Gut Microbiome Predicts Cognitive Function and Depressive Symptoms in Late Life

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AbstractBackgroundDepressive symptoms in older adults with cognitive impairment increase the likelihood of progression to dementia. Current mood and cognitive function associate with microbial composition, but the extent to which the microbiome may predict clinical trajectory is unknown. We investigated the capacity of the gut microbiome to reflect current and predict future cognitive function and depressive symptoms.MethodClinical assessments and stool samples were collected from 268 participants with varying cognitive function and depressive symptoms. Seventy participants underwent a 2‐year follow‐up. Microbial community diversity, structure, and composition was assessed using high‐resolution 16S rRNA marker gene sequencing (Figure 1). We implemented multiple linear regression to characterize the relationship between microbiome composition, current cognitive impairment, and depressive symptoms. We leveraged elastic net regression to discover microbial community metrics and microbial functional pathways that reflect current or predict future cognitive function and depressive symptoms (Figure 2).ResultGreater microbial community diversity, indicating a higher number and even distribution of species within a community, was associated with worse current cognitive function in the sample, as well as greater depression severity in participants not on antidepressants. Poor current cognitive function was associated with lower relative abundance of Bifidobacterium. On a functional level, we demonstrate an association between greater GABA degradation and greater current depression severity (Figure 2). Future cognitive decline was associated with lower cognitive function and increased anxiety at baseline. Future cognitive decline was also associated with decreased relative abundance of Firmicutes and Intestinibacter, higher glutamate degradation, and higher baseline histamine synthesis (Figure 2). Future increase in depressive symptoms was associated with higher baseline depression and anxiety, lower cognitive function, and lower relative abundance of Bacteroidota (Figure 2).ConclusionWe display utility in microbiome composition for predicting future cognitive function and depressive symptoms in late life. Our results suggest the gut microbiome may present a noninvasive prognostic for cognitive and psychiatric states. Advancing our understanding of gut‐brain axis in aging may inform the development of neurobiologically driven interventions to ameliorate cognitive decline and depressive symptoms in late life.