Gut denizens and t1d
The human gut is home to a large variety of microbes, even surpassing the number of human cells. These microbes are important for digestion, but recent studies are revealing the more complex roles that microbiota may play. More and more evidence of correlations between gut microbiota and intestinal immune functions are emerging. Changes in the gut microbiota can modulate the host’s immune system, having significant effects on autoimmune diseases. Type-1 diabetes (T1D) is no exception; recent studies in both animal and human models emphasize the role of gut microbiota and the gut immune system in T1D pathogenesis.
- Less diverse and less stable gut ecology, causing an imbalance in what metabolites are secreted and complicating molecular mechanisms1
- Higher lipopolysaccharide (LPS) levels, a toxin1
- A more porous intestinal epithelial layer1, and therefore increased gut permeability2: “leaky gut”
- IL-17 immunity, associated with beta-cell destruction2
So how does the gut relate to the development of T1D? The answer lies with the interactions between the gut microbiota and the host immune system.
- Gut microbiota can regulate Trp metabolism, and Trp metabolites can affect the gut microbiota and the immune system3
- Trp and its regulatory pathway are important in regulating inflammatory responses3
- Gluten can lead to coeliac disease, which may influence T1D1
- Gluten increases caecal and Gram-positive bacteria, both of which are present in higher levels in diabetics versus non-diabetics1
- Short breast-feeding period and early introduction of cow’s milk proteins during infancy can increase T1D risk2
- Foreign proteins may increase intestinal inflammation and increase gut permeability2
- Rotavirus infection may promote autoimmunity and accelerate diabetes development2
- Enterovirus may have a role as a gut regulator, involved with beta-cell destruction2
Call it a gut feeling. The takeaway? Increasing evidence connects the dots between the host immune system, the gut microbiome and T1D. Though much more research is needed to verify the connections, a focus on the gut immune system as a target could be crucial in finding T1D preventions and treatments.
- Han, H., Li, Y., Fang, J., Liu, G., Yin, J., Li, T., & Yin, Y. (2018). Gut Microbiota and Type 1 Diabetes. International journal of molecular sciences, 19(4), 995. https://doi.org/10.3390/ijms19040995
- Vaarala O. (2012). Is the origin of type 1 diabetes in the gut?. Immunology and cell biology, 90(3), 271–276. https://doi.org/10.1038/icb.2011.115
- Gao, J., Xu, K., Liu, H., Liu, G., Bai, M., Peng, C., Li, T., & Yin, Y. (2018). Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism. Frontiers in cellular and infection microbiology, 8, 13. https://doi.org/10.3389/fcimb.2018.00013