Table 2.
Gut metabolites and inflammatory factors in NAFLD.
| Study | Material | Result |
|---|---|---|
| D’Mello 201552 | Endotoxins | The metabolites of the gut microbiota, including endotoxins, activate the inflammatory response in the liver when they cannot be cleared by kuppfer cells |
| Ruiz 200753 | LPS, LBP | Elevated serum LBP levels and TNF-α overexpression were observed in NAFLD and NASH patients, and the serum LBP levels and TNF-α expression were higher in NASH patients than in NAFLD patients |
| Liu 201454 | Endotoxins | Activation of the endotoxins TLR4 signaling pathway significantly increases the release of a series of inflammatory cytokines, including TNF-α, IL-1β, IL-6 and IL-12, and participates in multiple steps of the development and progression of NAFLD |
| Leoni 201855 | Endotoxins | Dysregulation of proinflammatory cytokines and adipokines is almost universally present in NAFLD patients, which directly or indirectly (mainly through the TLR4 signaling pathway) lead to hepatocyte injury. In addition, oxidative stress and hepatocyte apoptosis are associated with the progression of NASH |
| Chavez-Talavera 201756 | BA | BAs regulate the metabolism and inflammation through FXR and Takeda G-protein receptor 5, which possess the function of controlling the metabolism of BAs, lipids and carbohydrates, and regulating the expression of inflammatory genes |
| Janssen 201757 | BA | FXR is able to activate small heterodimer partner to reduce the expression of sterol regulatory element-binding protein 1, which is a major regulator in new fat formation; inhibition of FXR(FXR, farnesoid X receptor) leads to the abnormal lipid metabolism and development of NAFLD |
| Zhang 201658 | BA, | Hereditary obesity, insulin resistance and NAFLD may be prevented or reversed by glycine-β-muricholic acid, an intestinal FXR antagonist, which possesses the ability to change the intestinal bacterial composition. |
| Fukunishi 201459 | LPS | Activation of TLR4 induced by LPS results in the secretion of inflammatory cytokines (e.g.,IL-6,IL-1β,and TNF-α) and chemokines from Kupffer cells, leadingtohepaticdamage and NASH. |
| Kawasaki 200860 | Peptidoglycan (PGN) | The sub-structures of PGN, such as meso-diaminopimelic acid PGN (meso-DAP PGN) and muramyl dipeptide PGN (MDP PGN), can mediate the generation of pro-inflammatory cytokines through nuclear factor-κB(NF-κB)/mitogen-activated protein kinase (MAPK) dependent activation of NOD1 (Nucleotide Binding Oligomerization Domain Containing 1) and NOD2 (Nucleotide Binding Oligomerization Domain Containing 2). |
| Gomes 201661 | Bacterial DNAs | Bacterial DNAs play a vital role in the progression of NASH by the direct activation of immune cells including macrophages, NK cells, B cells, and dendritic cells. The sensing of bacterial DNA by TLR9 in immune cells initiates the activation of NF-κB/MAPK, followed by the secretion of IL-12 and TNF-α |
| Natividad 201862 | Indole-3-acetic acid (IAA) | IAA dose dependently reduces the induction of pro-inflammatory cytokines including TNF-α, MCP-1, and IL-1β by LPS, leading to a reduction in the synthesis of FFAs and palmitate in macrophage cell line. Besides, IAA alleviates the lipogenesis mediated by cytokine and free fatty acids via its direct action on hepatocytes in an AhR-dependent manner. The evidences above suggest a protective role of IAA against NAFLD through acting on both macrophages and hepatocytes. |
| Ma 200663 | CA and BA | FXR activation by cholic acid (CA) reduces glucose levels by inhibiting expression of multiple genes related to gluconeogenesis in the liver. Aside from FXR, Takeda-G-protein-receptor-5 (TGR5) is another classic receptor for bile acids. In hepatic tissue, TGR5 is expressed in Kupffer and endothelial cells and functions to modulate liver inflammation and glucose metabolism, and to improve insulin sensitivity. TGR5 mitigates inflammatory response through the inhibition of NF-κB signaling and cytokines generation in macrophages. |
NAFLD, Nonalcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; LPS, lipopolysaccharides; LBP, Lipopolysaccharide-binding protein; SCFAs, Short-chain fatty acids; BA, bile acids; CA, Cholic acid; CRP, C-reactive protein; IL-6, interleukin 6; IL-8, interleukin 8; IL-10, interleukin 10; TC, total cholesterol; TG, Triglycerides; LDL-C, low density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; TNF-α: Tumor Necrosis Factor.