Helicobacter pylori infection reduces disease severity in an experimental model of multiple sclerosis

Abstract

Recent research has demonstrated that infection with the bacterial pathogen Helicobacter pylori is less common amongst patients with multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS). We aimed to compare the prevalence of H. pylori amongst MS patients and healthy controls, and also investigated the impact of this infection on an animal model for MS, experimental autoimmune encephalomyelitis (EAE). The H. pylori status of 71 MS patients and 42 healthy controls was determined by serology. Groups of C57BL/6 mice were infected with H. pylori, or given diluent alone as a placebo, prior to inducing EAE. Clinical scores were assessed for all mice, and spleens and spinal cord tissue were harvested. CD4+ T cell subsets were quantified by flow cytometry, and T cell proliferation assays were performed. In MS patients the seroprevalence of H. pylori was half that of healthy controls (p = 0.018). Over three independent experiments, prior H. pylori infection had a moderate effect in reducing the severity of EAE (p = 0.012). In line with this, the antigen-specific T cell proliferative responses of infected animals were significantly reduced (p = 0.001), and there was a fourfold reduction in the number of CD4+ cells in the CNS. CD4+ populations in both the CNS and the spleens of infected mice also contained greatly reduced proportions of IFNγ+, IL-17+, T-bet+, and RORγt+ cells, but the proportions of Foxp3+ cells were equivalent. There were no differences in the frequency of splenic CD4+cells expressing markers of apoptosis between infected and uninfected animals. H. pylori was less prevalent amongst MS patients. In mice, the infection exerted some protection against EAE, inhibiting both Th1 and Th17 responses. This could not be explained by the presence of increased numbers of Foxp3+ regulatory T cells, or T cell apoptosis. This is the first direct experimental evidence showing that H. pylori may provide protection against inflammatory demyelination in the CNS.

The Correlation Between Multiple Sclerosis and Helicobacter pylori Infection

“…This is a pilot study and it should be continued for better results. Some studies support our data [5][6][7][8][9][10] and they mentioned that H. pylori infection could have a protective effect in MS. This can be a part of the 'hygiene hypothesis. '…”

Meta-analysis of association between Helicobacter pylori infection and multiple sclerosis

“…Furthermore, some reports have discerned a relationship between H. pylori infection and extra-gastrointestinal diseases such as cirrhosis, pancreatic cancer, coronary heart disease, stroke, migraine, mild cognitive impairment, Alzheimer's There has recently been increased research interest in the association between H. pylori infection and MS. Several studies evaluating the possible association between H. pylori infection and MS have been published , although without consensus of the outcome. Some studies have reported a significant negative correlation and suggested that H. pylori infection might exert a protective effect to reduce the risk of MS [15][16][17][18][19][20][21][22][23][24][25][26]. However, others have failed to determine any association between H. pylori infection and MS [27][28][29][30][31][32][33][34][35], and some studies reported a high prevalence of H. pylori infection in MS patients [36,37].…”

<b><i>Helicobacter pylori</i></b>: Does Gastritis Prevent Colitis?

“…Interestingly, responses to unrelated (bystander) T-cell antigens are suppressed as well, including allergen-specific and maybe autoantigen-specific immune responses [29,30,32]. This finding explains why H. pylori -infected individuals are less likely to develop allergic disease manifestations [21,22,23,24], celiac disease [83] and possibly autoimmune diseases [84] (as well as of course IBD).…”

“…The same is true for certain allergic diseases with respiratory tract and skin manifestations, and is currently debated for autoimmune diseases [84,88]. These results have two main implications: they will on the one hand influence decisions of when and whether to treat H. pylori infections, and will on the other hand potentially open up new avenues of treatment for these immune-related disorders.…”