Impact of aging on gut-lung-adipose tissue interactions and lipid metabolism during influenza infection in mice
Influenza remains a major threat to human health, especially for the elderly. Aging leads to substantial changes to lung function, gut microbiota, and white adipose tissue (WAT)-a key endocrine organ regulating energy balance and lipid metabolism. In the current study, we performed a multi-omics analysis to investigate how influenza impacts the gut-lung-adipose tissue axis differently with age at days 2, 4, 7, 14, and 28 post-infection (dpi). Compared to young-adult mice, aged mice experienced worse disease outcomes following infection, along with distinct WAT alterations, including impaired browning, heightened inflammation, and reduced innate immune cell recruitment. Age-related differences were also evidenced in infection-driven shifts in gut microbiota. Akkermansia levels rose only in young mice from 4 dpi, while Faecalibaculum and Muribaculum expanded exclusively in aged mice at 7 dpi, the only timepoint at which their abundance correlated with lung pathology. Serum metabolomics at 7 dpi also revealed age-dependent metabolic responses to infection. Compared to their non-infected counterparts, young mice had lower levels of p-Cresol-sulfate and Indoxyl-sulfate alongside higher triglycerides, whereas aged mice showed disrupted glycerophospholipid metabolism. By pinpointing specific gut bacteria as potential probiotics and identifying lipid pathways associated with disease progression, these findings could lead to the development of targeted, age-specific strategies to mitigate influenza severity in the elderly.
Authors
- Patrícia Brito Rodrigues (ORCID: https://orcid.org/0000-0002-1687-7742)
- Laurence Macia (ORCID: https://orcid.org/0000-0003-0835-851X)
- Gemma Bogard (ORCID: https://orcid.org/0000-0002-1399-8709)
- Cyril Robil (ORCID: https://orcid.org/0000-0002-3607-244X)
- Cécile Lecœur (ORCID: https://orcid.org/0000-0003-0075-6417)
- Amandine Descat (ORCID: https://orcid.org/0000-0002-5981-4995)
- Corinne Grangette (ORCID: https://orcid.org/0000-0003-2398-448X)
- François Trottein (ORCID: https://orcid.org/0000-0003-3373-1814)
- Jean‐François Goossens (ORCID: https://orcid.org/0000-0002-8551-0899)
- Fabrice Bouilloux
- Isabelle Wolowczuk (ORCID: https://orcid.org/0000-0001-6692-6904)
- Philippe Gosset (ORCID: https://orcid.org/0000-0002-4043-6429)
- Olivier Molendi‐Coste (ORCID: https://orcid.org/0000-0002-0498-9456)
- Johanna Barthelemy (ORCID: https://orcid.org/0000-0003-3139-1879)
- Kassem Makki
Institutions
- Université Claude Bernard Lyon 1 (FR)
- Centre National de la Recherche Scientifique (FR)
- The University of Sydney (AU)
- Inserm (FR)
- Université de Lille (FR)
- Institut Pasteur de Lille (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- Centre Hospitalier Universitaire de Besançon (FR)
- Center for Infection and Immunity of Lille (FR)
- Hospices Civils de Lyon (FR)
- Laboratoire de recherche en cardiovasculaire, métabolisme, diabétologie et nutrition (FR)
Publication Details
- Journal
- Scientific Reports
- Published
- 2025-10-27
- DOI
- https://doi.org/10.1038/s41598-025-21363-1
- Citations
- 1
- Primary Topic
- Adipose Tissue and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 1.16
Funders
- Université de Lille
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Centre National de la Recherche Scientifique
- Région Hauts-de-France