scholarly journals The trans-kingdom battle between donor and recipient gut microbiome influences fecal microbiota transplantation outcome

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Negin Kazemian ◽  
Milad Ramezankhani ◽  
Aarushi Sehgal ◽  
Faizan Muhammad Khalid ◽  
Amir Hossein Zeinali Kalkhoran ◽  
...  
Keyword(s):  
Secondary Succession ◽  
Restoration Ecology ◽  
Short Chain Fatty Acid ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Chain Fatty Acid ◽  
Metagenomic Sequencing ◽  
Clostridioides Difficile ◽  
Stool Samples ◽  
Underlying Mechanisms

Abstract Fundamental restoration ecology and community ecology theories can help us better understand the underlying mechanisms of fecal microbiota transplantation (FMT) and to better design future microbial therapeutics for recurrent Clostridioides difficile infections (rCDI) and other dysbiosis-related conditions. In this study, stool samples were collected from donors and rCDI patients one week prior to FMT (pre-FMT), as well as from patients one week following FMT (post-FMT). Using metagenomic sequencing and machine learning, our results suggested that FMT outcome is not only dependent on the ecological structure of the recipients, but also the interactions between the donor and recipient microbiomes at the taxonomical and functional levels. We observed that the presence of specific bacteria in donors (Clostridioides spp., Desulfovibrio spp., Odoribacter spp. and Oscillibacter spp.) and the absence of fungi (Yarrowia spp.) and bacteria (Wigglesworthia spp.) in recipients prior to FMT could predict FMT success. Our results also suggested a series of interlocked mechanisms for FMT success, including the repair of the disturbed gut ecosystem by transient colonization of nexus species followed by secondary succession of bile acid metabolizers, sporulators, and short chain fatty acid producers.

scholarly journals Fecal microbiota transplantation efficacy for Clostridium difficile infection: A trans-kingdom battle between donor and recipient gut microbiomes

2020 ◽  
Author(s):  
Negin Kazemian ◽  
Milad Ramezankhani ◽  
Aarushi Sehgal ◽  
Faizan Muhammad Khalid ◽  
Amir Hossein Zeinali Kalkhoran ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Bile Acid ◽  
Clostridium Difficile ◽  
Secondary Succession ◽  
Short Chain Fatty Acid ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Chain Fatty Acid ◽  
Microbial Ecosystem ◽  
Underlying Mechanisms

AbstractFundamental restoration ecology and community ecology theories can help us better understand the underlying mechanisms of fecal microbiota transplantation (FMT) and to better design future microbial therapeutics for recurrent Clostridium difficile infections (rCDI) and other dysbiosis-related conditions. In a single cohort study, stool samples were collected from donors and rCDI patients one week prior to FMT (pre-FMT) as well as from patients one week following FMT (post-FMT). Using metagenomic sequencing and machine learning methods, our results suggested that the FMT outcome is not only dependent on the ecological structure of the recipients, but also the interactions between the donor and recipient microbiomes, both at the taxonomical and functional levels. Importantly, we observed that the presence of specific bacteria in donors (Clostridiodes spp., Desulfovibrio spp., Odoribacter spp. and Oscillibacter spp.) and the absence of specific fungi (Yarrowia spp.) and bacteria (Wigglesworthia spp.) in recipients prior to FMT could accurately predict FMT success. Our results also suggested a series of interlocked mechanisms for FMT success, including the repair of the disturbed gut microbial ecosystem by transient colonization of nexus species followed by secondary succession of bile acid metabolizers, sporulators, and short chain fatty acid producers. Therefore, a better understanding of such mechanisms can be fundamental key elements to develop adaptive, personalized microbial-based strategies for the restoration of the gut ecosystem.ImportanceThere have been a number of studies focusing on understanding the underlying mechanisms in FMT treatment, which can accordingly be used for the optimization of future treatments. However, the current scientific lens has mainly had a uni-kingdom major focus on bacteria, leading to the proposition of the existence of FMT “super-donors”. On the contrary, our preliminary study here suggests that FMT is not necessarily a ‘one stool fits all’ approach and that donor-recipient cross-kingdom microbiota interactions, along with their short-term fluctuations in the gut, bring profound implications in FMT success. The results also conceptualize a series of interlocked mechanisms for FMT success, including first repairing the disturbed gut microbial ecosystem by transient species, followed by secondary succession of indigenous or exogenous bile acid metabolizers, sporulators, and short chain fatty acid producers.

scholarly journals Identification and engraftment of new bacterial strains by shotgun metagenomic sequence analysis in patients with recurrent Clostridioides difficile infection before and after fecal microbiota transplantation and in healthy human subjects

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0251590
Author(s):  
Sandeep Verma ◽  
Sudhir K. Dutta ◽  
Elad Firnberg ◽  
Laila Phillips ◽  
Rakesh Vinayek ◽  
...  
Keyword(s):  
Relative Abundance ◽  
Fecal Microbiota Transplantation ◽  
Bacterial Species ◽  
Fecal Microbiota ◽  
Metagenomic Sequencing ◽  
Bacterial Strains ◽  
Metagenomic Sequence ◽  
Clostridioides Difficile ◽  
Healthy Donors ◽  
Before And After

Background Recurrent Clostridioides diffícile infection (RCDI) is associated with major bacterial dysbiosis and colitis. Fecal microbiota transplantation (FMT) is a highly effective therapeutic modality for RCDI. While several studies have identified bacterial species associated with resolution of symptoms in patients, characterization of the fecal microbiome at the bacterial strain level in RCDI patients before and after FMT and healthy donors, has been lacking. The aim of this study was to examine the ability of bacterial strains from healthy donors to engraft in the gastrointestinal tract of patients with RCDI following FMT. Methods Fecal samples were collected from 22 patients with RCDI before and after FMT and their corresponding healthy donors. Total DNA was extracted from each sample and analyzed by shotgun metagenomic sequencing. The Cosmos-ID analysis platform was used for taxonomic assignment of sequences and calculation of the relative abundance (RA) of bacterial species and strains. From these data, the total number of bacterial strains (BSI), Shannon diversity index, dysbiosis index (DI), and bacterial engraftment factor, were calculated for each strain. Findings A marked reduction (p<0·0001) in the RA of total and specific bacterial strains, especially from phylum Firmicutes, was observed in RCDI patients prior to FMT. This change was associated with an increase in the DI (p<0·0001) and in pathobiont bacterial strains from phylum Proteobacteria, such as Escherichia coli O157:H7 and Klebsiella pneumoniae UCI 34. BSI was significantly lower in this group of patients as compared to healthy donors and correlated with the Shannon Index. (p<0·0001). Identification and engraftment of bacterial strains from healthy donors revealed a greater diversity and higher relative abundance of short-chain fatty acid (SCFA)-producing bacterial strains, including Lachnospiraceae bacterium 5_1_63FAA_u_t, Dorea formicigenerans ATCC 27755, Anaerostipes hadrusand others, in RCDI patients after FMT. Interpretation These observations identify a group of SCFA-producing bacterial strains from healthy donors that engraft well in patients with RCDI following FMT and are associated with complete resolution of clinical symptoms and bacterial dysbiosis.

scholarly journals Fecal microbiota transplantation reconstructs the gut microbiota of septic mice and protects the intestinal mucosal barrier

2020 ◽  
Author(s):  
Xiaowei Gai ◽  
Huawei Wang ◽  
Yaqing Li ◽  
Haotian Zhao ◽  
Cong He ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Gut Microbiota ◽  
Tight Junction ◽  
Short Chain Fatty Acid ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Chain Fatty Acid ◽  
Mucosal Barrier ◽  
Mucus Layer ◽  
Intestinal Mucosal Barrier

AbstractThe gastrointestinal (GI) tract has long been hypothesized to play an integral role in the pathophysiology of sepsis, and gut microbiota (GM) dysbiosis may be the key factor. Previous studies has confirmed that microbiome is markedly altered in critical illness. We aimed to confirm the existence of gut microbiota imbalance in the early stage of sepsis, observe the effect of fecal microbiota transplantation (FMT) on sepsis, and explore whether FMT can reconstruct the GM of septic mice and restore its protective function on the intestinal mucosal barrier. Through the study of flora, mucus layer, tight junction, immune barrier, and short-chain fatty acid changes in septic mice and fecal microbiota transplanted mice, we found that GM imbalance exists early in sepsis. FMT can improve morbidity and effectively reduce mortality in septic mice. After the fecal bacteria were transplanted, the abundance and diversity of the gut flora were restored, and the microbial characteristics of the donors changed. FMT can effectively reduce epithelial cell apoptosis, improve the composition of the mucus layer, upregulate the expression of tight junction proteins, and reduce intestinal permeability and the inflammatory response, thus protecting the intestinal barrier function. After FMT, Lachnospiraceae contributes the most to intestinal protection through enhancement of the L-lysine fermentation pathway, resulting in the production of acetate and butanoate, and may be the key bacteria for short-chain fatty acid metabolism and FMT success.

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 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.

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