Gut microbial changes associated with obesity in youth with type 1 diabetes.
Gut microbial changes associated with obesity in youth with type 1 diabetes.
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DOI：
10.1101/2023.12.01.23299251
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发表时间：
2023-12
期刊：
影响因子：
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通讯作者：
Heba M Ismail;Dimuthu Perera;Rabindra K. Mandal;Linda A. DiMeglio;C. Evans-Molina;Tamara Hannon
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文献类型：
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作者：
Heba M Ismail;Dimuthu Perera;Rabindra K. Mandal;Linda A. DiMeglio;C. Evans-Molina;Tamara Hannon
肥胖在1型糖尿病（T1 D）中越来越普遍，并与管理问题和糖尿病并发症的高风险相关。在T1 D和肥胖症中分别描述了肠道微生物组的变化，然而，当肥胖症和T1 D同时发生时，肠道微生物组的变化程度尚不清楚。目的：描述与T1 D肥胖相关的肠道微生物组和微生物代谢物变化。我们假设T1 D青少年之间存在显着的肠道微生物和代谢物差异，这些青少年是瘦的（BMI：5-<85%）与肥胖的人（BMI：[≥]95%）。研究方法：我们分析了粪便样本的肠道微生物（使用宏基因组鸟枪测序）和短链脂肪酸（SCFA）代谢物的差异瘦（n=27）和肥胖（n=21）T1 D青年。平均+/-SD年龄为15.3 ± 2.2岁，A1 c为7.8 ± 1.3%，糖尿病病程为5.1 ± 4.4岁，42.0%为女性，94.0%为白色。线性判别分析（LDA）的效果大小（LEfSe）被用来确定分类最好区分BMI组之间。结果：BMI组的细菌群落组成在物种类型（{β}-多样性）方面存在差异（p=0.013）。在属水平上，肥胖组中普雷沃菌与拟杆菌的比例较高（p=0.0058）。LEfSe分析表明，显着丰富的类群在瘦或肥胖组中的差异分布，包括增加的相对丰度的普雷沃氏菌copri，在其他类群中的肥胖组。功能分析显示，肥胖组中与胰岛素敏感性降低相关的途径上调。与瘦型组相比，肥胖组的粪便SCFA（乙酸盐、丙酸盐和丁酸盐）更高（所有p<0.05）。结论：我们的研究结果确定了与T1 D肥胖相关的肠道微生物组，微生物代谢物和功能途径差异。这些发现可能有助于确定肠道微生物组靶向疗法，以管理T1 D肥胖。
Obesity is increasingly prevalent in type 1 diabetes (T1D) and is associated with management problems and higher risk for diabetes complications. Gut microbiome changes have been described separately in each of T1D and obesity, however, it is unknown to what extent gut microbiome changes are seen when obesity and T1D concomitantly occur. Objective: To describe the gut microbiome and microbial metabolite changes associated with obesity in T1D. We hypothesized significant gut microbial and metabolite differences between T1D youth who are lean (BMI: 5-<85%) vs. those with obesity (BMI: [≥]95%). Methods: We analyzed stool samples for gut microbial (using metagenomic shotgun sequencing) and short-chain fatty acid (SCFA) metabolite differences in lean (n=27) and obese (n=21) T1D youth. The mean+/-SD age was 15.3+/-2.2yrs, A1c 7.8+/-1.3%, diabetes duration 5.1+/-4.4yrs, 42.0% females, and 94.0% were White. Linear discriminant analysis (LDA) effect size (LEfSe) was used to identify taxa that best discriminated between the BMI groups. Results: Bacterial community composition showed differences in species type ({beta}-diversity) by BMI group (p=0.013). At the genus level, there was a higher ratio of Prevotella to Bacteroides in the obese group (p=0.0058). LEfSe analysis showed a differential distribution of significantly abundant taxa in either the lean or obese groups, including increased relative abundance of Prevotella copri, among other taxa in the obese group. Functional profiling showed that pathways associated with decreased insulin sensitivity were upregulated in the obese group. Stool SCFAs (acetate, propionate and butyrate) were higher in the obese compared to the lean group (p<0.05 for all). Conclusions: Our findings identify gut microbiome, microbial metabolite and functional pathways differences associated with obesity in T1D. These findings could be helpful in identifying gut microbiome targeted therapies to manage obesity in T1D.