The Role of Diet and Gut Microbiota in Regulating Gastrointestinal and Inflammatory Disease

Abstract

Diet is an important lifestyle factor that is known to contribute in the development of human disease. It is well established that poor diet plays an active role in exacerbating metabolic diseases, such as obesity, diabetes and hypertension. Our understanding of how the immune system drives chronic inflammation and disease pathogenesis has evolved in recent years. However, the contribution of dietary factors to inflammatory conditions such as inflammatory bowel disease, multiple sclerosis and arthritis remain poorly defined. A western diet has been associated as pro-inflammatory, in contrast to traditional dietary patterns that are associated as being anti-inflammatory. This may be due to direct effects of nutrients on immune cell function. Diet may also affect the composition and function of gut microbiota, which consequently affects immunity. In animal models of inflammatory disease, diet may modulate inflammation in the gastrointestinal tract and in other peripheral sites. Despite limitations of animal models, there is now emerging evidence to show that anti-inflammatory effects of diet may translate to human gastrointestinal and inflammatory diseases. However, appropriately designed, larger clinical studies must be conducted to confirm the therapeutic benefit of dietary therapy.

Keywords: diet; fermented (cultured) dairy products; gastrointestinal tract; gut microbiota; inflammation; inflammatory bowel disease; mucosal immunity.

Figure 1

Pro and anti-inflammatory effects of dietary fats. Dietary fats directly and indirectly act as both pro-inflammatory and anti-inflammatory mediators. Saturated fatty acids are pro-inflammatory in nature, through increased translocation and activation of LPS leading increased TLR4 signalling. n-3 PUFAs may be immunosuppressant through its effects on immune cells and intestinal barrier integrity. n-6 PUFAs are mainly pro-inflammatory, however can also produce anti-inflammatory eicosanoids. The ratio of n-6/n-3 PUFAs are important in determining the inflammatory state in the body. Red: pro-inflammatory; Green: anti-inflammatory; Orange: pro- & anti-inflammatory. AA, arachidonic acid; PUFA, polyunsaturated fatty acid; MUFA, monounsaturated fatty acids; LA, linoleic acid; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; COX, cyclooxygenase; LOX, lipoxygenase; PG, prostaglandin; LX, lipoxin. Created with BioRender.com.

Figure 2

Bioactive compounds produced by gut microbiota. 1) Dietary fibres are fermented by gut microbiota to produce short-chain fatty acids (SCFAs), 2) B vitamins may be produced from gut microbiota metabolism. 3) Amino acids from dietary proteins may be fermented to produce branched-chain fatty acids (BCFA), ammonia, phenols, and hydrogen sulfide. 4) Dietary tryptophan is metabolised by gut microbiota to indoles. Pro-inflammatory compounds represented in red, anti-inflammatory represented in green. These compounds affect host physiology via interactions with gut microbiota, colonic epithelial cells and mucosal immune cells. ROS: reactive oxygen species, MAIT, mucosal-associated invariant T cell. Created with BioRender.com.

Figure 3

Immune modulating compounds contained within Fermented foods. Bioactive compounds from fermented foods that have anti-inflammatory effects on the activity and phenotype of innate (macrophages, neutrophils, mast cells) and adaptive (T-cells) immune cells. GABA, gamma-aminobutyric acid. Created with BioRender.com.