scholarly journals High-resolution tracking of microbial colonization in Fecal Microbiota Transplantation experiments via metagenome-assembled genomes

2016 ◽  
Author(s):  
Sonny TM Lee ◽  
Stacy A. Kahn ◽  
Tom O. Delmont ◽  
Nathaniel J. Hubert ◽  
Hilary G. Morrison ◽  
...  
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Distribution Patterns ◽  
Fecal Microbiota ◽  
Microbial Colonization ◽  
Model Systems ◽  
Microbial Populations ◽  
Shotgun Metagenomics ◽  
Single Donor ◽  
Colonization Success ◽  
Cultivation Hypothesis

AbstractFecal microbiota transplantation (FMT) is an effective treatment for recurrentClostridium difficileinfection and shows promise for treating other medical conditions associated with intestinal dysbioses. However, we lack a sufficient understanding of which microbial populations successfully colonize the recipient gut, and the widely used approaches to study the microbial ecology of FMT experiments fail to provide enough resolution to identify populations that are likely responsible for FMT-derived benefits. Here we used shotgun metagenomics to reconstruct 97 metagenome-assembled genomes (MAGs) from fecal samples of a single donor and followed their distribution in two FMT recipients to identify microbial populations with different colonization properties. Our analysis of the occurrence and distribution patterns post-FMT revealed that 22% of the MAGs transferred from the donor to both recipients and remained abundant in their guts for at least eight weeks. Most MAGs that successfully colonized the recipient gut belonged to the order Bacteroidales. The vast majority of those that lacked evidence of colonization belonged to the order Clostridiales and colonization success was negatively correlated with the number of genes related to sporulation. Although our dataset showed a link between taxonomy and the ability of a MAG to colonize the recipient gut, we also identified MAGs with different colonization properties that belong to the same taxon, highlighting the importance of genome-resolved approaches to explore the functional basis of colonization and to identify targets for cultivation, hypothesis generation, and testing in model systems for mechanistic insights.

scholarly journals Benefits of fecal microbiota transplantation: A comprehensive review

2020 ◽  
Vol 14 (10) ◽  
pp. 1074-1080
Author(s):  
Muluneh Ademe
Keyword(s):  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Short Chain Fatty Acids ◽  
Fecal Microbiota ◽  
Microbial Colonization ◽  
Action Current ◽  
Therapeutic Benefits ◽  
Wide Range ◽  
The One ◽  
Host Metabolism

A growing body of literatures showed the interaction of dysbiotic gut with a wide range of disorders, and the clinical use of fecal microbiota transplantation (FMT) shifted from infectious disease to non-communicable disorders. Despite the promising therapeutic benefits of FMT, the exact mechanisms through which fecal recipients benefit from the fecal intervention are not well understood. However, owing to the advantages of having a healthy gut microbiome, possible mechanisms of actions of FMT has been described. On the one hand, through direct ecological competition, FMT may potentially stimulate decolonization of pathogenic microorganisms and increase host resistance to pathogens. Moreover, following dysbiosis, abnormal microbial colonization of the gastrointestinal tract may also cause excessive or dysregulated immune response, resulting in chronic inflam­mation and the development of mucosal lesions. In this regard, repopulating gut microbiome through FMT helps to restore immune function and reduce host damage. On the other hand, FMT helps to restore essential metabolites used for host metabolism, including short-chain fatty acids (SCFA), antimicrobial peptides (AMP), bacteriocins and bile acids. Therefore, in this review, the existing evidences regarding the mechanisms of action, current opportunities and challenges of FMT will be described.

scholarly journals Long-Term Efficacy of Low-Intensity Single Donor Fecal Microbiota Transplantation in Ulcerative Colitis and Outcome-Specific Gut Bacteria

2021 ◽  
Vol 12 ◽  
Author(s):  
Rongrong Ren ◽  
Xuefeng Gao ◽  
Yichao Shi ◽  
Jianfeng Li ◽  
Lihua Peng ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Bacteroides Fragilis ◽  
Fecal Microbiota ◽  
Low Intensity ◽  
Single Donor ◽  
Before And After

Aims: To assess the long-term efficacy and safety of single-donor, low-intensity fecal microbiota transplantation (FMT) in treating ulcerative colitis (UC), and to identify the outcome-specific gut bacteria.Design: Thirty-one patients with active UC (Mayo scores ≥ 3) were recruited, and all received FMT twice, at the start of the study and 2∼3 months later, respectively, with a single donor and a long-term follow-up. The fecal microbiome profile was accessed via 16S rRNA sequencing before and after FMT.Results: After the first FMT, 22.58% (7/31) of patients achieved clinical remission and endoscopy remission, with the clinical response rate of 67.74% (21/31), which increased to 55% (11/20) and 80% (16/20), respectively, after the second FMT. No serious adverse events occurred in all patients. During 4 years of follow-up, the mean remission period of patients was 26.5 ± 19.98 m; the relapse rate in the 12 remission patients was 33.33% within 1 year, and 58.3% within 4 years. At baseline, UC patients showed an enrichment in some proinflammatory microorganisms compared to the donor, such as Bacteroides fragilis, Clostridium difficile, and Ruminococcus gnavus, and showed reduced amounts of short-chain fatty acid (SCFA) producing bacteria especially Faecalibacterium prausnitzii. FMT induced taxonomic compositional changes in the recipient gut microbiota, resulting in a donor-like state. Given this specific donor, UC recipients with different outcomes showed distinct gut microbial features before and after FMT. In prior to FMT, relapse was characterized by higher abundances of Bacteroides fragilis and Lachnospiraceae incertae sedis, together with lower abundances of Bacteroides massiliensis, Roseburia, and Ruminococcus; Prevotella copri was more abundant in the non-responders (NR); and the patients with sustained remission (SR) had a higher abundance of Bifidobacterium breve. After FMT, the NR patients had a lower level of Bifidobacterium compared to those with relapse (Rel) and SR, while a higher level of Bacteroides spp. was observed in the Rel group.Conclusion: Low-intensity single donor FMT could induce long remission in active UC. The gut microbiota composition in UC patients at baseline may be predictive of therapeutic response to FMT.

scholarly journals High engraftment capacity of frozen ready-to-use human fecal microbiota transplants assessed in germ-free mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Magali Berland ◽  
Julie Cadiou ◽  
Florence Levenez ◽  
Nathalie Galleron ◽  
Benoît Quinquis ◽  
...  
Keyword(s):  
Mouse Model ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Fecal Microbiota Transplant ◽  
Shotgun Metagenomics ◽  
Germ Free ◽  
Important Group ◽  
Freeze Dried ◽  
The Family ◽  
Fresh Preparation

AbstractThe number of indications for fecal microbiota transplantation is expected to rise, thus increasing the needs for production of readily available frozen or freeze-dried transplants. Using shotgun metagenomics, we investigated the capacity of two novel human fecal microbiota transplants prepared in maltodextrin-trehalose solutions (abbreviated MD and TR for maltodextrin:trehalose, 3:1, w/w, and trehalose:maltodextrin 3:1, w/w, respectively), to colonize a germ-free born mouse model. Gavage with frozen-thawed MD or TR suspensions gave the taxonomic profiles of mouse feces that best resembled those obtained with the fresh inoculum (Spearman correlations based on relative abundances of metagenomic species around 0.80 and 0.75 for MD and TR respectively), while engraftment capacity of defrosted NaCl transplants most diverged (Spearman correlations around 0.63). Engraftment of members of the family Lachnospiraceae and Ruminoccocaceae was the most challenging in all groups of mice, being improved with MD and TR transplants compared to NaCl, but still lower than with the fresh preparation. Improvement of engraftment of this important group in maintaining health represents a challenge that could benefit from further research on fecal microbiota transplant manufacturing.

scholarly journals Tracking microbial colonization in fecal microbiota transplantation experiments via genome-resolved metagenomics

Microbiome ◽  
2017 ◽  
Vol 5 (1) ◽  
Author(s):  
Sonny T. M. Lee ◽  
Stacy A. Kahn ◽  
Tom O. Delmont ◽  
Alon Shaiber ◽  
Özcan C. Esen ◽  
...  
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Microbial Colonization ◽  
Transplantation Experiments

scholarly journals Donor-dependent Fecal Microbiota Transplantation Efficacy Against Necrotizing Enterocolitis in Preterm Pigs

2020 ◽  
Author(s):  
Yan Hui ◽  
Gisle Alberg Vestergaard ◽  
Ling Deng ◽  
Witold Piotr Kot ◽  
Thomas Thymann ◽  
...  
Keyword(s):  
Necrotizing Enterocolitis ◽  
Fecal Microbiota Transplantation ◽  
Gastrointestinal Disease ◽  
Amplicon Sequencing ◽  
Rectal Administration ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Shotgun Metagenomics ◽  
Pathological Evaluation ◽  
Cure Rates

Abstract BackgroundFecal microbiota transplantation (FMT) has shown high cure rates against recurrent Clostridioides difficile infection regardless of donor microbiota characteristics, whereas the clinical response of FMT in inflammatory bowel disease appears to be donor-dependent. We recently showed that FMT from healthy suckling piglet donors to newborn preterm piglets decreased the risk of necrotizing enterocolitis (NEC), a serious gastrointestinal disease of preterm infants, but could not replicate this finding in a follow-up study using phenotypically similar donors. This gave us the opportunity to directly investigate the microbiota dynamics of clinically efficient FMT. In this experiment, preterm piglets (n=38) were randomly allocated to receive control saline or FMT from inferior (FMT1) or superior donors (FMT2) by rectal administration. All animals were fed infant formula for four days to induce NEC-like lesions before necropsy and gut pathological evaluation. Donor and recipient colonic microbiotas were analyzed by 16S rRNA gene amplicon sequencing and shotgun metagenomics.ResultsAlthough the two donor microbiotas closely resembled one another, only FMT2 recipients had improved body growth and lower intestinal permeability relative to control, and were protected against NEC. Both FMT groups had shifted colon microbiota composition relative to CON, with increased lactobacilli relative abundance, but FMT2 recipients had a higher lactobacilli abundance relative to FMT1. Limosilactobacillus reuteri and Lactobacillus crispatus strains of FMT recipients showed high phylogenetic similarity with their respective donors, indicating successful engraftment. Further, NEC severity was positively associated with Clostridoides difficile, Clostridium perfringens and Enterococcus faecium abundance, while Lmb. reuteri and Lb. crispatus negatively correlated with diarrhea severity. Genome-resolved analysis indicated a higher gut replication rate of lactobacilli in FMT2 recipients, and identified specific glycosaminoglycan-degrading Bacteroides in the superior donor.ConclusionsFMT efficacy against NEC is donor-dependent, and introduced lactobacilli manifest strain-level differences with respect to colonizing recipients. Using shotgun metagenomics, we traced the engrafted strains back from donors and identified donor-specific microbes of potential importance. This may accelerate our understanding of optimal donor selection for clinical FMT.

scholarly journals The role of the microbiota in the management of intensive care patients

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Piotr Szychowiak ◽  
Khanh Villageois-Tran ◽  
Juliette Patrier ◽  
Jean-François Timsit ◽  
Étienne Ruppé
Keyword(s):  
Intensive Care ◽  
Gut Microbiota ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Fecal Microbiota Transplantation ◽  
Anaerobic Bacteria ◽  
Fecal Microbiota ◽  
Resistant Bacteria ◽  
Shotgun Metagenomics ◽  
Increased Risk

AbstractThe composition of the gut microbiota is highly dynamic and changes according to various conditions. The gut microbiota mainly includes difficult-to-cultivate anaerobic bacteria, hence knowledge about its composition has significantly arisen from culture-independent methods based on next-generation sequencing (NGS) such as 16S profiling and shotgun metagenomics. The gut microbiota of patients hospitalized in intensive care units (ICU) undergoes many alterations because of critical illness, antibiotics, and other ICU-specific medications. It is then characterized by lower richness and diversity, and dominated by opportunistic pathogens such as Clostridioides difficile and multidrug-resistant bacteria. These alterations are associated with an increased risk of infectious complications or death. Specifically, at the time of writing, it appears possible to identify distinct microbiota patterns associated with severity or infectivity in COVID-19 patients, paving the way for the potential use of dysbiosis markers to predict patient outcomes. Correcting the microbiota disturbances to avoid their consequences is now possible. Fecal microbiota transplantation is recommended in recurrent C. difficile infections and microbiota-protecting treatments such as antibiotic inactivators are currently being developed. The growing interest in the microbiota and microbiota-associated therapies suggests that the control of the dysbiosis could be a key factor in the management of critically ill patients. The present narrative review aims to provide a synthetic overview of microbiota, from healthy individuals to critically ill patients. After an introduction to the different techniques used for studying the microbiota, we review the determinants involved in the alteration of the microbiota in ICU patients and the latter’s consequences. Last, we assess the means to prevent or correct microbiota alteration.

scholarly journals The Efficacy of Fecal Microbiota Transplantation for Children With Tourette Syndrome: A Preliminary Study

2020 ◽  
Vol 11 ◽  
Author(s):  
Hui-Jun Zhao ◽  
Xi Luo ◽  
Yi-Chao Shi ◽  
Jian-Feng Li ◽  
Fei Pan ◽  
...  
Keyword(s):  
Tourette Syndrome ◽  
Fecal Microbiota Transplantation ◽  
Neurological Diseases ◽  
Reduction Rate ◽  
Fecal Microbiota ◽  
Severity Scale ◽  
Safe Alternative ◽  
Shotgun Metagenomics ◽  
Tic Severity ◽  
Preliminary Study

Therapies for Tourette syndrome (TS) are insufficient, and novel therapies are needed. Fecal microbiota transplantation (FMT) has been a potential therapy for several neurological diseases. Here, we report a preliminary study to investigate the effects of FMT on patients with TS. Five patients with TS received a single administration of FMT via endoscopy. Tic symptoms were assessed by Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) and adverse effects were recorded at week 8 following FMT. Lipopolysaccharide (LPS) levels and 14 cytokines levels were measured. The microbiota profile in feces were analyzed by shotgun metagenomics. Four patients (4/5) responded positively to FMT (YGTSS-TTS reduction rate >25%) at week 8 with high safety. The levels of LPS and cytokines varied after FMT. FMT shifted the composition of the gut microbiota in patients close to that of the donor and continuously changed the abundance of Bacteroides coprocola, Dialister succinatiphilus and Bacteroides vulgatus. The restoration of B.coprocola was correlated with the improvement in tic symptoms (Spearman R = −0.900, P = 0.037). In conclusion, FMT was indicated a potential effective and safe alternative for patients with TS. However, larger clinical trials are needed to confirm the influence of microbiota in TS.Trial Registration:chictr.org.cn Identifier: ChiCTR-IIR-17011871, URL: http://www.chictr.org.cn/showproj.aspx?proj=19941.

scholarly journals Adaptive ecological processes and metabolic independence drive microbial colonization and resilience in the human gut

2021 ◽  
Author(s):  
Andrea R Watson ◽  
Jessika Fuessel ◽  
Iva Veseli ◽  
Johanna Zaal DeLongchamp ◽  
Marisela Silva ◽  
...  
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Microbial Colonization ◽  
Human Gut ◽  
Ecological Processes ◽  
Disease States ◽  
Inflammatory Conditions ◽  
High Fitness ◽  
Formidable Challenge ◽  
Main Driver

A detailed understanding of human gut microbial ecology is essential to engineer effective microbial therapeutics and to model microbial community assembly in health and disease. However, establishing generalizable insights into the functional determinants of microbial fitness in the gut has been a formidable challenge. Here we employ fecal microbiota transplantation (FMT) as an in natura experimental model to identify determinants of microbial colonization and resilience. Our findings reveal adaptive ecological processes that favor high-fitness populations with higher metabolic competence as the main driver of microbial colonization outcomes after FMT. We further show that while healthy individuals harbor both low-fitness and high-fitness populations, individuals with inflammatory bowel disease are typically depleted of low-fitness populations. These results offer a model to explain why common yet typically rare members of healthy guts can dominate under inflammatory conditions without any need for them to be causally associated with, or contribute to, such disease states.

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