Figure 3.

Impact of diets on the gut microbiome underlying the pathogenesis of NCDs.

During urbanization, a variety of urbanization-associated factors induce the structural and compositional dysbiosis of the gut microbiome. The sulfur compounds and Choline/Carnitine in urban diets are metabolized into hydrogen sulfide and TMA, respectively, by the gut microbes.^28,53 The absorbed TMA is subsequently oxidized to TMAO in the liver.⁵⁴ Such reactions mediated by the gut microbiome pose risks to CRCs and CVDs.^41,54The influx of a large number of microbes and their metabolites through the dampened gut barrier due to urban lifestyles and western diet induces the proliferation of pro-inflammatory immune cells (such as Th1 and Th17 cells) and the release of pro-inflammatory cytokines (such as IL-6, IL-17, IFN-γ, and TNF).^55,56 The inflammatory state and pathogens mediate demyelination, axonal damage, and neurodegeneration, leading to multiple sclerosis.⁵⁷ The inflammation also enhances α-synuclein expression and misfolding, leading to Parkinson’s disease.⁵⁸ By contrast, high-fiber and certain regional and ethnic diets cultivate a diversified gut microbiome, which can metabolize MACs and food ingredients to an array of beneficial compounds and celobiotics, such as SCFAs and N-methylserotonin.^59,60 Such diversified gut microbiota and their metabolites strengthen the gut barrier function of the host by stimulating a thick mucus layer and activating a proper immune profile to counteract the invasion of pathogens.⁶¹ Under this circumstance, Treg cells suppress pro-inflammatory cells and prevent autoimmune diseases.⁶² A proper immune profile together with a steady secretion of gut hormones by enteroendocrine cells and a balanced enteric nervous system mediates mutualistic communication between the gut microbiome and the brain.⁵⁸ SCFAs regulate enteroendocrine L cells to release GLP-1, which reduces the level of blood glucose and increase the secretion of insulin.⁶³DC, dendritic cell; EEC, enteroendocrine cell; FFAR, free fatty acid receptor; GLP-1, Glucagon-like peptide-1; IFN-γ: interferon-γ; IL, interleukin; MACs, microbiota-accessible carbohydrates; NCDs, non-communicable diseases; SCFAs, short-chain fatty acids; Th, T helper cell; TMA, trimethylamine; TMAO, trimethylamine N-oxide; Treg, regulatory T cell; TNF, tumor necrosis factor; 5-HT, 5-hydroxytryptamine.