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Twin study finds gut microbiomes run in families

A United Kingdom genome-wide analysis of over 1,000 twins reveals that parts of our microbiome are shaped not only through the spread of external microbes given from parent to child, but through genetic inheritance.

A microbiome is that collection of microorganisms that live on our skin and deep in its layers, our saliva, mouth mucosa, mucous membranes that cover our eyes and inside our eyelids, as well as in our gastrointestinal tracts - Wikipedia

Recent research has found new examples of heritable bacterial species — including bacteria related to diet preference, metabolism, and immune defense. The work appears in the May 11 issue of Cell Host & Microbe, a special issue on "Genetics and Epigenetics of Host-Microbe Interactions."

"We set out to find out about human genes that are implicated in the regulation of the gut microbiome, and we found some that are," says senior author Ruth Ley, an Associate Professor in the Department of Microbiology at Cornell University and the study's senior author.

One connection they were able to make was between the LCT gene — an enzyme that helps digest lactose, a sugar found in milk and other dairy products — and a microorganism called Bifidobacterium, an anaerobic bacteria that inhabitants our gastrointestinal tract, vagina and mouth, and is commonly used in probiotics. They also found links between specific gut bacteria, blood pressure and self/non-self recognition (or allorecognition — the ability of an organism to distinguish its own tissues from those of another).

"Based on our research, we identified more than a dozen microbes with known links to health that are heritable. These microorganisms are environmentally acquired, but the genome also plays a part — by determining which microorganisms are more dominant than others."

Ruth Ley PhD, Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA; Director, Department of Microbiome Science, Max Planck Institute for Developmental Biology, Tübingen, Germany, and senior author of the work.

Investigators analyzed gut microbiomes of 1,126 pairs of twins who were part of the TwinsUK (United Kingdom) Study. This multiyear research effort included a total of 12,000 twins, and looked at a number of diseases and conditions. By including data from both identical and fraternal twin sets who were raised as twins in the same homes, the study accounts for both genetic bacterial and environmental contributions.

The twins had their genomes analyzed, along with 1.3 million small genetic variations (known as single-nucleotide polymorphisms or SNPs) for each participant. Investigators looked for connections in gene variations between twin pairs and those bacterial types present and stable in study subjects.

Analysis confirmed that several more types of bacteria are also heritable, but specific genes connected to those differences were not found.

"The overall numbers in this study were still small for genome-wide association analysis, but help validate some of the findings we've seen in smaller studies.

"This type of study opens up many questions but doesn't give us a lot of answers yet. It gives us lots of ideas to study."

Ruth Ley PhD

Diet differs among subjects and can rapidly alter microbial community composition (David et al., 2014), casting some doubt over the use of relative abundance data in genetic association studies. Davenport et al. (2015)) circumvented this issue with a genome-wide analysis of the fecal microbiome composition in the Hutterites, a founder population that lives and eats communally (Davenport et al., 2015, Davenport et al., 2014). These analyses revealed a suite of heritable taxa and highlighted links between microbial taxa and genes involved in barrier defense and immunity.

Studies in mice further reduce the environmental influences on the microbiome. Benson et al. (2010)) performed the first quantitative trait loci (QTL) mapping study, using 645 mice from an advanced intercross line (Benson et al., 2010). QTL analysis detected 13 genetic loci that were significantly associated with microbial abundances and five additional suggestive loci. Many of the QTL were in regions with genes that play roles in the immune system. Subsequent studies in mice have confirmed some of these results (Leamy et al., 2014, McKnite et al., 2012). Comparisons across mouse and human studies highlight some common themes: genetic control of certain bacterial taxa (e.g., Turicibacter) and associations with immune-related genes.

Here, we report heritability and gene-association analyses for the TwinsUK cohort. We tripled the size of our initial dataset of Goodrich et al. (2014)), now including 3,261 fecal samples from 2,731 individuals. This includes 489 dizygotic (DZ) twin pairs, 637 monozygotic (MZ) twin pairs, and 530 samples collected at a second time point. The goals of this study are to (1) calculate the heritabilities of specific components of the gut microbiota and (2) associate abundances of microbes with host gene alleles through candidate gene analysis and genome-wide association. Using this expanded dataset, we improve heritability estimates for taxa previously identified as heritable, expand the list of heritable taxa, and identify associations between a subset of the heritable taxa and candidate genes related to diet and immunity.

Cell Host & Microbe, Goodrich et al.: "Genetic Determinants of the Gut Microbiome in UK Twins" http://www.cell.com/cell-host-microbe/fulltext/S1931-3128(16)30153-6

This study was supported by the National Institutes of Health, a David and Lucile Packard Foundation Fellowship, the Arnold and Mabel Beckman Foundation, the Cornell Center for Comparative Population Genomics, a National Science Foundation Graduate Fellowship, the Wellcome Trust, and the European Community's Seventh Framework Programme.

Cell Host & Microbe (@cellhostmicrobe), published by Cell Press, is a monthly journal that publishes novel findings and translational studies related to microbes (which include bacteria, fungi, parasites, and viruses). The unifying theme is the integrated study of microbes in conjunction and communication with each other, their host, and the cellular environment they inhabit. Visit: http://www.cell.com/cell-host-microbe. To receive Cell Press media alerts, contact press@cell.com.
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May 12, 2016   Fetal Timeline   Maternal Timeline   News   News Archive   

Do genes from the host shape its own microbiome? This chart represents an analysis of 1,126 twins, making the association between host genes and select bacteria. Lactase nonpersistence is linked
to higher levels of Bifidobacteria. Other genes/microbes links relate to diet and barrier defense.

MZ-twins (identical) are monozygotic, developed from
one zygote, which splits and forms two embryos
DZ-twins (fraternal) are dizygotic and developed from
two different eggs fertilized at the same time

Image Credit: Goodrich et al.; Cell Host & Microbe 2016





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