Abstract

BackgroundRecurrent Clostridioides diffícile infection (RCDI) is associated with major bacterial dysbiosis and colitis. Fecal microbiota transplantation (FMT) is a highly effective therapeutic modality for RCDI. While several studies have identified bacterial species associated with resolution of symptoms in patients, characterization of the fecal microbiome at the bacterial strain level in RCDI patients before and after FMT and healthy donors, has been lacking. The aim of this study was to examine the ability of bacterial strains from healthy donors to engraft in the gastrointestinal tract of patients with RCDI following FMT.MethodsFecal samples were collected from 22 patients with RCDI before and after FMT and their corresponding healthy donors. Total DNA was extracted from each sample and analyzed by shotgun metagenomic sequencing. The Cosmos-ID analysis platform was used for taxonomic assignment of sequences and calculation of the relative abundance (RA) of bacterial species and strains. From these data, the total number of bacterial strains (BSI), Shannon diversity index, dysbiosis index (DI), and bacterial engraftment factor, were calculated for each strain.FindingsA marked reduction (p<0·0001) in the RA of total and specific bacterial strains, especially from phylum Firmicutes, was observed in RCDI patients prior to FMT. This change was associated with an increase in the DI (p<0·0001) and in pathobiont bacterial strains from phylum Proteobacteria, such as Escherichia coli O157:H7 and Klebsiella pneumoniae UCI 34. BSI was significantly lower in this group of patients as compared to healthy donors and correlated with the Shannon Index. (p<0·0001). Identification and engraftment of bacterial strains from healthy donors revealed a greater diversity and higher relative abundance of short-chain fatty acid (SCFA)-producing bacterial strains, including Lachnospiraceae bacterium 5_1_63FAA_u_t, Dorea formicigenerans ATCC 27755, Anaerostipes hadrusand others, in RCDI patients after FMT.InterpretationThese observations identify a group of SCFA-producing bacterial strains from healthy donors that engraft well in patients with RCDI following FMT and are associated with complete resolution of clinical symptoms and bacterial dysbiosis.

Highlights

  • Clostridioides difficile infection (CDI) continues to be a rising public health problem in elderly and hospitalized patients, both globally as well as in Western countries

  • The clinical outcome in patients with Recurrent Clostridioides diffıcile infection (RCDI) was defined as symptomatic resolution of CDI

  • Symptoms including diarrhea, bloating, abdominal pain, and cramping resolved in all patients within 3–7 days after Fecal microbiota transplantation (FMT)

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Summary

Introduction

Clostridioides difficile infection (CDI) continues to be a rising public health problem in elderly and hospitalized patients, both globally as well as in Western countries. Previous studies by our group and others have demonstrated that RCDI is associated with marked reductions in both the relative abundance (RA) of various bacterial communities and overall bacterial diversity [3, 4] Most of these earlier studies were performed using 16S rRNA marker gene analysis, which identifies a amplified target sequence of bacterial DNA rather than the entire genomic sequence which limits the identification of a bacterium to the genus level only. With application of this technology, several previous studies have reported that there is marked diminution of bacteria from families Lachnospiraceae, Ruminococcaceae and Eubacteriaceae in untreated RCDI patients [3,4,5,6].

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