Gut Microbiome of Indonesian Adults Associated with Obesity and Type 2 Diabetes: A Cross-Sectional Study in an Asian City, Yogyakarta

Abstract

Indonesia is a developing country facing the national problem of the growing obesity and diabetes in its population due to recent drastic dietary and lifestyle changes. To understand the link between the gut microbiome, diet, and health of Indonesian people, fecal microbiomes and metabolomes of 75 Indonesian adults in Yogyakarta City, including obese people (n = 21), type 2 diabetes (T2D) patients (n = 25), and the controls (n = 29) were characterized together with their dietary and medical records. Variations of microbiomes showed a triangular distribution in the principal component analysis, driven by three dominant bacterial genera, namely Bacteroides, Prevotella, and Romboutsia. The Romboutsia-driven microbiome, characterized by low bacterial diversity and high primary bile acids, was associated with fat-driven obesity. The Bacteroides-driven microbiome, which counteracted Prevotella but was associated with Ruminococcaceae concomitantly increased with high-carbohydrate diets, showed positive correlation with T2D indices but negative correlation with body mass index. Notably, Bacteroides fragilis was increased in T2D patients with a decrease in fecal conjugated bile acids, particularly tauroursodeoxycholic acid (TUDCA), a farnesoid X receptor (FXR) antagonist with anti-diabetic activity, while these features disappeared in patients administered metformin. These results indicate that the gut microbiome status of Indonesian adults is differently associated with obesity and T2D under their varied dietary habits.

Analyzing Type 2 Diabetes Associations with the Gut Microbiome in Individuals from Two Ethnic Backgrounds Living in the Same Geographic Area

“…Previous sequence data of the gut microbiome in individuals with African and South-Asian genetic backgrounds have already revealed taxa associated with type 2 diabetes in those ethnic groups [ 16 , 17 , 21 , 61 , 70 , 71 , 72 , 73 ]. In Indian subjects, several studies have reported a higher abundance of Escherichia in treated T2D cases and a higher abundance of Lactobacillus in both treated and untreated T2D cases [ 16 , 17 , 73 ].…”

“…In our study, Romboutsia was identified as a robust and strong biomarker in the relation between Met-T2D and the gut microbiome in both ethnicities. Besides its potential relation to metformin use [24,61,62], Romboutsia was also previously negatively correlated with the abundance of Enterobacteriaceae, in line with the observed higher abundance of Escherichia/Shigella in Met-T2D cases in our study [63]. As for the other overlapping ASVs, the effect of Met-T2D remained significant on the abundance of Clostridium sensu stricto 1, Peptostreptococcaceae Terrisporobacter and Intestinibacter bartlettii, and Escherichia/Shigella after all adjustments in African Surinamese, while those significant effects vanished in South-Asian Surinamese after adjustment for other medication use (often not addressed in the previous studies).…”

Unique Pakistani gut microbiota highlights population-specific microbiota signatures of type 2 diabetes mellitus

“…To compare the Pakistan gut microbiota with that of other cohorts or populations, we systemically searched for publicly available 16S rRNA gene amplicon (targeting the V3-V4 region) datasets of T2D case-control studies with available metadata or identification of T2D status. Sequences from five published studies were subsequently downloaded from the National Center for Biotechnology Information and the DNA Data Bank of Japan: PRJNA661673 (China), 65 PRJNA766337 (Japan), 66 PRJDB9293 (Indonesia), 67 PRJNA588353 (Sudan), 68 and PRJNA554535 (Pakistan; an independent cohort consisting of participants residing in Islamabad). 15 An endogamous agriculturist Indian cohort of healthy adults (PRJNA399246) was also included, 69 representative of a non-industrialized population from the same geographic region.…”

Crisis of the Asian gut: associations among diet, microbiota, and metabolic diseases

“…A similar phenomenon was found in Indonesian T2D patients. A study by Therdtatha et al found that a T2D group of subjects harboring a high abundance of B. fragilis showed low levels of conjugated BAs, especially TUDCA, the level of which was restored by the administration of metformin [ 18 ].…”

“…For instance, a trend toward an increase in consumption of calorie-dense diets by Asian people, such as diets containing refined carbohydrates, fat, red meats, and low fiber contents, has been largely confirmed by several studies [ 13 , 14 , 15 ]. This occasionally distresses the gut microbiota of Asian people, eventually leading to dysfunction of their gut microbial communities [ 16 , 17 , 18 ].…”