Microbiota transplantation restores normal fecal bile acid composition in recurrentClostridium difficileinfection

Abstract

Fecal microbiota transplantation (FMT) has emerged as a highly effective therapy for refractory, recurrent Clostridium difficile infection (CDI), which develops following antibiotic treatments. Intestinal microbiota play a critical role in the metabolism of bile acids in the colon, which in turn have major effects on the lifecycle of C. difficile bacteria. We hypothesized that fecal bile acid composition is altered in patients with recurrent CDI and that FMT results in its normalization. General metabolomics and targeted bile acid analyses were performed on fecal extracts from patients with recurrent CDI treated with FMT and their donors. In addition, 16S rRNA gene sequencing was used to determine the bacterial composition of pre- and post-FMT fecal samples. Taxonomic bacterial composition of fecal samples from FMT recipients showed rapid change and became similar to the donor after the procedure. Pre-FMT fecal samples contained high concentrations of primary bile acids and bile salts, while secondary bile acids were nearly undetectable. In contrast, post-FMT fecal samples contained mostly secondary bile acids, as did non-CDI donor samples. Therefore, our analysis showed that FMT resulted in normalization of fecal bacterial community structure and metabolic composition. Importantly, metabolism of bile salts and primary bile acids to secondary bile acids is disrupted in patients with recurrent CDI, and FMT corrects this abnormality. Since individual bile salts and bile acids have pro-germinant and inhibitory activities, the changes suggest that correction of bile acid metabolism is likely a major mechanism by which FMT results in a cure and prevents recurrence of CDI.

Successful Therapy of Clostridium Difficile Infection with Fecal Microbiota Transplantation

“…Although the present study did not investigate the metabonomic changes after FMT, previous studies indicate that FMT is associated with increased production of secondary bile acids by the gut bacteria that are inhibitory to C. difficile (29).…”

Bloodstream infections in patients with liver cirrhosis

“…[27][28][29] In animal models of LC, portal hypertension and intestinal hypo-mobility lead to bacterial overgrowth in the small bowel and is considered the primum movens of translocation in these models. 30 In a clinical study of 24 patients with liver cirrhosis the bacterial overgrowth was enhanced by portal hypertension, as suggested by animal models.…”

Cross-talk between bile acids and intestinal microbiota in host metabolism and health

“…Recently, Weingarden et al (2014) showed that FMT can restore the intestinal microbiota and fecal BA composition in patients with recurrent CDI. The process in which primary BAs are converted into secondary BAs is disrupted in patients with CDI.…”

“…The process in which primary BAs are converted into secondary BAs is disrupted in patients with CDI. However, the normalization of gut microbial composition via FMT can correct BA metabolism, thereby developing an adverse environment for C. difficile spore germination (Weingarden et al, 2014). Importantly, a recent study identified C. scindens, a resistance-associated gut microbe which can efficiently inhibit C. difficile infection.…”

“…For instance, fecal microbiota transplantation (FMT) can restore the intestinal microbiota and fecal BA composition in patients with recurrent CDI (Weingarden et al, 2014). The spore germination of C. difficile can be stimulated by some primary BAs except for chenodeoxycholic acids (CDCAs) (Sorg and Sonenshein, 2008) or inhibited by secondary BAs such as lithocholic acids (LCAs) and ursodeoxycholic acids (UDCAs) , and FMT can restore gut microbes which can convert primary BAs to secondary BAs, thus inhibiting C. difficile spore germination.…”