Figure 3.

The figure provides an outline of various proinflammatory cytokines and growth factors produced as a result of dysbiosis of the microbiome indicating the crucial role that the microbiome plays in the initiation of inflammation leading to oversecretion of proinflammatory cytokines like IL6, IL-1β, CXCL8, IL-17a, IL1Ra, MIP-1α, G-CSF, VEGF, EGF, Myd88, p-p65, TLR4, and TNF-α. It shows that decreased diversity of the microbiome favors the expression of defense and stress-related host genes, which are constantly stimulated leading to tissue injury. These include NLRC4, PGLYRP1, MMP9, and DEFA4. This also promotes the accumulation of LPS in certain organs. It has been found from various studies that beneficial commensals, if present in the correct proportion, inhibit proinflammatory cytokines and promote the secretion of anti-inflammatory cytokines, promote Treg differentiation, inhibit HDACs, and increase the epithelial ratio of P-IKβα/IKβα. Indole acrylic acid (IA) produced by commensals promotes barrier function and inhibits inflammatory response. Commensals help in immunomodulation, fine-tune the balance between pro- and anti-inflammatory molecules, and regulate the immune response by regulating the differentiation of different immune cell subsets and by regulating the activity of T_reg cells, thereby helping in the maintenance of immune homeostasis.