Abstract
Approximately 30% of patients who have Clostridioides difficile infection (CDI) will suffer at least one incident of reinfection. While the underlying causes of CDI recurrence are poorly understood, interactions between C. difficile and commensal gut bacteria are thought to play an important role. In this study, an in silico pipeline was used to process 16S rRNA gene amplicon sequence data of 225 stool samples from 93 CDI patients into sample-specific models of bacterial community metabolism. Clustered metabolite production rates generated from post-diagnosis samples generated a high Enterobacteriaceae abundance cluster containing disproportionately large numbers of recurrent samples and patients. This cluster was predicted to have significantly reduced capabilities for secondary bile acid synthesis but elevated capabilities for aromatic amino acid catabolism. When applied to 16S sequence data of 40 samples from fecal microbiota transplantation (FMT) patients suffering from recurrent CDI and their stool donors, the community modeling method generated a high Enterobacteriaceae abundance cluster with a disproportionate large number of pre-FMT samples. This cluster also was predicted to exhibit reduced secondary bile acid synthesis and elevated aromatic amino acid catabolism. Collectively, these in silico predictions suggest that Enterobacteriaceae may create a gut environment favorable for C. difficile spore germination and/or toxin synthesis.
Highlights
The anaerobic bacterium Clostridioides difficile is an opportunistic pathogen responsible for infections of the human colon [1]
The objective of the current study was to utilize computational metabolic modeling to investigate the hypothesis that recurrent infections are related to the composition of the gut bacterial community within each
Our modeling results suggest that patients who have high abundances of the bacterial family Enterobacteriaceae following antibiotic treatment are more likely to develop recurrent infections due to a metabolically-disrupted gut environment
Summary
The anaerobic bacterium Clostridioides difficile is an opportunistic pathogen responsible for infections of the human colon [1]. C. difficile infection (CDI) is most common in elderly patients previously treated with broad spectrum antibiotics that disrupt the healthy gut microbiota and produce a dysbiotic environment conducive to C. difficile germination, expansion and pathogenicity [2,3]. Commensal bacterial species in the healthy gut can provide resistance against C. difficile pathogenic colonization through a variety of metabolic mechanisms, including competition for dietary nutrients such as carbohydrates and amino acids [10] and conversion of host-derived primary bile acids that promote C. difficile spore germination to secondary bile acids that inhibit germination and growth [11]. Recurrence is a major challenge associated with CDI treatment, as approximately 30% of patients develop at least one occurrence of reinfection [12]. Despite its remarkable success rate approaching 90% [16], FMT remains controversial [17] as the donor microbiota confer poorly understood functions to the endogenous community [18] and may contain pathogenic strains not recognized during screening of donor stool [19]
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