Increased intestinal bacterial metabolism of tryptophan, especially indole and its derivatives IAA and IPA, activates the Ahr pathway. AHR acts as a sensor of the microbiota community and, through its established role of modulating immune functions, maintains host-microbe homeostasis50. IPA is also a pregnane X receptor (PXR) agonist mediating its responses through TLR451. GUT-108 therapy increased both IAA and IPA levels in stool (Fig. 4f) and colonic Ahr gene expression (Fig. 5c). AHR is a critical mediator of anti-inflammatory responses to infection by bacterial pathogens and of the differentiation and function of immune cells including T cells, innate lymphoid cells, macrophages and DC28. AHR promotes the expression of the anti-inflammatory cytokine IL-10 and inhibits macrophage apoptosis, decreases the expression of inflammatory cytokines (IL-6 and TNF-α) and inhibits activation of NF-κB. Therefore, the Ahr pathway is critical to protect from excessive inflammatory cytokine expression and septic shock. In addition, Ahr pathway activation protects the mucosa during inflammation52.
Pdf Pro 10 Activation Key 108
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