A Bacteria Triggers Arthritis.

The gut microbiomes of humans and mice are broadly similar which is helpful as this paper has used the mouse model to explain how a resident bacteria in the gut can induce arthritis. In both hosts human and mouse upwards of ∼1000 different microbial species from ∼10 different divisions colonise the gastrointestinal tract, but just two bacterial divisions—the Bacteroidetes and Firmicutes—and one member of the Archaea appear to dominate, together accounting for ∼98% of the 16S rRNA sequences obtained from this site.[1] 16SrRNA is a laboratory method for analysing bacterial and provides species-specific signature sequences useful for bacterial identification but is not routinely used in diagnostic settings yet.

Their analysis revealed that despite the enormous species variation in the gut a single species of bacteria that lives here is able to trigger a cascade of immune responses that can ultimately result in the development of arthritis.[2] Gut-residing bacteria can also play a role in disorders of the immune system, especially autoimmune disorders in which the body attacks its own cells. The gut microbiota is now known to shape intestinal immune responses during health and disease with systemic effects.

It must be explained at this point that the bacteria is not acting as an infectious agent – no mouse is developing arthritis because they have ‘caught’ a bug in this case. Rather this is where their genetic susceptibility has been adversely expressed by virtue of a change in the microbial composition in the gut. It is a disease outcome derived from an internal interplay between the genetics of the host and the bacterial environment it supports.

The reason the bacteria can induce arthritis in a genetically sensitive host is complex, but essentially the segmented filamentous bacteria (SFB) cause the animals to produce more of a particular subset of T cells called Th17 cells. The immune system reacts to the activity of the T cells as if to a foreign threat and produces auto antibodies that trigger the devastating disease. Th17 cells are one of a newly recognised T cell family that are providing distinct links between the gut and the CNS as well as other organs and tissues. They are natural self defence cells acting against bacteria, viruses and candida species through the production of a cytokine called IL17.

segmented filamentous bacteria

The bacteria involved are known as segmented filamentous bacteria, these are gram positive (refers to bacteria that have a single cell wall that does not contain lipopolysaccharide; these bacteria retain a violet stain when rinsed), spore-forming obligate anaerobes that have not yet been successfully cultured in vitro.[3] Most closely related to Clostridia, and provisionally designated Candidatus arthromitus.

The relatively surprising finding was that bacteria in the gut could influence the development of an autoimmune disease affecting tissues distant from the gut. Diseases such as irritable bowel syndrome have been linked to gut-residing bacteria, but this study is unique in showing the mechanism by which a bacterium in the gut can influence the development of an autoimmune response that ends in inflammation and pain in the joints.

Comment

Commensal microflora has long been recognised to have a variety of beneficial effects on host development and physiology. The composition of the microbial communities that colonise humans, particularly in the lower gastrointestinal tract, is difficult to evaluate because many commensal bacteria are unculturable obligatory anaerobes. However, studies have begun to demonstrate remarkably specific and profound effects of seemingly subtle variations in microbial composition on host immunity and susceptibility to diseases.[4]

In addition, the innate immune system may have a role in the defense against noninfectious noxious insults, such as toxic xenobiotics, environmental irritants and venoms.[5]

Comments

The clinical selection of prebiotics and probiotics has traditionally been constructed around the concept of ecological manipulation, that is that the use of a pro, or friendly bacterium would act positively regardless of the microbial mechanisms involved.

The evolving comprehension of mucosal immunity and probiotics and prebiotics is that each strain has a unique impact on the receptors in the immune system, which in turn are affected by their genetic composition and by the ecological balance. As Nutritional Therapists looking to impact on a specific state of altered health a careful selection of probiotics and allied therapies is required to simply avoid the non specific practice of indiscriminate probiotics supplementation that has no significant clinical endpoint and produces a disappointing outcome for practitioner and patient.

This is an exciting albeit complex area of therapy that has for a long time been managed by the idea that all probiotics are safe, whilst that is true where the patient has no underlying pathology, the difference between ‘safe-ish and benign’ outcomes and ‘safe and positive’ outcomes is what defines the effective practitioner and satisfied patient.

References


[1] Ley RE, Lozupone CA, Hamady M, Knight R, Gordon JI. Worlds within worlds: evolution of the vertebrate gut microbiota. Nat Rev Microbiol. 2008 Oct;6(10):776-88 View Full Paper

[2] Hsin-Jung Wu, Ivaylo I. Ivanov, Jaime Darce, Kimie Hattori, Tatsuichiro Shima, Yoshinori Umesaki, Dan R. Littman, Christophe Benoist, Diane Mathis Gut-Residing Segmented Filamentous Bacteria Drive Autoimmune Arthritis via T Helper 17 Cells. Immunity, Volume 32, Issue 6, 815-827, 17 June 2010 View Abstract

[3] Klaasen HL, Koopman JP, Poelma FG, Beynen AC. Intestinal, segmented, filamentous bacteria. FEMS Microbiol Rev. 1992 Jun;8(3-4):165-80. View Abstract

[4] Gaboriau-Routhiau V, Rakotobe S, Lécuyer E, Mulder I, Lan A, Bridonneau C, Rochet V, Pisi A, De Paepe M, Brandi G, Eberl G, Snel J, Kelly D, Cerf-Bensussan N. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity. 2009 Oct 16;31(4):677-89. View Abstract

[5] Medzhitov R. Innate immunity: quo vadis? Nat Immunol. 2010 Jul;11(7):551-3. No Abstract Available

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Responses

2 Responses to “A Bacteria Triggers Arthritis.”

  • Olga Rice says:

    I agree that it can be frustrating finding the right probiotic supplementation that works for a specific patient. Which products would you recommend for somebody with severe arthritis that started in this particular case at the age of 17? The patient is now 42 and is partially diabled by this crippling condition.

    • Michael Ash says:

      Hello Olga
      As you will have seen from previous replies, I provide overall guidance as I cannot make presonal recommendations. I have some suggestions for you though:
      First – have a stool sample tested from a reputable and experienced lab to see if there are any pathogenic bacteria or parasites present. If so consider having these treated.
      Second -the probiotics need o favour the production of IL-10 and TGFb at this stage, Saccharomyces Boulardii and LGG will do this and may be taken without further work – others may be suggested on return of your results from your health care provider.
      Third – Consider the use of nutrients to heal the digestive tract these include, glutamine, epithelial growth factor, slippery elm and others as long term GI distress is often compunded by the epithelial cells compromisingy intercellular junction proteins composed of tight junctions, adherens junctions and desmosomes because of ltered mucosal tolerance.

      A chronic case such as this really requires personalised support and I suggest that if this is the route to be taken that you find a suitable health care professional to assist.

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