Host-Microbiota Interaction in Chronic Inflammation and CRC
Host-Microbiota Interaction in Chronic Inflammation and CRC
The role of intestinal stem cells and TLR signaling in IBD and CRC are being separately investigated. Both diseases can be described as stem cell disorders in a susceptible host in the context of host–microbiota dysbiosis. Normal gut homeostasis is dependent on both TLR and stem cell-regulatory Wnt pathways. TLR signaling has been shown to alter intestinal homeostasis and affect proliferation and apoptosis rates in the crypt. Murine Lgr5 stem cells express TLR4. It is plausible that a stem cell-specific response to microbiota composition is crucial in both diseases. Microbiota are required for normal intestinal homeostasis. It has been shown that axenic flies have a reduced level of stem cell activity. Recent evidence suggests a crosstalk between Wnt and Notch pathways with TLR signaling and microbiota. Germfree and MyD88 mice have an altered Wnt pathway at the gene expression level in the intestinal tract. TLRs also seem to regulate stem cell lineage-specific differentiation in mice. Stem cell differentiation is dysregulated in IBD, as exemplified by the loss of Paneth cells in ileal CD and goblet cells in UC and appearance of Paneth cells in UC. New therapeutic strategies could be devised to specifically target the ISC differentiation in a predefined direction. In addition, stem cells could be employed to regenerate the intestinal damage in IBD. The interaction between microbiota and intestinal stem cells is a new and promising field of science that could contribute to a better understanding of IBD and cancer, as well as novel diagnostic and therapeutic approaches.
Conclusion
The role of intestinal stem cells and TLR signaling in IBD and CRC are being separately investigated. Both diseases can be described as stem cell disorders in a susceptible host in the context of host–microbiota dysbiosis. Normal gut homeostasis is dependent on both TLR and stem cell-regulatory Wnt pathways. TLR signaling has been shown to alter intestinal homeostasis and affect proliferation and apoptosis rates in the crypt. Murine Lgr5 stem cells express TLR4. It is plausible that a stem cell-specific response to microbiota composition is crucial in both diseases. Microbiota are required for normal intestinal homeostasis. It has been shown that axenic flies have a reduced level of stem cell activity. Recent evidence suggests a crosstalk between Wnt and Notch pathways with TLR signaling and microbiota. Germfree and MyD88 mice have an altered Wnt pathway at the gene expression level in the intestinal tract. TLRs also seem to regulate stem cell lineage-specific differentiation in mice. Stem cell differentiation is dysregulated in IBD, as exemplified by the loss of Paneth cells in ileal CD and goblet cells in UC and appearance of Paneth cells in UC. New therapeutic strategies could be devised to specifically target the ISC differentiation in a predefined direction. In addition, stem cells could be employed to regenerate the intestinal damage in IBD. The interaction between microbiota and intestinal stem cells is a new and promising field of science that could contribute to a better understanding of IBD and cancer, as well as novel diagnostic and therapeutic approaches.