Diet alters the effects of lipopolysaccharide on intestinal health and cecal microbiota composition in C57Bl/6 male mice

Lipopolysaccharide (LPS), a component of the gram-negative bacteria, induces an inflammatory cascade in mice, negatively impacting aspects of the microbiota gut-brain axis (mGBA). Flaxseed (FS), an oilseed enriched in dietary fiber and n3 poly-unsaturated fatty acids, has been shown to partially attenuate LPS-induced systemic and neuroinflammation. In this study, we investigated the impact of FS and FS oil (FO) diets on microbial dysbiosis, biomarkers of intestinal health, hepatic inflammation and oxidative stress, and metabolic homeostasis in male mice, 24-hours post LPS-exposure. Compared to saline-treated mice, LPS mice showed diet-dependent shifts in the cecal microbiome. Most notably, LPS-treated basal diet (BD)-fed mice had reduced Muribaculaceae and Lachnospiraceae, FS-LPS mice had elevated Akkermansia and Enterobacteriaceae, and both the FS-LPS and FO-LPS mice had increased Bacteroides. LPS increased cecal short-chain fatty acid concentrations, the highest of which were found in FS-fed mice. Intestinal health biomarkers were modulated by LPS in a diet-specific manner such that ileal mucous content was elevated in FS- and FO-fed mice, while LPS-induced inflammation (IL-1β) was attenuated in FS-fed mice. On the other hand, LPS-induced hepatic inflammation and oxidative stress, which were not attenuated by FS or FO diets. Bacteroides abundance and serum Il-10 levels, and cecal butyrate concentrations and hippocampal IL-6 mRNA, were negatively correlated in FS-fed mice only, suggesting a potential role of the microbiome in the anti-inflammatory effects of FS post-LPS treatment. Collectively, LPS exposure negatively impacted the cecal microbiome and markers of intestinal, hepatic, and metabolic health, the former being beneficially altered by FS diet.