SUN-551 - Metformin–Microbiome Interactions in Alzheimer’s Disease: Evidence from a pilot Hispanic Cohort

Context: Metformin may influence the gut microbiome, a key regulator of metabolic and inflammatory pathways relevant to Alzheimer’s disease (AD). Understanding this interaction in Hispanic populations could help identify microbiome-related mechanisms and therapeutic targets.

Objective: To evaluate the association between metformin use and gut microbiome composition in a Hispanic cohort with AD compared with cognitively healthy controls.

Methods: We analyzed 108 Hispanic participants (55 AD, 53 controls). Among AD participants, 4 used metformin and 51 did not; among controls, 10 used metformin and 43 did not. Controls included individuals with and without diabetes. Microbial diversity was assessed using Shannon and Chao1 indices (alpha diversity) and Bray–Curtis distances with ANOSIM and PERMANOVA (beta diversity). Differential abundance at genus and phylum levels was evaluated using MaAsLin2, adjusting for BMI, MoCA, and CDR.
Alpha diversity showed no significant differences in microbial richness between groups, regardless of metformin use. Beta diversity revealed similar overall microbial composition across groups. The most abundant genus was Blautia. In AD participants, metformin use was associated with lower levels of Agathobacter and Faecalibacterium (typically linked to anti-inflammatory functions) and higher levels of Streptococcus and Akkermansia. In controls, metformin use was associated with higher abundance of several genera, including Escherichia/Shigella, Eubacterium, and Eisenbergiella, after adjustment. Bacterial biomarkers differ between Alzheimer’s Disease patients and Cognitively Healthy patients that use metformin. At the genus level, Escherichia-Shigella, Rhunebacterium, Odonibacter, Eubacterium, and Eisenbergiella are more differentially abundant in control patients that use metformin when corrected for BMI Status, CDR Status, and MOCA Status.However, Faecalimonas are more abundant in Alzheimer’s Disease patients that use metformin. These findings suggest that metformin may shift specific bacterial groups rather than overall diversity. Some of these changes may be beneficial (e.g., Akkermansia, linked to metabolic health), while others may reflect potentially pro-inflammatory profiles, indicating a mixed microbial effect.

Conclusions: Metformin use was associated with selective changes in gut microbiome composition in AD, characterized by reductions in anti-inflammatory bacteria and increases in taxa linked to metabolic regulation. These results support a potential interaction between metformin and the microbiome in AD, although small sample size and metabolic confounding limit interpretation. Larger studies are needed to clarify the clinical significance of these findings.

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