The Gut Microbiota of Bali among the World Populations: Connecting Diet, Urbanisation, and Obesity.

Community assembly of the gut microbiota is believed to be achieved through an interaction between the host’s lifestyle and genetic. Failure to address these population-specific factors may lead to unsuccessful detection of obesity patterns in the human gut microbiota. This thesis aimed to extricate lifestyle and genotypic patterns from the human gut microbiota, and to identify obesity patterns in the microbiota of a population with defined lifestyle and ethnogeography. This study utilized the unique cultural and ethnogeography characteristics of Bali people. In the first part of this thesis, the faecal microbiota of 36 ethnic Balinese individuals was compared by obesity, diet patterns (through food frequency questionnaire), and genetic lineage (through mitochondrial DNA [mtDNA] haplotyping). Subjects with non-R mtDNA haplogroup were found to have a higher prevalence of Prevotella-dominated enterotype and higher risk of developing obesity. Moreover, the enterotypes were found to be linked to long-term diet patterns, particularly to choices of staple foods in meals. In the second part of this thesis, the microbiota of 41 Bali individuals was contrasted with the microbiota of 283 other people from 7 ethnogeographically distinct rural and urban populations. Principal Coordinate Analyses of the unweighted Unifrac distance placed Bali individuals between the rural and urban samples, reflecting Bali’s status as a newly-industrialised society. Urbanisation is also associated with the abundance of Prevotella and Bacteroides across populations, but not obesity. Collectively, these findings highlighted that perpetuating host factors (lifestyle, genotype) are drivers of microbial community assembly in the human gut. Importantly, this thesis showed that understanding the genetic and socio-cultural context of a population could be the key to effective identification of microbial biomarkers in obesity

Uncoupling protein 2 gene polymorphisms are associated with obesity

Abstract 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.</p

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