Comparison of Gut Microbiota Between Type-2 Diabetes Mellitus Patients and Healthy Population Across the Three Major Malaysian Ethnic Groups in Ampang, Selangor

Type 2 diabetes (T2DM) is a major risk factor for cardiovascular diseases and the leading cause of death in Malaysia. Accumulating evidence suggests that dysbiosis in the gut microbiota composition plays an important role in the pathogenesis of several metabolic disorders including T2DM. However, in Malaysia, the association between the gut microbiota composition of the multi-ethnic community with T2DM remains unexplored. Hence, this study aimed to investigate the gut microbiota composition in T2DM subjects when compared to non-diabetic subjects (nonDM) among the three major ethnic groups in Malaysia i.e., Malays, Chinese and Indians. This case-control study consisted of 45 T2DM and 45 nonDM participants, matched by ethnicity (N=90). The composition of gut microbiota was investigated using 16S rDNA sequencing targeting the V3 – V4 hypervariable regions. Phyla Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria were found to be dominant across all study groups. Alpha diversity measures found significantly reduced diversity in the overall T2DM group. Also, a significant difference in beta diversity between the T2DM and nonDM groups was reflected in Malay and Indian ethnicity. In comparison to the respective nonDM groups, T2DMs had increased prevalence and/or abundance of phyla Proteobacteria, Synergistetes and genus Escherichia-Shigella as well as the reduction of genera Anaerostipes, Fusicatenibacter and Clostridium. In addition, the altered clinical characteristics found among T2DMs, i.e., age, fasting plasma glucose (FPG), alkaline phosphatase (ALP), urea, creatinine, and triglyceride (TG) associated positively with phylum Proteobacteria as well as genus Escherichia-Shigella specifically with age, BMI, urea and TG. On the other hand, negative correlations were observed between BMI, FPG and TG with genus Anaerostipes, BMI and TG with genus Fusicatenibacter along with FPG and TG with genus Clostridium. This study also conducted a systematic review to summarise the existing evidence related to microbiota
composition and diversity in prediabetic (preDM) and newly diagnosed T2DM (newDM) individuals in comparison to nonDM. In a total of 18 studies (5,489 participants), the preDM and newDM individuals exhibited low gut microbial diversity along with a decreased abundance of Faecalibacterium prausnitzii, Roseburia, Dialister, Flavonifractor, Alistipes, Haemophilus, Akkermansia muciniphila and increased abundance of Lactobacillus, Streptococcus, Escherichia, Veillonella and Collinsella. Lactobacillus was also found to positively correlate with FPG, HbA1c and HOMA-IR. In conclusion, findings from this study have provided us with a better insight into the diversity and composition of the diabetic gut microbiota in a multiethnic Malaysian population, while the systematic review has improved our understanding of gut microbial dysbiosis during the early stages of glucose intolerance.