TCS Research, Tata Consultancy Services Limited, 54B Hadapsar Industrial Estate, Pune, 411013, India.
Madras Diabetes Research Foundation, No. 4, Conran Smith Road, Gopalapuram, Chennai, 600 086, India.
Genome Med. 2021 Mar 3;13(1):36. doi: 10.1186/s13073-021-00851-9.
Recent studies have indicated an association of gut microbiota and microbial metabolites with type 2 diabetes mellitus (T2D). However, large-scale investigation of the gut microbiota of "prediabetic" (PD) subjects has not been reported. Identifying robust gut microbiome signatures of prediabetes and characterizing early prediabetic stages is important for the understanding of disease development and could be crucial in early diagnosis and prevention.
The current study performed amplification and sequencing on the variable regions (V1-V5) of the 16S rRNA genes to profile and compare gut microbiota of prediabetic individuals (N = 262) with normoglycemic individuals (N = 275) from two cohorts in India and Denmark. Similarly, fasting serum inflammatory biomarkers were profiled from the study participants.
After correcting for strong country-specific cohort effect, 16 operational taxonomic units (OTUs) including members from the genera Prevotella9, Phascolarctobacterium, Barnesiella, Flavonifractor, Tyzzerella_4, Bacteroides, Faecalibacterium, and Agathobacter were identified as enriched in normoglycaemic subjects with respect to the subjects with prediabetes using a negative binomial Wald test. We also identified 144 OTUs enriched in the prediabetic subjects, which included members from the genera Megasphaera, Streptococcus, Prevotella9, Alistipes, Mitsuokella, Escherichia/Shigella, Prevotella2, Vibrio, Lactobacillus, Alloprevotella, Rhodococcus, and Klebsiella. Comparative analyses of relative abundance of bacterial taxa revealed that the Streptococcus, Escherichia/Shigella, Prevotella2, Vibrio, and Alloprevotella OTUs exhibited more than fourfold enrichment in the gut microbiota of prediabetic subjects. When considering subjects from the two geographies separately, we were able to identify additional gut microbiome signatures of prediabetes. The study reports a probable association of Megasphaera OTU(s) with impaired glucose tolerance, which is significantly pronounced in Indian subjects. While the overall results confirm a state of proinflammation as early as in prediabetes, the Indian cohort exhibited a characteristic pattern of abundance of inflammatory markers indicating low-grade intestinal inflammation at an overall population level, irrespective of glycemic status.
The results present trans-ethnic gut microbiome and inflammation signatures associated with prediabetes, in Indian and Danish populations. The identified associations may be explored further as potential early indicators for individuals at risk of dysglycemia.
最近的研究表明，肠道微生物群及其代谢产物与 2 型糖尿病（T2D）有关。然而，尚未有大规模研究“糖尿病前期”（PD）受试者的肠道微生物群。鉴定出糖尿病前期的稳健肠道微生物组特征，并描述早期糖尿病前期阶段，对于了解疾病的发展非常重要，并且可能对早期诊断和预防至关重要。
本研究对来自印度和丹麦两个队列的糖尿病前期个体（N=262）和血糖正常个体（N=275）的 16S rRNA 基因的可变区（V1-V5）进行扩增和测序，以对肠道微生物群进行分析和比较。同样，从研究参与者中分析了空腹血清炎症生物标志物。
在纠正了强烈的特定国家队列效应后，使用负二项式 Wald 检验，有 16 个操作分类单元（OTUs），包括Prevotella9、Phascolarctobacterium、Barnesiella、Flavonifractor、Tyzzerella_4、Bacteroides、Faecalibacterium 和 Agathobacter 属的成员，被鉴定为在血糖正常的个体中丰富，而在糖尿病前期个体中则较少。我们还鉴定了 144 个在糖尿病前期个体中丰富的 OTUs，其中包括 Megasphaera、Streptococcus、Prevotella9、Alistipes、Mitsuokella、Escherichia/Shigella、Prevotella2、Vibrio、Lactobacillus、Alloprevotella、Rhodococcus 和 Klebsiella 属的成员。对细菌分类群相对丰度的比较分析表明，Streptococcus、Escherichia/Shigella、Prevotella2、Vibrio 和 Alloprevotella OTUs 在糖尿病前期个体的肠道微生物群中富集了四倍以上。当分别考虑两个地理位置的个体时，我们能够鉴定出糖尿病前期的其他肠道微生物组特征。该研究报告了 Megasphaera OTU(s) 与葡萄糖耐量受损之间可能存在的关联，这在印度个体中尤为明显。尽管总体结果证实了糖尿病前期就存在炎症状态，但印度队列表现出炎症标志物丰度的特征模式，表明无论血糖状态如何，整体人群的肠道炎症程度都较低。
本研究在印度和丹麦人群中呈现了跨种族的肠道微生物组和炎症特征与糖尿病前期相关联。鉴定出的关联可以进一步作为血糖异常个体的潜在早期指标进行探索。
