A common bacterium found in improperly cooked chicken causes Guillain-Barre Syndrome, a Michigan State University research team has shown.
The US federally funded research not only demonstrates how this food-borne bacterium, known as Campylobacter jejuni, triggers GBS, but offers new information for a cure. If chicken isn't cooked to the proper minimum internal temperature, bacteria can still exist.
“What our work has told us is that it takes a certain genetic makeup combined with a certain Campylobacter strain to cause this disease,” said Linda Mansfield, lead author and MSU College of Veterinary Medicine professor. “The concerning thing is that many of these strains are resistant to antibiotics and our work shows that treatment with some antibiotics could actually make the disease worse.”
GBS is the world’s leading cause of acute neuromuscular paralysis in humans and despite much speculation, the exact mechanisms of how this autoimmune disease develops have been widely unknown.
“We have successfully produced three preclinical models of GBS that represent two different forms of the syndrome seen in humans,” Mansfield said. “Our models now provide a unique opportunity to understand how your personal genetic type may make you more susceptible to certain forms of GBS.”
Another area of concern more recently among scientists is related to an increase of the disease due to the Zika virus. Mansfield said there are many other bacteria and viruses associated with GBS and her models and data could be useful in studying these suspected causes, as well as finding better treatment and prevention options.
Despite the severity of GBS, treatments have been very limited and fail in many cases. In fact, the use of certain antibiotics in Mansfield’s study aggravated neurological signs, lesions and the number of immune antibodies that can mistakenly attack a patient’s own organs and tissues.
“These models hold great potential for discovery of new treatments for this paralysis,” Mansfield said. “Many patients with GBS are critically ill and they can’t participate in clinical trials. The models we identified can help solve this.”
Those suffering from GBS can initially experience vomiting and diarrhoea, but can often write the symptoms off as eating bad food. One to three weeks later, they can begin to develop weakness and tingling in the feet and legs. Gradually, paralysis can spread to the upper body and arms, and even a respirator may be needed for breathing.
Mansfield now wants to move forward quickly to test drugs against GBS in her models.
“Of course new treatments would be wonderful,” she said, “but therapeutics to prevent GBS from developing in the first place would be the best strategy so that people don’t have to suffer with paralysis.”
Campylobacter jejuni infects more than a million people yearly in the US and is also known to trigger other autoimmune disorders such as inflammatory bowel disease and Reiter’s arthritis.
Abstract
Campylobacter jejuni is a leading cause of bacterial gastroenteritis linked to several serious autoimmune sequelae such as the peripheral neuropathies Guillain Barré syndrome (GBS) and Miller Fisher syndrome (MFS). We hypothesized that GBS and MFS can result in NOD wild type (WT) mice or their congenic interleukin (IL)-10 or B7-2 knockouts secondary to C. jejuni infection. Mice were gavaged orally with C. jejuni strains HB93-13 and 260.94 from patients with GBS or CF93-6 from a patient with MFS and assessed for clinical neurological signs and phenotypes, anti-ganglioside antibodies, and cellular infiltrates and lesions in gut and peripheral nerve tissues. Significant increases in autoantibodies against single gangliosides (GM1, GQ1b, GD1a) occurred in infected NOD mice of all genotypes, although the isotypes varied (NOD WT had IgG1, IgG3; NOD B7-2−/− had IgG3; NOD IL-10−/− had IgG1, IgG3, IgG2a). Infected NOD WT and NOD IL-10−/− mice also produced anti-ganglioside antibodies of the IgG1 isotype directed against a mixture of GM1/GQ1b gangliosides. Phenotypic tests showed significant differences between treatment groups of all mouse genotypes. Peripheral nerve lesions with macrophage infiltrates were significantly increased in infected mice of NOD WT and IL-10−/− genotypes compared to sham-inoculated controls, while lesions with T cell infiltrates were significantly increased in infected mice of the NOD B7-2−/− genotype compared to sham-inoculated controls. In both infected and sham inoculated NOD IL-10−/− mice, antibiotic treatment exacerbated neurological signs, lesions and the amount and number of different isotypes of antiganglioside autoantibodies produced. Thus, inducible mouse models of post-C. jejuni GBS are feasible and can be characterized based on evaluation of three factors—onset of GBS clinical signs/phenotypes, anti-ganglioside autoantibodies and nerve lesions. Based on these factors we characterized 1) NOD B-7−/− mice as an acute inflammatory demyelinating polyneuropathy (AIDP)-like model, 2) NOD IL-10−/− mice as an acute motor axonal neuropathy (AMAN)-like model best employed over a limited time frame, and 3) NOD WT mice as an AMAN model with mild clinical signs and lesions. Taken together these data demonstrate that C. jejuni strain genotype, host genotype and antibiotic treatment affect GBS disease outcomes in mice and that many disease phenotypes are possible.
Authors
JL St Charles, JA Bell, BJ Gadsden, A Malik, H Cooke, LK Van de Grift, HY Kim, EJ Smith, LS Mansfield
[link url="http://msutoday.msu.edu/news/2016/new-evidence-shows-how-bacterium-in-undercooked-chicken-causes-gbs/"]Michigan State University material[/link]
[link url="http://www.sciencedirect.com/science/article/pii/S0896841116301421"]Journal of Autoimmunity abstract[/link]