A password will be e-mailed to you.

Connection Between Microbiome and Autoimmune Disorders

Summary: A new mechanism in the gut microbiome has implications for autoimmune disorders, a new study reveals.

Source: University of Calgary.

Many people associate the word “bacteria” with something dirty and disgusting. Dr. Pere Santamaria disagrees. Called the microbiome, the bacteria in our bodies have all kinds of positive effects on our health, Santamaria says. “The bacteria we have in our gut actually have many beneficial functions. They help in our digestion, prevent infection by pathogens and educate our immune system on what to fight.” Now, a new function of a protein in the gut microbiome reveals potential impacts for those who suffer from inflammatory bowel disease (IBD).

Published last week in Cell, a study by Santamaria and Kathy McCoy, PhD, from the University of Calgary’s Cumming School of Medicine (CSM) reveals a new mechanism in the gut microbiome that regulates pro- and anti-inflammatory cells. “We found that a protein expressed by gut bacteria called Bacteroides works to prevent IBD by rapidly recruiting white blood cells to kill a cell of the immune system that is responsible for orchestrating IBD,” says McCoy. “We think that this mechanism is likely involved in preventing most people from developing IBD.”

However, there is a flipside to the protein’s call for help. “In some people, the white blood cells overreact to the presence of the IBD bacteria. This is what causes problems like IBD — it’s not the bacteria itself, but the immune system’s severe reaction triggered by the protein. These same overstimulated white blood cells are also the cells that cause other autoimmune disorders like diabetes,” says Santamaria. “This discovery demonstrates the effect the gut microbiome has on the immune system and unearths a novel mechanism via which changes in the gut microbiome can increase the risk of autoimmune disorders. While we looked specifically at IBD, it is likely there are many proteins in the gut that contribute to the development of other autoimmune disorders via similar mechanisms.”

Image shows a drawing of a stomach and bacteria.

Study reveals a new mechanism in the gut microbiome that regulates pro- and anti-inflammatory cells. NeuroscienceNews.com image is in the public domain. Credit: NIH.

Research into the gut microbiome requires the isolation of a single bacterium in animal models in order to rule out other environmental factors. “It was germ-free mice that first began our research collaboration,” says McCoy. Prior to joining UCalgary, McCoy was working with germ-free mice at the University of Bern, Switzerland. “Dr. Santamaria sent me his mouse strains to make them germ-free and then we were able to add back single microbial species that did or did not express the protein in the gut to investigate their effect.” Six years later, the pair are still working together and looking ahead to the future impacts of their discoveries.

While more research is necessary, Santamaria and McCoy are optimistic that new therapies will be developed that harness the power of the gut microbiome. The new Western Canadian Microbiome Center (WCMC)’s germ-free facility, opening in November 2017 at the CSM, will provide the perfect space to investigate gut bacteria. “We will be able to study specific gut microbiomes without other environmental variables to consider,” says McCoy, who is the director of the WCMC. “This will help us further this research, as well as complete many other studies into the effects of the microbiome.”

About this neuroscience research article

Pere Santamaria, MD, PhD, is a professor in the Department of Microbiology, Immunology and Infectious Diseases at the Cumming School of Medicine. He is a member of the Snyder Institute of Chronic Diseases and the Hotchkiss Brain Institute.

Kathy McCoy, PhD, is a professor in the Department of Physiology and Pharmacology at the Cumming School of Medicine. She is a member of the Snyder Institute of Chronic Diseases.

Source: Genevieve Juillet – University of Calgary
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain. Credit: NIH.
Original Research: Full open access research for “A Gut Microbial Mimic that Hijacks Diabetogenic Autoreactivity to Suppress Colitis” by Roopa Hebbandi Nanjundappa, Francesca Ronchi, Jinguo Wang, Xavier Clemente-Casares, Jun Yamanouchi, Channakeshava Sokke Umeshappa, Yang Yang, Jesús Blanco, Helena Bassolas-Molina, Azucena Salas, Hamza Khan, Robyn M. Slattery, Madeleine Wyss, Catherine Mooser, Andrew J. Macpherson, Laura K. Sycuro, Pau Serra, Derek M. McKay, Kathy D. McCoy, and Pere Santamaria in Cell. Published online October 19 2017 doi:10.1016/j.cell.2017.09.022

Cite This NeuroscienceNews.com Article
University of Calgary “Connection Between Microbiome and Autoimmune Disorders.” NeuroscienceNews. NeuroscienceNews, 23 October 2017.
<http://neurosciencenews.com/autoimmune-disorders-microbiome-7789/>.
University of Calgary (2017, October 23). Connection Between Microbiome and Autoimmune Disorders. NeuroscienceNews. Retrieved October 23, 2017 from http://neurosciencenews.com/autoimmune-disorders-microbiome-7789/
University of Calgary “Connection Between Microbiome and Autoimmune Disorders.” http://neurosciencenews.com/autoimmune-disorders-microbiome-7789/ (accessed October 23, 2017).

Abstract

A Gut Microbial Mimic that Hijacks Diabetogenic Autoreactivity to Suppress Colitis

Highlights
•The Bacteroides integrase encodes a low-avidity mimotope of IGRP206-214
•The microbial epitope recruits diabetogenic CD8+ T cells to the gut
•Crossreactive CD8+ T cells suppress colitis by targeting gut DCs
•Suppression of colitis is MHC class I-, Itgb7-, and perforin-dependent

Summary
The gut microbiota contributes to the development of normal immunity but, when dysregulated, can promote autoimmunity through various non-antigen-specific effects on pathogenic and regulatory lymphocytes. Here, we show that an integrase expressed by several species of the gut microbial genus Bacteroides encodes a low-avidity mimotope of the pancreatic β cell autoantigen islet-specific glucose-6-phosphatase-catalytic-subunit-related protein (IGRP206-214). Studies in germ-free mice monocolonized with integrase-competent, integrase-deficient, and integrase-transgenic Bacteroides demonstrate that the microbial epitope promotes the recruitment of diabetogenic CD8+ T cells to the gut. There, these effectors suppress colitis by targeting microbial antigen-loaded, antigen-presenting cells in an integrin β7-, perforin-, and major histocompatibility complex class I-dependent manner. Like their murine counterparts, human peripheral blood T cells also recognize Bacteroides integrase. These data suggest that gut microbial antigen-specific cytotoxic T cells may have therapeutic value in inflammatory bowel disease and unearth molecular mimicry as a novel mechanism by which the gut microbiota can regulate normal immune homeostasis.

“A Gut Microbial Mimic that Hijacks Diabetogenic Autoreactivity to Suppress Colitis” by Roopa Hebbandi Nanjundappa, Francesca Ronchi, Jinguo Wang, Xavier Clemente-Casares, Jun Yamanouchi, Channakeshava Sokke Umeshappa, Yang Yang, Jesús Blanco, Helena Bassolas-Molina, Azucena Salas, Hamza Khan, Robyn M. Slattery, Madeleine Wyss, Catherine Mooser, Andrew J. Macpherson, Laura K. Sycuro, Pau Serra, Derek M. McKay, Kathy D. McCoy, and Pere Santamaria in Cell. Published online October 19 2017 doi:10.1016/j.cell.2017.09.022

Feel free to share this Neuroscience News.
Join our Newsletter
Sign up to receive the latest neuroscience headlines and summaries sent to your email daily from NeuroscienceNews.com
We hate spam. Your email address will not be sold or shared with anyone else.
No more articles