Gut community-level analysis reveals an altered balance between Phocaeicola vulgatus and Bacteroides fragilis in Alzheimer's disease

Abstract

Gut microbiome differences in Alzheimer's disease (AD) are typically cataloged taxon by taxon, yet bacterial competition and cross-feeding make species' roles dependent on the entire community. We analyzed 274 stool metagenomes from 119 older adults (18 with AD) as communities, retaining 22 recurring across 1,000 runs. Using our AI framework, we identified 15 species differing in abundance in AD, particularly the commensal Phocaeicola vulgatus (Cohen's d -0.91, 95% CI [-1.23, -0.59]), a finding robust to repeated sampling. It correlated negatively with its sister species, Phocaeicola dorei (r -0.57), suggesting possible niche competition; this replicated in an independent cohort (r -0.43). P. vulgatus was depleted in AD and the opportunistic pathogen Bacteroides fragilis enriched, shifting their balance toward B. fragilis (d -0.70), a modestly reproduced AD-associated pattern (d -0.24). Our findings suggest that AD-associated gut microbiome variation extends beyond taxon-specific abundance to the balance between specific species within a community matrix.