Oyama Sakurako, Arslanian Kendall J, Savo Sardaro Maria Luisa, Duckham Rachel L, Kershaw Erin E, Wood Ashlee N, Fidow Ulai T, Naseri Take, Reupena Muagututia S, Amato Katherine R, Hawley Nicola L
Department of Anthropology, Yale University, New Haven, Connecticut, United States.
Yale School of Medicine, New Haven, Connecticut, United States.
Physiol Genomics. 2025 Aug 1;57(8):473-484. doi: 10.1152/physiolgenomics.00014.2024. Epub 2025 May 14.
Over 40% of Samoans have at least one copy of the minor A allele at rs373863828 in encoding CREB3 regulatory factor (), which is associated with increased body mass index (BMI) but decreased odds of type 2 diabetes mellitus. The mechanisms underlying this paradoxical effect remain unknown. We hypothesized that gut microbiota may play a role and examined associations between genotype and gut microbial diversity and composition among Samoan infants. Fecal samples were collected from Samoan infants aged 0 ( = 23), 4 ( = 20), and 21 ( = 27) mo. Microbiota community structure was analyzed using 16S rRNA bacterial gene sequencing. Both cross-sectional and longitudinal analyses revealed no associations between genotype and overall microbiome composition or diversity at 0 or 4 mo. Cross-sectional analysis at 21 mo revealed a significant association between genotype and unweighted UniFrac distances ( = 1.855, = 0.072, = 0.015). Longitudinal differential abundance analysis also revealed several differentially abundant taxa at 21 mo. Notably, the AG genotype was associated with a lower relative abundance of (β = -6.741, SE = 2.243, = 0.004, = 0.042). Significant genotype differences in gut microbiome composition and diversity at 21 mo suggest that gut microbiota may be involved in relationships between genotype and metabolic health. No genotype differences were observed at 0 or 4 mo, suggesting that environmental and/or maternal variables have a greater influence on the gut microbiome in early infancy, and genotype effects emerge later. Further research should examine whether genotype differences in gut microbiota are associated with functional differences in metabolic or immune signaling pathways or energy extraction. Missense variant rs373863828 in is associated with higher odds of obesity but lower odds of diabetes among Polynesians. We examined associations between genotype and gut microbial diversity and composition among Samoan infants and identified significant differences at age 21 mo but not at age 0 or 4 mo. These results suggest that gut microbiota may contribute to the mechanisms through which genotype impacts metabolic health.
超过40%的萨摩亚人在编码CREB3调节因子的rs373863828位点至少有一份次要A等位基因拷贝，这与体重指数（BMI）升高但2型糖尿病几率降低有关。这种矛盾效应背后的机制尚不清楚。我们推测肠道微生物群可能起作用，并研究了萨摩亚婴儿的该基因型与肠道微生物多样性和组成之间的关联。从0个月（n = 23）、4个月（n = 20）和21个月（n = 27）的萨摩亚婴儿中采集粪便样本。使用16S rRNA细菌基因测序分析微生物群落结构。横断面和纵向分析均显示，在0个月或4个月时，该基因型与总体微生物组组成或多样性之间无关联。21个月时的横断面分析显示，基因型与未加权UniFrac距离之间存在显著关联（F = 1.855，P = 0.072，q = 0.015）。纵向差异丰度分析还显示，在21个月时有几种差异丰富的分类群。值得注意的是，AG基因型与某菌属的相对丰度较低有关（β = -6.741，SE = 2.243，P = 0.004，q = 0.042）。21个月时肠道微生物组组成和多样性的显著基因型差异表明，肠道微生物群可能参与了该基因型与代谢健康之间的关系。在0个月或4个月时未观察到基因型差异，这表明环境和/或母体变量在婴儿早期对肠道微生物群有更大影响，而基因型效应在后期出现。进一步的研究应检查肠道微生物群中的基因型差异是否与代谢或免疫信号通路或能量提取中的功能差异相关。编码CREB3调节因子的错义变体rs373863828与波利尼西亚人中较高的肥胖几率但较低的糖尿病几率相关。我们研究了萨摩亚婴儿的该基因型与肠道微生物多样性和组成之间的关联，并确定在21个月龄时有显著差异，而在0个月或4个月龄时没有。这些结果表明，肠道微生物群可能有助于该基因型影响代谢健康的机制。
