Variants in genes of innate immunity, appetite control and energy metabolism are associated with host cardiometabolic health and gut microbiota composition

Abstract

Identifying the genetic and non-genetic determinants of obesity and related cardiometabolic dysfunctions is cornerstone for their prevention, treatment, and control. While genetic variants contribute to the cardiometabolic syndrome (CMS), non-genetic factors, such as the gut microbiota, also play key roles. Gut microbiota is intimately associated with CMS and its composition is heritable. However, associations between this microbial community and host genetics are understudied. We contribute filling this gap by genotyping 60 variants in 39 genes of three modules involved in CMS risk, measuring cardiometabolic risk factors, and characterizing gut microbiota in a cohort of 441 Colombians. We hypothesized that CMS risk variants were correlated with detrimental levels of clinical parameters and with the abundance of disease-associated microbes. We found several polymorphisms in genes of innate immunity, appetite control, and energy metabolism that were associated with metabolic dysregulation and microbiota composition; the associations between host genetics and cardiometabolic health were independent of the participants' gut microbiota, and those between polymorphisms and gut microbes were independent of the CMS risk. Associations were also independent of the host genetic ancestry, diet and lifestyle. Most microbes explaining genetic-microbiota associations belonged to the families Lachnospiraceae and Ruminococcaceae. Multiple CMS risk alleles were correlated with increased abundance of beneficial microbiota, suggesting that the phenotypic outcome of the evaluated variants might depend upon the genetic background of the studied population and its environmental context. Our results provide additional evidence that the gut microbiota is under the host genetic control and present pathways of host-microbe interactions.

Compositional and functional features of the female premenopausal and postmenopausal gut microbiota

“…Moreover, menopause can induce metabolic syndrome, and whether gene variants can lead to aberrant metabolic response is of considerable interest. Furthermore, variants in genes related to innate immunity and energy metabolism have been reported to correlate with gut microbiota composition , and therefore, metabolic syndrome after menopause may be associated with changes in the gut microbiome. In conclusion, we revealed different risks of immunity and metabolic diseases for pre‐ and postmenopausal women, which might be caused by the compositional and functional discrepancy in the gut microbiome.…”

Pharmacological Therapy Determines the Gut Microbiota Modulation by a Pomegranate Extract Nutraceutical in Metabolic Syndrome: A Randomized Clinical Trial

“…Recently, Ortega‐Vega et al. [ 77 ] published an interesting study that described in 441 adults, several associations between microbial groups, cardiometabolic risk markers, and various SNPs; some of them also included in our trial. Overall, their conclusions supported the inconsistency of associations between host genetics cardiometabolic health and gut microbiota, that is, genetic risk variants with impaired cardiometabolic markers were associated with both beneficial and detrimental microbial groups.…”

“…Overall, their conclusions supported the inconsistency of associations between host genetics cardiometabolic health and gut microbiota, that is, genetic risk variants with impaired cardiometabolic markers were associated with both beneficial and detrimental microbial groups. [ 77 ]…”

Correlation study on gut microbiota and omentin-1 gene polymorphism in Uyghur newly diagnosed type 2 diabetes

“…Dysbosis of gut microbiota is related to T2DM [3]. Furthermore, recent studies have reported speci c human genetic variants that were associated with gut microbiota [4][5][6][7][8]. But the relationship between gut microbiota and host genetics remains incompletely elucidated.…”