Specific Microbiome Signature Dynamics Could Predict Aging Continuum and Cognitive Impairment in Older Adults

The global population is aging, facing a substantial burden of age-related disorders, including cognitive impairment (CI), Alzheimer's disease (AD), and related dementias (ADRD). The lack of effective strategies for preventing and treating these conditions can be attributed to our incomplete understanding of the biology of aging. Emerging evidence strongly suggests that the gut microbiome plays a pivotal role in aging and its association with cognitive decline and ADRD. Yet, the transformations occurring within the microbiome during the aging continuum remain insuffciently studied. We have addressed these significant knowledge gaps by analysing samples and data from 176 older adults participating in the multi-site Microbiome in Aging Gut and Brain (MiaGB) consortium. Whole-genome metagenomic analysis unveiled distinct microbiome profiles among three aging categories: (i) 60-69 (n=62), (ii) 70-79 (n=78), and (iii) 80+ (n=36), spanning from phyla to species-level phylogeny. Notably, in older adults, changes in the microbiome were observed with respect to the aging continuum and cognitive impairment (CI). The abundance of Lachnospiraceae, Eggerthellaceae, Dorea, Blautia, and Eggerthella decreased, while Veillonellaceae increased in the gut of older adults with CI but not within the aging continuum. Interestingly, only Proteobacteria, Firmicutes, Candidatus melainabacteria, Coriobactericeae, Ruminococcaceae, Anerostipe hadrus, and Collinsella aerofaciens decreased, while Bacteroidetes, Bacteroidiceae, and Bacteroides uniformis increased within the aging continuum but were not impacted in CI sub-groups. However, both Ruminococcus torques and Streptococcus thermophilus decreased with aging continuum and CI. These results indicate unique microbiome changes specific to the aging continuum, as well as distinct changes with CI, independent of age. Thus, they not only hold promise as prognostic markers for assessing the risk of cognitive decline and dementia in older adults but also pave the way for designing precision microbiome interventions to mitigate the risks posed by these debilitating public health issues. We thank the Ed and Ethel Moore Alzheimer’s Disease Research Program, Florida Department of Health (22A17), National Institutes of Health, National Institute of Aging (R56AG069676, R56AG064075, RF1AG071762, R21AG072379, U01AG076928), and Department of Defense (W81XWH-18-PRARP AZ180098) for funding support. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.