CSIR- Institute of Genomics and Integrative Biology, New Delhi, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
Sci Rep. 2023 Jul 7;13(1):11038. doi: 10.1038/s41598-023-37720-x.
The gut microbiome influences the pathogenesis and course of metabolic disorders such as diabetes. While it is likely that duodenal mucosa associated microbiota contributes to the genesis and progression of increased blood sugar, including the pre-diabetic stage, it is much less studied than stool. We investigated paired stool and duodenal microbiota in subjects with hyperglycemia (HbA1c ≥ 5.7% and fasting plasma glucose > 100 mg/dl) compared to normoglycemic. We found patients with hyperglycemia (n = 33) had higher duodenal bacterial count (p = 0.008), increased pathobionts and reduction in beneficial flora compared to normoglycemic (n = 21). The microenvironment of duodenum was assessed by measuring oxygen saturation using T-Stat, serum inflammatory markers and zonulin for gut permeability. We observed that bacterial overload was correlated with increased serum zonulin (p = 0.061) and higher TNF-α (p = 0.054). Moreover, reduced oxygen saturation (p = 0.021) and a systemic proinflammatory state [increased total leukocyte count (p = 0.031) and reduced IL-10 (p = 0.015)] characterized the duodenum of hyperglycemic. Unlike stool flora, the variability in duodenal bacterial profile was associated with glycemic status and was predicted by bioinformatic analysis to adversely affect nutrient metabolism. Our findings offer new understanding of the compositional changes in the small intestine bacteria by identifying duodenal dysbiosis and altered local metabolism as potentially early events in hyperglycemia.
肠道微生物群会影响糖尿病等代谢紊乱的发病机制和病程。虽然十二指肠黏膜相关微生物群可能有助于血糖升高（包括糖尿病前期）的发生和进展，但与粪便相比，其研究要少得多。我们研究了高血糖（HbA1c≥5.7%且空腹血糖>100mg/dl）患者与血糖正常者的粪便和十二指肠微生物群的配对情况。与血糖正常者（n=21）相比，我们发现高血糖患者（n=33）的十二指肠细菌计数更高（p=0.008），病原菌增加，有益菌群减少。通过 T-Stat 测量十二指肠氧饱和度、血清炎症标志物和肠通透性标志物 zonulin 来评估十二指肠微环境。我们发现细菌过载与血清 zonulin 增加（p=0.061）和 TNF-α 升高（p=0.054）相关。此外，低氧饱和度（p=0.021）和全身促炎状态[白细胞总数增加（p=0.031）和 IL-10 减少（p=0.015）]也与高血糖患者的十二指肠特征一致。与粪便菌群不同，十二指肠细菌谱的可变性与血糖状态相关，并且通过生物信息学分析预测会对营养代谢产生不利影响。我们的发现通过识别十二指肠菌群失调和局部代谢改变，为理解小肠细菌的组成变化提供了新的认识，这些改变可能是高血糖的早期事件。
