The promoting effect of high-fat diet-induced trained immunity on ulcerative colitis and the mechanism of the therapeutic effect of Dahuang Mudan Decoction

Abstract

Background

Ulcerative colitis (UC) is a chronic inflammatory disease driven by intestinal immune imbalance. In addition, its pathogenesis includes environment, genetics, microbiota, genes, and diet. Epidemiological and related studies have shown that a high-fat diet habit can promote the progression of UC. The trained immunity induced by a high-fat diet is a key factor in the occurrence and development of chronic inflammatory diseases. As a chronic inflammatory disease, the research on how the trained immunity induced by a high-fat diet promotes the progression of UC is still unclear. Previous studies have shown that Dahuang Mudan Decoction can effectively alleviate the progression of UC, but whether its mechanism of action can also inhibit trained immunity is not clear.

Methods

To explore the promoting effect of trained immunity induced by a high-fat diet on UC, in this study, mice were fed a high-fat diet for 4 weeks and then modeled with 2 % DSS. Subsequently, by transplanting the bone marrow of a high-fat diet, it was repeatedly verified that a high-fat diet can promote the progression of UC through trained immunity. Then, to explore the therapeutic effect of Dahuang Mudan Decoction (DMD) and its mechanism, the above-mentioned model was intervened with DMD (125, 250, 500mg/kg). By transplanting the bone marrow of a high-fat diet and intervening with DMD, it was repeatedly verified that DMD can alleviate UC promoted by a high-fat diet by inhibiting trained immunity.

Results

The results of this study showed that the intervention of a high-fat diet promoted the progression of UC, aggravated the disease-related indicators of UC, promoted the damage of the colonic mucosal structure, reduced the expression of colonic mucin tight junction proteins, increased the number of bone marrow hematopoietic stem and progenitor cells (HSPCs), granulocyte-monocyte progenitor cells (GMPs), splenic monocytes, and colonic macrophages; promoted the expression of colonic inflammatory factors (IL-6, TNF-α). After transplanting the bone marrow intervention with a high-fat diet can promote the progression of UC, which is consistent with the trend of the above indicators. After the intervention of DMD, the above indicators were alleviated, and the subsequent transplantation of the bone marrow from a high-fat diet intervened with DMD can effectively alleviate the UC-related symptoms.

Conclusion

A high-fat diet promotes the progression of UC disease by promoting trained immunity and increasing the proportion of bone marrow HSPCs and GMPs, thereby increasing the proportion of splenic monocytes, the number of colonic tissue macrophages, and the level of inflammatory factors. DMD can alleviate the inflammatory response of UC mice intervened with a high-fat diet by inhibiting bone marrow trained immunity.