MicrobiotaMi Comment 01_20 by Marco Tonelli

Related Journal Article: The role of the microbiota in human genetic adaptation. Science  04 Dec 2020: Vol. 370, Issue 6521, eaaz6827. DOI: 10.1126/science.aaz6827

The relationship between microbiota and human local adaptation

It is well known that human beings had to genetically adapt themselves to the different local conditions across the entire world: in particular they had to adapt to different climates, diets and pathogens that can be encountered during lifetime. As an example, it is very clear the important role of hypoxia-inducible factor 2-alpha (encoded by EPAS1) for people who live in high altitudes, or even the beta-globin gene haplotypes (encoded by HBB) for the resistance to malaria.

Somehow less intuitive is that also microbiota plays a central role in human adaptation, since it can dynamically change its composition and, under environmental pressure, it can improve host fitness in a variety of different ways. We know that microbiota continuously changes from birth to adulthood, reconfiguring itself in response to daily variations in diet or specific physiological or immunological needs. However, we tend to forget how microbiota plasticity has also been crucial to face changes in lifestyle and diet along the course of our evolution and local geographic adaptation.

A review on this fascinating topic has recently been published on Science  (Suzuki and Ley, Science 370, eaaz6827, 4 December 2020). The authors explain how, in certain cases, microbiota can also replace human functions. This is for example the case of lactase enzyme. We all know that, after weaning , the production of lactase (LCT gene) ends in some people, since milk is no more part of their diet. Lactose is then found undigested in the colon and can be processed by microbial enzymes (beta-galactosidase): in particular, recent studies found how these people have a relative abundance of Bifidobacterium in their microbiota. This is a clear example of how dietary pressure (consumption of dairy products) can select a stronger “lactose-digesting” microbiome, when human lactase is lacking.

Another example of dietary adaptation is the association between AMY1 copy number (encoding for salivary amylases) and Ruminococcus, a genus important in resistant-starch fermentation. The increase in consumption of starchy food after the development of agriculture, led to an increase in AMY1 copy numbers and to a “resistant-starch-digesting” microbiome with a relative abundance of Ruminococcus in the large intestine.

These are just two examples of gene-microbe interactions related to diet modification, but this is also true for climate adaptation. In fact, the role of human skin and gut microbiota in regulating skin pigmentation, blood pressure and body temperature is emerging and, in the future, we will be able to better understand how it can interact with human genetic adaptive traits in order to replicate similar physiological pathways.

Pathogen adaptation is also considered one of the most important things in adaptive evolution in humans. As stated above, resistance to Plasmodium infection in certain areas of the world is of crucial importance and is mainly linked to beta-globin genes adaptation. Microbiota may play a role as well in determining malaria severity in a variety of different ways, such as the production of compounds by skin microbiota lowering mosquito attraction to human skin.

In conclusion, it is clear that microbiota is involved in host-adaptive evolution, but so far studies involving human genetics and the microbiota have been made mainly in Western populations. In order to better understand microbiota-mediated adaptations, it is of crucial importance to study a wider range of populations and locations. A better understanding of the mechanisms underlying the interactions between human hosts and their microbiota could lead to a deeper knowledge on microbiota-related diseases and may contribute to a deeper comprehension on how humans have adapted, and – why not? – may go on adapting to a changing world.

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<a href="https://microbiotami.com/author/marco/" target="_self">Marco Tonelli</a>

Marco Tonelli

He graduated from Medical School in 2015 from Università Tor Vergata, Rome, Italy. In 2020 he completed specialty training in Microbiology and Virology at Università Vita-Salute San Raffaele, Milan, Italy. Since then he has been a consultant microbiologist in the Microbiology and Virology laboratory, directed by Prof. Massimo Clementi, in San Raffaele hospital. He currently works in the Virology unit and his main field of interest is the molecular diagnosis of SARS-CoV-2 infection. Tonelli Marco - Research Fellow