scholarly journals Intestinal Microbiome Changes in Fecal Microbiota Transplant (FMT) vs. FMT Enriched with Lactobacillus in the Treatment of Recurrent Clostridioides difficile Infection

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Elvira Garza-González ◽  
Soraya Mendoza-Olazarán ◽  
Rayo Morfin-Otero ◽  
Andrea Ramírez-Fontes ◽  
Patricia Rodríguez-Zulueta ◽  
...  

Aim. In this study, we conducted a comparative study to explore the differences in therapeutic efficacy and intestinal microbiome of fecal microbiota transplant (FMT) vs. FMT in addition with Lactobacillus (FMT-L) for treatment of recurrent Clostridioides difficile infection (R-CDI). Methods. We designed a double-blinded randomized comparative two-arm pilot multicenter study to assess the efficacy and impact in the intestinal microbiome of standard capsules of FMT vs. FMT-L enriched with 3 species of Lactobacillus for patients with R-CDI. A 90-day follow-up of 21 patients was performed, starting at the beginning of the study. From the selected patients, fecal samples were obtained at days 0, 3, 7, and 28 after treatment. Fecal samples and FMT were analyzed by 16S rRNA sequencing. Results. We included 21 patients (13 in the FMT group and 8 in the FMT-L group). Overall, both groups had a reduction in bowel movements per day, from 8.6 to 3.2 in the first 48 h (62.7% reduction, p=0.001). No severe adverse reactions or recurrences were recorded. Firmicutes were the most abundant phylum in donors. A low relative abundance of Proteobacteria was detected and mostly found in patients even at higher proportions than the donor. The donor’s pool also had relatively few Bacteroidetes, and some patients showed a higher abundance of this phylum. Based on the ANOSIM R values, there is a significant difference between the microbial communities of basal samples and samples collected on day 7 (p=0.045) and at day 28 (0.041). Conclusion. Fecal microbiota transplant by capsules was clinically and genomically similar between traditional FMT and enriched FMT with Lactobacillus spp. Restoration of bacterial diversity and resolution of dysbiosis at days 7 and 28 were observed. Patients with a first episode of recurrence treated with FMT had an excellent response without severe adverse events; FMT should be considered as an early treatment during R-CDI.

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3234
Author(s):  
Tanya M. Monaghan ◽  
Niharika A. Duggal ◽  
Elisa Rosati ◽  
Ruth Griffin ◽  
Jamie Hughes ◽  
...  

Fecal microbiota transplantation (FMT) is highly effective in recurrent Clostridioides difficile infection (CDI); increasing evidence supports FMT in severe or fulminant Clostridioides difficile infection (SFCDI). However, the multifactorial mechanisms that underpin the efficacy of FMT are not fully understood. Systems biology approaches using high-throughput technologies may help with mechanistic dissection of host-microbial interactions. Here, we have undertaken a deep phenomics study on four adults receiving sequential FMT for SFCDI, in which we performed a longitudinal, integrative analysis of multiple host factors and intestinal microbiome changes. Stool samples were profiled for changes in gut microbiota and metabolites and blood samples for alterations in targeted epigenomic, metabonomic, glycomic, immune proteomic, immunophenotyping, immune functional assays, and T-cell receptor (TCR) repertoires, respectively. We characterised temporal trajectories in gut microbial and host immunometabolic data sets in three responders and one non-responder to sequential FMT. A total of 562 features were used for analysis, of which 78 features were identified, which differed between the responders and the non-responder. The observed dynamic phenotypic changes may potentially suggest immunosenescent signals in the non-responder and may help to underpin the mechanisms accompanying successful FMT, although our study is limited by a small sample size and significant heterogeneity in patient baseline characteristics. Our multi-omics integrative longitudinal analytical approach extends the knowledge regarding mechanisms of efficacy of FMT and highlights preliminary novel signatures, which should be validated in larger studies.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S627-S627
Author(s):  
Jae Hyun Shin ◽  
R Ann Hays ◽  
Cirle Warren

Abstract Background There are limited options for Clostridioides difficile infection (CDI) refractory to conventional antibiotic therapy (metronidazole, vancomycin, or fidaxomicin). Fecal microbiota transplant (FMT) is considered a safe and effective treatment for recurrent CDI but has not been widely utilized for refractory CDI due to concerns about safety. Even when included in studies, refractory CDI has not been analyzed separately from recurrent CDI. We reviewed cases of FMT performed in the inpatient setting for CDI to evaluate its safety and efficacy for refractory CDI. Methods Patients who received FMT inpatient at University of Virginia Health System for recurrent or refractory CDI after Infectious Diseases and Gastroenterology consultation signed informed consent acknowledging that FMT was considered investigational use in CDI not responding to standard of care as per 2014 FDA guidance. Charts were reviewed as part of quality improvement efforts to evaluate safety and efficacy of FMT in inpatient setting. Results Starting in July 2014, 13 patients received FMT for CDI as inpatients. Six received FMT for recurrent CDI, with four having complete resolution, one had recurrent CDI, and one had persistent C. difficile-negative diarrhea, for cure rate of 83%, comparable to published studies. Seven patients received FMT for refractory CDI, with three resulting in complete resolution. One responded to FMT but refused further care, one died from multiorgan failure after initial response to FMT that was possibly related to CDI, strongyloides, and/or CMV. Two patients had ongoing diarrhea suggestive of post-infectious irritable bowel syndrome, one was C. difficile-negative and one was not tested. The cure rate was 57%, lower than that of the recurrent CDI, but without any clear evidence of microbiologic failure. Outcome of patients undergoing FMT for CDI in the inpatient setting at University of Virginia Health System Conclusion Cure rate for FMT for refractory CDI was lower than recurrent CDI, but review of the cases of treatment failures did not reveal any microbiologic evidence of failure. FMT should be considered an alternative option when treating refractory CDI. Disclosures All Authors: No reported disclosures


2021 ◽  
Vol 14 (01) ◽  
pp. 016-020
Author(s):  
Juliana Peloso Signorette ◽  
Rômulo Tadeu Dias de Oliveira ◽  
José Maria Montiel ◽  
Priscila Larcher Longo

Abstract Objective This study aimed to perform a comprehensive review of clinical trials using fecal microbiota transplantation in cases of Clostridioides difficile infection. Methods This manuscript reviews clinical studies published from 2003 to 2020 at the Scientific Electronic Library Online (SciELO Brazil), Latin American and Caribbean Health Sciences Literature (LILACS) and US National Library of Medicine (MedLine/PubMed) databases using the descriptors antibiotic/antimicrobial, Clostridium difficile/Clostridioides difficile, intestinal microbiota/intestinal microbiome and fecal transplantation. Results Interventions on microbiota include the use of probiotics, prebiotics, and fecal microbiota transplantation as therapeutic methods. Results show that fecal microbiota transplantation is an excellent alternative for the treatment of recurrent C. difficile infections.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S841-S842
Author(s):  
Annie S Hong ◽  
Wen Yuan Yu ◽  
Jenny M Hong ◽  
Mohamed Azab ◽  
Gordon V Ohning ◽  
...  

Abstract Background Current guidelines include fecal microbiota transplantation (FMT) in the management of recurrent Clostridioides difficile infections (CDI). However, FMT protocols are often facility dependent, and one variable is whether proton pump inhibitors (PPI) are given during preparation. Theoretically, PPIs reduce acidity and protects the transplanted microbiome for the most potent dose. On the other hand, PPIs have also been shown to negatively alter the microbiome and increase the risk of CDI. We conducted a systematic review of the literature to study PPI use on the efficacy of FMT delivered by the trans-oral route. Methods We searched PubMed/Medline, Cochrane Library, Embase, Scopus, and Web of Science through December 16th, 2018 using variations of keywords “fecal microbiota transplant” and “Clostridium difficile infection” with 4210 results. Two independent authors reviewed and excluded studies with unrelated topics, abstracts, case reports, or a low level of evidence. Studies with data on trans-oral FMT, PPI use, and the success rate were included. Final review yielded 11 studies including randomized controlled, case–control, cohort, retrospective and prospective trials. The primary outcome was the rate of FMT failure, defined as recurrence of symptoms with positive CDI testing at follow-up. Results Out of 233 included patients, 131 received a PPI per FMT protocol resulting in 27 cases of treatment failure. There were 23 cases of recurrence out of 102 patients who did not receive pre-FMT PPI. The primary outcome occurred in 20.6% in the group with PPI use vs. 22.6% in the group without (RR 0.91; CI 0.56 - 1.50). Limitations include the lack of studies directly comparing outcomes with respect to PPI use, and inability to control possible confounders such as chronic PPI use, amount of stool transplanted, and pre-FMT antibiotics. Conclusion We did not find a significant difference in efficacy between FMT protocols with regard to PPI use. It is possible that the theoretical benefit from increased survival of transplanted microbiota is offset by negative effects associated with PPIs. We suggest that routine use of PPIs in FMT be reconsidered in the absence of clear benefit. Further investigation is needed to optimize protocols for safety and efficacy. Disclosures All authors: No reported disclosures.


2019 ◽  
Vol 8 (6) ◽  
pp. 580-584
Author(s):  
Jillian M Cotter ◽  
Maribeth R Nicholson ◽  
Larry K Kociolek

Abstract Fecal microbiota transplantation (FMT) is efficacious for treatment of recurrent Clostridioides difficile infections (rCDIs). Pediatric experience with FMT for rCDIs is increasing, particularly at large centers. While retrospective studies suggest that FMT is generally safe in the short term, particularly in immunocompetent patients and with rigorous donor screening, additional large prospective studies are needed. This particularly includes those at high risk for infectious complications, such as immunocompromised hosts. Further, long-term implications of altering the intestinal microbiome with FMT are not well understood. The role of FMT in children, particularly in high-risk patients, will require continual reexamination with future availability of pediatric safety and efficacy data. This review summarizes key points for infectious diseases physicians to consider when evaluating a child for FMT.


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