Table 1.

Summary of key pathways involving the gut-liver axis important for NASH

Receptor	Type of deficiency	Mechanism	Model used	Effect	Ref
Pattern recognition receptors
TLR4	Global deficiency	TLR4/MD2 mediated signals contribute to liver pathology via NADPH-dependent lipid-peroxidation and oxidative stress	MCD diet	Detrimental	[26]
TLR5	TLR5 deficiency in hepatocytes	Loss of hepatocyte TLR5 potentiates high-fat diet induced pro-inflammatory gene expression via Nod-like receptor C4 inflammasome	MCD diet; HFD	Protective	[28]
TLR9	TLR9 deficiency in lysosome producing cells (neutrophils and KCs)	Pro-inflammatory response via TLR9 activation	HFD	Detrimental	[27]
Bile acid receptors
FXR	Intestine specific deficiency	Reduced triglyceride accumulation due to low ceramide synthesis genes[29]; Gut-restricted FXR activation reduces diet-induced weight gain, inflammation, hepatic glucose production and enhances thermogenesis and browning of white adipose tissue [30]	HFD	Controversial	[29, 30]
TGR5	Global deficiency	Antilipogenic effects of intestinal FXR agonist are TGR5 dependent	HFD	Part of the protective effect of the intestinal specific FXR agonist is reduced in TGR5 deficient mice	[30]

HFD, high-fat diet; TLR, Toll-like Receptor; MCD, methionine and choline deficient diet; NASH, nonalcoholic steatohepatitis; FXR, farnesoid X receptor: TGR, Takeda-G-protein coupled receptor 5; KC, Kupffer cell;