LAUSR

The intestinal flora plays an important role in the inflammatory response to the systemic or local infections in the host. A high‐calorie diet has been shown to aggravate pneumonia and delay recovery, especially in children. However, the underlying mechanisms remain unclear. Our previous studies demonstrated that a high‐calorie diet and LPS atomization synergistically promoted lung inflammation injury in juvenile rats. In this study, specific pathogen‐free juvenile rats were placed in a routine environment, and subjected to a high‐calorie diet or LPS atomization in isolation as well as combination. Our data revealed that LPS nebulization combined with a high‐calorie diet resulted in significant changes in rats, such as slow weight gain, increased lung index, and aggravated lung inflammatory damage. Meanwhile, we found that the aggravation of LPS‐induced pneumonia by a high‐calorie diet disturbs the balance of Th17/Treg cells. Furthermore, high‐throughput sequencing of intestinal contents revealed that a high‐calorie diet changed the gut microbiome composition, decreased microbial diversity, and particularly reduced the abundance of the intestinal microbiota associated with the production of short‐chain fatty acids (SCFAs) in rats. Consequently, the levels of SCFAs, especially acetate, propionate, and butyrate, were significantly decreased following the intervention of a high‐calorie diet. More critically, the effects of a high‐calorie diet were shown to be transmissible among pneumonia rats through cohousing microbiota transplantation. Taken together, we provide evidence to support that a high‐calorie diet can potentially reset the gut microbiome and metabolites, disrupt Th17/Treg cell balance and immune homeostasis, and aggravate LPS‐induced lung inflammatory damage, which may provide a new perspective on the pathogenesis of lung inflammation injury, and suggest a novel microbiota‐targeting therapy for inflammatory lung diseases.