Table 2.

Microbial metabolites and their effect on the intestinal epithelial barrier.

Metabolite	Microbial Source in the Gut	Mammalian Receptors	Effect on the Intestinal Epithelial Barrier
Short chain Fatty acids Butyrate, Acetate, Propionate, Lactate, Succinate, Valerate, etc.	Butyrate: Clostridium clusters I, III, IV, XI, XIVa, XV, and XVI [90] Acetate: Bacteroides spp. and Prevotella spp. Propionate: Bacteroides spp., Veillonella spp., Dialister spp. or Ruminococcus spp. [91]	Butyrate: GPR41, GPR109A, GPR65 (predicted) Acetate: GPR43 Propionate: GPR 41, GPR43 Lactate: GPR81 Succinate: GPR91 [92]	-Increase histone acetylation in IECs to modulate global gene expression [91] -Butyrate stimulates TGF-β secretion by IECs [92] -Butyrate inhibits proliferation of crypt stem cells via the transcription factor Foxo3 and promotes differentiation [91] -Butyrate utilization creates physiologic hypoxia and increases tight junction proteins such as Occludin and ZO-1 via hypoxia inducible factor (HIF). [92,96] -SCFAs promote antimicrobial production [93] -Lactate activates Wnt/β-catenin signalling in Paneth cells and Stromal cells to induce epithelial regeneration [94]
Bile acids Cholic acid, Lithocholic acid (LCA), Deoxycholic acid (DCA), Ursodeoxycholic acid (UDCA) etc.	Bacteroides spp., Eubacterium spp., Lactobacillus spp. and Clostridium spp. [115]	Farnesoid X receptor (FXR), GPBAR-1/TGR5, Pregnane X receptor (PXR), Vitamin D receptor (VDR), [115]	-FXR KO mice have higher intestinal permeability, high bacterial translocation and heightened bile acid reabsorption [117] -UDCA and LCA both inhibit epithelial apoptosis to limit DSS-induced barrier damage and inflammation [123] -DCA and LCA treatment in Caco-2 cells, reduce IL-1β induced IL-8 production [65] -UDCA promotes enterocyte migration [124]
Tryptophan metabolites Kynurenic acid, hydroxytryptamine, Indole derivatives	Lactobacillus spp., Clostridium spp. and Bacteroides spp.	GPR35 (predicted), Aryl hydrocarbon receptor (AHR), Pregnane X receptor (PXR) [106,111]	-Indole derivatives promote expression of anti-microbials [108] -Indoles regulate epithelial repair and differentiation [109,112] -Indoles promote IL-10 signalling to increase goblet cell differentiation and strengthen mucus barrier [113] -Indoles increase IL-10R1 expression on epithelial cells and reduces severity of DSS colitis [110] -Indoles prevent disassembly of adherens junction complexes during DSS colitis to maintain barrier integrity [114]