Abstract

Background: New therapeutic alternatives to corticosteroids in severe alcohol-associated hepatitis (SAH) is unmet need. Fecal microbiota transplantation (FMT) has been proposed as it targets well-established pathophysiological pathway but, data is scarce and many unanswered questions remain. One of the principal tools for personalized management of SAH is selection of patients whose potential to benefit from FMT is increased based on their pre-FMT gut-microbiome analysis.

Aim: To search for patterns in the pre-FMT gut microbiome of patients with SAH which are associated with increased probability of response to FMT (survival).

Methods: We enrolled 36 adult consenting patients with SAH and 20 healthy controls; fecal samples were collected at time of SAH diagnosis at HEGITO and from healthy controls at the Faculty of Chemical and Food Technology. After DNA isolation using QIAamp PowerFecal Pro DNA Kit (Qiagen), microbial profiling was performed using 16S ribosomal RNA amplicon sequencing. The libraries were prepared using the (PCR) products according to the MiSeq System guidelines (Illumina), obtained data were analyzed with QIIME 2.

Results: Dysbalanced gut microbiota of SAH patients was typical for elevated levels of pathogens and opportunistic pathogens including Enterococcus, Eggerthella, Fusobacterium and decrease of beneficial bacteria like Faecalibacterium, Eubacterium, Coprococcus, Barnesiella and Roseburia. Antibiotic treatment of infections preceding FMT (ATB) affected microbiota community with significantly prevailing Enterococcus spp., hence compromising the informativeness of its composition. On the other hand, microbiome of patients without ATB was enriched in Streptococcus sp., Actinomyces sp. or Escherichia/Shigella sp., (p<0.05), and we were able to determine a predictive potential of gut microbiome for survival after FMT. Survivors possessed higher relative abundance of short-chain-fatty acids (SCFA) producers Faecalibacterium, Subdligranulum or unspecified Ruminococcaceae.

Conclusion: Pre-FMT abundance of certain SCFA producing taxa is associated with better survival after FMT for SAH which might prove to be of predictive and therapeutic potential, respectively; ATB for infections erase predictive potential.