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

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 elevated fecal calprotectin concentrations. Together, these findings demonstrate that bacterial enteric infections are associated with distinct microbiota configurations that distinguish pathogen-specific signatures from general infection-related dysbiosis. The enrichment of oral-associated taxa in Campylobacter and Salmonella infections suggests a potential role for the oral-gut microbial axis in bacterial gastroenteritis and provides a foundation for future mechanistic studies and the development of microbiota-informed diagnostic, preventive, and therapeutic strategies. Author SummaryBacterial infections of the intestine can cause severe diarrhea and inflammation, but their effects on the community of microbes living in the gut are not fully understood. Most previous studies have focused on a single disease-causing organism, making it difficult to determine which microbiome changes are shared across infections and which are specific to particular pathogens. In this study, we compared gut microbiota profiles from people infected with Clostridioides difficile, Campylobacter, or Salmonella, and examined these alongside samples from individuals with viral gastroenteritis, diagnostic-negative diarrhea, and healthy controls. We found that bacterial enteric infections were associated with two distinct patterns of microbiome disruption. C. difficile infection was linked to an overgrowth of Enterococcus, whereas Campylobacter and Salmonella infections were characterized by increased levels of several bacterial groups that are commonly found in the mouth. In contrast, expansion of Enterobacteriaceae was observed across different infections and appeared to reflect general intestinal disturbance rather than a specific pathogen. Our findings identify microbial signatures that distinguish different bacterial infections and suggest that bacteria originating from the oral cavity may play an important role in some forms of gastroenteritis. These results provide a foundation for future studies aimed at understanding how microbial communities influence intestinal infection and recovery.