Fecal short-chain fatty acids vary by sex and amyloid status.
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Kuehn Jessamine F, Zhang Qijun, Heston Margo B, Kang Jea Woo, Harding Sandra J, Davenport-Sis Nancy J, Peter Darby C, Kerby Robert L, Vemuganti Vaibhav, Schiffmann Emma C, Tallon Michael M, Harpt Joseph, Hajra Arun, Wheeler J L, Shankar Sushma, Mickol Alissa, Zemberi Justus, Chow Hana, Zhang Eric, Clements Eleanor, Noughani Hanna, Forst Allison, Everitt Grace, Kollmorgen Gwendlyn, Quijano-Rubio Clara, Christian Bradley T, Carlsson Cynthia M, Johnson Sterling C, Asthana Sanjay, Zetterberg Henrik, Blennow Kaj, Ulland Tyler K, Rey Federico E, Bendlin Barbara B
Аннотация
METHODS: We measured SCFAs and bacterial abundances in fecal samples from 287 participants in the Wisconsin Alzheimer's Disease Research Center and Wisconsin Registry for Alzheimer's Prevention. We performed regressions examining associations between SCFAs or gut microbes and AD pathology and cognition.
RESULTS: Fecal propionate, isovalerate, and propionate-producing bacteria are inversely associated with amyloid status. Mediation analysis found that propionate mediates sex-specific associations between SCFAs and cerebrospinal fluid biomarkers. SCFA levels are associated with slower cognitive decline.
DISCUSSION: These results link SCFAs and propionate-producing bacteria with AD. This may inform efforts to leverage diet and specific bacteria to boost SCFA production and potentially ameliorate AD progression.
HIGHLIGHTS: Fecal SCFAs link to lower amyloid burden and microglial activation, notably in females. SCFA-producing gut microbes have reduced abundance in amyloid-positive participants. Fecal propionate mediates relationships between gut microbes and amyloid status. SCFAs are associated with slower plasma pTau217 accumulation in females. SCFAs are associated with slower cognitive decline.