Effect of temperature stress on gut-brain axis in mice: Regulation of intestinal microbiome and central NLRP3 inflammasomes

Abstract

Background: Temperature stress was reported to impact the gut-brain axis including intestinal microbiome and neuroinflammation, but the molecular markers involved remain unclear. We aimed to examine the effects of different temperature stress on the intestinal microbiome and central nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes.

Materials and methods: Mice models were established under low temperature (LT), room temperature (RT), high temperature (HT), and temperature variation (TV) respectively for seven days. We examined temperature-induced changes of intestinal microbiome composition and the levels of its metabolites short-chain fatty acids (SCFAs), as well as the expressions of central NLRP3 inflammasomes and inflammatory cytokines. Redundancy analysis and Spearman correlation analysis were performed to explore the relationships between microbiome and NLRP3 inflammasomes and other indicators.

Results: HT and LT significantly increased the Alpha diversity of intestinal microbiome. Compared with RT group, Bacteroidetes were most abundant in LT group while Actinobacteria were most abundant in HT and TV groups. Nineteen discriminative bacteria were identified among four groups. LT increased the expressions of acetate and propionate while decreased that of NLRP3 inflammasomes; HT decreased the expression of butyrate while increased that of NLRP3 inflammasomes, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α; TV decreased the expression of propionate while increased that of NLRP3 inflammasomes and TNF-α. Microbiome distribution could significantly explain the differences in NLRP3 between comparison groups (LT&RT: R² = 0.82, HT&RT: R² = 0.86, TV&RT: R² = 0.94; P < 0.05). The discriminative bacteria were significantly correlated with SCFAs but were correlated with NLRP3 inflammasomes and cytokines in the opposite direction.

Conclusions: LT inhibits while HT and TV promote the activation of NLRP3 inflammasomes in brain, and intestinal microbiome and its metabolites may be the potential mediators. Findings may shed some light on the impact of temperature stress on gut-brain axis.

Keywords: Gut-brain axis; Inflammasome; NLRP3; Temperature stress.