New York (GenomeWeb) – An international research team led by investigators from Cornell University has found that parts of the human gut microbiome may be inherited and shaped through our genes.
As they reported today in Cell Host & Microbe, the researchers performed a genome-wide association study on samples from 1,126 twin pairs in the TwinsUK registry, and found that not only are certain microbial taxa heritable, but that the genome of each individual can play a role in determining the shape of the microbiome.
"These microorganisms are environmentally acquired, but the genome also plays a part by determining which microorganisms are more dominant than others," Ruth Ley, senior author and professor in the department of microbiology at Cornell University, said in a statement. "Based on our research, we identified more than a dozen microbes with known links to health that are heritable."
The study cohort came from TwinsUK, a registry run through the department of twin research at King's College London that researchers can use to study the environmental and genetic conditions of humans over time. It is currently made up of 12,000 identical and non-identical twins from across the UK, ranging from ages 16 to 98.
Ley and her colleagues collected fecal samples from 489 fraternal twin pairs and 637 identical twin pairs from the registry, extracted DNA, and collected both genotype and 16S rRNA gene sequence data using Illumina's MiSeq platform. They then analyzed the 16S rRNA data using QIIME version 1.8, calculated heritability using the ACE model, and performed stability analysis for individuals who supplied two or more serial fecal samples.
They found microorganisms associated with the lactase gene locus, ALDH1L1 gene function, genes involved in barrier defense, and genes involved in self or non-self recognition. They also found that certain genes are implicated in the regulation of the gut microbiome, Ley said.
After analysis, the team validated an association between Bifidobacterium, a microorganism that is part of the lactic acid group, and the LCT gene, which provides instructions for the body to produce lactase. However, they also found an association between Bifidobacterium and two protein coding genes, RABGAP1 and R3HDM1, which are in linkage disequilibrium with LCT — these three genes are either inherited together or have a functional interaction, making it difficult to determine which of the three genes are driving the association with the Bifidobacterium, the researchers wrote.
They also identified an association in the host gene ALDH1L1 and SHA-98 bacteria, suggesting a link between the production of the carboxylate anion formate and blood pressure.
Ley and her colleagues also found microbes associated with several other genes. The researchers found that olfactory receptor gene OR6A2 has been associated with Erysipelotrichaceae bacteria, microorganisms that have been linked to cholesterol metabolism. The CD36 gene, involved in a variety of long-chain fatty acid tasting on the tongue, was associated with Blautia, a bacteria group that metabolizes H2/CO2 and reduces total gas volume in the colon. The researchers also detected an association between genes SMB53 and variants in GNA12, both involved in barrier defense that help fight infections, with ulcerative colitis.
"The overall numbers in this study were still small for genome-wide association analysis, but they help validate some of the findings we've seen in smaller studies," Ley said in the statement. Some earlier findings have noted that several other types of bacteria are also heritable, but specific gene associations connected to those microorganisms were not found in this study.
The researchers also wrote in their paper that the gene-microbe findings still need to be validated across multiple studies, but these results do support incorporating diet and microbiome data in studies involving disease-susceptibility assessment. "This type of study opens up many questions, but doesn't give us a lot of answers yet," Ley said. "It gives us lots of ideas to study."