Safety of fecal microbiota transplantation for Clostridioides difficile infection focusing on pathobionts and SARS-CoV-2.
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ABSTRACT:
SUBMITTER: Yadav D
PROVIDER: S-EPMC8064662 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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: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:Background: Cancer patients are at increased risk of recurrent Clostridioides difficile infection (rCDI) due to malignancy itself, cancer therapy, and frequent antibiotic use and have a lower response rate to standard oral antibiotics. There are limited data on the safety and efficacy of fecal microbiota transplantation (FMT) for treating rCDI in cancer patients. We aim to describe our experience of using FMT to treat rCDI at a tertiary cancer center. Methods: We conducted a retrospective study of cancer patients who underwent FMT for rCDI at The University of Texas MD Anderson Cancer Center from June 2017 through January 2020. Baseline clinical data and risk factors related to rCDI and FMT were evaluated and compared between cancer types and between cases with remission and recurrence. Results: A total of 19 patients were studied: 12 with solid malignancies and 7 with hematologic malignancies. Most patients had stage IV cancer, and 21% of patients were in cancer remission. On average, patients had 2 episodes of CDI and received 3 courses of antibiotics within 1 year before FMT. 84% of patients with rCDI responded to FMT. Compared with patients who had CDI remission following FMT, non-remission cases were more likely to have received antibiotics following FMT. There were no serious adverse events or mortality within 30 days associated with FMT. Conclusions: FMT is safe, well-tolerated, and efficacious in treating rCDI in selected cancer patients. However, additional antibiotic use for complications from chemotherapy or immunosuppression negatively affected the efficacy of FMT in this population with advanced cancer.
| S-EPMC8489149 | biostudies-literature
Project description:Secretory immunoglobulin A (IgA) interacts with intestinal microbiota and promotes mucosal homeostasis. IgA-bacteria interactions are altered during inflammatory diseases, but how these interactions are shaped by bacterial, host, and environmental factors remains unclear. In this study, we utilized IgA-SEQ to profile IgA-bound fecal bacteria in 48 recurrent Clostridioides difficile patients before and after successful fecal microbiota transplantation (FMT) to gain further insight. Prior to FMT, Escherichia coli was the most highly IgA-targeted taxon; following restoration of the microbiota by FMT, highly IgA-targeted taxa included multiple Firmicutes species. Post-FMT IgA-targeting was unaffected by the route of FMT delivery (colonoscopy versus capsule), suggesting that both methods lead to the establishment of healthy immune-bacterial interactions in the gut. Interestingly, IgA-targeting in FMT recipients closely resembled the IgA-targeting patterns of the donors, and fecal donor identity was significantly associated with IgA-targeting of the recipient microbiota. These data support the concept that intrinsic bacterial properties drive IgA recognition across genetically distinct human hosts. Together, this study suggests that IgA-bacterial interactions are reestablished in human FMT recipients to resemble that of the healthy fecal donor.
| S-EPMC7781654 | biostudies-literature
Project description:Abstract Background Severe or fulminant Clostridioides difficile infection (SFCDI) is associated with significant morbidity and mortality. Emerging evidence suggests fecal microbiota transplant (FMT) may be a promising therapy for SFCDI. Aim This systematic review determines the safety and efficacy of FMT in medically refractory SFCDI. Methods A systematic search of the literature was conducted using PubMed (1965 to 2020), Web of Science (1900 to 20), EMBASE (1974 to 2020), and Cochrane Review (1945 to 2020). Quality appraisal by NIH Study Quality Assessment tools, and data extraction were performed by two teams of independent researchers. The primary outcome was resolution of SFCDI 4 weeks after the final FMT. Pooled resolution rates were calculated using generalized linear mixed models estimates. Results Two hundred and forty patients from 10 studies (8 case series, 1 case–control and 1 randomized study) were included with 209 individual patient-level data. FMT resulted in resolution of SFCDI within 4 weeks in 211/240 individuals for a pooled estimate of 88% (95% confidence interval [CI]: 0.83 to 0.91). The mean number of FMT required was 1.6 for severe and 2.0 for fulminant CDI resolution. The pooled proportional estimates for patients requiring CDI-directed antimicrobials after FMT was 50% (95% CI: 0.06 to 0.94) for severe CDI and 67.0% (95% CI: 0.30 to 0.91) for fulminant CDI. Serious adverse event rates were low. Conclusion FMT appears effective in treating SFCDI patients with low adverse events, but requires multiple treatments with a significant proportion of patients requiring additional anti-CDI antibiotics to achieve resolution. The optimal route of FMT delivery remains unknown. The presence of pseudomembranous colitis may guide additional FMT or anti-CDI antibiotic treatment.
| S-EPMC8806043 | biostudies-literature
Project description:Background and aimsThe molecular mechanisms underlying successful fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (rCDI) remain poorly understood. The primary objective of this study was to characterize alterations in microRNAs (miRs) following FMT for rCDI.MethodsSera from 2 prospective multicenter randomized controlled trials were analyzed for miRNA levels with the use of the Nanostring nCounter platform and quantitative reverse-transcription (RT) polymerase chain reaction (PCR). In addition, rCDI-FMT and toxin-treated animals and ex vivo human colonoids were used to compare intestinal tissue and circulating miRs. miR inflammatory gene targets in colonic epithelial and peripheral blood mononuclear cells were evaluated by quantitative PCR (qPCR) and 3'UTR reporter assays. Colonic epithelial cells were used for mechanistic, cytoskeleton, cell growth, and apoptosis studies.ResultsmiRNA profiling revealed up-regulation of 64 circulating miRs 4 and 12 weeks after FMT compared with screening, of which the top 6 were validated in the discovery cohort by means of RT-qPCR. In a murine model of relapsing-CDI, RT-qPCR analyses of sera and cecal RNA extracts demonstrated suppression of these miRs, an effect reversed by FMT. In mouse colon and human colonoids, C difficile toxin B (TcdB) mediated the suppressive effects of CDI on miRs. CDI dysregulated DROSHA, an effect reversed by FMT. Correlation analyses, qPCR ,and 3'UTR reporter assays revealed that miR-23a, miR-150, miR-26b, and miR-28 target directly the 3'UTRs of IL12B, IL18, FGF21, and TNFRSF9, respectively. miR-23a and miR-150 demonstrated cytoprotective effects against TcdB.ConclusionsThese results provide novel and provocative evidence that modulation of the gut microbiome via FMT induces alterations in circulating and intestinal tissue miRs. These findings contribute to a greater understanding of the molecular mechanisms underlying FMT and identify new potential targets for therapeutic intervention in rCDI.
| S-EPMC8579492 | biostudies-literature
Project description:BACKGROUNDFecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection (rCDI) in adults and children, but donor stool samples are currently screened for only a limited number of potential pathogens. We sought to determine whether putative procarcinogenic bacteria (enterotoxigenic Bacteroides fragilis, Fusobacterium nucleatum, and Escherichia coli harboring the colibactin toxin) could be durably transmitted from donors to patients during FMT.METHODSStool samples were collected from 11 pediatric rCDI patients and their respective FMT donors prior to FMT as well as from the patients at 2-10 weeks, 10-20 weeks, and 6 months after FMT. Bacterial virulence factors in stool DNA extracts and stool cultures were measured by quantitative PCR: Bacteroides fragilis toxin (bft), Fusobacterium adhesin A (fadA), and Escherichia coli colibactin (clbB).RESULTSFour of 11 patients demonstrated sustained acquisition of a procarcinogenic bacteria. Whole genome sequencing was performed on colony isolates from one of these donor/recipient pairs and demonstrated that clbB+ E. coli strains present in the recipient after FMT were identical to a strain present in the donor, confirming strain transmission. Conversely, 2 patients exhibited clearance of procarcinogenic bacteria following FMT from a negative donor.CONCLUSIONBoth durable transmission and clearance of procarcinogenic bacteria occurred following FMT, suggesting that additional studies on appropriate screening measures for FMT donors and the long-term consequences and/or benefits of FMT are warranted.FUNDINGCrohn's & Colitis Foundation, the Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins University School of Medicine, the National Cancer Institute, and the Canadian Institutes of Health Research.
| S-EPMC6795395 | biostudies-literature
Project description:Persistent reservoirs of multidrug-resistant microorganisms (MDRO) that are prevalent in hospital settings and communities can lead to the spread of MDRO. Currently, there are no effective decolonization strategies, especially non-pharmacological strategies without antibiotic regimens. Our aim was to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for the eradication of MDRO. A systematic literature search was performed to identify studies on the use of FMT for the decolonization of MDRO. PubMed, EMBASE, Web of Science, and Cochrane Library were searched from inception through January 2019. Of the 1395 articles identified, 20 studies met the inclusion and exclusion criteria. Overall, the efficacy of FMT for the eradication of each MDRO was 70.3% (102/146) in 121 patients from the 20 articles. The efficacy rates were 68.2% (30/44) for gram-positive bacteria and 70.6% (72/102) for gram-negative bacteria. Minor adverse events, including vomiting, diarrhea, abdominal pain, and ileus, were reported in patients who received FMT. FMT could be a promising strategy to eradicate MDRO in patients. Further studies are needed to confirm these findings and establish a comprehensive FMT protocol for standardized treatment.Key messagesThe development of new antibiotics lags behind the emergence of multidrug-resistant microorganisms (MDRO). New strategies are needed.Theoretically, fecal microbiota transplantation (FMT) might recover the diversity and function of commensal microbiota from dysbiosis in MDRO carriers and help restore colonization resistance to pathogens.A literature review indicated that FMT could be a promising strategy to eradicate MDRO in patients.
| S-EPMC7877873 | biostudies-literature
Project description: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.IMPORTANCE Clostridioides 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.
| S-EPMC7857531 | biostudies-literature