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. 2024 Oct;29(10):3064-3075.
doi: 10.1038/s41380-024-02551-3. Epub 2024 Apr 25.

Gut microbiome predicts cognitive function and depressive symptoms in late life

A Kolobaric  1 , C Andreescu  2 , E Jašarević  3   4   5 , C H Hong  6 , H W Roh  6 , J Y Cheong  7 , Y K Kim  8 , T S Shin  8 , C S Kang  8 , C O Kwon  8 , S Y Yoon  8 , S W Hong  6 , H J Aizenstein  2   9 , H T Karim  10   11 , S J Son  12   13
Affiliations

Gut microbiome predicts cognitive function and depressive symptoms in late life

A Kolobaric et al. Mol Psychiatry. 2024 Oct.

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.

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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

Fig. 1
Fig. 1. Overview of data processing and results.
A Stool samples were collected and pre-processed to create an amplicon sequence variant table. B Multiple Alpha Diversity Indices were calculated to quantify gut microbiota community richness and evenness. C–F We ran four linear regression models to examine whether gut microbiome community diversity was associated with current depression severity (and its dependence on antidepressant use), cognitive function, and whether these sets of factors moderated one-another given the deleterious effect of comorbid cognitive decline and depressive symptoms. Before interpreting any of the models, we used visual inspection to ensure normally distributed model residuals. The model containing the Shannon Index as the dependent variable had the residual distribution most representative of a normal distribution, which did not violate the normality assumption. G Distribution of cognitive symptoms, alpha diversity, and depressive symptoms. H Higher microbial community diversity (alpha diversity) was associated with and greater depression severity in those participants who were not currently on antidepressants. I Higher microbial community diversity was associated with lower cognitive function in the whole sample. This figure was created with BioRender.com.
Fig. 2
Fig. 2. Summary of findings.
A Lower current cognitive function is associated with lower education, no antidepressant use, higher relative levels of Bacteroidota, lower Bifidobacterium, lower BMI, and lower anxiety. Higher current depression is associated with antidepressant use, lower education, diabetes, higher anxiety, and higher GABA degradation. B Lower cognition after 2 years is associated with lower baseline cognition, lower baseline abundance of Intestinibacter, absence of hypertension, lower baseline glutamate degradation, and higher baseline histamine synthesis. Higher depression after 2 years is associated with higher baseline anxiety and depression, diabetes, lower baseline cognition, lower baseline Bacteroidota, and lower baseline glutamate degradation. This figure was created with BioRender.com.
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References

    1. Factsheet W. The top 10 causes of death. Geneva: World Health Organization; 2020.
    1. Organization WH. Global status report on the public health response to dementia. 2021.
    1. Cooper C, Li R, Lyketsos C, Livingston G. Treatment for mild cognitive impairment: systematic review. Br J Psychiatry. 2013;203:255–64. - PMC - PubMed
    1. ongsiriyanyong S, Limpawattana P. Mild cognitive impairment in clinical practice: a review article. Am J Alzheimer’s Dis Other Dement. 2018;33:500–7. - PMC - PubMed
    1. Langa KM, Levine DA. The diagnosis and management of mild cognitive impairment: a clinical review. Jama. 2014;312:2551–61. - PMC - PubMed

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