title: The effect of heritability and host genetics on the gut microbiota and metabolic syndrome.
abstract: Metabolic syndrome (MetS) arises from complex interactions between host genetic and environmental factors. Although it is now widely accepted that the gut microbiota plays a crucial role in host metabolism, current knowledge on the effect of host genetics on specific gut microbes related to MetS status remains limited. Here, we investigated the links among host genetic factors, gut microbiota and MetS in humans.
  
  
  
  We characterised the gut microbial community composition of 655 monozygotic (n=306) and dizygotic (n=74) twins and their families (n=275), of which approximately 18% (121 individuals) had MetS. We evaluated the association of MetS status with the gut microbiota and estimated the heritability of each taxon. For the MetS-related and heritable taxa, we further investigated their associations with the apolipoprotein A-V gene (APOA5) single nucleotide polymorphism (SNP) rs651821, which is known to be associated with triglyceride levels and MetS.
  
  
  
  Individuals with MetS had a lower gut microbiota diversity than healthy individuals. The abundances of several taxa were associated with MetS status;Sutterella,MethanobrevibacterandLactobacilluswere enriched in the MetS group, whereasAkkermansia,OdoribacterandBifidobacteriumwere enriched in the healthy group. Among the taxa associated with MetS status, the phylum Actinobacteria, to whichBifidobacteriumbelongs, had the highest heritability (45.7%). Even after adjustment for MetS status, reduced abundances of Actinobacteria andBifidobacteriumwere significantly linked to the minor allele at theAPOA5SNP rs651821.
  
  
  
  Our results suggest that an altered microbiota composition mediated by a specific host genotype can contribute to the development of MetS.
authors.affiliation: Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.|Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea.
authors.forename: Mi Young
authors.initials: MY
authors.lastname: Lim
authors.affiliation: Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.|Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea.|Center for Human and Environmental Microbiome, Seoul National University, Seoul, Republic of Korea.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: You
authors.affiliation: Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.
authors.forename: Hyo Shin
authors.initials: HS
authors.lastname: Yoon
authors.affiliation: Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.
authors.forename: Bomi
authors.initials: B
authors.lastname: Kwon
authors.affiliation: Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jae Yoon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sunghee
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Family Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Yun-Mi
authors.initials: YM
authors.lastname: Song
authors.affiliation: Department of Family Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Kayoung
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.
authors.forename: Joohon
authors.initials: J
authors.lastname: Sung
authors.affiliation: Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.|Center for Human and Environmental Microbiome, Seoul National University, Seoul, Republic of Korea.|N-Bio, Seoul National University, Seoul, Republic of Korea.
authors.forename: GwangPyo
authors.initials: G
authors.lastname: Ko
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000072040:Apolipoprotein A-V / Q000235:genetics*; D041963:Bacteroidetes / Q000302:isolation & purification; D020562:Betaproteobacteria / Q000302:isolation & purification; D001644:Bifidobacterium / Q000302:isolation & purification; D064806:Dysbiosis / Q000382:microbiology; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D007778:Lactobacillus / Q000302:isolation & purification; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics* / Q000382:microbiology*; D041581:Methanobrevibacter / Q000302:isolation & purification; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012336:RNA, Ribosomal, 16S / Q000032:analysis*; D061327:Verrucomicrobia / Q000302:isolation & purification; D055815:Young Adult
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D012336:RNA, Ribosomal, 16S
keywords: ENERGY METABOLISM; ENTERIC BACTERIAL MICROFLORA; GENETIC POLYMORPHISMS