Abstract
The gut microbiome has been recognized as a tool for understanding adiposity accumulation and for providing personalized nutrition advice for the management of obesity and accompanying metabolic complications. The genetic background is also involved in human energy homeostasis. In order to increase the value of nutrigenetic dietary advice, the interplay between genetics and microbiota must be investigated. The purpose of the present study was to evaluate interactive associations between gut microbiota composition and 95 obesity-related single nucleotide polymorphisms (SNPs) searched in the literature. Oral mucosa and fecal samples from 360 normal weight, overweight and obese subjects were collected. Next generation genotyping of these 95 SNPs and fecal 16S rRNA sequencing were performed. A genetic risk score (GRS) was constructed with 10 SNPs statistically or marginally associated with body mass index (BMI). Several microbiome statistical analyses at family taxonomic level were applied (LEfSe, Canonical Correspondence Analysis, MetagenomeSeq and Random Forest), and Prevotellaceae family was found in all of them as one of the most important bacterial families associated with BMI and GRS. Thus, in this family it was further analyzed the interactive association between BMI and GRS with linear regression models. Interestingly, women with higher abundance of Prevotellaceae and higher GRS were more obese, compared to women with higher GRS and lower abundance of Prevotellaceae. These findings suggest relevant interrelationships between Prevotellaceae and the genetic background that may determine interindividual BMI differences in women, which opens the way to new precision nutrition-based treatments for obesity.
Highlights
Obesity prevalence is rising dramatically around the world, which is associated with important public health burdens [1,2]
In order to visualize the relationship between bacterial families with body mass index (BMI) and Genetic Risk Score (GRS), a canonical correspondence analysis was performed
An important strength of this investigation is the screening of multiple single nucleotide polymorphisms (SNPs) related to BMI, which resulted in the construction of a specific GRS. To our knowledge, this is the first study that has evaluated the combined effects of a set of obesity-related SNP and gut microbiota composition on human obesity. This proof of principle study has statistically shown that a sex-specific association occurs between host genetics and Prevotellaceae, evidencing differences in BMI according to the sex
Summary
Obesity prevalence is rising dramatically around the world, which is associated with important public health burdens [1,2]. In this context, it has been largely demonstrated that obese subjects have a different gut microbiota composition than lean subjects [3]. Genome-wide association studies in humans [4,5] have identified multiple loci that contribute to obesity and its associated metabolic abnormalities. Genome-wide association studies in human twins have already identified heritable bacterial taxa and single nucleotide polymorphisms (SNPs) associated with specific gut microbes. Further research in humans have described that some SNPs are associated with the abundance of specific microbial taxa. Some studies have recently found that gut microbiota composition may differ between sexes and that these differences may be influenced by the severity of obesity [14,15]
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