Supplementation of Miso to a Western-Type Diet Stimulates ILC3s and Decreases Inflammation in the Small Intestine

Background/Objectives: Western-type diets (WDs) damage the intestinal barrier by disrupting the gut microbiota composition and causing inflammation, leading to the development of obesity, type 2 diabetes, and non-alcoholic fatty liver disease. Short-chain fatty acids (SCFAs) are produced by the gut microbiota and found in fermented foods and can stimulate the anti-inflammatory action of type 3 innate lymphoid cells (ILCS3s) in the intestine. This study hypothesised that supplementing miso, a Japanese fermented food, to a WD could increase the levels of SCFAs and thus stimulate ILC3s, decreasing inflammation in the intestine and protecting intestinal barrier integrity. Methods: Mice with ROR&gamma:t total (KI/KI) or partial (KI/w) knockout were fed a high-fat high-sugar diet (HFHSD) for eight weeks as a model of WD. Half of the mice received miso supplementation in addition to the HFHSD. Weight gain, glucose tolerance and insulin resistance, intestinal barrier integrity, intestinal immunity, and liver condition were assessed. Results: Miso supplementation increased SCFA levels in the small intestine, which stimulated ILC3 function in KI/w mice. Glucose tolerance was improved, intestinal barrier integrity was ameliorated, and mucus production was increased. The level of IL-22 was increased, while pro-inflammatory ILC1s, M1 macrophages, TNF-&alpha:, and IL-1&beta: were decreased. Liver condition was not affected. Conclusions: This study demonstrated that miso supplementation influenced several factors involved in inflammation and intestinal barrier integrity by stimulating ILC3s in ROR&gamma:t heterozygous mice. Moreover, it showed that the number of ILC3s is not the key factor in immune regulation, but rather the ability of ILC3 to produce IL-22 and employ it to control the immune response in the small intestine.