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 complex immune diseases like inflammatory bowel disease (IBD), it is assumed that therapeutic microbes and their beneficial functions and immune interactions must colonize the recipient and persist in sufficient quantity and for a long enough period of time to result in a clinical benefit. But few studies have comprehensively profiled the colonization and persistence of transferred microbes along with the transfer of their microbial and immune functions. 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 a range of competitive dynamics among donor and patient strains, showing that persistence of transferred microbes is far from static. Indeed, one patient experienced dramatic loss of donor bacteria 10 weeks into the trial, coinciding with a bloom of pathogenic bacteria and worsening clinical symptoms. We similarly evaluated transfer of microbial functions, including desired ones like butyrate production and unintended ones like antibiotic resistance. By profiling bacteria coated with IgA, we identified IgA-coated bacteria associated with inflammation, and we found that microbial interactions with the host immune system can be transferred across people. This transfer of immune function is likely critical for gut microbiome therapeutics for immune-related diseases. Our findings elucidate the colonization dynamics of gut microbes as well as their functions in the context of FMT to treat a complex disease--information that may provide a critical foundation for the development of more-targeted therapeutics.