Immunomodulatory effects of inulin and its intestinal metabolites

Abstract

"Dietary fiber" (DF) refers to a type of carbohydrate that cannot be digested fully. DF is not an essential nutrient, but it plays an important part in enhancing digestive capacity and maintaining intestinal health. Therefore, DF supplementation in the daily diet is highly recommended. Inulin is a soluble DF, and commonly added to foods. Recently, several studies have found that dietary supplementation of inulin can improve metabolic function and regulate intestinal immunity. Inulin is fermented in the colon by the gut microbiota and a series of metabolites is generated. Among these metabolites, short-chain fatty acids provide energy to intestinal epithelial cells and participate in regulating the differentiation of immune cells. Inulin and its intestinal metabolites contribute to host immunity. This review summarizes the effect of inulin and its metabolites on intestinal immunity, and the underlying mechanisms of inulin in preventing diseases such as type 2 diabetes mellitus, inflammatory bowel disease, chronic kidney disease, and certain cancer types.

Keywords: intestinal epithelial cells; intestinal immune cells; intestinal immunity; intestinal microbiota; inulin; short-chain fatty acids.

Figure 1

Effects of inulin on the mucosal immune system. The gut contains many immune cells. Inulin can regulate the differentiation and proliferation of these immune cells (e.g., T_reg) to limit intestinal inflammation. Inulin promotes expression of TJ proteins and induces secretion of sIgA and Muc2 by plasma cells and goblet cells, which helps to maintain intestinal-barrier homeostasis. Inulin promotes IL-22 secretion by γδ T cells and ILC3s, which also helps to improve the intestinal barrier. However, inulin increases the circulating level of bile acids and triggers ILC2s to induce eosinophils, thereby exacerbating airway allergic responses. Inulin provides carbon sources for histone acetylation, regulates epigenetics, and inhibits tumor growth. In tumors, inulin can also promote the infiltration of CD8⁺ T cells and γδ T cells to enhance the anti-tumor effect. SCFAs, short-chain fatty acids; sIgA, secretory immunoglobulin A; FFARs, free fatty acid receptors; Muc2, mucin 2; TJ, tight junction; GLP-1, glucagon-like peptide 1; PYY, peptide YY, FXR, farnesoid X receptor; HDAC, histone deacetylase; ILC, innate lymphoid cell.

Figure 2

Overview of the involvement of inulin in disease. Inulin and its metabolites regulate energy metabolism and immune function, thus ameliorating various disease. However, inulin can also cause some side effects, such as nausea, bloating, flatulence, itching, and heartburn. In addition, people with inflammatory bowel disease or allergies should be more cautious about inulin intake to avoid serious adverse events.