scholarly journals Intraspecies strain exclusion, antibiotic pretreatment, and donor selection control microbiota engraftment after fecal transplantation

2021 ◽  
Author(s):  
Daniel Podlesny ◽  
Marija Durdevic ◽  
Sudarshan Paramsothy ◽  
Nadeem O. Kaakoush ◽  
Christoph Hoegenauer ◽  
...  
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Tumor Therapy ◽  
Species Abundance ◽  
Ecological Factors ◽  
Fecal Microbiota ◽  
Donor Strain ◽  
Fecal Transplantation ◽  
Clostridioides Difficile ◽  
Therapeutic Benefits ◽  
Promising Therapeutic Approach

Fecal microbiota transplantation (FMT) is both a promising therapeutic approach to treat microbiota-associated pathologies and an experimental tool to establish a causal role of microbiome dysbiosis in human pathologies. Although clearly efficacious in resolving recurrent Clostridioides difficile infection (rCDI), the therapeutic value of FMT in other pathologies is not yet established, and our mechanistic and ecological understanding of how FMT alters the microbiome in patients is incomplete. Here, we assembled the most comprehensive FMT trial microbiota dataset to date, including new and previously generated fecal metagenomes from FMT trials in rCDI, inflammatory bowel disease (IBD), metabolic syndrome (MetS), drug-resistant pathogen colonization (MDR), and resistance to immune checkpoint inhibitor anti-tumor therapy (ICI). We characterized post-FMT microbiota assembly in the recipients by establishing the origin of the detected strains, and we identified the clinical and ecological factors that determine the engraftment of donor strains. Our findings showed little coexistence of donor and recipient strains and linked the magnitude of donor strain engraftment to dysbiosis of the recipient microbiome. Dysbiosis and strain engraftment were low in pathologies other than rCDI but could be enhanced through pretreatment with antibiotics and lavage. Using generalized linear mixed-effects models, we demonstrate that both ecological (low recipient and high donor ɑ-diversity and relative species abundance) and clinical (antibiotic pretreatment, bowel lavage, multiple rounds of FMT) variables are associated with increased donor microbiota engraftment, and that donor strain engraftment events are predictable for individual patients and strains. Overall donor strain engraftment was not linked to FMT outcome in IBD patients but was higher in ICI patients that responded to immunotherapy after FMT. Our findings provide an ecological framework for post-FMT microbiota assembly that can predict donor strain engraftment and determine its importance for clinical outcomes, informing more targeted and personalized approaches to increase the therapeutic benefits of FMTs.

scholarly journals Applications of Fecal Microbiota Transplantation: Emphasis on Clostridioides difficile Infections

2021 ◽  
Vol 14 (01) ◽  
pp. 016-020
Author(s):  
Juliana Peloso Signorette ◽  
Rômulo Tadeu Dias de Oliveira ◽  
José Maria Montiel ◽  
Priscila Larcher Longo
Keyword(s):  
Latin American ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Intestinal Microbiome ◽  
National Library ◽  
Electronic Library ◽  
Fecal Transplantation ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Latin American And Caribbean

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.

scholarly journals Microbial Strain Engraftment, Persistence and Replacement after Fecal Microbiota Transplantation

2020 ◽  
Author(s):  
Daniel Podlesny ◽  
W. Florian Fricke
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Sequence Data ◽  
Fecal Microbiota ◽  
Functional Restoration ◽  
Donor Strain ◽  
Metagenomic Sequence ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Species Specific ◽  
Microbial Strain

Fecal Microbiota Transplantation (FMT) has been clinically validated as a treatment for recurrent Clostridioides difficile infection (rCDI) and associated with the compositional and functional restoration of the patient gut microbiota. To characterize the underlying microbiota dynamics of patient and donor strain engraftment, persistence and replacement during FMT, we combined new and existing metagenomic sequence data and developed the bioinformatic SameStr program for the species-specific detection of shared subspecies lineages, including non-dominant strains. We show that personal gut strain profiles are identifiable and detect engraftment after successful and failed FMT in rCDI recipients, specifically of those donor strains that are abundant and stable in healthy individuals. We identify microbiota parameters in statistical models to predict donor species and strain engraftment, as well as recipient strain persistence and replacement. Our findings raise concerns over FMT consequences from questionable donors and suggest that personalized FMT strategies are feasible for targeted microbiota modulation.

scholarly journals Quantification of discrete gut bacterial strains following fecal transplantation for recurrent Clostridioides difficile infection demonstrates long-term stable engraftment in non-relapsing recipients

2020 ◽  
Author(s):  
Varun Aggarwala ◽  
Ilaria Mogno ◽  
Zhihua Li ◽  
Chao Yang ◽  
Graham J. Britton ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Systematic Evaluation ◽  
Late Relapse ◽  
Metagenomic Sequencing ◽  
Sequencing Data ◽  
Bacterial Strains ◽  
Fecal Transplantation ◽  
Clostridioides Difficile

AbstractFecal Microbiota Transplantation (FMT), while successful for the treatment of recurrent Clostridioides difficile (rCDI) infection, lacks a quantitative identification of the discrete bacterial strains that transmit and stably engraft in recipients, and their association with clinical outcomes. Using >1,000 unique bacterial strains isolated and sequenced from a combination of 22 FMT donors and recipients, we develop a statistical approach Strainer to detect and track sequenced bacterial strains from low depth metagenomic sequencing data. On application to 14 FMT interventions, we detect stable and high engraftment of ∼71% of gut microbiota strains in recipients at even 5-years post-transplant, a remarkably durable therapeutic from a single administration. We found differential transmission and engraftment efficacy across bacterial taxonomic groups over short and long-time scales. Although ∼80% of the original pre-FMT recipient strains were eliminated by the FMT, those strains that remain persist even 5 years later, along with newer strains acquired from the environment. The precise quantification of donor bacterial strains in recipients independently explained the clinical outcomes of early and late relapse. Our framework identifies the consistently engrafting discrete bacterial strains for use in Live Biotherapeutic Products (LBP) as a safer, scalable alternative to FMT and enables systematic evaluation of different FMT and LBP study designs.

scholarly journals Clostridioides difficile Infection, Still a Long Way to Go

2021 ◽  
Vol 10 (3) ◽  
pp. 389
Author(s):  
Eleftheria Kampouri ◽  
Antony Croxatto ◽  
Guy Prod’hom ◽  
Benoit Guery
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Diagnostic Algorithm ◽  
Fecal Microbiota ◽  
Diagnostic Methods ◽  
Special Focus ◽  
Surveillance Systems ◽  
Main Question ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
The Right

Clostridioides difficile is an increasingly common pathogen both within and outside the hospital and is responsible for a large clinical spectrum from asymptomatic carriage to complicated infection associated with a high mortality. While diagnostic methods have considerably progressed over the years, the optimal diagnostic algorithm is still debated and there is no single diagnostic test that can be used as a standalone test. More importantly, the heterogeneity in diagnostic practices between centers along with the lack of robust surveillance systems in all countries and an important degree of underdiagnosis due to lack of clinical suspicion in the community, hinder a more accurate evaluation of the burden of disease. Our improved understanding of the physiopathology of CDI has allowed some significant progress in the treatment of CDI, including a broader use of fidaxomicine, the use of fecal microbiota transplantation for multiples recurrences and newer approaches including antibodies, vaccines and new molecules, already developed or in the pipeline. However, the management of CDI recurrences and severe infections remain challenging and the main question remains: how to best target these often expensive treatments to the right population. In this review we discuss current diagnostic approaches, treatment and potential prevention strategies, with a special focus on recent advances in the field as well as areas of uncertainty and unmet needs and how to address them.

scholarly journals Fecal microbiota transplantation increases colonic IL-25 and dampens tissue inflammation in patients with recurrent Clostridioides difficile

2021 ◽  
Author(s):  
Ning-Jiun Jan ◽  
Noah Oakland ◽  
Pankaj Kumar ◽  
Girija Ramakrishnan ◽  
Brian W. Behm ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Fecal Microbiota Transplantation ◽  
Alpha Diversity ◽  
The United States ◽  
Fecal Microbiota ◽  
Peripheral Blood Mononuclear ◽  
Clostridioides Difficile ◽  
Rdna Sequencing ◽  
Clostridioides Difficile Infection ◽  
The Impact

Background: Clostridioides difficile infection (CDI) is the most common hospital-acquired infection in the United States. Antibiotic-induced dysbiosis is the primary cause of susceptibility and fecal microbiota transplantation (FMT) has emerged as an effective therapy for recurrence. We previously demonstrated in the mouse model of CDI that antibiotic-induced dysbiosis reduced colonic expression of IL-25, and that FMT protected in part by restoring gut commensal bacteria-mediated IL-25 signaling. Here we conducted a prospective clinical trial to test the impact of FMT on immunity, specifically testing in humans if FMT induced IL-25 expression in the colon. Methods: Subjects received colonic biopsies and blood sampling at the time of FMT and 60-days later. Colon biopsies were assayed for IL-25 by immunoassay, for mRNA by RNAseq, and for bacterial content by 16 S rDNA sequencing. High dimensional flow cytometry was also conducted on peripheral blood mononuclear cells pre- and post-FMT. Results: All 10 subjects who received FMT had no CDI recurrences over a 2 year follow-up post FMT. FMT increased alpha diversity of the colonic microbiota and was associated with several immunologic changes. The cytokine IL-25 was increased in colonic tissue. In addition, increased expression of homeostatic genes and repression of inflammatory genes was observed in colonic mRNA transcripts. Finally, circulating Th17 cells were decreased post-FMT. Conclusion: The increase in the cytokine IL-25 accompanied by decreased inflammation is consistent with FMT acting in part to protect from recurrent CDI via restoration of commensal activation of type 2 immunity.

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