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Age and Gut Bacteria Contribute to Multiple Sclerosis Progression

Summary: Genetic risk factors, age and gut bacteria appear to work in collaboration to trigger multiple sclerosis, a new study reports.

Source: Rutgers.

Researchers at Rutgers Robert Wood Johnson Medical School published a study suggesting that gut bacteria at young age can contribute to Multiple sclerosis (MS) disease onset and progression.

In this study, published in the October 31 issue of the Proceedings of the National Academy of Sciences, Sudhir Yadav PhD, a neuroimmunology post-doctoral fellow in the laboratories of Drs. Kouichi Ito, associate professor of neurology, and Suhayl Dhib-Jalbut, professor and chair of neurology, tested mice that were engineered to have a pre-disposition for MS. Because mice would not normally develop MS, researchers used MS-associated risk genes from real patients to genetically engineer mice for this study. Dr. Ito created this unique model of genetically engineered mice to specifically study the cause of MS.

Image shows a diagram of how ms affects the body.

The study showed a link between gut bacteria and MS-like disease incidence, which was more prominent at a younger age, when MS is also more prevalent. NeuroscienceNews.com image is in the public domain.

At first, when the genetically modified mice were put in a sterile, germ-free environment, they did not develop MS. When exposed to a normal environment that would normally contain bacteria, the mice did develop MS-like disease and inflammation in their bowels, suggesting gut bacteria is a risk factor that triggers MS disease development.

The study showed a link between gut bacteria and MS-like disease incidence, which was more prominent at a younger age, when MS is also more prevalent. The younger mice were more prone to develop MS than the older mice. Together, age, gut bacteria, and MS-risk genes collaboratively seem to trigger disease. This study is also the first to identify mechanisms by which gut bacteria triggers changes in the immune system that underlie MS progression.

“The findings could have therapeutic implications on slowing down MS progression by manipulating gut bacteria,” says Suhayl Dhib-Jalbut, Director of Rutgers-Robert Wood Johnson Center for Multiple Sclerosis. Future research could lead to the elimination of harmful types of gut bacteria that wereshown to cause MS progression, or conversely enhance beneficial bacteria that protects from disease progression. The investigators recently received NIH funding to examine their findings in MS patients.

About this neuroscience research article

Source: Jillian Prior – Rutgers
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “Gut dysbiosis breaks immunological tolerance toward the central nervous system during young adulthood” by Sudhir K. Yadav, Sridhar Boppana, Naoko Ito, John E. Mindur, Martin T. Mathay, Ankoor Patel, Suhayl Dhib-Jalbut, and Kouichi Ito in PNAS. Published online OCtober 16 2017 doi:10.1073/pnas.1615715114

Cite This NeuroscienceNews.com Article
Rutgers “Age and Gut Bacteria Contribute to Multiple Sclerosis Progression.” NeuroscienceNews. NeuroscienceNews, 18 November 2017.
<http://neurosciencenews.com/age-microbiome-multiple-sclerosis-7981/>.
Rutgers (2017, November 18). Age and Gut Bacteria Contribute to Multiple Sclerosis Progression. NeuroscienceNews. Retrieved November 18, 2017 from http://neurosciencenews.com/age-microbiome-multiple-sclerosis-7981/
Rutgers “Age and Gut Bacteria Contribute to Multiple Sclerosis Progression.” http://neurosciencenews.com/age-microbiome-multiple-sclerosis-7981/ (accessed November 18, 2017).

Abstract

Gut dysbiosis breaks immunological tolerance toward the central nervous system during young adulthood

Multiple sclerosis (MS) is an autoimmune disease targeting the central nervous system (CNS) mainly in young adults, and a breakage of immune tolerance to CNS self-antigens has been suggested to initiate CNS autoimmunity. Age and microbial infection are well-known factors involved in the development of autoimmune diseases, including MS. Recent studies have suggested that alterations in the gut microbiota, referred to as dysbiosis, are associated with MS. However, it is still largely unknown how gut dysbiosis affects the onset and progression of CNS autoimmunity. In this study, we investigated the effects of age and gut dysbiosis on the development of CNS autoimmunity in humanized transgenic mice expressing the MS-associated MHC class II (MHC-II) gene, HLA-DR2a, and T-cell receptor (TCR) genes specific for MBP87-99/DR2a that were derived from an MS patient. We show here that the induction of gut dysbiosis triggers the development of spontaneous experimental autoimmune encephalomyelitis (EAE) during adolescence and early young adulthood, while an increase in immunological tolerance with aging suppresses disease onset after late young adulthood in mice. Furthermore, gut dysbiosis induces the expression of complement C3 and production of the anaphylatoxin C3a, and down-regulates the expression of the Foxp3 gene and anergy-related E3 ubiquitin ligase genes. Consequently, gut dysbiosis was able to trigger the development of encephalitogenic T cells and promote the induction of EAE during the age window of young adulthood.

“Gut dysbiosis breaks immunological tolerance toward the central nervous system during young adulthood” by Sudhir K. Yadav, Sridhar Boppana, Naoko Ito, John E. Mindur, Martin T. Mathay, Ankoor Patel, Suhayl Dhib-Jalbut, and Kouichi Ito in PNAS. Published online OCtober 16 2017 doi:10.1073/pnas.1615715114

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