Tweet
What does it all mean? We don't know yet, and the tests were done on a mouse model, but this research is intriguing. -D
Here is the Harvard abstract. Warning: It is pretty sciency. -D
Microglial control of astrocytes in response to microbial metabolites
Veit Rothhammer, Davis M. Borucki, Emily C. Tjon, Maisa C. Takenaka, Chun-Cheih Chao, Alberto Ardura-Fabregat, Kalil Alves de Lima, Cristina Gutiérrez-Vázquez, Patrick Hewson, Ori Staszewski, Manon Blain, Luke Healy, Tradite Neziraj, Matilde Borio, Michael Wheeler, Loic Lionel Dragin, David A. Laplaud, Jack Antel, Jorge Ivan Alvarez, Marco Prinz & Francisco J. Quintana
Nature (2018)
doi:10.1038/s41586-018-0119-x
Published: 16 May 2018
Abstract
Microglia and astrocytes modulate inflammation and neurodegeneration in the central nervous system (CNS)1,2,3. Microglia modulate pro-inflammatory and neurotoxic activities in astrocytes, but the mechanisms involved are not completely understood4,5. Here we report that TGFα and VEGF-B produced by microglia regulate the pathogenic activities of astrocytes in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Microglia-derived TGFα acts via the ErbB1 receptor in astrocytes to limit their pathogenic activities and EAE development. Conversely, microglial VEGF-B triggers FLT-1 signalling in astrocytes and worsens EAE. VEGF-B and TGFα also participate in the microglial control of human astrocytes. Furthermore, expression of TGFα and VEGF-B in CD14+ cells correlates with the multiple sclerosis lesion stage. Finally, metabolites of dietary tryptophan produced by the commensal flora control microglial activation and TGFα and VEGF-B production, modulating the transcriptional program of astrocytes and CNS inflammation through a mechanism mediated by the aryl hydrocarbon receptor. In summary, we identified positive and negative regulators that mediate the microglial control of astrocytes. Moreover, these findings define a pathway through which microbial metabolites limit pathogenic activities of microglia and astrocytes, and suppress CNS inflammation. This pathway may guide new therapies for multiple sclerosis and other neurological disorders.
Researchers Uncover Gut Bacteria's Potential Role In Multiple Sclerosis
Victoria Forster , CONTRIBUTOR
A new study by researchers at Harvard University Medical School, published today in Nature, has uncovered new pathways mediating inflammation in Multiple Sclerosis (MS), involving molecules produced by gut bacteria breaking down food, which could lead to new treatment options for patients....
"We essentially discovered a remote control by which the gut flora can control what is going on at a distant site in the body, in this case the central nervous system," said Dr Francisco Quintana, lead author of the paper from Brigham and Women’s Hospital.
Full article, in FORBES: https://www.forbes.com/sites/victori.../#91d34074232e
Victoria Forster , CONTRIBUTOR
A new study by researchers at Harvard University Medical School, published today in Nature, has uncovered new pathways mediating inflammation in Multiple Sclerosis (MS), involving molecules produced by gut bacteria breaking down food, which could lead to new treatment options for patients....
"We essentially discovered a remote control by which the gut flora can control what is going on at a distant site in the body, in this case the central nervous system," said Dr Francisco Quintana, lead author of the paper from Brigham and Women’s Hospital.
Full article, in FORBES: https://www.forbes.com/sites/victori.../#91d34074232e
Microglial control of astrocytes in response to microbial metabolites
Veit Rothhammer, Davis M. Borucki, Emily C. Tjon, Maisa C. Takenaka, Chun-Cheih Chao, Alberto Ardura-Fabregat, Kalil Alves de Lima, Cristina Gutiérrez-Vázquez, Patrick Hewson, Ori Staszewski, Manon Blain, Luke Healy, Tradite Neziraj, Matilde Borio, Michael Wheeler, Loic Lionel Dragin, David A. Laplaud, Jack Antel, Jorge Ivan Alvarez, Marco Prinz & Francisco J. Quintana
Nature (2018)
doi:10.1038/s41586-018-0119-x
Published: 16 May 2018
Abstract
Microglia and astrocytes modulate inflammation and neurodegeneration in the central nervous system (CNS)1,2,3. Microglia modulate pro-inflammatory and neurotoxic activities in astrocytes, but the mechanisms involved are not completely understood4,5. Here we report that TGFα and VEGF-B produced by microglia regulate the pathogenic activities of astrocytes in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Microglia-derived TGFα acts via the ErbB1 receptor in astrocytes to limit their pathogenic activities and EAE development. Conversely, microglial VEGF-B triggers FLT-1 signalling in astrocytes and worsens EAE. VEGF-B and TGFα also participate in the microglial control of human astrocytes. Furthermore, expression of TGFα and VEGF-B in CD14+ cells correlates with the multiple sclerosis lesion stage. Finally, metabolites of dietary tryptophan produced by the commensal flora control microglial activation and TGFα and VEGF-B production, modulating the transcriptional program of astrocytes and CNS inflammation through a mechanism mediated by the aryl hydrocarbon receptor. In summary, we identified positive and negative regulators that mediate the microglial control of astrocytes. Moreover, these findings define a pathway through which microbial metabolites limit pathogenic activities of microglia and astrocytes, and suppress CNS inflammation. This pathway may guide new therapies for multiple sclerosis and other neurological disorders.
Comment