Gut Microbiota in Constipation and Mild Cognitive Impairment: A Mendelian Randomization and Observational Study of...

In geriatric syndrome (GS), conditions like cognitive impairment and constipation reduce quality of life. Gut microbiota may influence GS progression via the gut-brain axis. This exploratory study investigated potential causal associations and microbial characteristics between gut microbiota and constipation, including constipation with mild cognitive impairment.

Two-sample Mendelian randomization (MR) was performed to explore potential causality between gut microbiota and constipation. Inverse variance weighted (IVW) was the primary method, with sensitivity analyses using MR-Egger, weighted median, and MR-PRESSO. False discovery rate (FDR) correction was applied for multiple testing. Two-sample MR used summary statistics from MiBioGen (n=18,340) and FinnGen (51,956 cases). The observational study included 88 participants. Subsequently, fecal samples from 88 elderly participants (30 constipation+MCI, 28 constipation, 30 controls) were analyzed using 16S rDNA sequencing.Gut microbiota was profiled by 16S rDNA V3-V4 sequencing. Alpha diversity (Chao1, Shannon, Simpson) and beta diversity (Bray - Curtis PCoA with Adonis) were assessed. LEfSe (LDA > 4) identified differentially abundant taxa. Functional potential was predicted by Tax4Fun2.

MR analysis indicated that the genus Oscillibacter may exert a protective effect against constipation, whereas the family Rikenellaceae, genus Enterorhabdus, and genus Victivallis were identified as risk factors. 16S sequencing showed significant structural differences among groups, though these findings are observational.LEfSe analysis identified Enterococcus-related taxa as characteristic features of the constipation+MCI group, whereas Bifidobacterium-related taxa were enriched in controls. Relative abundance analysis also suggested group-specific differences in Escherichia-Shigella, Prevotella_9, and Enterobacter.

The findings offer preliminary evidence that specific gut microbes may be associated with constipation. Distinct microbial features and functional changes are associated with constipation and constipation+MCI. Gut microbiota dysbiosis might link constipation and cognitive impairment, providing exploratory clues rather than definitive conclusions for future hypothesis-driven and microbiota-targeted studies.