Ismail Heba M, Perera Dimuthu, Mandal Rabindra, DiMeglio Linda A, Evans-Molina Carmella, Hannon Tamara, Petrosino Joseph, Javornik Cregeen Sara, Schmidt Nathan W
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
J Clin Endocrinol Metab. 2025 Jan 21;110(2):364-373. doi: 10.1210/clinem/dgae529.
CONTEXT: Obesity is prevalent in type 1 diabetes (T1D) and is problematic with higher risk for diabetes complications. It is unknown to what extent gut microbiome changes are associated with obesity and T1D. OBJECTIVE: This work aimed to describe the gut microbiome and microbial metabolite changes associated with obesity in T1D. We hypothesized statistically significant gut microbial and metabolite differences in lean T1D youth (body mass index [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) differences in lean (n = 27) and obese (n = 21) T1D youth in a pilot study. The mean ± SD age was 15.3 ± 2.2 years, glycated hemoglobin A1c 7.8 ± 1.3%, diabetes duration 5.1 ± 4.4 years, 42.0% female, and 94.0% were White. RESULTS: Bacterial community composition showed between sample diversity differences (β-diversity) by BMI group (P = .013). There was a higher ratio of Prevotella to Bacteroides in the obese group (P = .0058). There was 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 an upregulation of branched-chain amino acid (BCAA) biosynthesis in the obese group and upregulation of BCAA degradation, tyrosine metabolism, and secondary bile acid biosynthesis in the lean group. Stool SCFAs were higher in the obese vs the lean group (P < .05 for all). CONCLUSION: Our findings identify a gut microbiome and microbial metabolite signature associated with obesity in T1D. These findings could help identify gut microbiome-targeted therapies to manage obesity in T1D.
背景:肥胖在1型糖尿病(T1D)中很常见,并且是糖尿病并发症高风险的一个问题。目前尚不清楚肠道微生物群的变化在多大程度上与肥胖和T1D相关。 目的:这项研究旨在描述与T1D肥胖相关的肠道微生物群和微生物代谢物变化。我们假设,在体重正常的T1D青少年(体重指数[BMI]:5%-<85%)与肥胖青少年(BMI:≥95%)之间,肠道微生物和代谢物存在统计学上的显著差异。 方法:在一项初步研究中,我们分析了体重正常(n = 27)和肥胖(n = 21)的T1D青少年粪便样本中的肠道微生物(使用宏基因组鸟枪法测序)和短链脂肪酸(SCFA)差异。平均年龄±标准差为15.3±2.2岁,糖化血红蛋白A1c为7.8±1.3%,糖尿病病程为5.1±4.4年,女性占42.0%,白人占94.0%。 结果:细菌群落组成显示,按BMI分组,样本间存在多样性差异(β多样性)(P = 0.013)。肥胖组中普氏菌与拟杆菌的比例更高(P = 0.0058)。在体重正常或肥胖组中,显著丰富的分类群分布存在差异,包括肥胖组中其他分类群在内,普氏粪杆菌的相对丰度增加。功能分析显示,肥胖组中支链氨基酸(BCAA)生物合成上调,而体重正常组中BCAA降解、酪氨酸代谢和次级胆汁酸生物合成上调。肥胖组的粪便SCFAs高于体重正常组(所有P < 0.05)。 结论:我们的研究结果确定了与T1D肥胖相关的肠道微生物群和微生物代谢物特征。这些发现有助于确定以肠道微生物群为靶点的治疗方法来管理T1D中的肥胖。
J Clin Endocrinol Metab. 2025-1-21
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