Mechansims Underpinning Successful Faecal Microbiota Transplantation (FMT) for Recurrent Clostridium Difficile Infection

Abstract

Introduction FMT is safe effective treatment for patients with recurrent Clostridium difficile infection (CDI). Microbiota analysis of both donor and recipent stool provides opportunity to better understand the abnormal microbiota of patients with CDI the changes that occur with and factors that determine successful FMT as well as the mechanisms that underpin susceptibility to CDI. Previous studies have suggested a role for bile acid dehydroxylating bacteria in resistance to CDI. Aims To characterise donor microbiota and recipient microbiota changes post FMT. To study the potential role for bile acids and fatty acids in CDI and in response to FMT and the interactions between the microbiota and both bile and fatty acids. Methods FMT was performed in patients with recurrent CDI attending Cork University Hospital.Faecal samples from donors and patient's pre and post FMT. DNA extraction,16S rRNA amplicon sequencing, bile and fatty acid extraction was performed. FMT resulted in partial recovery of microbial diversity and establishment of a more donor-like microbiota. Alpha diversity was significantly decreased (p<0.01) prior to FMT but recovered to levels observed in the donor sample post.The abundance of individual genera, including Proteus, Fusobacterium, Clostridium-XVIII, Escherichia/Shigella, and Streptococcus was significantly increased in patients with CDI in comparison to donors (p < 0.0001). The levels of most such bacteria approached donor-levels post-FMT indicating successful colonization and established communities from the donor microbiota. Conversely, decreased levels of genera including Prevotella, Clostridium XIVb, Faecalibacterium and Roseburia was seen. Combined levels of secondary and tertiary bile acids were significantly increased in donors and patients post-FMT compared to the concentration detected pre-FMT. Several individual bile acids were also significantly different. The overall profile of faecal bile acids as well as individual bile acids were significantly correlated with the abundance of several bacterial OTU's. Network plots were used to examine the relationship between OTU's and bile acids. Lachnospiraceae, Ruminococcus and Clostridium XIVa, that are negatively associated with primary bile acids are also positively related with secondary bile acids and GDCA. Bacterial OTU's such as Anaerostipes, Enterococcus and Sutterella, were found to be positively associated to primary bile acids and negatively related to secondary bile acids and GDCA. Significant changes were also seen in a number of fecal fatty acids post FMT. Conclusions FMT results in an microbiota that resembles the donor and a significant increase in microbiota diversity. FMT leads to restoration of secondary bile acids that is microbota dependent. This study supports a bile acid mechanism to underpin efficacy of FMT and susceptibility to CDI. (Figure presented).