Common bacteria may aggravate MS

By Abram Katz
Register Science Editor
Otherwise harmless bacteria that live in almost all humans can aggravate multiple sclerosis, a disease in which the immune system mistakenly attacks its own host, University of Connecticut Health Center scientists have found.
While results are preliminary and far more research must be done, the findings suggest that someday autoimmune diseases — MS, lupus, rheumatoid arthritis, scleroderma and others — might be treatable by altering the bacterial balance in the mouth, intestines, or vaginal tract.
Robert B. Clark, associate professor of immunology at UConn and one of his graduate students, William Housely, presented their findings at a meeting of the American Association of Immunologists in San Diego.
Clark said that autoimmune diseases apparently result from several factors, including genetic predisposition, environmental influences and probably many others.
“Finding the other factors is the hard part,” Clark said.
In the past, disease-causing bacteria were suspected of contributing to autoimmune diseases, but the hypothesis has not been confirmed, he said.
Research led Clark and colleagues to suspect the seemingly harmless “commensal” bacteria that live throughout the body. These bacteria prevent pathogens from taking root and otherwise mind their own business.
Clark said he and his colleagues came to suspect these benign bacteria after substances that they make were associated with inflammation.
Dr. Frank Nichols, professor of periodontology at the UConn School of Dental Medicine, found that lipids produced by the bacterium Porphyromonas gingivalis, a cause of gum disease, were also present in inflamed atherosclerotic blood vessels. Whether they were the cause of the inflammation, or were coincidental, is not definitely known.
Nichols concluded that a link exists between the bacterial lipids and human inflammatory processes, although the bacteria were not close to the sites.
Clark and colleagues found that the lipid phosphoethanolamine dihydroceramide (pEDHC), a component of the bacterial cell membrane, stimulates receptors in dendritic cells, the vanguard of the immune system that initiates attacks against hostile organisms.
This makes sense, because the dendritic cells are intended to recognize and respond to bacteria, Housely said.
Clark said that under certain circumstances, dendritic cells may react to pEDHC and mistakenly mount an attack on surrounding tissues. Among the cells they summon are T-cells, which cause most of the damage to myelin sheaths surrounding nerves in MS.
“We know that lipids that are associated with inflammation can be found in humans. We tested the lipids in mice and they aggravated an MS-like disease in the mouse model,” Clark said.
Lab mice do not develop MS. However, the type in the experiment can develop an analogous disorder called experimental autoimmune encephalomyelitis, or EAE. Using this animal model is one of the only ways to conduct MS research.
The pEDHC activates toll-like receptors on dendritic cells, so that the immune system can trigger a response.
“Under certain circumstances, the dendritic cells misinterpret signals from the commensal bacteria,” Clark said.
It might be possible to alter the course of an autoimmune disease by eliminating the commensal lipids in the mouth and gums, gastrointestinal system, and vaginal tract, he said.
While eliminating all, or even most bacteria from a person would be extremely difficult, it might be possible to banish a specific bacterium like P. gingivalis, Clark said.
Clark said future research will concentrate on specifically how the lipid acts on the dendritic cells, and whether the lipids affect T-cells as well. Clark said he would also like to see whether the bacterial lipid causes the dendritic cells to call in other immune system cells.
“All of us have the potential for autoimmune diseases. This lipid may be a factor, and possibly an important tipping point,” Clark said.