Bitter side of sweet: A stage-dependent immunometabolic model linking metabolic syndrome and inflammatory bowel disease

Figure 1 Proposed immunological features associated with a regulatory immune phenotype in ulcerative colitis patients with concomitant metabolic syndrome. The figure summarizes immunological observations reported in patients exhibiting metabolic characteristics consistent with an early-stage metabolic syndrome profile, including increased frequencies of regulatory T cells (Tregs) and elevated interleukin-10 production. Dendritic cells may sense microbial components through Toll-like receptor (TLR)-2 and TLR-4 signaling pathways and contribute to Treg differentiation, potentially supporting an anti-inflammatory immune environment. Increased representation of M2 macrophages and markers associated with epithelial repair have also been observed. In parallel, lower activity of T helper cell (Th) 1- and Th17-associated immune responses was identified in comparison with patients lacking these immunometabolic features. CVD: Cardiovascular disease; NAFLD: Non-alcoholic fatty liver disease; IL: Interleukin; Treg: Regulatory T cells; IDO: Indoleamine 2,3-dioxygenase; DC: Dendritic cell; TLR: Toll-like receptor; Th0: T helper type 0 cells; TNF: Tumor necrosis factor.

Figure 2 Proposed immunological features associated with advanced metabolic dysfunction in ulcerative colitis. The figure summarizes immunological observations identified in ulcerative colitis patients with metabolic characteristics consistent with advanced or late-stage of metabolic syndrome. Impaired intestinal barrier integrity may be associated with increased activation of dendritic cells and M1-polarized macrophages, accompanied by enhanced T helper cell (Th) 1- and Th17-associated immune responses. These immune populations are linked to increased production of interferon-γ, interleukin-17, and other pro-inflammatory mediators, together with greater recruitment of innate immune cells. Concurrently, reduced regulatory immune activity and predominance of pro-inflammatory signaling pathways have been observed in association with increased inflammatory burden and epithelial injury. CVD: Cardiovascular disease; NAFLD: Non-alcoholic fatty liver disease; IL: Interleukin; TLR: Toll-like receptor; Th1: T helper type 1 cells; Th0: T helper type 0 cells; Th17: T helper type 17 cells; IFN: Interferon; TNF: Tumor necrosis factor.