A high-calorie diet aggravates LPS-induced pneumonia by disturbing the gut microbiota and Th17/Treg balance

Abstract

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.

Effect of a high-calorie diet on pro- to anti-inflammatory macrophage ratio through fat accumulation in rat lung tissue

“…Obesity causes proinflammatory mediators that cause macrophages to migrate to the lung tissue. Liu et al 11 reported that a high-calorie diet combined with pneumonia increases the lung organ coefficient, indicating that LPSinduced lung tissue hypertrophy occurred due to the infiltration of macrophages in rat lung tissue. In obese mice, adipocyte cell death, which can be caused by hypoxia, increases in adipose tissue, attracting proinflammatory macrophages to adipose tissue.…”

People are an organic unity: Gut-lung axis and pneumonia

“…Thus, they play opposite roles in inflammation and immune responses [ 46 ]. It was demonstrated that disrupting the balance of Th17/Treg cells could exacerbate LPS-induced inflammatory lung injury [ 47 ]. Commensal microorganisms can regulate the Th17/Treg balance, which modulates the local inflammatory response.…”

Causal effects of gut microbiota on ARDS: a two-sample Mendelian randomization study

“…SCFAs show immunomodulatory effects by maintaining intestinal integrity and exhibiting anti-in ammatory response [45]. Supplementation with SCFAs has been reported to reduce pro-in ammatory cytokines, phagocyte activation, and oxidative stress in ALI mice [46].A recent study showed that SCFAs signi cantly alleviated the imbalance of Th17/Treg cells and lung in ammatory injury [47]. WANG et al[48] demonstrated the importance of gut microbiome-derived succinate in the pathogenesis of ALI.…”