Letchumanan Geetha, Marlini Muhamad, Baharom Nizam, Lawley Blair, Syed Mohideen Fathima Begum, Jogulu Sathya Rao, Addnan Faizul Helmi, Nur Fariha Mohd Manzor, Omar Mohd Rahman, Pathmanathan Siva Gowri
Department of Medical Sciences, Faculty of Medicine & Health Sciences, Universiti Sains Islam Malaysia (USIM), Nilai, Negeri Sembilan, Malaysia.
Public Health Unit, Department of Primary Health Care, Faculty of Medicine & Health Sciences, Universiti Sains Islam Malaysia (USIM), Nilai, Negeri Sembilan, Malaysia.
J Med Microbiol. 2025 Jan;74(1). doi: 10.1099/jmm.0.001963.
Type 2 diabetes mellitus (T2DM) is a major global health issue projected to exceed 700 million cases by 2045. In Malaysia, T2DM prevalence has risen, with notable ethnic disparities. The gut microbiota's role in T2DM pathogenesis is well recognized, yet its composition in Malaysia's ethnically diverse population remains underexplored. This study aimed to characterize gut microbiota composition among T2DM and ethnicity-matched adults without diabetes (nonDM) in Malaysia. A case-control study was conducted with 45 T2DM and 45 nonDM participants matched by ethnicity from a primary care clinic in Klang Valley, Malaysia. Faecal DNA was subjected to 16S rRNA sequencing to identify microbiota diversity and composition differences and compare predicted functional capabilities. Correlations between bacterial taxa, clinical characteristics and dietary intake were analysed. T2DM participants showed decreased alpha diversity (observed, -value=0.002, =0.69; Shannon, -value<0.001, =0.73) and significant differences in beta diversity (permutational multivariate ANOVA, ²=0.036, -value=0.001). Linear discriminant analysis effect size and multiple regression analysis, adjusted for covariates age, gender, BMI and intakes of protein, fat, carbohydrate and fibre, identified the phylum and genera to be increased, while the genera and decreased in T2DM. These bacteria were associated with various clinical characteristics and dietary intake. However, these 'potential biomarkers' were not uniformly present across all participants, suggesting that individual bacterial taxa may not serve as universal biomarkers. Significant gut microbiota differences exist between T2DM and nonDM individuals in Malaysia, indicating a dysbiosis characterized by increased pro-inflammatory bacteria and reduced short-chain fatty acid-producing bacteria in T2DM. While these findings highlight the potential functional relevance of gut microbiota in T2DM pathogenesis, addressing limitations such as participant matching for confounding factors in future studies could uncover additional significant differences in microbiota composition. Furthermore, the variability in taxa prevalence across individuals suggests that targeting microbial metabolic products may offer more promising strategies to inform microbiota-targeted interventions than relying solely on specific bacterial taxa as biomarkers.
2型糖尿病（T2DM）是一个重大的全球健康问题，预计到2045年病例数将超过7亿。在马来西亚，T2DM患病率呈上升趋势，且存在显著的种族差异。肠道微生物群在T2DM发病机制中的作用已得到充分认识，但其在马来西亚种族多样化人群中的组成仍未得到充分研究。本研究旨在描述马来西亚T2DM患者和种族匹配的非糖尿病成年人（非DM）的肠道微生物群组成。在马来西亚巴生谷的一家初级保健诊所进行了一项病例对照研究，纳入45例T2DM患者和45例种族匹配的非DM参与者。对粪便DNA进行16S rRNA测序，以确定微生物群多样性和组成差异，并比较预测的功能能力。分析了细菌分类群、临床特征和饮食摄入之间的相关性。T2DM参与者的α多样性降低（观察值，P值=0.002，效应量=0.69；香农指数，P值<0.001，效应量=0.73），β多样性存在显著差异（置换多元方差分析，R²=0.036，P值=0.001）。线性判别分析效应大小和多元回归分析，在调整协变量年龄、性别、BMI以及蛋白质、脂肪、碳水化合物和纤维摄入量后，确定T2DM患者中门和属增加，而属和属减少。这些细菌与各种临床特征和饮食摄入相关。然而，这些“潜在生物标志物”并非在所有参与者中都一致存在，这表明单个细菌分类群可能无法作为通用生物标志物。马来西亚T2DM患者和非DM个体之间存在显著的肠道微生物群差异，表明T2DM患者存在以促炎细菌增加和短链脂肪酸产生细菌减少为特征的生态失调。虽然这些发现突出了肠道微生物群在T2DM发病机制中的潜在功能相关性，但在未来研究中解决诸如参与者混杂因素匹配等局限性，可能会发现微生物群组成的其他显著差异。此外，个体间分类群患病率的变异性表明，针对微生物代谢产物可能比仅依靠特定细菌分类群作为生物标志物提供更有前景的策略，为以微生物群为靶点的干预措施提供依据。
