Translocation of bacteria from the gut to the brain in mice

TL;DR

This study shows that bacteria can travel from the gut to the brain in mice, especially when they are on a high-fat diet, suggesting a new link between gut health and neurological conditions.

Contribution

The study demonstrates direct bacterial translocation from the gut to the brain via the vagus nerve in mice under high-fat diet conditions.

Findings

Bacteria translocate from the gut to the brain in mice on a high-fat diet.

The vagus nerve serves as a conduit for bacterial translocation to the brain.

Bacterial presence in the brain is reversible with a return to normal diet.

Abstract

Recent advances suggest a correlation between gut dysbiosis and neurological diseases, however, relatively little is known about how gut bacteria impact the brain. Here, we reveal that bacteria can translocate directly from the gut to the brain in small numbers when mice are fed an atherogenic, high-fat diet (Paigen diet) that causes alterations in gut microbiome composition and gut barrier permeability. The bacteria were not found in other systemic sites or the blood, but were detected in the vagus nerve. Right cervical vagotomy reduced bacterial burden in the brain, implicating the vagus nerve as a conduit for bacterial translocation from the gut to the brain. Antibiotic treatment perturbed the composition of the gut microbiome and correspondingly changed the bacteria that localized to the brain in the setting of Paigen diet feeding. To further establish the gut as the origin of bacterial translocation to the brain, we gavaged exogenous Enterobacter cloacae into Paigen diet-fed mice, subsequently detecting the E. cloacae in the gut and brain. In addition, we monocolonized germ-free mice with E. cloacae and only cultured the bacteria from the brains of mice fed Paigen diet, but not those fed standard diet. Localization of bacteria to the brain in Paigen diet-fed mice was reversible with return to normal diet. Bacteria were also detected in the brain of murine models of Alzheimer’s, Parkinson’s, and autism spectrum disorder fed standard diet. These data reveal a bacterial translocation axis from the gut to the brain, impacted by environmental (diet) and genetic factors, and warrant further investigation to determine if this phenomenon also occurs in humans and to elucidate whether it may play a role in diverse neurological conditions.

Recent studies link gut dysbiosis to neurological disease, but the underlying mechanisms remain unclear. This study shows that a high-fat diet increases gut permeability and enables bacterial translocation from the gut to the brain via the vagus nerve in mice.

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