Distinctive Microbiome Type Distribution in a Young Adult Balinese Cohort May Reflect Environmental Changes Associated with Modernization.

An important public health question is understanding how changes in human environments can drive changes in the gut microbiota that influence risks associated with human health and wellbeing. It is well-documented that the modernization of societies is strongly correlated with intergenerational change in the frequency of nutrition-related chronic diseases in which microbial dysbiosis is implicated. The population of Bali, Indonesia, is well-positioned to study the interconnection between a changing food environment and microbiome patterns in its early stages, because of a recent history of modernization. Here, we characterize the fecal microbiota and diet history of the young adult women in Bali, Indonesia (n = 41) in order to compare microbial patterns in this generation with those of other populations with different histories of a modern food environment (industrialized supply chain). We found strong support for two distinct fecal microbiota community types in our study cohort at similar frequency: a Prevotella-rich (Type-P) and a Bacteroides-rich (Type-B) community (p < 0.001, analysis of similarity, Wilcoxon test). Although Type-P individuals had lower alpha diversity (p < 0.001, Shannon) and higher incidence of obesity, multivariate analyses with diet data showed that community types significantly influenced associations with BMI. In a multi-country dataset (n = 257), we confirmed that microbial beta diversity across subsistent and industrial populations was significantly associated with Prevotella and Bacteroides abundance (p < 0.001, generalized additive model) and that the prevalence of community types differs between societies. The young adult Balinese microbiota was distinctive in having an equal prevalence of two community types. Collectively, our study showed that the incorporation of community types as an explanatory factor into study design or modeling improved the ability to identify microbiome associations with diet and health metrics.

Transcription factor 7-like 2 single nucleotide polymorphisms are associated with lipid profile in the Balinese.

Transcription factor 7-like 2 (TCF7L2) protein plays an important role in glucose and lipid metabolisms. Single nucleotide polymorphisms (SNPs) in the TCF7L2 gene contribute to increased fasting plasma glucose (FPG) and body mass index (BMI), and altered lipid concentrations in various population. We investigated whether the TCF7L2 SNPs were associated with obesity, high FPG and altered lipid profile in the Balinese. A total of 608 Balinese from rural and urban Bali, Indonesia, were recruited. Triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC) and FPG were measured, and BMI was calculated. Ratios of TG/HDL-C, LDL-C/HDL-C, and TC/HDL-C were determined. Genotyping of SNPs rs7903146, rs10885406, and rs12255372 were done in all samples. Genetic association analyses under a dominant model showed that the rs7903146 (OR 5.50, 95% CI 2.34-12.91, p = 8.5 × 10-5), rs12255372 (OR 4.15, 95% CI 1.66-10.33, p = 0.003) and rs10885406 (OR 2.43, 95% CI 1.39-4.25, p = 0.003) were significantly associated with high TC/HDL-C ratio. The rs10885406 also presented a significant association with high TG (OR 2.21, 95% CI 1.29-3.81, p = 0.004) and low HDL-C (OR 3.02, 95% CI 1.58-5.80, p = 0.001) concentrations, as well as high TG/HDL-C ratio (OR 1.95, 95% CI 1.16-3.27, p = 0.013). None of the SNPs exhibited significant association with obesity or high FPG. SNPs in the TCF7L2 gene are associated with altered lipid profile in the Balinese.

Uncoupling protein 2 gene polymorphisms are associated with obesity.

BACKGROUND: Uncoupling protein 2 (UCP2) gene polymorphisms have been reported as genetic risk factors for obesity and type 2 diabetes mellitus (T2DM). We examined the association of commonly observed UCP2 G(-866)A (rs659366) and Ala55Val (C > T) (rs660339) single nucleotide polymorphisms (SNPs) with obesity, high fasting plasma glucose, and serum lipids in a Balinese population. METHODS: A total of 603 participants (278 urban and 325 rural subjects) were recruited from Bali Island, Indonesia. Fasting plasma glucose (FPG), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were measured. Obesity was determined based on WHO classifications for adult Asians. Participants were genotyped for G(-866)A and Ala55Val polymorphisms of the UCP2 gene. RESULTS: Obesity prevalence was higher in urban subjects (51%) as compared to rural subjects (23%). The genotype, minor allele (MAF), and heterozygosity frequencies were similar between urban and rural subjects for both SNPs. All genotype frequencies were in Hardy-Weinberg equilibrium. A combined analysis of genotypes and environment revealed that the urban subjects carrying the A/A genotype of the G(-866)A SNP have higher BMI than the rural subjects with the same genotype. Since the two SNPs showed strong linkage disequilibrium (D' = 0.946, r2 = 0.657), a haplotype analysis was performed. We found that the AT haplotype was associated with high BMI only when the urban environment was taken into account. CONCLUSIONS: We have demonstrated the importance of environmental settings in studying the influence of the common UCP2 gene polymorphisms in the development of obesity in a Balinese population.

Association of FTO rs1421085 single nucleotide polymorphism with fat and fatty acid intake in Indonesian adults.

OBJECTIVE: Recent studies showed that genetic polymorphisms in the fat mass and obesity-associated gene (FTO) were associated with obesity and dietary intake. In this study of 71 adults in Jakarta, Indonesia, we investigated FTO rs1421085 association with body mass index (BMI), macronutrient intake, and fatty acid intake. The association was evaluated using linear regression analyses assuming co-dominant, dominant, recessive, over-dominant, and additive genetic models. RESULTS: Only individuals with the CC genotype had a considerably higher BMI (p < 0.001), which indicates a recessive genetic trait, but the incidence for this genotype is low (68 TT + TC vs. 3 CC). Individuals with the minor C allele had an estimated increase of fat intake by 3.45-4.06% across various genetic models (dominant: p < 0.010, over-dominant: p < 0.030, additive: p < 0.010). Subjects with TC/CC genotypes had increased dietary monounsaturated fatty acid (MUFA; 1.14%, p = 0.046) and saturated fatty acid (SAFA; 2.06%, p = 0.023) intakes, compared to those with the TT genotype. In conclusion, our study provided evidence for the association between FTO rs1421085 risk allele with higher BMI and individual preferences for consuming more fat, MUFA, and SAFA. This study highlights the important role of FTO gene in food preference, and its influence on body weight.

Obesity in the Balinese is associated with FTO rs9939609 and rs1421085 single nucleotide polymorphisms.

Obesity prevalence is increasing worldwide, including in the Bali Province, Indonesia, a popular tourism destination area. The common single nucleotide polymorphisms (SNPs) rs9939609 and rs1421085 of the fat mass and obesity-associated (FTO) gene have been repeatedly reported as one of the important obesity genetic risk factors. We have examined the associations of FTO rs9939609 and rs1421085 SNPs with obesity in the 612 unrelated Balinese subjects living in urban and rural areas. Linear and logistic regression analyses with adjustment for age and gender were employed to investigate the association between FTO genotypes, haplotypes and obesity parameters. We found that the FTO SNPs genotypes increased BMI by 1.25 kg/m2 (p = 0.012) for rs9939609 AA and 1.12 kg/m2 (p = 0.022) for rs1421085 CC, particularly in females and in rural population. Subjects carrying these genotypes also showed a tendency to maintain high BMI, regardless of their age. Our result showed that the FTO rs9939609 and rs1421085 risk alleles were associated with increased BMI and obesity in the Balinese.