The Gut Microbiome May Have an Impact on Modulating the Expression of Genetic Diseases
Dr Jeffrey Bland made a rare appearance in the UK on Saturday 15th June 2019 at Nutri Advanced’s annual functional medicine conference, The Science of Health. In his inimitable style, Dr Bland focused on how we can apply what we’ve learned about gut function to make a difference in managing chronic disease. With a systems-thinking approach, a mind that’s way ahead of its time and hard-wired to join the dots, he is truly an inspiring functional medicine pioneer.
A small section of his brilliant presentation, on how the gut microbiome may have an impact on modulating the expression of even genetic diseases such as sickle cell anaemia was one highlight of many.
Dr Bland introduced the concept, “monogenetic diseases such as sickle cell anaemia are considered to be deterministic, and to some extent that’s true. Let’s consider though that these things are not as fixed, immutable and deterministic as we first thought. Even the monogenetic diseases have some variables in how they are expressed in the phenotype.”
He followed with a whirlwind, yet crystal clear tour through the underlying physiology of sickle cell anaemia; why a new born baby, although carrying the genes, doesn’t have sickle cell crises, the mechanisms at play that make the risk of these more prevalent as a baby moves through infancy, and into adulthood, and why some people with sickle cell anaemia may be more at risk of crises than others.
The proportional ratio of fetal: adult haemoglobin in the blood may be a crucial factor involved in the increasing risk of sickle cell crises as an infant grows. And it turns out that the genes involved in the expression of fetal haemoglobin, including BCL11A may be positively modulated by butyrate; a short chain fatty acid produced endogenously by bacteria in the gut microbiome.
He asked the question, “so is there a connection between gut health and sickle cell crises in people who are genetic carriers?”
There’s still a way to go with this, but it’s certainly an emerging possibility.
Dr Bland explained, “people who have dysbiosis and carry the sickle cell gene have many more crises of much greater severity, and it’s tied through the linkage with the genes that suppress fetal haemoglobin that’s associated with butyrate produced endogenously through the gut. It seems that gut health has something to do with the modulation of a genetic metabolism disease through gene expression effects”
And there are fascinating research studies to dive into if you want to explore this further, as well as a thought-provoking article published in the Journal of Translational Medicine entitled, “Sickle cell vaso-occlusive crisis: It’s a gut feeling”.1-3
The takeaway message here though has even wider meaning. It’s about staying open as a practitioner, about digging deep and continuing to ask why.
Dr Bland concluded, “what I want you to understand is that when we say network medicine, it’s about how these things are connected. They are connected in ways that you only understand when you dig more deeply. You have to ask the right questions, and the questions you ask determine the answers you get. And if you never ask the question, you’ll never get the answer.”
At The Science of Health, Dr Jeffrey Bland was joined by a world-class line up of speakers including Dr Steven Sandberg-Lewis, Jo Gamble and Amanda Hamilton. Packed full of invaluable clinical insights, the whole day was filmed and the high-quality recording is now available to purchase.
1. Lim SH, Fast L et al. Sickle cell vaso-occlusive crisis: It’s a gut feeling. J Transl Med 2016; 14: 334-39
2. Zhang D, Chen G et al. Neutrophil ageing is regulated by the microbiome. Nature 2015 Sep 24; 525: 528-38
3. Lim SH, Methe BA et al. Invasive non-typhoidal Salmonella in sickle cell disease in Africa: is increased permeability the missing link? J Transl Med 2018; 16: 239-46
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