Genes, Viruses, Microbes and IBD

Crohn’s disease is common and miserable to suffer from, yet its actual cause is still under some debate as no clear understanding has yet been fully elucidated. It is known that there are some gene variations and that the environment has an impact. A paper out in Cell suggests, based on a mouse model that it may be a virus that makes the difference between health and inflammation. demonstrate that a viral infection, a toxic insult to the gut, commensal bacteria, and a Crohn’s disease susceptibility gene collude to cause inflammatory disease in the mouse gut.[1]

To be clear, Cadwell and co-workers are not arguing that Crohn’s disease is caused by infection with norovirus (as used in this study) or by any other single microbe. The environmental factors that predispose to and protect from Crohn’s disease remain uncertain, but the balance among commensal and pathogenic gut bacteria and viral infections is likely to be part of the story. These studies make an urgent and compelling case for characterising the human virome as well as the microbiome and defining its effects on physiology and gene expression. In addition, further explanations to help us to understand how the virome interacts with polymorphisms in the host genome and how numerous toxins in the environment alter this complex interplay will need to be unravelled.

The host’s genetic make-up can account for around 50% of the risk of Crohn’s disease.[2] Genome-wide association studies (GWAS) have pinpointed more than 30 genomic regions (loci) variations in which are associated with an increased risk of developing the disease. So what contributes to the remaining 50% of risk? Certainly environmental factors, and in particular the resident microorganisms (the microbiome), are strong contenders, although direct evidence for an environmental contribution in humans with Crohn’s disease has yet to be published.

Immune responses to viruses rely on sensors of infection in the shape of ‘pattern-recognition receptors’, which recognize evolutionarily conserved motifs present in microorganisms; in the case of viruses, these are often viral nucleic acids and the number one receptor that seems to be involved in crohn’s initiation is the NOD2 a possible intracellular sensor of nucleic acid.[3]

Comment

So what does this mean to Nutritional Therapy, is understanding that a small viral particulate can knock a normal healthy gut into a chronic inflammatory state of interest – well yes! When discussing with a patient about the initiation or onset, careful history needs to look at the likelihood of viral infection and then viral prolongation – is the mucosal immune system unable to stimulate appropriate removal, or is it just ‘knocked’ forward into a persistent state of inflammation that in turn limits the commensals ability to reduce inflammation. Should a natural antiviral agent such as olive leaf extract be used.[4] Or should it be considered as a specific antimicrobial for H. pylori, C. jejuni, S. aureus and MRSA.[5]

Clinically all three organisms plus non specific viruses may be involved in patients with Crohn’s and suitable assays of the stool will help to identify the bacterial elements but not the viral ones. Olive leaf extract may also be able to confer anti-inflammatory benefits[6] and so represents a potential strategy for suspected bacterial or viral induced IBD.

References


[1] Cadwell K, Patel KK, Maloney NS, Liu TC, Ng AC, Storer CE, Head RD, Xavier R, Stappenbeck TS, Virgin HW. Virus-plus-susceptibility gene interaction determines Crohn’s disease gene Atg16L1 phenotypes in intestine. Cell. 2010 Jun 25;141(7):1135-45. View Abstract

[2] Van Limbergen, J., Russell, R. K., Nimmo, E. R. & Satsangi, J. Am. J. Gastroenterol. 102, 2820–2831 (2007). View Abstract

[3] Sabbah A, Chang TH, Harnack R, Frohlich V, Tominaga K, Dube PH, Xiang Y, Bose S. Activation of innate immune antiviral responses by Nod2. Nat Immunol. 2009 Oct;10(10):1073-80. Epub 2009 Aug 23 View Full Paper

[4] Heinze JE, Hale AH, Carl PL.  Specificity of the antiviral agent calcium elenolate.  Antimicrob Agents Chemother. 1975 Oct;8(4):421-5.  View Full Paper

[5] Sudjana AN, D’Orazio C, Ryan V, Rasool N, Ng J, Islam N, Riley TV, Hammer KA. Antimicrobial activity of commercial Olea europaea (olive) leaf extract. Int J Antimicrob Agents. 2009 May;33(5):461-3. Epub 2009 Jan 9. View Abstract

[6] Süntar IP, Akkol EK, Baykal T. Assessment of anti-inflammatory and antinociceptive activities of Olea europaea L. J Med Food. 2010 Apr;13(2):352-6. View Abstract

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