According to the Department of Health and Human Services (US), Rheumatoid arthritis (RA) affects nearly 2 million (~1% of the population). Autoimmunity (when antibodies are generated against self antigens of the body) is the reason behind RA. RA causes inflammatory responses with acute pain of the joints, degradation of cartilage and even destruction of the bone and hence is associated with considerable disability and problems in life quality. Available therapeutics like monoclonal antibodies provide only but non-persistent relief from the disease symptoms. There is therefore, a definite need for safer and long term benefit producing therapies that can provide relief from the arthritic pain. The disease gains severity with an imbalance between the levels of pro-inflammatory and anti-inflammatory cytokines. There were previous data to suggest that the microbes in the GI tract, systemic and mucosal immune responses and the arthritic development share a relationship. The use of probiotics in the treatment and relief of arthritic and unnatural inflammatory responses has a bright future.
Probiotics in the relief of arthritis:
There are existing evidences of the beneficial effects of probiotics in the relief of acute symptoms in RA. The probiotic products can cause its effects-directly or indirectly. The direct effects are exerted within the gastro-intestinal tract locally that involves the alteration of the inhabitant microbiota and the synthesis of compounds like vitamins. The indirect effects on the other hand are caused outside their domain of colonization, viz., lungs, skin, joints which may be brought about by a change in the immunological responses. The group of Marteau proposed that arthritis mediated inflammation may be alleviated with the use of probiotics. Researchers have observed that in juvenile arthritis, the defense mechanism of the gut is severely compromised. In a study by Malin et al. thirty juvenile arthritis patients were administered with Lactobacillus GG for a period of two weeks and the gut defences were observed. The oral dosage of Lactobacillus GG could reinstate barrier processes of the mucosa in the disorder. The gastro-intestinal tract induced inflammation becomes a linkage between inflammatory disorders of the GI tract and arthritis. According to Vanderhoof, decrease in immune response and permeability of the GI tract is caused due to the consumption of probiotics. David R. Mandel, MD Rheumatology & Osteoporosis, Mayfield Village, Ohio suggests adjunctive treatment of the probiotic B. coagulans as safe and effective to be administered to patients with RA. According to the work of Kano et al. L. delbrueckii strain fermented milk intake could sufficiently reduce collagen associated arthritis. The same study demonstrated that RA patients on a diet of uncooked vegetables supplemented with lactobacilli showed signs of decreased arthritic symptoms. While other groups have found suppression in collagen-mediated arthritis with the intake of L. casei concomitantly elucidating a reduction in paw swelling, infiltration of the lymphocyte and cartilage destruction. In a completed clinical trial conducted by the Lawson Health Research Institute in collaboration with St. Joseph’s Health Care London, it was hypothesized that administration of selective strains of probiotics like L. rhamnosus and L. reuteri can improve the state of inactivity in RA patients by relieving them of their acute painful symptoms.
Probiotic mediated immuno-modulation in RA:
The major route of activity of the probiotic bacteria in relieving the situation of acute inflammatory disorders and arthritis is through the alteration of the immune system. Studies have shown that the specific dosage of probiotics bacteria like Lactobacillus GG could induce the proliferation of lymphocytes (both B and T cells) with a resultant decrease to mitogen sensitivity. The probiotics also cause a balance between the inflammatory (pro- and anti-) cytokines. Lactobacillus GG administration could increase the production of the anti-inflammatory interleukin 10 (IL-10) while lactobacilli intake enhanced the Th1 production as also reduced IgE antibody generation. Various preparations (live or heat inactivated) of the bacteria produced similar effect irrespective of the time of treatment. The reason behind such similarity is elusive though. Data indicate that feeding patients with fermented products supplemented with lactobacilli could produce greater beneficial effects than the oral intake of the bacteria alone. This further confirms the earlier reports of probiotic effect well past its colonization and adhesion in the GI tract. L. casei oral administration results in reduced production of interferon-γ and an enhanced level of IL-2. Although, earlier results demonstrated that live L. casei administered infants showed greater IgA serum titers than the one who had taken the heat killed forms of the bacteria. But the results with Lactobacillus GG suggest the form of the microorganism is not important and that any component of the cells might as well be involved in the beneficial effects. Indeed some researchers have shown that the heat inactivated Lactobacillus GG cytoplasmic extracts could inhibit the mononuclear cells in humans. Thus, the probiotic cells have in possession some anti-proliferative factors which are heat stable in nature. There are also possibilities of potential immuno-alteration by secreted bacterial components. This theory is supported by the observation that Lactobacilli degraded casein inhibits the activation of T-cells and downregulates the IL-2 transcript levels and PKC compartmentalization. Lactobacillus strains reduce the levels of pro-inflammatory cytokines. Some of the common members affected being IFN-γ, TNFα and IL-12. But they do not alter the levels of the cytokines like TGF-β or IL-10 which results in anti-inflammatory responses in RA. In a recent report, it was shown that in patients receiving probiotics, IgA and IgM immunoglobulin levels increased significantly as compared to the control group who did not receive it. In a study conducted by the group of Seon So, L. casei inhibits collagen induced arthritis by reducing Th1 effector actions. The intake of the bacteria resulted in the reduction of proinflammatory cytokines (IL-2, IL-12, TNF-α, IFN-γ, IL-6, etc) through CD4+ T-cells with a decrease in levels of immunoregulatory IL-10. All these cytokines are Collagen type-II reactive molecules. The administration also prevented the NF-κB translocation into the nucleus.
Therefore, the potential of the probiotic strains to modulate the immune system has provided sufficient basis to use them as effective modes of therapeutic interventions in combating abnormal inflammations such as those observed in arthritis.
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