Common genetic variants in vitamin D metabolism-related genes affect gut microbiota diversity in postmenopausal women.

IF 2.8 3区医学 Q2 GENETICS & HEREDITY

Genes and Nutrition Pub Date : 2026-05-19 DOI:10.1186/s12263-026-00806-y

Adriana Becerra-Cervera, Rogelio F Jiménez-Ortega, Diana I Aparicio-Bautista, Tania V López-Pérez, Edgar Denova-Gutiérrez, Berenice Palacios-González, Alberto Hidalgo-Bravo, Samuel Canizales-Quinteros, Jorge Salmerón, Berenice Rivera-Paredez, Rafael Velázquez-Cruz

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引用次数: 0

Abstract

Background: Recent studies have demonstrated that vitamin D (VD) influences gut microbiota (GM) by regulating epithelial barrier function and immune responses, thereby affecting microbial composition and diversity. Additionally, host genetic factors, particularly single-nucleotide variants (SNVs) in genes related to VD metabolism, may influence GM composition. Postmenopausal women are a particularly relevant population to assess the impact of these SNVs, as this group experiences reduced hormonal variability and a higher burden of vitamin D deficiency (VDD), enabling clearer evaluation of the association between vitamin D-related genetic variants and gut microbiota composition.

Objective: To explore the relationship between SNVs in genes involved in VD metabolism and their impact on GM.

Methods: We genotyped nine variants: rs10741657 (CYP2R1), rs6013897 (CYP24A1), rs10877012 (CYP27B1), rs10783219 and rs4516035 (VDR), rs4588 and rs7041 (GC), rs4944957 and rs3794060 (NADSYN1). GM was characterized by sequencing the V4 hypervariable region of the 16S rRNA gene. We compared taxon abundance at the genus level across host genotypes using the dominant model. Quantile regression was used to analyze non-mean diversity responses, and PICRUSt2 identified functional pathways. We also calculated the genetic risk score (GRS) using rs4516035, rs3794060, and rs4944957, which were associated with lower alpha diversity.

Results: Alpha microbial diversity differed significantly for the VDR (rs4516035) and NADSYN1 (rs3794060, rs4944957) variants, both for risk alleles and genotypes. Differential abundance analysis identified taxonomic disparities, notably in the genera DTU014, Fusobacterium, Negativibacillus, Pseudomonas, Peptococcus, and [Clostridium]_innocuum_group. PICRUSt2-predicted functional pathways for the rs4516035- C allele revealed significant glutamine-glutamate, folate, galactose, and fatty acid metabolism. A GRS was associated with lower alpha diversity indices and differences in the insulin signaling pathway and oxidative phosphorylation.

Conclusions: These findings highlight the role of SNVs in GM modulation and suggest potential implications for VD metabolism and host health.

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维生素D代谢相关基因的常见遗传变异影响绝经后妇女肠道微生物群的多样性。

背景：最近的研究表明，维生素D （VD）通过调节上皮屏障功能和免疫反应来影响肠道微生物群（GM），从而影响微生物的组成和多样性。此外，宿主遗传因素，特别是VD代谢相关基因中的单核苷酸变异（snv），可能影响转基因成分。绝经后妇女是评估这些snv影响的特别相关人群，因为这一群体的激素变异性较低，维生素D缺乏症（VDD）负担较高，因此可以更清楚地评估维生素D相关遗传变异与肠道微生物群组成之间的关系。目的：探讨VD代谢相关基因SNVs与gm的关系。方法：对9个变异rs10741657 （CYP2R1）、rs6013897 （CYP24A1）、rs10877012 （CYP27B1）、rs10783219和rs4516035 （VDR）、rs4588和rs7041 （GC）、rs4944957和rs3794060 （NADSYN1）进行基因分型。通过对16S rRNA基因的V4高变区进行测序鉴定。我们使用优势模型比较了不同宿主基因型在属水平上的分类群丰度。分位数回归用于分析非平均多样性响应，PICRUSt2识别功能途径。我们还使用与α多样性较低相关的rs4516035、rs3794060和rs4944957计算遗传风险评分（GRS）。结果：VDR （rs4516035）和NADSYN1 （rs3794060、rs4944957）变异的α微生物多样性在风险等位基因和基因型上均存在显著差异。差异丰度分析发现了分类学上的差异，特别是在DTU014属、Fusobacterium、Negativibacillus、Pseudomonas、Peptococcus和Clostridium _innocuum_group中。picrust2预测的rs4516035- C等位基因的功能通路显示了显著的谷氨酰胺-谷氨酸、叶酸、半乳糖和脂肪酸代谢。GRS与较低的α多样性指数以及胰岛素信号通路和氧化磷酸化的差异有关。结论：这些发现突出了snv在转基因调控中的作用，并提示了VD代谢和宿主健康的潜在影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Genes and Nutrition 生物-遗传学

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： This journal examines the relationship between genetics and nutrition, with the ultimate goal of improving human health. It publishes original research articles and review articles on preclinical research data coming largely from animal, cell culture and other experimental models as well as critical evaluations of human experimental data to help deliver products with medically proven use.