The Role of Gut Microbiome in Mild Cognitive Impairment: A Twin Study

Background and Objectives: Recent studies have revealed the potential roles of gut microbiota and microbial metabolites in influencing mild cognitive impairment (MCI) and Alzheimer’s disease via the gut–brain axis. This relationship has not yet been investigated in monozygotic twin pairs, which represent an ideal model for minimizing genetic confounding. Materials and Methods: Seven twin pairs discordant for ACE and 15 for MoCA were enrolled. Stool samples were subjected to 16S ribosomal RNA-based microbiome analysis. Results: No significant differences in alpha or beta diversity were observed between MCI-discordant twin pairs at the genus or family level. The most robust finding was a significantly lower abundance of Lachnospiraceae in MCI-affected twins, identified independently by ANCOM-BC and LEfSe. Additional exploratory findings included higher abundances of Sutterella, Succinivibrio, Odoribacter, and Ruminococcus. However, several taxa showed opposing patterns between ACE- and MoCA-derived cohorts, highlighting the methodological impact of cognitive instrument selection. Conclusions: The convergent reduction of Lachnospiraceae across two independent analytical methods represents the most substantive finding. The remaining results are exploratory, limited by small sample size, restricted statistical power, and lack of availability to fully control for dietary habits, physical activity, and medication use. Validation in larger longitudinal twin cohorts with a standardized cognitive assessment is warranted.