Response of the gut microbiome to acute enteric pathogen infection and antibiotic treatment

Enterotoxigenic Escherichia coli (ETEC) is among the most significant enteric pathogens worldwide, as it ranks among the primary causes of diarrheal illnesses in low and middle income countries. However, our understanding of how the broader gut ecosystem can mitigate virulence or respond to acute infection (and recovery) remains limited. Here, we present a comprehensive exploration of functional dysbiosis in the gut microbiome in response to ETEC infection and antibiotic treatment in a laboratory environment. We conducted a longitudinal analysis on six adult participants, tracking their microbial community and activity profiles before, during, and after controlled exposure to ETEC and antibiotic-mediated recovery. This analysis profiled 106 shotgun metagenomic samples and 102 paired metatranscriptomes. Notably, the gut microbiome’s response to both ETEC and antibiotic treatment varied dramatically among individuals, consistent with the high variation of their clinical diarrheal outputs (from 0 mL to 3923 mL). Taxonomic profiles varied from 0.32 to 0.75 (i.e. Bray-Curtis dissimilarities within subject), for example, with around 36% of differentially abundant species more abundant in cases of severe disease. These included Ruminococcus bromii, Lachnospira eligens, and unclassified Eggerthellaceae species, likely a result of gut microbial growth dysfunction during diarrhea. Additionally, transcriptional changes shed light on how the gut microbiome responds to the pathogenic challenge and antibiotic treatment. Differentially expressed genes within the same species often participated in similar metabolic processes, such as glutamine metabolism in Bacteroides massiliensis, phage integration in Bifidobacterium adolescentis, and sporulation-related processes in Blautia wexlerae. This study offers valuable insights into how the gut microbiome reacts to pathogenic challenges and antibiotic exposure, deepening our understanding of ecological protective factors and responses during acute infection, diarrhea, and recovery. These findings have implications for mitigating the effects of enteric pathogens via the microbiome in both adults and vulnerable infant populations.