GCK-MODY和HNF1A-MODY的肠道微生物群β -多样性和属级丰度差异：一项初步研究

IF 0.3 Q4 NUTRITION & DIETETICS

CAHIERS DE NUTRITION ET DE DIETETIQUE Pub Date : 2026-08-01 Epub Date: 2026-09-24 DOI:10.1016/j.cnd.2026.08.015

Érika Duarte Ostemberg, Jullyanne Gil, Luma de Sousa Silva, Maria Fernanda Pessoa Maia, Gabriella de Medeiros Abreu, Eliane Lopes Rosado, Mário Campos Junior

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引用次数: 0

摘要

目的探讨葡萄糖激酶成熟型糖尿病（GCK-MODY）和肝细胞核因子1- α (HNF1A-MODY)患者肠道微生物群(GM) β -多样性和属级丰度差异。研究葡萄糖激酶成熟型糖尿病（GCK-MODY）和肝细胞核因子1- α (HNF1A-MODY)患者之间肠道微生物群(GM) β -多样性和属级丰度差异。方法本观察性研究纳入33例经遗传学证实由GCK （n = 16）和HNF1A （n = 17）基因致病性或可能致病性变异引起的MODY患者，根据美国医学遗传学与基因组学学院指南进行分类。参与者的平均年龄为38.3±14.7岁。采集血样进行基因分析，粪便样本采用拭子粪便采集试剂盒进行DNA提取和16S rRNA基因测序。采用Bray-Curtis、Jaccard、un加权UniFrac和加权UniFrac距离指标评估转基因β多样性。采用LinDA、limma- oom和MaAsLin2进行属水平的差异丰度分析。R版本4.2.1进行统计学分析，P <； 0.05认为有统计学意义。该研究获得了huff /UFRJ （CAAE 04232512.4.0000.5257）、IPPMG/UFRJ（批准号6.126.045）和IOC/FIOCRUZ （CAAE 44726720.4.0000.5248）的伦理批准。本观察性研究纳入了33例经遗传学证实由GCK （n = 16）和HNF1A （n = 17）基因致病性或可能致病性变异引起的MODY患者，根据美国医学遗传学与基因组学学院指南进行分类。参与者的平均年龄为38.3±14.7岁。采集血样进行基因分析，粪便样本采用拭子粪便采集试剂盒进行DNA提取和16S rRNA基因测序。采用Bray-Curtis、Jaccard、un加权UniFrac和加权UniFrac距离指标评估转基因β多样性。采用LinDA、limma- oom和MaAsLin2进行属水平的差异丰度分析。R版本4.2.1进行统计学分析，P <； 0.05认为有统计学意义。该研究获得了huff /UFRJ （CAAE 04232512.4.0000.5257）、IPPMG/UFRJ（批准号6.126.045）和IOC/FIOCRUZ （CAAE 44726720.4.0000.5248）的伦理批准。结果各组间β -多样性无显著差异。加权UniFrac分析显示，GCK-MODY个体与HNF1A-MODY个体的GM群落结构存在差异（PERMANOVA, R2 = 0.078, P = 0.014），但经多重检验校正后，差异无统计学意义（调整后P = 0.072）。差异丰度分析没有发现任何在错误发现率校正后仍然显著的属。然而，Enterorhabdus、Anaerotruncus和Collinsella在各种分析方法中一致显示出更高的HNF1A-MODY丰度。用MaAsLin2鉴定的非培养属的相关性最强（P = 0.0004，经fdr校正P = 0.071）。这些分类群涉及代谢和炎症过程，包括葡萄糖和脂质代谢。各组间β -多样性无显著差异。加权UniFrac分析显示，GCK-MODY个体与HNF1A-MODY个体的GM群落结构存在差异（PERMANOVA, R2 = 0.078, P = 0.014），但经多重检验校正后，差异无统计学意义（调整后P = 0.072）。差异丰度分析没有发现任何在错误发现率校正后仍然显著的属。然而，Enterorhabdus、Anaerotruncus和Collinsella在各种分析方法中一致显示出更高的HNF1A-MODY丰度。用MaAsLin2鉴定的非培养属的相关性最强（P = 0.0004，经fdr校正P = 0.071）。这些分类群涉及代谢和炎症过程，包括葡萄糖和脂质代谢。结论经过多次检验校正后，虽然没有属间存在显著差异，但加权UniFrac分析和多种分析方法间一致的丰度模式提示GCK-MODY和HNF1A-MODY个体间转基因成分存在潜在差异。这些初步发现支持进一步的研究，以更好地表征与不同MODY亚型相关的GM谱。尽管经过多次检验校正后，没有属存在显著差异，但加权UniFrac分析和多种分析方法一致的丰度模式表明，GCK-MODY和HNF1A-MODY个体之间的转基因成分存在潜在差异。这些初步发现支持进一步的研究，以更好地表征与不同MODY亚型相关的GM谱。

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Gut microbiota beta-diversity and genus-level differential abundance in GCK-MODY and HNF1A-MODY: A pilot study

Objective

To investigate differences in gut microbiota (GM) beta-diversity and genus-level differential abundance between individuals with glucokinase-maturity-onset diabetes of the young (GCK-MODY) and hepatocyte nuclear factor 1-alpha (HNF1A-MODY).

Methods

This observational study included 33 individuals with genetically confirmed MODY caused by pathogenic or likely pathogenic variants in the GCK (n = 16) and HNF1A (n = 17) genes, classified according to the American College of Medical Genetics and Genomics guidelines. Participants had a mean age of 38.3 ± 14.7 years. Blood samples were collected for genetic analysis, and fecal samples were obtained using a swab-based stool collection kit for DNA extraction and 16S rRNA gene sequencing. GM beta-diversity was assessed using Bray–Curtis, Jaccard, unweighted UniFrac, and weighted UniFrac distance metrics. Differential abundance analyses at the genus level were performed using LinDA, limma-voom, and MaAsLin2. Statistical analyses were conducted in R version 4.2.1, with P < 0.05 considered statistically significant. The study received ethical approval from HUCFF/UFRJ (CAAE 04232512.4.0000.5257), IPPMG/UFRJ (Approval No. 6.126.045), and IOC/FIOCRUZ (CAAE 44726720.4.0000.5248).

Results

No significant differences in beta-diversity were observed between groups. Weighted UniFrac analysis suggested differences in GM community structure between GCK-MODY and HNF1A-MODY individuals (PERMANOVA, R² = 0.078, P = 0.014), although statistical significance was not maintained after multiple-testing correction (adjusted P = 0.072). Differential abundance analyses did not identify any genera that remained significant after false discovery rate correction. However, Enterorhabdus, Anaerotruncus, and Collinsella consistently showed higher abundance in HNF1A-MODY across analytical approaches. The strongest association was observed for an uncultured genus identified by MaAsLin2 (P = 0.0004; FDR-adjusted P = 0.071). These taxa have been implicated in metabolic and inflammatory processes including glucose and lipid metabolism.

Conclusion

Although no genera remained significantly different after multiple-testing correction, weighted UniFrac analysis and consistent abundance patterns across multiple analytical methods suggest potential differences in GM composition between GCK-MODY and HNF1A-MODY individuals. These preliminary findings support further investigation to better characterize GM profiles associated with distinct MODY subtypes.

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来源期刊

CAHIERS DE NUTRITION ET DE DIETETIQUE NUTRITION & DIETETICS-

CiteScore

0.60

自引率

33.30%

发文量

审稿时长

65 days

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