Restoring intestinal barrier function in obesity and diabetes.
Final Report Abstract
The ongoing COVID-19 pandemic and associated working-restrictions and lockdowns led to major adjustments of the initial work program. At times where no lab work was possible, I strengthened my bioinformatics skills and got familiar with the UK biobank leading to several interesting projects and publications. Furthermore, this extra time allowed me to delve deeply into the fascinating research on neuro-immune interactions and the enteric nervous system. Together with Christoph Thaiss and my students, we outlined our vision for this emerging scientific field in a recent review article. Once we could resume lab work, I have decided to fully dedicate my time to a project dealing with neuron-immune interactions in the enteric nervous system. It was previously known that mental health profoundly impacts inflammatory responses in the body. This is particularly apparent in inflammatory bowel disease (IBD), where psychological stress is associated with disease flares. I discovered a critical role for the enteric nervous system (ENS) in mediating the aggravating effect of chronic stress on intestinal inflammation. I found that chronically elevated levels of glucocorticoids drive the generation of an inflammatory subset of enteric glia that promotes monocyte- and TNF-mediated colitis via CSF1. Additionally, glucocorticoids cause transcriptional immaturity in enteric neurons, acetylcholine deficiency, and dysmotility via TGFβ2. We verified the connection between the psychological state, intestinal inflammation, and dysmotility in two cohorts of human IBD patients. Together, these findings offer a mechanistic explanation for the impact of the brain on peripheral inflammation, define the ENS as a relay between psychological stress and gut inflammation, and suggest that stress management could serve as a valuable component of IBD care.
Publications
- Physical activity is associated with reduced risk of liver disease in the prospective UK Biobank cohort. JHEP Reports (2021)
C. V. Schneider, I. Zandvakili, C. A. Thaiss, K. M. Schneider
(See online at https://doi.org/10.1016/j.jhepr.2021.100263) - (2022). Environmental perception and control of gastrointestinal immunity by the enteric nervous system. Trends Mol. Med. 28, 989– 1005
Schneider, K.M., Kim, J., Bahnsen, K., Heuckeroth, R.O., and Thaiss, C.A.
(See online at https://doi.org/10.1016/j.molmed.2022.09.005) - β-Hydroxybutyrate suppresses colorectal cancer. Nature. 605, 160–165 (2022)
O. Dmitrieva-Posocco, A. C. Wong, P. Lundgren, A. M. Golos, H. C. Descamps, L. Dohnalová, Z. Cramer, Y. Tian, B. Yueh, O. Eskiocak, G. Egervari, Y. Lan, J. Liu, J. Fan, J. Kim, B. Madhu, K. M. Schneider, S. Khoziainova, N. Andreeva, Q. Wang, N. Li, E. E. Furth, W. Bailis, J. R. Kelsen, K. E. Hamilton, K. H. Kaestner, S. L. Berger, J. A. Epstein, R. Jain, M. Li, S. Beyaz, C. J. Lengner, B. W. Katona, S. I. Grivennikov, C. A. Thaiss, M. Levy
(See online at https://doi.org/10.1038/s41586-022-04649-6)
