Inflammatory bowel disease and immunonutrition: novel therapeutic approaches through modulation of diet and the gut microbiome

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract, thought to at least in part reflect an aberrant immune response to gut bacteria. IBD is increasing in incidence, particularly in populations that have recently immigrated to western countries. This suggests that environmental factors are involved in its pathogenesis. We hypothesize that the increase in IBD rates might reflect the consumption of an unhealthy Western diet, containing excess calories and lacking in key nutritional factors, such as fibre and vitamin D. Several recent studies have determined that dietary factors can dramatically influence the activation of immune cells and the mediators they release through a process called immunonutrition. Moreover, dietary changes can profoundly affect the balance of beneficial versus pathogenic bacteria in the gut. This microbial imbalance can alter levels of microbiota-derived metabolites that in turn can influence innate and adaptive intestinal immune responses. If the diet-gut microbiome disease axis does indeed underpin much of the 'western' influence on the onset and progression of IBD, then tremendous opportunity exists for therapeutic changes in lifestyle, to modulate the gut microbiome and to correct immune imbalances in individuals with IBD. This review highlights four such therapeutic strategies - probiotics, prebiotics, vitamin D and caloric restriction - that have the potential to improve and add to current IBD treatment regimens.

Keywords: fasting; gut; immunonutrition; microbiome; prebiotics; probiotics; vitamin D.

Figure 1

Complex interactions that exist between diet, gut microbiota, colonocytes and immune cells during intestinal homeostasis and inflammation. (a) Intestinal homeostasis is associated with a healthier dietary pattern, microbial diversity, higher abundance of beneficial bacteria such as Bifidobacterium spp., Faecalibacterium prausnitzii and Lactobacillus spp., and increased short‐chain fatty acid production, particularly butyrate. Butyrate possesses powerful anti‐inflammatory properties as it promotes regulatory T (Treg) cell proliferation and enhances intestinal barrier function. Dendritic cells within the lamina propria sample commensal microbiota antigens within the intestinal lumen. In response to these commensal antigens, dendritic cells release transforming growth factor‐β (TGF‐β) which activates Treg cells to release interleukin‐10 (IL‐10) and TGF‐β, leading to a more tolerant immune phenotype. A thicker mucus layer is another characteristic of intestinal homeostasis, providing a protective barrier between luminal bacteria and epithelial cells. Lastly, aryl hydrocarbon receptor (AhR) ligands, derived from fruits and vegetables, induce innate lymphoid cell 3 (ILC3) to produce IL‐22, which helps maintain intestinal barrier function. (b) Conversely, intestinal inflammation is associated with a Western dietary pattern and bacterial dysbiosis (i.e. lower microbial diversity, reduced short‐chain fatty acid production, lower abundance of beneficial bacteria, and higher abundance of pathobionts such as Clostridium difficile and Escherichia coli). A thinner, more patchy mucus layer provides less of a protective barrier between the luminal bacteria and colonocytes. Along with a reduction in expression of cellular tight junctions this leads to impaired intestinal barrier function resulting in leakage of bacterial products, such as lipopolysaccharides (LPS), from the intestinal lumen into the lamina propria. LPS bind to toll‐like receptors (TLR) activating macrophages to produce tumour necrosis factor‐α (TNF‐α) which promotes T helper cell type 1 (Th1) to proliferate and release pro‐inflammatory cytokines [i.e. TNF‐α and interferon‐γ (IFN‐γ)] leading to inflammation, which also compromises intestinal barrier function. Additionally, a reduction in IL‐10‐producing Treg cells further contributes to intestinal inflammation.

Figure 2

Summary of immunonutrition strategies that modulate the gut microbiota and help alleviate and re‐balance an inflamed gut. DAI, disease activity index; DC, dendritic cells; HB, hydroxybutyrate; IFN, interferon; IL, interleukin; mTOR, mechanistic target of rapamycin; NF, nuclear factor; SCFA, short‐chain fatty acids; Th, T helper cell; TLR, toll‐like receptors; TNF, tumour necrosis factor; Treg, regulatory T cell.