VEGF, TGF, and AHR Walk into a Multiple Sclerosis Convention

            A Functional MD like myself has to remember a plethora of acronyms.  We must keep in mind  how they fit together in carrying out healthy biological functions and how they dysfunction and produce illness.  To stay sane, we sometimes piece together some rather corny riddles like this article title.  Despite my weak attempt at humor, the punch line to the riddle may garner your attention – even if it does not trigger a chuckle or guffaw.  Drum roll please……

….. Gut bacteria may lower brain inflammation…….

Meaning ……

……. Modulating the gut bacteria may play an important part in treating Multiple Sclerosis and other autoimmune brain diseases.

Now that you know the punch line, lets connect the dots.  Our first two characters in this riddle are VEGF alpha (Vascular Endothelial Growth Factor)- the Bad Guy-  and TGF alpha (Transforming Growth Factor) – the Good Guy. When these two immune hormones are release by the microglia (the immune cells in our brain), they turn up the Bad Guy (VEGF) or turn down the Good Guy (TGF alpha) and thereby influence the level of inflammation. Different studies point to these characters role in debilitating diseases like Multiple Sclerosis. Multiple Sclerosis is the name we give an autoimmune process against our nerve cell “insulation” called myelin. Severe disability, even death may result.

So, what influences calm “guard dog” microglia (immune cell) sitting in our brain to release the Bad Guy (VEGF alpha hormone) or the Good Guy (TGF alpha hormone)?  Once scientists linked these hormones to inflammation, the next step was this very question.  The answer could lead to therapies for Multiple Sclerosis and save countless lives.

In a study published in Nature, researchers linked the microlglia’s production and release of varying amounts of the good and bad hormones to a third character.  This one is known as AHR (Aryl Hydrocarbon Receptor).  Despite its unassuming alias, this receptor does more than just influence detoxification of environmental toxins.  In this case, when the receptor is bound to certain chemicals, the AHR turns off VEGF beta (the Bad Guy) and turns up TGF alpha (the Good Guy) in brain tissue.  Basically, this combination lowers inflammation. Treating brain inflammation can lead to improvement in autoimmune brain diseases like Multiple Sclerosis.

This is how research goes, one question leads to another, and you understand why scientists like acronyms.  We would all get tired of writing VEGF and TGF out in full every time.  The next question is… What binds AHR to trigger a lowering of inflammation?  The researchers in this study report that a variety of gut related chemicals participate in this anti-inflammatory process.  Let me repeat that punch line one more time…

…. Gut bacteria produce chemicals that may turn down inflammation in the brain.

Some potential anti-inflammatory substances that bind to AHR and trigger a decrease in inflammation may arise from the diet or from the gut bacteria’s processing of foods like broccoli and tryptophan derivatives.  Tryptophan is a simple amino acid that comes from eating protein.  When either of these chemicals travels up to the brain, they may bind to this AHR character.  Teamed up they bind the DNA (coding area of the brain) and do two things.  One, they turn down VEGF beta- the Bad Guy.  Two, they turn up TGF alpha – the Good Guy.

If you haven’t put two and two together yet, this paper is suggesting that dietary choices or a natural therapy like tryptophan or a probiotic that processes tryptophan might be helpful in treating multiple sclerosis.  Therefore, the riddle ends with the fact that VEGF- the Bad Guy- is kicked out of the Multiple Sclerosis convention while AHR- our third character-  is welcomed.  Since tryptophan escorts AHR and rolls out the red carpet for TGF- the Good Guy, he is a good companion.  Don’t worry if you can’t follow my riddle ending.  Just remember that food is medicine and Functional Medicine at Sanctuary Functional loves to use food medicine along with natural therapies to help you live a healthier more abundant life- even if we’re not very good at telling jokes or riddles.

Nature Article abstract

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