Neonatal microbiota colonization primes maturation of goblet cell–mediated protection in the pre-weaning colon
Regulated host-microbe interactions are a critical aspect of lifelong health. Colonic goblet cells protect from microorganisms via the generation of a mucus barrier structure. Bacteria-sensing sentinel goblet cells provide secondary protection by orchestrating mucus secretion when microbes breach the mucus barrier. Mucus deficiencies in germ-free mice implicate a role for the microbiota in programming barrier generation, but its natural ontogeny remains undefined. We now investigate the mucus barrier and sentinel goblet cell development in relation to postnatal colonization. Combined in vivo and ex vivo analyses demonstrate rapid and sequential microbiota-dependent development of these primary and secondary goblet cell protective functions, with dynamic changes in mucus processing dependent on innate immune signaling via MyD88 and development of functional sentinel goblet cells dependent on the NADPH/dual oxidase family member Duox2. Our findings identify new mechanisms of microbiota-goblet cell regulatory interaction and highlight the critical importance of the pre-weaning period for the normal development of protective systems that are key legislators of host-microbiota interaction.
Authors
- Mahadevan Venkita Subramani (ORCID: https://orcid.org/0000-0003-0442-919X)
- Andy Wullaert (ORCID: https://orcid.org/0000-0001-5012-654X)
- Malin Johansson (ORCID: https://orcid.org/0000-0002-4237-6677)
- Felix Sommer (ORCID: https://orcid.org/0000-0002-6545-3487)
- Liisa Arike (ORCID: https://orcid.org/0000-0002-2184-0960)
- Thaher Pelaseyed (ORCID: https://orcid.org/0000-0002-6434-3913)
- Elena Layunta (ORCID: https://orcid.org/0000-0001-5573-6144)
- Lars Vereecke (ORCID: https://orcid.org/0000-0002-1593-862X)
- Philip Rosenstiel (ORCID: https://orcid.org/0000-0002-9692-8828)
- Elisabeth Nyström (ORCID: https://orcid.org/0000-0002-6970-7894)
- George Birchenough (ORCID: https://orcid.org/0000-0003-2283-2353)
- Louise Mannerås-Holm (ORCID: https://orcid.org/0000-0001-8783-6107)
- Bahtiyar Yılmaz (ORCID: https://orcid.org/0000-0003-1888-9226)
- Åsa Johansson
Institutions
- University of Bern (CH)
- University of Antwerp (BE)
- Ghent University Hospital (BE)
- Institute for Biomedicine (IT)
- VIB-UGent Center for Inflammation Research (BE)
- University of Gothenburg (SE)
Publication Details
- Journal
- The Journal of Experimental Medicine
- Published
- 2025-04-04
- DOI
- https://doi.org/10.1084/jem.20241591
- Citations
- 1
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Deutsche Forschungsgemeinschaft
- Cancerfonden
- Svenska Sällskapet för Medicinsk Forskning
- IngaBritt och Arne Lundbergs Forskningsstiftelse
- Knut och Alice Wallenbergs Stiftelse
- Göteborgs Universitet
- Sahlgrenska Akademin
- National Institute of Allergy and Infectious Diseases