OP12 - Gut microbiome is rescued by dietary nitrate during dysbiosis: the impact on epithelial fence function and inflammatory pathways during antibiotic therapy.

Nitrate from green-leafy vegetables is sequentially reduced to nitrite in the oral cavity and to nitric oxide (ŸNO) in the stomach. Here, ŸNO increases mucosal blood flow, mucus thickness and prevents microbial infections. Gut microbiota is pivotal in the maintenance of local and systemic welfare as dysbiosis is associated with increased epithelial permeability and with the activation of inflammatory pathways. Herein, we investigated the impact of nitrate on gut microbiome and ensued mucosal effects. Wistar rats were divided in 4 groups and the drinking water was supplemented with 1) antibiotic cocktail (neomycin, bacitracin, imipenem), 2) antibiotic cocktail nitrate, 3) nitrate, 4) tap water (control). Animals were weighted daily. After 7 days they were anesthetized and euthanized. Feces were collected before and after the treatment. Ceca were collected and weighted. The stomach and ascending colon were isolated and occludin, claudin-5, -15 as well as myeloperoxidase (MPO) and iNOS were analyzed. Bacterial DNA was analyzed by DGGE. Antibiotics induced weight loss and cecamegalia (p<0.05) in all animals but nitrate supplementation prevented such effects, likely through a more efficient harvesting of nutrients and preserved motility. The gastric expression of occludin and claudin-5 was decreased during dysbiosis, but both protein levels were recovered by nitrate (p<0.05). Similarly, nitrate prevented MPO and iNOS overexpression under dysbiosis (p<0.05) in the rat stomach. In the large intestine, nitrate increased claudin-5 expression under dysbiosis (p<0.01) but had the opposite effect on occludin (p<0.001). Rats treated with antibiotics and nitrate showed a microflora richness similar to control animals, which suggests that gastric generation of ŸNO recovers gut microbiota during dysbiosis. This data supports that dietary nitrate may rescue gastric epithelial integrity and gut microbiota during dysbiosis and therefore its consumption may be useful when antibiotics are prescribed to treat infections. [ABSTRACT FROM AUTHOR]