Figure 1.

Intestinal dysbiosis and aggravated inflammation in NASH.

Abbreviations: IL, interleukin; LPS, lipopolysaccharides; TGF-β, transforming growth factor-beta; TNF-β, tumor necrosis factor-alpha; Tregs, regulatory T-cells.

Reduced butyrate production in dysbiosis causes decreased intestinal barrier, leading to translocation of LPS, antigens, and bacteria to the liver which activate macrophages and dendritic cells to produce pro-inflammatory cytokines IL-6, IL-17, and TNF-α. Macrophages and Dendritic cells also present antigens to and activate CD8⁺ T-cells, CD4⁺ T-cells, and B-cells. Accumulated pro-inflammatory cytokines further stimulate both innate and adaptive immune cells, forming feed-forward regulation. Butyrate activates Tregs to secrete anti-inflammatory cytokines IL-10, IL-35, and TGF-β to reduce innate and adaptive immunities.