Gut microbiome predicts cognitive function and depressive symptoms in late life
- PMID: 38664490
- PMCID: PMC11449789
- DOI: 10.1038/s41380-024-02551-3
Gut microbiome predicts cognitive function and depressive symptoms in late life
Abstract
Depression in older adults with cognitive impairment increases progression to dementia. Microbiota is associated with current mood and cognition, but the extent to which it predicts future symptoms is unknown. In this work, we identified microbial features that reflect current and predict future cognitive and depressive symptoms. Clinical assessments and stool samples were collected from 268 participants with varying cognitive and depressive symptoms. Seventy participants underwent 2-year follow-up. Microbial community diversity, structure, and composition were assessed using high-resolution 16 S rRNA marker gene sequencing. We implemented linear regression to characterize the relationship between microbiome composition, current cognitive impairment, and depressive symptoms. We leveraged elastic net regression to discover features that reflect current or future cognitive function and depressive symptoms. Greater microbial community diversity associated with lower current cognition in the whole sample, and greater depression in participants not on antidepressants. Poor current cognitive function associated with lower relative abundance of Bifidobacterium, while greater GABA degradation associated with greater current depression severity. Future cognitive decline associated with lower cognitive function, lower relative abundance of Intestinibacter, lower glutamate degradation, and higher baseline histamine synthesis. Future increase in depressive symptoms associated with higher baseline depression and anxiety, lower cognitive function, diabetes, lower relative abundance of Bacteroidota, and lower glutamate degradation. Our results suggest cognitive dysfunction and depression are unique states with an overall biological effect detectable through gut microbiota. The microbiome may present a noninvasive readout and prognostic tool for cognitive and psychiatric states.
© 2024. The Author(s).
Conflict of interest statement
AK serves as a consultant for Radicle Science. CA, EJ, CHH, HWR, JYC, YKK, TSS, CSK, COK, SYY, SWH, HJA, HTK and SJS report no biomedical financial interests or potential conflicts of interest.
Figures


Similar articles
-
Music-based therapeutic interventions for people with dementia.Cochrane Database Syst Rev. 2025 Mar 7;3(3):CD003477. doi: 10.1002/14651858.CD003477.pub5. Cochrane Database Syst Rev. 2025. PMID: 40049590
-
Pramipexole in addition to mood stabilisers for treatment-resistant bipolar depression: the PAX-BD randomised double-blind placebo-controlled trial.Health Technol Assess. 2025 May;29(21):1-216. doi: 10.3310/HBFC1953. Health Technol Assess. 2025. PMID: 40455248 Free PMC article. Clinical Trial.
-
New generation antidepressants for depression in children and adolescents: a network meta-analysis.Cochrane Database Syst Rev. 2021 May 24;5(5):CD013674. doi: 10.1002/14651858.CD013674.pub2. Cochrane Database Syst Rev. 2021. PMID: 34029378 Free PMC article.
-
Cognitive behavioural therapy (CBT), third-wave CBT and interpersonal therapy (IPT) based interventions for preventing depression in children and adolescents.Cochrane Database Syst Rev. 2016 Aug 9;2016(8):CD003380. doi: 10.1002/14651858.CD003380.pub4. Cochrane Database Syst Rev. 2016. PMID: 27501438 Free PMC article.
-
Psychological therapies for treatment-resistant depression in adults.Cochrane Database Syst Rev. 2018 May 14;5(5):CD010558. doi: 10.1002/14651858.CD010558.pub2. Cochrane Database Syst Rev. 2018. PMID: 29761488 Free PMC article.
Cited by
-
The Association of the Oral Microbiota with Cognitive Functioning in Adolescence.Genes (Basel). 2024 Sep 27;15(10):1263. doi: 10.3390/genes15101263. Genes (Basel). 2024. PMID: 39457387 Free PMC article.
-
The mind, brain, and body study: A protocol for examining the effects of the gut-brain-immune axis on internalizing symptoms in youth exposed to caregiving-related early adversity.Brain Behav Immun Health. 2024 Oct 5;42:100880. doi: 10.1016/j.bbih.2024.100880. eCollection 2024 Dec. Brain Behav Immun Health. 2024. PMID: 39881818 Free PMC article.
-
Better objective sleep quality is associated with higher gut microbiota richness in older adults.Geroscience. 2025 Jun;47(3):4121-4137. doi: 10.1007/s11357-025-01524-w. Epub 2025 Jan 31. Geroscience. 2025. PMID: 39888583 Free PMC article.
-
Microbiome: A Key Regulator of Body-Brain Interactions.Adv Exp Med Biol. 2025;1477:139-203. doi: 10.1007/978-3-031-89525-8_6. Adv Exp Med Biol. 2025. PMID: 40442386 Review.
-
Advances in research on the pathogenesis and signaling pathways associated with postoperative delirium (Review).Mol Med Rep. 2025 Aug;32(2):220. doi: 10.3892/mmr.2025.13585. Epub 2025 Jun 6. Mol Med Rep. 2025. PMID: 40476568 Free PMC article. Review.
References
-
- Factsheet W. The top 10 causes of death. Geneva: World Health Organization; 2020.
-
- Organization WH. Global status report on the public health response to dementia. 2021.
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical