Pathogenicity of commensal gut biofilm in prefrail aging
Pathophysiological mechanisms of unhealthy aging, particularly the transition from robustness to frailty, remain poorly understood. Despite extensive microbiome research on taxonomy, the behavior of early prefrail gut bacteria in their natural community-host mucosal tissue context remains unexplored. Using fecal samples from the INSPIRE-T aging human cohort, we characterized gut microbiota phenotype during prefrailty stages using a polymicrobial biofilm model. Results revealed that prefrail-derived biofilms exhibited distinct taxonomic and physical alterations, enhanced dispersal, and increased epithelial virulence compared to robust counterparts. Multiparametric analyses linked biofilm characteristics to clinical traits, suggesting their potential as aging status indicators. Polyphenol-rich grape pomace extract partially reversed prefrail biofilm alterations and reduced proinflammatory prefrail biofilm responses in vitro. Microbiota from prefrail-aged mice induced colon damage in antibiotic-treated recipients, establishing a prefrail microbiome-inflammation causality. Overall, the findings identified novel prefrail microbiome characteristics, established causal inflammatory links, and supported microbiota-targeted geroprotective interventions for the prefrail populations.
Authors
- Sophie Guyonnet (ORCID: https://orcid.org/0000-0001-9527-5282)
- Julie Thevenin
- Guillaume Le Cosquer (ORCID: https://orcid.org/0000-0001-8416-5432)
- Nathalie Vergnolle (ORCID: https://orcid.org/0000-0003-1825-6015)
- Jean‐Paul Motta (ORCID: https://orcid.org/0000-0002-9464-0695)
- Céline Deraison (ORCID: https://orcid.org/0000-0002-9013-4592)
- Bruno Vellas
- Elodie Meunier
- Bruno P. Guiard (ORCID: https://orcid.org/0000-0002-6873-9966)
- Angelo Parini (ORCID: https://orcid.org/0000-0002-9848-8838)
- Yohan Santin (ORCID: https://orcid.org/0000-0002-9229-1161)
- Barbara Bournet (ORCID: https://orcid.org/0000-0002-3679-9454)
- Damien Guillemet (ORCID: https://orcid.org/0000-0002-6638-0531)
- Louis Buscail (ORCID: https://orcid.org/0000-0003-4276-1003)
- Melissa Pannier
- Elise Pyhourquet
Institutions
- Université Toulouse III - Paul Sabatier (FR)
- Inserm (FR)
- University of Calgary (CA)
- École Nationale Vétérinaire de Toulouse (FR)
- Université Fédérale de Toulouse Midi-Pyrénées (FR)
- Centre de Recherches sur la Cognition Animale (FR)
- Toulouse Mathematics Institute (FR)
- Institut de Recherche en Santé Digestive (FR)
- Institut des Maladies Métaboliques et Cardiovasculaires (FR)
- Nexira (France) (FR)
Publication Details
- Journal
- npj Biofilms and Microbiomes
- Published
- 2025-05-22
- DOI
- https://doi.org/10.1038/s41522-025-00716-8
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Pfizer
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Région Occitanie Pyrénées-Méditerranée
- European Regional Development Fund