Effect of Aging on the Composition of Fecal Microbiota in Donors for FMT and Its Impact on Clinical Outcomes.

Abstract

Fecal microbiota transplantation (FMT) is emerging as an effective therapy for the treatment of recurrent Clostridium difficile infection (RCDI). Selecting an appropriate donor is vital to the success of FMT. However, the relationship between age of donors and the efficacy of FMT has not been examined to date. The aim of this study was to examine the effect of age of healthy donors on their fecal microbiota and assess the impact of these changes on the clinical efficacy of FMT. This IRB-approved prospective study enrolled donors who were deemed healthy for FMT after careful detailed screening for infectious diseases per institutional protocol. The study was conducted between January 2011 and October 2014. Fecal samples were processed and analyzed using 16S rRNA gene amplicon sequencing. Differences in relative abundance and diversity of the donor fecal microbiota were analyzed in donors above and below 60years of age. Effect of fecal microbiota from donors of different age groups on the efficacy of FMT was also evaluated. Twenty-eight healthy human subjects from ages 20-82years were enrolled as donors for FMT. All patients receiving FMT from their respective donors had resolution of RCDI symptoms and had a negative C. difficile toxin test 4-12weeks after FMT. Genomic analysis showed that the relative abundance of phylum Actinobacteria and family Bifidobacteriaceae was reduced in the donors ≥60years of age (p<0.05). However, Bacteroidetes-to-Fermicutes ratio did not demonstrate a significant change between the two groups. Furthermore, microbial diversity did not change significantly with advancing age. These observations suggest that aging in healthy donors is associated with compositional alterations in the fecal microbiome without change in the overall microbial diversity. These changes do not seem to affect the clinical efficacy of FMT in RCDI patients over 12months.