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

mBio

Ramnik Xavier¹  Nathaniel D. Chu¹  Eric J. Alm¹  Sean M. Kearney¹  Le T. T. Nguyen¹  Zain Kassam²  Mark B. Smith²  Peter L. Moses³  Cheryl Collins³  Jessica W. Crothers³ 

[1] Center for Microbiome Informatics and Therapeutics, Broad Institute, Cambridge, Massachusetts, USA;Finch Therapeutics, Somerville, Massachusetts, USA;Larner College of Medicine, University of Vermont, Burlington, Vermont, USA;

关键词: 16S RNA;    bacteria;    competition;    fecal microbiota transplant;    immunoglobulins;    inflammatory bowel disease;   

DOI  :  10.1128/mBio.00975-21

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown