Dynamic Colonization of Microbes and Their Functions after Fecal Microbiota Transplantation for Inflammatory Bowel Disease

ABSTRACT For fecal microbiota transplantation (FMT) to be successful in immune diseases like inflammatory bowel disease, it is assumed that therapeutic microbes and their beneficial functions and immune interactions must colonize a recipient patient and persist in sufficient quantity and for a suffi...

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Autores principales:	Nathaniel D. Chu, Jessica W. Crothers, Le T. T. Nguyen, Sean M. Kearney, Mark B. Smith, Zain Kassam, Cheryl Collins, Ramnik Xavier, Peter L. Moses, Eric J. Alm
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	16S RNA bacteria competition fecal microbiota transplant immunoglobulins inflammatory bowel disease Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c4c9335cabb34f56ad49f7697539f45e
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spelling	oai:doaj.org-article:c4c9335cabb34f56ad49f7697539f45e2021-11-10T18:37:50ZDynamic Colonization of Microbes and Their Functions after Fecal Microbiota Transplantation for Inflammatory Bowel Disease10.1128/mBio.00975-212150-7511https://doaj.org/article/c4c9335cabb34f56ad49f7697539f45e2021-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00975-21https://doaj.org/toc/2150-7511ABSTRACT For fecal microbiota transplantation (FMT) to be successful in immune diseases like inflammatory bowel disease, it is assumed that therapeutic microbes and their beneficial functions and immune interactions must colonize a recipient patient and persist in sufficient quantity and for a sufficient period of time to produce a clinical benefit. Few studies, however, have comprehensively profiled the colonization and persistence of transferred microbes along with the transfer of their microbial functions and interactions with the host immune system. Using 16S, metagenomic, and immunoglobulin A (IgA) sequencing, we analyzed hundreds of longitudinal microbiome samples from a randomized controlled trial of 12 patients with ulcerative colitis who received fecal transplant or placebo for 12 weeks. We uncovered diverse competitive dynamics among donor and patient strains, showing that persistence of transferred microbes is far from static. Indeed, one patient experienced a dramatic loss of donor bacteria 10 weeks into the trial, coinciding with a bloom of pathogenic bacteria and worsening symptoms. We evaluated the transfer of microbial functions, including desired ones, such as butyrate production, and unintended ones, such as antibiotic resistance. By profiling bacteria coated with IgA, we identified bacteria associated with inflammation and found that microbial interactions with the host immune system can be transferred across people, which could play a role in gut microbiome therapeutics for immune-related diseases. Our findings shed light on the colonization dynamics of gut microbes and their functions in the context of FMT to treat a complex disease—information that may provide a foundation for developing more-targeted therapeutics. IMPORTANCE Fecal microbiota transplantation (FMT)—transferring fecal microbes from a healthy donor to a sick patient—has shown promise for gut diseases such as inflammatory bowel disease. Unlike pharmaceuticals, however, fecal transplants are complex mixtures of living organisms, which must then interact with the microbes and immune system of the recipient. We sought to understand these interactions by tracking the microbes of 12 inflammatory bowel disease patients who received fecal transplants for 12 weeks. We uncovered a range of dynamics. For example, one patient experienced successful transfer of donor bacteria, only to lose them after 10 weeks. We similarly evaluated transfer of microbial functions, including how they interacted with the recipient’s immune system. Our findings shed light on the colonization dynamics of gut microbes, as well as their functions in the context of FMT—information that may provide a critical foundation for the development of more-targeted therapeutics.Nathaniel D. ChuJessica W. CrothersLe T. T. NguyenSean M. KearneyMark B. SmithZain KassamCheryl CollinsRamnik XavierPeter L. MosesEric J. AlmAmerican Society for Microbiologyarticle16S RNAbacteriacompetitionfecal microbiota transplantimmunoglobulinsinflammatory bowel diseaseMicrobiologyQR1-502ENmBio, Vol 12, Iss 4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	16S RNA bacteria competition fecal microbiota transplant immunoglobulins inflammatory bowel disease Microbiology QR1-502
spellingShingle	16S RNA bacteria competition fecal microbiota transplant immunoglobulins inflammatory bowel disease Microbiology QR1-502 Nathaniel D. Chu Jessica W. Crothers Le T. T. Nguyen Sean M. Kearney Mark B. Smith Zain Kassam Cheryl Collins Ramnik Xavier Peter L. Moses Eric J. Alm Dynamic Colonization of Microbes and Their Functions after Fecal Microbiota Transplantation for Inflammatory Bowel Disease
description	ABSTRACT For fecal microbiota transplantation (FMT) to be successful in immune diseases like inflammatory bowel disease, it is assumed that therapeutic microbes and their beneficial functions and immune interactions must colonize a recipient patient and persist in sufficient quantity and for a sufficient period of time to produce a clinical benefit. Few studies, however, have comprehensively profiled the colonization and persistence of transferred microbes along with the transfer of their microbial functions and interactions with the host immune system. Using 16S, metagenomic, and immunoglobulin A (IgA) sequencing, we analyzed hundreds of longitudinal microbiome samples from a randomized controlled trial of 12 patients with ulcerative colitis who received fecal transplant or placebo for 12 weeks. We uncovered diverse competitive dynamics among donor and patient strains, showing that persistence of transferred microbes is far from static. Indeed, one patient experienced a dramatic loss of donor bacteria 10 weeks into the trial, coinciding with a bloom of pathogenic bacteria and worsening symptoms. We evaluated the transfer of microbial functions, including desired ones, such as butyrate production, and unintended ones, such as antibiotic resistance. By profiling bacteria coated with IgA, we identified bacteria associated with inflammation and found that microbial interactions with the host immune system can be transferred across people, which could play a role in gut microbiome therapeutics for immune-related diseases. Our findings shed light on the colonization dynamics of gut microbes and their functions in the context of FMT to treat a complex disease—information that may provide a foundation for developing more-targeted therapeutics. IMPORTANCE Fecal microbiota transplantation (FMT)—transferring fecal microbes from a healthy donor to a sick patient—has shown promise for gut diseases such as inflammatory bowel disease. Unlike pharmaceuticals, however, fecal transplants are complex mixtures of living organisms, which must then interact with the microbes and immune system of the recipient. We sought to understand these interactions by tracking the microbes of 12 inflammatory bowel disease patients who received fecal transplants for 12 weeks. We uncovered a range of dynamics. For example, one patient experienced successful transfer of donor bacteria, only to lose them after 10 weeks. We similarly evaluated transfer of microbial functions, including how they interacted with the recipient’s immune system. Our findings shed light on the colonization dynamics of gut microbes, as well as their functions in the context of FMT—information that may provide a critical foundation for the development of more-targeted therapeutics.
format	article
author	Nathaniel D. Chu Jessica W. Crothers Le T. T. Nguyen Sean M. Kearney Mark B. Smith Zain Kassam Cheryl Collins Ramnik Xavier Peter L. Moses Eric J. Alm
author_facet	Nathaniel D. Chu Jessica W. Crothers Le T. T. Nguyen Sean M. Kearney Mark B. Smith Zain Kassam Cheryl Collins Ramnik Xavier Peter L. Moses Eric J. Alm
author_sort	Nathaniel D. Chu
title	Dynamic Colonization of Microbes and Their Functions after Fecal Microbiota Transplantation for Inflammatory Bowel Disease
title_short	Dynamic Colonization of Microbes and Their Functions after Fecal Microbiota Transplantation for Inflammatory Bowel Disease
title_full	Dynamic Colonization of Microbes and Their Functions after Fecal Microbiota Transplantation for Inflammatory Bowel Disease
title_fullStr	Dynamic Colonization of Microbes and Their Functions after Fecal Microbiota Transplantation for Inflammatory Bowel Disease
title_full_unstemmed	Dynamic Colonization of Microbes and Their Functions after Fecal Microbiota Transplantation for Inflammatory Bowel Disease
title_sort	dynamic colonization of microbes and their functions after fecal microbiota transplantation for inflammatory bowel disease
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/c4c9335cabb34f56ad49f7697539f45e
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Dynamic Colonization of Microbes and Their Functions after Fecal Microbiota Transplantation for Inflammatory Bowel Disease

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