Journal article
Age and sex dependent shift in murine gut microbiome reveals pathological links to host cardiovascular and metabolic pathways
GeroScience
06/05/2026
DOI: 10.1007/s11357-026-02336-2
PMID: 42247160
Abstract
The gut microbiome undergoes dynamic, sex-dependent changes across the lifespan. However, comprehensive studies examining the combined effects of age and sex are limited. This study investigated both compositional and functional alterations in the gut microbiome of young (4 months, n = 14) and aged (20 months, n = 20) C57BL/6 J mice of both sexes using 16S rRNA gene (V3-V5) sequencing. Microbial community structure and predicted functional profiles were analyzed via QIIME2 and PICRUSt2, with pathway annotation based on MetaCyc. Compared to aged mice, young mice exhibited higher alpha diversity, with the highest increase observed in young females. This sex-specific difference was lost in aged mice. Aging was also associated with an increased Firmicutes-to-Bacteroidetes ratio, and distinct shifts in key taxa, including increased Lactobacillus and Roseburia and reduced Bacteroides and Lachnospiraceae. Functional prediction revealed substantial age-related metabolic shifts, especially in females showing alteration in 45 pathways including upregulation of branched-chain amino acid (BCAA) metabolism, uric acid metabolism, and lipopolysaccharide biosynthesis. To directly link alterations in microbial BCAA metabolism with host metabolic outcomes, fecal abundance of the bacterial BCAA aminotransferase gene (ilvE) was quantified and found to be significantly increased in aged mice. Concurrently, aged mice exhibited higher plasma levels of BCAA, insulin, and random glucose, indicating age-associated metabolic dysregulation. Fecal ilvE abundance associated positively with plasma BCAA levels, and negatively with blood glucose in aged mice, suggesting a link between microbial BCAA metabolism and host glucose homeostasis. Our findings demonstrate that gut microbiome composition and function are influenced by both age and sex. We also showed that these alterations in microbial BCAA metabolism are associated with host metabolic parameters during aging. Our findings underscore the importance of incorporating both age and sex as biological variables in microbiome research and may inform development of age- and sex-specific microbiome-targeted interventions.
Details
- Title: Subtitle
- Age and sex dependent shift in murine gut microbiome reveals pathological links to host cardiovascular and metabolic pathways
- Creators
- Meena Kumari Palani Kumar - University of IowaKrishna S Iyer - University of IowaShailesh K Shahi - University of IowaJuan Antonio Raygoza Garay - University of IowaAshutosh Mangalam - University of IowaSanjana Dayal - University of Iowa
- Resource Type
- Journal article
- Publication Details
- GeroScience
- DOI
- 10.1007/s11357-026-02336-2
- PMID
- 42247160
- NLM abbreviation
- Geroscience
- ISSN
- 2509-2723
- eISSN
- 2509-2723
- Publisher
- Springer Nature; DORDRECHT
- Grant note
- AI162778 / National Institute of Allergy and Infectious Diseases P30 ES005605 / NIEHS NIH HHS BX007087 / U.S. Department of Veterans Affairs HL007344 / NHLBI NIH HHS HL168630 / NHLBI NIH HHS 18IPA4180014 / American Heart Association 1I01CX002212 / Iowa City Veterans Affairs Medical Center
- Language
- English
- Electronic publication date
- 06/05/2026
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Dental Research; Holden Comprehensive Cancer Center; Internal Medicine
- Record Identifier
- 9985173066602771
Metrics
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