The Gut Microbiome and Cognition and Their Response to a Mediterranean Diet and Weight Loss

In the United States, dementia affects 14% of older adults, with another 15-20% exhibiting mild cognitive impairment (MCI), a prodrome to dementia. Moreover, African Americans have a higher incidence of dementia than other racial groups. One contributor to dementia may be the gut microbiota since it may reduce the systemic inflammation and oxidative stress that contributes to dementia. Moreover, a Mediterranean Diet and intentional weight loss (IWL) may decrease dementia risk by improving the gut microbiota’s ability to produce anti-inflammatory molecules and prevent oxidative stress. However, no study has characterized the differences in the gut microbiota of African Americans with or without MCI or characterized the role the gut microbiota has in connecting a Mediterranean Diet and IWL to cognition. First, we conducted a case-control study of predominately older, obese, African American adults to characterize the gut microbiota of 30 individuals with and 30 without MCI, matched on age, sex, and BMI. Those with MCI had higher levels of microbiota associated with cognitive decline, i.e., Dialister invisus. These relationships were dependent on levels of bacterial translocation, systemic inflammation, or oxidative stress. Second, within the context of an 8-month Randomized Controlled Trial (RCT) called the Building Research in Diet and Cognition (BRIDGE) trial, we tested the cognitive and microbial effect of a Mediterranean Diet with (MedWL) or without IWL (MedA), compared to controls, in a subsample of participants highly adherent to their intervention assignment. Results did not reveal a large shift to the gut microbiota in MedA, MedWL, or controls. However, in the MedA group, M. massilensies increased and was negatively associated with changes to memory performance, independent of changes to inflammation and oxidative stress. Also, an increase in Mediterranean Diet adherence was significantly correlated with an increase in butyrate production potential. These data suggest that an 8-month Mediterranean Diet intervention can induce changes to the gut microbiota that relate to cognition. Future studies in this field should include measurement of several microbial metabolites and functions and larger cohorts with more frequent stool sampling to describe more fully the relationship between the gut microbiota and cognition.