.
| S-EPMC9176232 | biostudies-literature
Project description:The importance of the commensal microbiota to human health and well-being has become increasingly evident over the past decades. From a therapeutic perspective, the popularity of fecal microbiota transplantation (FMT) to restore a disrupted microbiota and amend imbalances has increased. To date, most clinical experience with FMT originates from the treatment of recurrent or refractory Clostridioides difficile infections (rCDI), with resolution rates up to 90%. In addition to CDI, a role for the intestinal microbiome has been implicated in several disorders. FMT has been tested in several randomized controlled trials for the treatment of inflammatory bowel disease, irritable bowel disease and constipation with mixed results. FMT has also been explored for extra-gastrointestinal disorders such as metabolic syndrome, hepatic encephalopathy and graft-versus-host disease. With the exception of recurrent CDI, FMT is currently used in experimental settings only and should not yet be offered as standard care. In addition, it is critical to further standardize and optimize procedures for FMT preparation. This includes determination of active components of FMT to develop (personalized) approaches to treat disease.
| S-EPMC6606746 | biostudies-literature
Project description:ObjectiveFecal microbiota transplantation (FMT) is a highly effective treatment for Clostridioides difficile infection (CDI). However, the fecal transplant's causal components translating into clearance of the CDI are yet to be identified. The commensal bacteria Faecalibacterium prausnitzii may be of great interest in this context, since it is one of the most common species of the healthy gut microbiota and produces metabolites with anti-inflammatory properties. Although there is mounting evidence that F. prausnitzii is an important regulator of intestinal homeostasis, data about its role in CDI and FMT are relatively scarce.MethodsStool samples from patients with recurrent CDI were collected to investigate the relative abundance of F. prausnitzii before and after FMT. Twenty-one patients provided fecal samples before the FMT procedure, at 2 weeks post-FMT, and at 2-4 months post-FMT. The relative abundance of F. prausnitzii was determined using quantitative polymerase chain reaction.ResultsThe abundance of F. prausnitzii was elevated in samples (N = 9) from donors compared to pre-FMT samples (N = 15) from patients (adjusted P<0.001). No significant difference in the abundance of F. prausnitzii between responders (N = 11) and non-responders (N = 4) was found before FMT (P = 0.85). In patients with CDI, the abundance of F. prausnitzii significantly increased in the 2 weeks post-FMT samples (N = 14) compared to the pre-FMT samples (N = 15, adjusted P<0.001). The increase persisted 2-4 months post-FMT (N = 15) compared to pre-FMT samples (N = 15) (adjusted P<0.001).ConclusionsFMT increases the relative abundance of F. prausnitzii in patients with recurrent CDI, and this microbial shift remains several months later. The baseline abundance of F. prausnitzii in donors or recipients was not associated with future treatment response, although a true predictive capacity cannot be excluded because of the limited sample size. Further studies are needed to discern whether F. prausnitzii plays an active role in the resolution of CDI.
| S-EPMC8034738 | biostudies-literature
Project description:BackgroundBoth the American College of Gastroenterology and the Infectious Diseases Society of America (IDSA)/Society for Healthcare Epidemiology of America 2021 Clostridioides difficile infection (CDI) guidelines recommend fecal microbiota transplantation (FMT) for persons with multiple recurrent CDI. Emerging data suggest that FMT may have high cure rates when used for first recurrent CDI. The aim of this study was to assess the cost-effectiveness of FMT for first recurrent CDI.MethodsWe developed a Markov model to simulate a cohort of patients presenting with initial CDI infection. The model estimated the costs, effectiveness, and cost-effectiveness of different CDI treatment regimens recommended in the 2021 IDSA guidelines, with the additional option of FMT for first recurrent CDI. The model includes stratification by the severity of initial infection, estimates of cure, recurrence, and mortality. Data sources were taken from IDSA guidelines and published literature on treatment outcomes. Outcome measures were quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs).ResultsWhen FMT is available for first recurrent CDI, the optimal cost-effective treatment strategy is fidaxomicin for initial nonsevere CDI, vancomycin for initial severe CDI, and FMT for first and subsequent recurrent CDI, with an ICER of $27 135/QALY. In probabilistic sensitivity analysis at a $100 000 cost-effectiveness threshold, FMT for first and subsequent CDI recurrence was cost-effective 90% of the time given parameter uncertainty.ConclusionsFMT is a cost-effective strategy for first recurrent CDI. Prospective evaluation of FMT for first recurrent CDI is warranted to determine the efficacy and risk of recurrence.
| S-EPMC9617579 | biostudies-literature
Project description:Clostridium difficile, a major cause of healthcare-associated diarrhea due to perturbation of the normal gastrointestinal microbiome, is responsible for significant morbidity, mortality, and healthcare expenditures. The incidence and severity of C difficile infection (CDI) is increasing, and recurrent disease is common. Recurrent infection can be difficult to manage with conventional antibiotic therapy. Fecal microbiota transplantation (FMT), which involves instillation of stool from a healthy donor into the gastrointestinal tract of the patient, restores the gut microbiome to a healthy state. FMT has emerged as a promising new treatment for CDI. There are limited data on FMT for treatment of primary CDI, but FMT appears safe and effective for recurrent CDI. The safety and efficacy of FMT in patients with severe primary or severe recurrent CDI has not been established. Patients with inflammatory bowel disease (IBD) who undergo FMT for CDI may be at increased risk of IBD flare, and caution should be exercised with use of FMT in that population. The long-term safety of FMT is unknown; thus, rigorously conducted prospective studies are needed.
| S-EPMC4908581 | biostudies-other
Project description:Background:Fecal microbiota transplantation (FMT) is a well-established therapeutic option for patients with antibiotic resistant Clostridioides difficile infection (CDI). However, the efficacy of FMT in patients with chronic liver disease remains elusive. Aims:We studied the effect of FMT on chronic liver disease (CLD) patients with CDI at our tertiary medical center. Methods:A cohort of all patients who received FMT from December 2012 to May 2014 for refractory or recurrent CDI was identified. Patients were monitored for a year after FMT. Descriptive analysis was conducted to compare the effect of FMT in patients with and without CLD. Results:A total of 201 patients with CDI received FMT, 14 of which had a history of CLD. Nine of these patients exhibited cirrhosis of the liver with a mean Child-Turcotte-Pugh score of 8. CDI development in these patients was associated with recent exposure to antibiotics and was observed to be significantly different between both groups (17% of CLD patients vs. 58% in the general cohort, p = 0.01). Four patients with CLD received >1 FMT, of which 2 did not respond to treatment. There was no significant difference between patients with liver disease and the rest of the cohort with regard to FMT response (12/14 (87%) vs. 164/187 (88%), p = 0.01). Four patients with CLD received >1 FMT, of which 2 did not respond to treatment. There was no significant difference between patients with liver disease and the rest of the cohort with regard to FMT response (12/14 (87%) vs. 164/187 (88%). Conclusion:FMT is a safe and effective therapy against CDI for patients with CLD and cirrhosis.
| S-EPMC7007953 | biostudies-literature
Project description:AbstractFecal microbiota transplantation (FMT) is currently the most effective but loosely regulated therapy, for recurrent Clostridioides difficile infection (rCDI) in pediatrics. Over the last 2 years, there have been mounting challenges in the ability to provide FMT to pediatric patients. Firstly, an Food and Drug Administration (FDA) safety alert in 2019 reported transmission of a multidrug resistant organism from FMT donor to recipient resulting in the death of 1 patient. Secondly, the coronavirus disease 2019 (COVID-19) pandemic induced further safety and regulatory challenges. Biotherapeutics are promising and more readily regulated treatment options for rCDI, which may replace FMT in the near future for adults upon regulatory agency approvals. Such approvals, however, are expected to be significantly delayed for children, raising concerns for limited access to effective treatment for children with rCDI. In this commentary, we discuss the recent challenges and future directions of FMT and microbial therapeutics in children with rCDI.
| S-EPMC8455422 | biostudies-literature
Project description:Background and aimsFecal microbiota transplantation (FMT) is a commonly used therapy for multiply recurrent Clostridioides difficile (mrCDI). By altering the gut microbiota, there is the potential for FMT to impact the risk for cardiometabolic, intestinal or immune-mediated conditions. Likewise, the microbiota disturbance associated with mrCDI could potentially lead to these conditions. We aimed to assess the associations of mrCDI and FMT with cardiometabolic, immune-mediated diseases, and irritable bowel syndrome.MethodsThis retrospective cohort study using a United States commercial claims database included persons diagnosed with CDI or undergoing FMT. We created 2 pairwise comparisons: mrCDI vs non-mrCDI, and non-mrCDI or mrCDI treated with FMT vs mrCDI without FMT.ResultsWe found no significant association between mrCDI (vs non-mrCDI) and inflammatory bowel disease (adjusted hazard ratio (aHR) = 1.65; 95% confidence interval, 0.67-4.04), rheumatoid arthritis (HR = 0.86; 0.47-1.56), psoriasis (HR = 0.72; 0.23-2.27), diabetes (aHR = 0.97; 0.67-1.40), hypertension (aHR = 1.05; 0.76-1.44), myocardial infarction (aHR = 0.82; 0.63-1.06), stroke (aHR = 0.83; 0.62-1.12), or irritable bowel syndrome (HR = 0.94; 0.61-1.45). Similarly, we found no association of CDI with FMT (vs mrCDI without FMT) and diabetes (aHR = 0.92; 0.27-3.11), hypertension (aHR = 1.41; 0.64-3.15), stroke (aHR = 1.27; 0.69-2.34) or inflammatory bowel syndrome (aHR = 0.80; 0.26-2.46). However, the incidence of myocardial infarction was increased following FMT (aHR = 1.68; 1.01-2.81).ConclusionRelative to those with CDI, persons with mrCDI do not appear to be intrinsically at higher risk of cardiometabolic, immune-mediated diseases, or irritable bowel syndrome. However, those who underwent FMT for CDI had a higher incidence of myocardial infarction. Future studies should assess this association to assess reproducibility.
| S-EPMC8184854 | biostudies-literature
Project description:Faecal microbiota transplantation (FMT) is the transfer of screened and minimally processed faecal material from a 'healthy' donor to 'diseased' recipient. It has an established role, and is recommended as a therapeutic strategy, in the management of recurrent Clostridioides difficile infection (CDI). Recognition that gut dysbiosis is associated with, and may contribute to, numerous disease states has led to interest in exploiting FMT to 'correct' this microbial imbalance. Conditions for which it is proposed to be beneficial include inflammatory bowel disease, irritable bowel syndrome, liver disease and hepatic encephalopathy, neuropsychiatric conditions such as depression and anxiety, systemic inflammatory states like sepsis, and even coronavirus disease 2019. To understand what role, if any, FMT may play in the management of these conditions, it is important to consider the potential risks and benefits of the therapy. Regardless, there are several barriers to its more widespread adoption, which include incompletely understood mechanism of action (especially outside of CDI), inability to standardise treatment, disagreement on its active ingredients and how it should be regulated, and lack of long-term outcome and safety data. Whilst the transfer of faecal material from one individual to another to treat ailments or improve health has a history dating back thousands of years, there are fewer than 10 randomised controlled trials supporting its use. Moving forward, it will be imperative to gather as much data from FMT donors and recipients over as long a timeframe as possible, and for trials to be conducted with rigorous methodology, including appropriate control groups, in order to best understand the utility of FMT for indications beyond CDI. This review discusses the history of FMT, its appreciable mechanisms of action with reference to CDI, indications for FMT with an emerging evidence base above and beyond CDI, and future perspectives on the field.
| S-EPMC7841662 | biostudies-literature
Project description:Purpose:Fecal microbiota transplantation (FMT) is an effective treatment option for patients with recurrent Clostridioides difficile infection (rCDI). However, there is a paucity of evidence regarding its efficacy and safety in patients with rCDI and concurrent inflammatory bowel disease (IBD). Here, we present a single-center experience of FMT for treatment of rCDI in Iranian patients with IBD. Patients and Methods:Eight patients with established IBD (7 with ulcerative colitis and 1 with Crohn's disease) who underwent at least one FMT via colonoscopy for treatment of rCDI were enrolled in this study. Demographics, pre-FMT and post-FMT IBD activity, efficacy for rCDI and adverse events (AEs) were assessed during a 6-month follow-up period. All patients had experienced 3 episodes of rCDI and were refractory to conventional therapies with metronidazole and vancomycin. Primary cure and secondary cure rates were assessed after FMT treatments. Results:A total of 10 FMTs were performed via colonoscopy in 8 patients (6/8; 75% men) with a median age of 35 years (range: 22-60). Two patients received a second FMT. Overall, the primary and secondary cure rates were 75% and 100%, respectively. Two patients developed CPE-producing C. perfringens diagnoses after second FMTs. There were no other AEs, and no patient experienced IBD flare. Conclusion:We demonstrated that FMT appears to be an effective, safe and rational therapeutic alternative for resolution of rCDI in patients with underlying IBD. Furthermore, we suggest implementing the CPE-producing C. perfringens testing in the screening of FMT donors.
| S-EPMC7509309 | biostudies-literature