Pathogen dynamics and lasting host consequences of early-life enteric infection
Year: 2026
Type: article
Abstract: Early-life enteric infections are associated with long-term consequences that extend beyond acute gastrointestinal disease, including impaired growth, altered immunity, and adverse neurodevelopmental outcomes. However, the mechanisms linking developmental susceptibility to enteric infection with persistent effects on host physiology remain poorly understood. Leveraging the murine enteric pathogen Citrobacter rodentium as a model of human enteropathogenic Escherichia coli enteric infection, this thesis investigated how the developing intestinal ecosystem influences pathogen colonization and long-term host outcomes. This work demonstrates that the post-weaning period represents a unique window of susceptibility to enteric infection, characterized by distinct microbiota composition, reduced colonization resistance, and altered mucosal responses. Infection further remodels this ecosystem, inducing dysbiosis and accumulation of the microbiota-derived metabolite D-lactate. C. rodentium further exploits D-lactate to enhance colonization and differentially regulate growth and virulence depending on environmental conditions. Beyond its role in the gut, transient infection during the post-weaning window resulted in persistent cognitive deficits, altered hippocampal gene expression, and changes in neuronal populations in female mice (male mice not tested). These effects were associated with increased hippocampal D-lactate levels, while experimental D-lactate exposure exacerbated neuronal deficits and behavioral impairments under inflammatory conditions. Together, this work identifies key developmental features of the early-life gut that influence susceptibility to enteric infection and demonstrates how infection-induced alterations in microbial metabolism can contribute to long-term consequences extending beyond the site of infection. These findings also provide a mechanistic framework linking microbiota, pathogen dynamics, and neurodevelopment, and highlight microbial metabolites as potential targets for preventing the lasting sequelae of enteric infection.
Source: Open Collections
DOI: 10.14288/1.0457097
Author: Tabusi, Mahebali
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7225415131