Potential effects of antibiotic‐induced gut microbiome alteration on blood–brain barrier permeability compromise in rhesus monkeys

The blood–brain barrier (BBB) contributes to the maintenance of brain homeostasis. Gut microbiome composition affects BBB development and expression of tight junction proteins in rodents. However, we still do not know if there is any direct effect of gut microbial composition on BBB permeability and function in normal adult animals. In the current study, we determined temporal and spatial changes in BBB permeability of rhesus monkeys receiving amoxicillin‐clavulanic acid (AC) by monitoring the cerebrospinal fluid/serum albumin ratio and the volume transfer constant (Ktrans). We showed that oral, but not intravenous, AC was associated with subsequent significant alteration in gut microbial composition and an increase in BBB permeability in all monkeys, especially in the thalamus area. Acetic and propionic acids might play a pivotal role in this newly found communication between the gut and the central nervous system. Antibiotic‐induced gut microbial composition change, especially the decrease in acetic acid– and propionic acid–producing phyla and genera, might have a potential effect on the increase in BBB permeability, which may contribute to a variety of neurological and psychological diseases. Our study provides strong evidence that antibiotic‐induced gut microbial composition changes, especially the decrease in acetate‐ and propionate‐producing bacterial genera, are correlated with the increase in BBB permeability. These results may be an important component in some of the emerging links between the alterations in intestinal microbial composition and pathologies as significant as depression, Alzheimer's disease, Parkinson's disease, and autism spectrum disorder.