Enteropathy produced in mice by intergenerational transmission of small intestinal microbiota from undernourished children
Environmental enteric dysfunction (EED), a small intestinal disorder prevalent in undernourished children with stunted growth and their undernourished mothers, is associated with gut mucosal barrier disruption and decreased absorptive capacity. Here we provide preclinical evidence that intergenerational transmission of a perturbed small intestinal microbiota contributes to pathogenesis. One of two bacterial consortia cultured from duodenal aspirates obtained from Bangladeshi children with EED induced local and systemic inflammation in female gnotobiotic mice, resulting in impaired prenatal and postnatal growth in their offspring. Immunologic changes in pups phenocopied features of EED in children, and dam-to-pup transmission of this consortium altered signalling pathways related to intestinal epithelial cell renewal, barrier integrity and immune function. Screening of co-housed mice harbouring the inflammatory or non-inflammatory consortia identified Campylobacter concisus as an inducer of pro-inflammatory cytokine signalling in a host nitric oxide synthase-dependent manner. This preclinical model could facilitate small intestinal microbiota-targeted therapeutics for intergenerational undernutrition.
Authors
- Christian Maueröder (ORCID: https://orcid.org/0000-0002-7563-883X)
- Andrei L. Osterman (ORCID: https://orcid.org/0000-0002-3810-9824)
- Robert Y. Chen (ORCID: https://orcid.org/0000-0002-3680-2609)
- Alexandra Byrne (ORCID: https://orcid.org/0000-0002-4324-3964)
- Y Wang
- Haoxin Liu
- Michael J. Barratt (ORCID: https://orcid.org/0000-0003-3794-1296)
- Dmitry A. Rodionov (ORCID: https://orcid.org/0000-0002-0939-390X)
- Keshav Nepal
- Kali M. Pruss (ORCID: https://orcid.org/0000-0002-8619-5886)
- Laura Karvelyte (ORCID: https://orcid.org/0000-0002-8198-9425)
- Marco Colonna (ORCID: https://orcid.org/0000-0001-5222-4987)
- Jeffrey I. Gordon (ORCID: https://orcid.org/0000-0001-8304-3548)
- Reyan Coskun (ORCID: https://orcid.org/0000-0001-8294-3122)
- Daniel M. Webber (ORCID: https://orcid.org/0000-0001-6109-8118)
- Blanda Di Luccia (ORCID: https://orcid.org/0000-0002-0137-953X)
- Tahmeed Ahmed (ORCID: https://orcid.org/0000-0002-4607-7439)
- Kodi S. Ravichandran (ORCID: https://orcid.org/0000-0001-9049-1410)
- C.-Y. Kao (ORCID: https://orcid.org/0000-0003-2210-5447)
- Matthew Charles Hibberd (ORCID: https://orcid.org/0000-0001-6520-677X)
- Mackenzie Lemieux
Institutions
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Washington University in St. Louis (US)
- International Centre for Diarrhoeal Disease Research (BD)
- Discovery Institute (US)
- Ghent University (BE)
- VIB-UGent Center for Inflammation Research (BE)
Publication Details
- Journal
- Nature Microbiology
- Published
- 2026-06-16
- DOI
- https://doi.org/10.1038/s41564-026-02394-4
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Bill and Melinda Gates Foundation
- National Institute of Diabetes and Digestive and Kidney Diseases