Saturday, December 26, 2020

Genes and microbes

The body’s assortment of microorganisms depends on what we eat, drugs we take, the stress we are subjected to and the environment we interact with (eg, the infamous SARS-CoV-2 virus). Yet genes also have their say.

In a study of 977 twins in UK, the most heritable taxonomic group of bacteria was found to be Christensenellaceae (Goodrich et al, 2014). These bacteria is present in higher amounts in genetically-lean individuals. It encourages growth of other microbes connected to body weight and energy conservation such as methanogenic Archaea.

A study of over 1500 healthy individuals in Canada (Turpin et al, 2016), associated another abundant bacteria Faecalibacterium with immune system gene CNTN6 (rs1394174), and linked several other genes and bacteria of minor clinical importance (rs59846192 of DMRTB1 - Lachnospira, rs28473221 of SALL3 - Eubacterium, ), rs62171178 nearest UBR3 - Rikenellaceae).

A new paper posted this month on BioRxiv, reports results of a larger genome-wide association study performed for 7,738 individuals from the northern Netherlands.

The authors investigated 5.5 million common genetic variants using linear mixed models on hundreds of bacterial groups and pathways. Potential confounders such as medication usage, anthropometric data and stool characteristics were carefully considered along with dietary information. 

The strongest associations were identified in intronic regions of genes. In particular, between rs182549 in intronic region of the MCM6 gene and Bifidobacteria. This SNP was found to be responsible for lactose intolerance in European population. And so was Bifidobacteria - the most researched and most effective probiotic against lactose intolerance.

Another interesting microbe Collinsella and its family Coriobacteriaceae, associated with rheumatoid arthritis, cholesterol metabolism and leaky gut, was linked to several SNPs regulating genes responsible for the blood group antigens. Blood types does matter. 

Genetic factors might influence our preferences of vegetables, fruit, starchy foods, meat, fish, dairy and snacks. The Dutch study confirmed an earlier finding that rs642387, a genetic variation near genes influencing brain function, is linked to microbial family Rikenellaceae. The paper found that these bacteria, when present in large numbers in the gut, led to decreased consumption of salt. They also showed that an increase in the bacterial pathway of histidine degradation led to increased intake of processed meat.

The paper provides a wealth of information and comes with a lot of supplementary material.



REEFERENES

Goodrich JK, Waters JL, Poole AC, Sutter JL, Koren O, Blekhman R, Beaumont M, Van Treuren W, Knight R, Bell JT, Spector TD. Human genetics shape the gut microbiome. Cell. 2014 Nov 6;159(4):789-99. 

Turpin W, Espin-Garcia O, Xu W, Silverberg MS, Kevans D, Smith MI, Guttman DS, Griffiths A, Panaccione R, Otley A, Xu L. Association of host genome with intestinal microbial composition in a large healthy cohort. Nature genetics. 2016 Nov;48(11):1413.

Lopera-Maya EA, Kurilshikov A, van der Graaf A, Hu S, Andreu-Sánchez S, Chen L, Vila AV, Gacesa R, Sinha T, Collij V, Klaassen MA. Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project. bioRxiv. 2020 Jan 1.

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