(P19-011-25) An Interim Analysis of the Brain Health & the Microbiome Proof-of-Concept Study in Patients With Mild Cognitive Impairment

Objectives: To investigate relationships between diet, inflammation, gut microbiota, and physical, mental, and social health in patients with mild cognitive impairment (MCI) and healthy controls.

Methods: We analyzed 23 stool samples from 15 participants (8 healthy controls, 7 MCI) using EzBiome pipelines (previously published). Participants completed PROMIS-29 (Physical Function, Anxiety, Depression, Fatigue, Sleep Disturbance, Ability to Participate in Social Roles, Pain Interference, Pain Intensity). Samples dominated by Enterobacteriaceae (n=15; 6 HC, 5 MCI) were plotted (exponential regression) against the EzBiome Inflammation Index (EII), a complex, AI-generated numerical value, distilling multiple streams of complex information. Correlations between EII and PROMIS-29 T-scores were assessed (Pearson coefficients). GMI (Gut Microbiome Index), Diversity Index (DI), and proportion of vitamin producing, serotonin producing, and bile-decomposing microorganisms were compared between MCI and healthy controls (one-tailed T-tests). Dietary pattern and Healthy Eating Index (HEI) were determined with DietID, a validated dietary assessment tool. HEI was plotted vs. EII and Enterobacteriaceae ratio.

Results: EII and Enterobacteriaceae ratio showed a strong exponential relationship (r²=0.93); PROMIS-29 and EII did not (r≤0.40). DI and proportion of vitamin producing microorganisms were lower in MCI vs. control (p < 0.05). There were no significant differences for GMI, serotonin producing, and bile-decomposing microorganisms. Regression analyses (HEI vs. EII and Enterobacteriaceae ratio) showed no discernible relationship.

Conclusions: The exponential relationship between EII and Enterobacteriaceae ratio may be driving inflammation in this population. The lack of significant correlations between EII and PROMIS-29 measures is likely due to small sample size. DI and proportion of vitamin producing microorganisms were lower in MCI vs. controls, indicating potential markers to be explored. The lack of association with diet could be due to limited HEI range, which were healthier (HEI range: 57-98; HEI mean: 87) than average Americans (HEI=58), presenting limited variation. Future studies should include larger sample sizes and diverse dietary intakes.

Funding Sources: TMCity Foundation