Non-neuronal crosstalk promotes an inflammatory response in nodose ganglia cultures after exposure to byproducts from gram positive, high-fat-diet-associated gut bacteria.

Vagal afferent neurons (VAN) projecting to the lamina propria of the digestive tract are the primary source of gut-originating signals to the central nervous system (CNS). VAN cell bodies are found in the nodose ganglia (NG). Responsiveness of VAN to gut-originating signals is altered by feeding status with sensitivity to satiety signals such as cholecystokinin (CCK) increasing in the fed state. Chronic high-fat (HF) feeding results in inflammation at the level of the NG associated with a loss of VAN ability to switch phenotype from the fasted to the fed state. HF feeding also leads to compositional changes in the gut microbiota. HF diet consumption notably drives increased Firmicutes to Bacteroidetes phyla ratio and increased members of the Actinobacteria phylum. Firmicutes and Actinobacteria are largely gram positive (GP). In this study, we aimed to determine if byproducts from GP bacteria can induce an inflammatory response in cultured NG and to characterize the mechanism and cell types involved in the response. NG were collected from male Wistar rats and cultured for a total of 72 hours. At 48-68 hours after plating, cultures were treated with neuronal culture media in which Serinicoccus chungangensis had been grown and removed (SUP), lipoteichoic acid (LTA), or meso-diaminopimelic acid (meso-DAP). Some treatments included the glial inhibitors minocycline (MINO) and/or fluorocitrate (FC). The responses were evaluated using immunocytochemistry, qPCR, and electrochemiluminescence. We found that SUP induced an inflammatory response characterized by increased interleukin (IL)-6 staining and increased expression of genes for IL-6, interferon (IFN)γ, and tumor necrosis factor (TNF)α along with genes associated with cell-to-cell communication such as C-C motif chemokine ligand-2 (CCL2). Inclusion of inhibitors attenuated some responses but failed to completely normalize all indications of response, highlighting the role of immunocompetent cellular crosstalk in regulating the inflammatory response. LTA and meso-DAP produced responses that shared characteristics with SUP but were not identical. Our results support a role for HF associated GP bacterial byproducts' ability to contribute to vagal inflammation and to engage signaling from nonneuronal cells.