Hypertension, obesity, and diabetes have been identified as risk factors for severe COVID-19. Intriguingly, these are diseases that are linked with the microbiome.

The microbiota is the collection of microbes that inhabit our bodies. The microbiome is the collection of all of the genes of the microbiota. The vast majority of the microbes and their genes are in the gut, mostly in the colon. About 30 trillion cells makes up the microbiota, about the same number as human cells. The microbiome consists of 10-100 times the number of genes as exist in the human genome.

The microbiome as a phenomenon in medicine does not typically get much attention in  medical education. But it should. Recent research by Rob Knight and others has demonstrated that the microbiome has a measurable imprint, a signature,  apparent in many disease states. The impact of the microbiome in many chronic and acute diseases is undeniable. The microbiome is vastly important in shaping the trajectory of a patient through health and disease. Here are some examples:

Early life exposures, like c-section birth, antibiotics, and formula feeding are associated with changes in the microbiome that influence autoimmune and inflammatory conditions. Interesting recent work in humans links gut microbiota composition with the risk of developing Type 1 diabetes. Link: Alkani et. al Diabetes. 2015 Oct; 64(10): 3510–3520.

This review by Tanaka and colleagues in Current Hypertension Reports outlines how the microbiome influences hypertension. Hypertension as a metabolic disorder and the novel role of the gut.

As for obesity, there is strong signal that implicates the microbiome in excessive weight gain. In 2004, Backhed and colleagues first demonstrated that the obese, insulin resistant phenotype could be transferred from one animal to another by transferring the fecal microbiota. The investigators accomplished this by raising mice genetically predisposed to obesity under sterile conditions. Germ free mice did not become obese, despite typical energy intake and activity levels. Backhed and collegues inserted fecal pellets from conventionally raised obese mice into the food of lean germ-free mice. After this experimental inoculation, the previously germ-free mice rapidly became obese. Link: The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15718-23.

Cani and colleagues showed that one way the microbiome affects obesity and diabetes is by a mechanisms involving lipopolysaccharide (the pro-inflammatory cell wall component of gram-negative bacteria). Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008 Jun;57(6):1470-81. doi: 10.2337/db07-1403.

West-Eberhard has written about evolutionary reasons for excess fat storage: Nutrition, the visceral immune system, and the evolutionary origins of pathogenic obesity. Proceedings of the National Academy of Sciences. ” Read the  full text version here: https://doi.org/10.1073/pnas.1809046116

So is it possible, as Portuguese researchers have proposed, that the composition of the microbiome affects the outcome of COVID-19?

This is a biologically plausible claim. Researchers have shown that the microbiome affects interferon defenses – which are important in establishing a defense against coronaviruses. Antiviral host defenses depend in part on dendritic cells and natural killer cells.  Activated dendritic cells can prime antiviral defenses by producing cytokines involved in interferon production that influence natural killer cell survival and function.

Putting these lines of evidence together, it is possible that excess weight, higher than normal blood pressure or blood sugar themselves are not dangerous when one is infected by COVID-19. Instead it might be that altered immunity is a consequence of altered microbiome composition in hypertension and other chronic conditions. If that is true, then perhaps the microbiome should be a target of treatment for coronavirus prevention or even treatment.

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Joe Alcock

Emergency Physician, Educator, Researcher, interested in the microbiome, evolution, and medicine