Abstract

AbstractBackgroundBowel movement frequency and the gut microbiome may be associated with the risk of dementia.MethodWe examined the association between bowel movement frequency and cognitive function in 112,753 women and men from Nurses’ Health Study (NHS), Nurses’ Health Study II (NHSII), and Health Professionals Follow‐Up Study (HPFS) and explored the role of the gut microbiome in explaining these associations in a sub‐cohort of 515 NHSII and HPFS participants. We collected data on bowel movement frequency in 2012/13 and subjective cognitive function from 2014 to 2017 in all participants and objective cognitive function using a neuropsychological battery between 2014 and 2018 in 12,696 NHSII participants. We profiled the gut microbiome using shotgun metagenomics.ResultBowel movement frequency was associated with overall objective cognitive function and learning and working memory in an inverse J‐shape dose‐response manner (both Pnon‐linearity<0.05). Compared to those with once daily bowel movements, participants with bowel movement frequency of every 3+ days had significantly worse cognition, equivalent to 3.0 (95% confidence interval (CI),1.2, 4.7) years of additional aging. We observed similar J‐shape dose‐response relationships of bowel movement frequency with the odds of subjective cognitive decline and the likelihood of having more subjective cognitive complaints over time. Bowel movement frequencies of every 3+ days and ≥twice /day, compared to once daily bowel movement, were associated with odds ratios of subjective cognitive decline of 1.73 (95% CI, 1.60, 1.86) and 1.37 (95% CI, 1.33, 1.44), respectively. These relationships were generally consistent across three cohorts and subgroups. Bowel movement frequency and subjective cognition were significantly associated with the overall variation of the gut microbiome (both P <0.005) and specific microbial species. Butyrate producers were depleted in those with less frequent bowel movements and worse cognitive function, while a higher abundance of dysbiosis‐related, pro‐inflammatory species was associated with bowel movement frequency of ≥twice/day and worse cognitive function.ConclusionLess frequent bowel movements were associated with worse cognitive function. The gut microbiome may be a mechanistic link underlying the association between intestinal motility patterns and cognitive function.

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