Mediterranean versus Western diet and the gut‐brain axis: Diet‐induced links between gut Oscillospira abundance, plasma branched‐chain amino acid concentrations and insulin resistance, and change in white matter volumes in nonhuman primates
Authors: Negrey Jacob D. , Frye Brett M. , Nagpal Ravinder , Kim Jeongchul , Barcus Richard A. , Lockhart Samuel N. , Whitlow Christopher T. , Tooze Janet A , Yadav Hariom , Craft Suzanne , Register Thomas C. , Shively Carol A. 
Published: December 2023

AbstractBackgroundWestern vs. Mediterranean patterned diets have been associated with divergent effects on neurodegenerative diseases including Alzheimer’s Disease (AD). Such effects may be mediated through the gut microbiome, although the exact mechanisms linking diet, microbiome, and brain outcomes remain unclear. Oscillospira, a genus of gut‐dwelling bacteria, appears to be a good candidate which may help explain the mechanistic underpinnings of this relationship. Previous studies have shown associations between Oscillospira abundance, blood biomarkers, and brain physiology in rodents, and patients with neurodegenerative diseases including AD exhibit decreased gut Oscillospira abundances. Notably, Oscillospira may alter myelination by modifying branched‐chain amino acid (BCAA) concentrations in blood and preventing or minimizing insulin resistance.MethodIn the present study, we test a mechanistic role for Oscillospira on white matter volumes in cynomolgus monkeys (Macaca fascicularis) experimentally fed either a Mediterranean or Western‐type diet. We analyzed associations between gut Oscillospira abundances, plasma BCAA concentrations (i.e., leucine, isoleucine, and valine), plasma insulin, beta‐amyloid (Aβ) 42 to 40 ratio in cerebrospinal fluid (CSF), and magnetic resonance imaging‐derived white matter volumes.ResultWe found that Oscillospira abundance was significantly higher in the Mediterranean diet cohort than in the Western cohort (β = 0.258, SE = 0.084, p = 0.004). Oscillospira abundance was significantly negatively associated with plasma leucine (β = ‐0.169, SE = 0.059, p = 0.007) and valine concentrations (β = ‐0.206, SE = 0.069, p = 0.005); a similar, non‐significant (p = 0.066) trend was observed for isoleucine. Similarly, Oscillospira abundance was negatively associated with insulin area under the curve (AUC) at 26 months (β = ‐0.282, SE = 0.125, p = 0.031) and change in insulin AUC from baseline to 26 months (β = ‐14.6, SE = 6.97, p = 0.044), suggesting better insulin sensitivity in individuals with higher Oscillospira abundance. Oscillospira abundance was also positively associated with CSF Aβ42:40 ratio (β = 0.013, SE = 0.004, p = 0.007). Furthermore, the percent change in white matter volume over the study period was positively associated with Oscillospira abundance (β = 2.45, SE = 0.915, p = 0.012) and negatively associated with leucine (β = ‐2.39, SE = 0.920, p = 0.014), isoleucine (β = ‐2.67, SE = 0.895, p = 0.005), and valine concentrations (β = ‐2.28, SE = 0.929, p = 0.020) as well as change in insulin AUC (β = ‐2.04, SE = 0.947, p = 0.039).ConclusionThese results suggest that diet impacts the central nervous system by altering gut microbiome composition and highlight the complexity of relationships between BCAAs and brain health.