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Distinct types of gut dysbiosis and oral–gut microbial signatures differentiate C. difficile, Campylobacter, and Salmonella infections: a cross-sectional study

A. Mahnič, R. Markovič, Marko Marhl, Andrej Golle, N. Stopnišek, Maja Rupnik

bioRxiv, 2026

Abstract

Gastrointestinal bacterial infections are associated with substantial perturbations of the gut microbiota, yet most microbiome studies have examined individual pathogens in isolation, limiting identification of shared and pathogen-specific microbial signatures across enteric infections. We performed a comparative analysis of fecal microbiota profiles from 586 stool samples using 16S rRNA gene sequencing, encompassing infections caused by Clostridioides difficile, Campylobacter spp., and Salmonella spp., alongside viral gastroenteritis, diagnostic-negative samples, and healthy controls. Fecal calprotectin concentrations were measured in a subset of samples to assess intestinal inflammation. Comparative analyses revealed two major dysbiotic configurations among bacterial enteric infections. C. difficile infection was characterized by an Enterococcus-dominated community structure, whereas Campylobacter and Salmonella infections were associated with enrichment of a tightly correlated consortium of oral-associated taxa, including Streptococcus, Granulicatella, and Haemophilus. These taxa were among the most informative features in an XGBoost machine-learning classifier, which accurately discriminated bacterial infection types from one another and from viral infections and healthy-associated microbiota profiles (macro F1 score = 0.74). In contrast, expansion of Enterobacteriaceae represented a shared, non-specific signature of intestinal disturbance and was associated with…

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Evidence Hub reads this as a cross-sectional, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause.

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