Factoring the intestinal microbiome into the pathogenesis of autoimmune hepatitis

Table 2 Microbial mechanisms for breeching intestinal barrier

Microbial Effect	Features	Mechanisms
Translocation	Migration of gut-derived products[195,224]	Gut-derived SCFA affect tight junctions[200]
	Tight junctions weakened[218]	Butyrate strengthens intestinal barrier[203]
	Increased intestinal permeability[195,218]	Induces mucin synthesis[201,203]
	Paracellular migration[37,224]	Reduces bacterial translocation[204]
	Consequences[192]	Increases peripheral Tregs[205]
	LPS and CpG delivered to liver[123,130,195]	Inhibits NF-κB and inflammation[207]
	Activated immune cells translocate[118,193]	Lactate strengthens intestinal barrier[37]
	Translocated microbial antigens activate peripheral immune cells[185]	Fermented to butyrate[215,216]
	TLRs and NLRs activated[123,130]	Low butyrate- and lactate- producing bacteria associated with weak barrier[217,218]
Increased mucosal permeability	Intestinal epithelial cells bound together by junctional complex of proteins[222,223]	TLRs affect molecular mediators[225,226]
	Occludin main component[222]	Signaling pathways disrupted[223]
	Zona occludens couples cytoskeleton[222]	Junctional binding proteins dissociated[224]
	Cingulin contacts cells[222]	Paracellular migration routes formed[37,224]
	Actin and myosin anchor cells[222]	E. coli and C. difficile key effectors[37]
	Intermediate filaments bind cells[222]
	Signaling pathways seal junction[223]
	Protein kinase C modulates occludin[222]
Active transport	Bacterial antigens actively transported across intestinal barrier[230]	M cells in Peyer’s patches capable of active transport[230]

Superscripted numbers in brackets are references. Cpg: Un-methylated cytosine-phosphorothioate-guanine oligonucleotide; LPS: Lipopolysaccharide; NF-κB: Nuclear factor kappa B; NLRs: Non-obese diabetes-like receptors; SCFA: Short chain fatty acids; TLRs: Toll-like receptors; Tregs: Regulatory T cells.