Abstract
Inflammatory bowel disorder is accompanied by the destruction of immunity homeostasis, gut microbiota perturbation, and chronic inflammatory liver diseases. Butyrate is known as a primary energy source for colonocytes and functional substances for mitigating pathological features of colitis. However, it is still unclear whether butyrate alleviates colitis progression by regulation of microbiota and metabolism in the gut–liver axis. In the present study, we aimed to determine the role of microbiota and metabolism of the gut–liver axis in ameliorating lipopolysaccharide (LPS)-induced colitis in piglets using protected butyrate administration. Eighteen crossbred male piglets were weaned at 30 days old and were randomly allocated to three treatments, with CON (basal diet), LPS (basal diet + LPS), and BT-LPS (basal diet + 3.0 g/kg protected butyrate + LPS). On days 19 and 21, piglets in the LPS and BT-LPS groups were intraperitoneally challenged with LPS at 100 μg/kg body weight. Butyrate administration significantly decreased LPS-induced rise in the clinical score of piglets and colonic histological scores and reduced the susceptibility to LPS-induced severe inflammatory response by decreasing proinflammatory (IL-1β, IL-6, IL-8, and TNF-α) cytokines. Butyrate supplementation accelerated the prevalence of Faecalibacterium and Lactobacillus by enhancing the tricarboxylic acid (TCA) cycle of colonocytes. Dietary supplementation with protected butyrate significantly targeted increased concentrations of butyric acid in the colon and portal venous circulation, and enhanced the TCA cycle in the gut–liver axis by mobilizing amino acid and vitamin B group as a coenzyme. Meanwhile, during this progress, LPS increased fatty acid synthesis that was reversed by butyrate treatment, which was reflected by decreased acylcarnitines. Butyrate-reshaped colonic microbial community and metabolism in the gut–liver axis contributed to morphology integrity and immunity homeostasis by promoting anti-inflammatory (IL-10 and TGF-β) cytokines and suppressing inflammatory mediator hypoxia-inducible factor 1α and its downstream response elements cyclooxygenase 2 and inducible nitric oxide synthase. These results identified the pivotal role of colonic microbiota and metabolism in the gut–liver axis for alleviating inflammatory progression and possible therapeutic targets.
Highlights
Inflammatory bowel disorders (IBDs), which include Crohn’s disease and ulcerative colitis, are worldwide diseases characterized by a chronic and recurrent inflammatory response and injury of the colon (Shi et al, 2016)
Accompanied by the present results in correlation analysis and pathway analysis, those of acylcarnitines were significantly positively associated with proinflammatory factors in the colon (Figure 8), as well as connected with CoA biosynthesis. These results indicated that butyrate supplementation suppressed lipid acid metabolism in the gut–liver axis, which was contributed to immunity homeostasis
The present study showed that protected butyrate reshaping of colonic microbiota and energy metabolism in the gut–liver axis was protective against colitis (Figure 9)
Summary
Inflammatory bowel disorders (IBDs), which include Crohn’s disease and ulcerative colitis, are worldwide diseases characterized by a chronic and recurrent inflammatory response and injury of the colon (Shi et al, 2016). Emerging data based on highthroughput sequencing and metabolomics methods link the pathogenesis of IBD and metabolic disorders to an aberrant gut microbiota composition (Koh et al, 2016). Some clinical applications of therapies have focused on exploring efficient therapies for IBD in a microbial manipulation-dependent method such as intervention therapy of antibiotics, probiotics, and prebiotics (Anna et al, 2011). Gut microbiome analysis has demonstrated a significant decrease in the number of butyrate-producing bacteria in the colons of patients with IBD (Frank et al, 2007). Direct application of butyrate by colonic irrigation alleviates inflammation during IBD (Hamer et al, 2008; Postler and Ghosh, 2017). Butyrate has received much attention for its effects on gut health
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