Prebiotic inulin and sodium butyrate attenuate barrier dysfunction by induction of antimicrobial peptides in diet-induced obese mice

Obesity and related metabolic comorbidities represent the most relevant diet-induced diseases. An impaired intestinal barrier function has been associated with obesity and may therefore play a critical role in the development of the disease. In previous work we have shown that the intestinal barrier function is impaired in mice receiving a high-fat and high-sugar diet, so called Western-style diet (WSD). High sugar and high fat consumption causes an increase in intestinal permeability, bacterial endotoxin translocation and subsequent liver steatosis. Besides this, WSD-fed mice are characterized by decreased α-defensin expression in the small intestine suggesting that diet-induced barrier dysfunction involves impaired antimicrobial peptide function.

To examine whether the fibre inulin or the short chain fatty acid sodium butyrate could have a protective effect in diet-induced obesity and whether gut barrier dysfunction could be attenuated by supplementation with inulin or sodium butyrate, healthy C57BL/6 mice were fed a WSD or a control diet (CD) ± fructose supplemented with either 10 % inulin or 5 % sodium butyrate for 12 weeks respectively. Body weight changes, markers of liver steatosis and barrier function were assessed.

Inulin and sodium butyrate attenuated hepatosteatitis in the WSD-induced obesity mouse model by reducing weight gain, liver weight and hepatic triglyceride level but also by improving gut barrier function. Supplementation of WSD with inulin or sodium butyrate led to a significant induction of intestinal Paneth cell α-cryptdin-1 mRNA expression and cryptdin-related sequence peptide CRS1C mRNA expression. Both inulin and butyrate also induced mRNA expression of lysozyme, another Paneth cell antimicrobial, though effects were only significant for inulin. Furthermore, the ileal mRNA expression of matrix metalloproteinase-7 (MMP-7) which activates Paneth cells pro-α-defensin precursors in mouse Paneth cells and was impaired by high-fat and high-sugar diet, was increased by the administration of inulin and sodium butyrate.

In summary our data show that inulin and sodium butyrate attenuate diet-induced barrier dysfunction and induce expression of Paneth cell antimicrobial peptides. The administration of prebiotics could be an interesting therapeutic approach to improve diet-induced obesity by modulation of the intestinal barrier function.

Publication History

Article published online:
16 June 2020