Multi-omic analyses identify mucosa bacteria and fecal metabolites associated with weight loss after fecal microbiota transplantation.

Fecal microbiota transplantation (FMT) has shown promising results in animal models of obesity, while results in human studies are inconsistent. We aimed to determine factors associated with weight loss after FMT in nine obese subjects using serial multi-omics analysis of the fecal and mucosal microbiome. The mucosal microbiome, fecal microbiome, and fecal metabolome showed individual clustering in each subject after FMT. The colonic microbiome in patients showed more marked variance after FMT compared with the duodenal microbiome, characterized by an increased relative abundance of Bacteroides. Subjects who lost weight after FMT sustained enrichment of Bifidobacterium bifidum and Alistipes onderdonkii in the duodenal, colonic mucosal, and fecal microbiome and increased levels of phosphopantothenate biosynthesis and fecal metabolite eicosapentaenoic acid (EPA), compared with those without weight loss. Fecal levels of amino acid metabolism-associated were positively correlated with the fecal abundance of B. bifidum, and fatty acid metabolism-associated metabolites showed positive correlations with A. onderdonkii. We report for the first time the individualized response of fecal and mucosa microbiome to FMT in obese subjects and highlight that FMT is less capable of shaping the small intestine microbiota. These findings contribute to personalized microbe-based therapies for obesity.