Gut microbiota dysbiosis exaggerates ammonia-induced tracheal injury Via TLR4 signaling pathway

Abstract

Ammonia is a toxic air pollutant that causes severe respiratory tract injury in animals and humans. Gut microbiota dysbiosis has been found to be involved in the development of respiratory tract injury induced by air pollutants, however, the specific mechanism requires investigation. Here, we found that, inhaled ammonia induced tracheal injury by reducing expression of claudin-1, increasing expression of muc5ac, TLR4, MyD88, NF-κB and cytokines (TNF-α, IL-1β, IL-6 and IL-10), and also altering tracheal microbiota composition. Spearman correlation analysis indicated that gut microbiota dysbiosis positively correlated with TLR4 level in the trachea. Antibiotic depletion intestinal microbiota treatment reduced the severity of ammonia-induced tracheal injury via TLR4 signaling pathway. Microbiota transplantation induced the tracheal injury via TLR4 signaling pathway even without the ammonia exposure. These results indicate that gut microbiota dysbiosis exaggerates ammonia-induced tracheal injury via TLR4 signaling pathway. In addition, the [Ruminococcus]_torques_group, Faecalibacterium, unclassified_f_Lachnospiraceae may be the key gut microbiota contributing to the alterations of tracheal microbiota composition.