The gut microbiome and cognitive function in midlife: The CARDIA study

Abstract

AbstractBackgroundBased on experimental and clinical studies of specific patients, a gut‐brain axis has been hypothesized as mechanism connecting peripheral metabolic and immunologic activity to the brain, including cognitive functioning. Few studies have investigated the association of gut microbial composition to cognition in large community samples.MethodCross‐sectional data were from a subsample (n=597) of participants in the U.S.‐based bi‐racial Coronary Artery Risk Development in Young Adults (CARDIA) study (2015‐16). Participants were aged 48‐60 years, 45% male, and 45% Black (Table). V3‐V4 regions of 16S rRNA were sequenced from stool DNA with Illumina MiSeq technology and. microbial taxonomic measures generated from the sequenced data. After filtering out rare taxa, 107 genera (of 375 originally assigned) were included in the analysis. Participants completed six interviewer‐administered cognitive tests: Montreal Cognitive Assessment (MoCA), Digit Symbol Substitution Test (DSST), Rey‐Auditory Verbal Learning Test (RAVLT), timed Stroop test, and letter and category fluency tests. Higher scores on all tests reflect greater cognitive functioning, except for Stroop, for which faster (lower time) is better.ResultRegression analysis of cognitive test scores on genera included adjustment for sequencing batch; and participant age, sex, race, BMI, and diabetes. Eleven genera were associated with two or more cognitive measures at FDR<0.10, and 31 genera were associated with two or more at FDR<0.20 (Figure): Barnesiella was positively associated with DSST and category fluency; Lachnospira was positively associated with DSST, RAVLT, MoCA, category fluency, and negatively associated with the timed Stroop test; Sutterella was negatively associated with MoCA, RAVLT, and DSST. Seven of the 11 genera with shared associations at FDR<0.10 (and 22 of the 31 at FDR<0.20) were from within the Clostridia class.ConclusionTests of global cognition and psychomotor speed were associated with specific microbes in the gut. These microbes, particularly those stemming from Clostridia class, may be involved in short‐chain fatty acid production and inflammatory pathways. Our data contribute to a growing body of literature suggesting that the gut microbiota may relate to cognitive function. These signals must be replicated and further researched to identify relevant genetic, metabolic, and inflammatory pathways.