Figure 3.

Interaction of Gut Microbiota-derived or influenced metabolites on ISC niche during homeostasis (left panel) and IBD (right panel); Homeostatic levels of primary and secondary bile acid pools, through membrane-bound TGR and cytosolic FXR, is critical for maintaining ISC proliferation (a). Deterioration of microbiota producing the secondary BAs during IBD, promotes uncontrolled ISC proliferation (b). SCFAs modulate ISC physiology through transcriptional and epigenetic regulation (c). IBD- associated dwindling levels of SCFAs, disturbs these regulatory pathways (d). Microbiota-derived AhR ligands checks the ISC proliferation through degradation of β-catenin, by ubiquitination and preventing the cell surface expression of Wnt ligands on ISCs (e) The loss of these regulatory pathways due to IBD-associated degradation of gut indole pool, may drive uncontrolled ISC proliferation (f). TRG (G-protein coupled bile acid receptor), BA (Bile acid), FXR (Farnesoid X Receptor), SCFA (Short-chain fatty acids), HDACs (Histone deacetylases), KYN (Kynurenine), AhR (Aryl-hydrocarbon receptor), Fzd (Frizzled)