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Fecal Microbiota Transplantation for Clostridioides Difficile Infection in Patients with Chronic Liver Disease.

ABSTRACT: 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.

SUBMITTER: Meighani A

PROVIDER: S-EPMC7007953 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Fecal Microbiota Transplantation for Clostridioides Difficile Infection in Patients with Chronic Liver Disease.

Meighani Alireza A Alimirah Maryam M Ramesh Mayur M Salgia Reena R

International journal of hepatology 20200127

<h4>Background</h4>Fecal microbiota transplantation (FMT) is a well-established therapeutic option for patients with antibiotic resistant <i>Clostridioides difficile</i> infection (CDI). However, the efficacy of FMT in patients with chronic liver disease remains elusive.<h4>Aims</h4>We studied the effect of FMT on chronic liver disease (CLD) patients with CDI at our tertiary medical center.<h4>Methods</h4>A cohort of all patients who received FMT from December 2012 to May 2014 for refractory or ...[more]

PMID: 32047670

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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.

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.

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.

Dataset Information

Fecal Microbiota Transplantation for Clostridioides Difficile Infection in Patients with Chronic Liver Disease.

Publications

Fecal Microbiota Transplantation for Clostridioides Difficile Infection in Patients with Chronic Liver Disease.

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