人乳寡糖与儿童早期肥胖反弹之间的关联：东北医学大数据库项目出生及三代队列研究的病例对照研究

Association Between Human Milk Oligosaccharides and Early Adiposity Rebound in Children: A Case-Control Study of the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

作者信息

Sawane Kento, Takahashi Ippei, Ishikuro Mami, Takumi Hiroko, Orui Masatsugu, Noda Aoi, Shinoda Genki, Ohseto Hisashi, Onuma Tomomi, Ueno Fumihiko, Murakami Keiko, Higuchi Naoko, Tanaka Tomoko, Furuyashiki Takashi, Nakamura Tomohiro, Koshiba Seizo, Ohneda Kinuko, Kumada Kazuki, Ogishima Soichi, Hozawa Atsushi, Sugawara Junichi, Kuriyama Shinichi, Obara Taku

机构信息

Ezaki Glico Co.,Ltd., Osaka, Japan.

Division of Molecular Epidemiology, Graduate School of Medicine, Tohoku University, Sendai, Japan.

出版信息

J Nutr. 2025 May;155(5):1498-1507. doi: 10.1016/j.tjnut.2025.02.024. Epub 2025 Mar 8.

DOI:10.1016/j.tjnut.2025.02.024

PMID:40058699

Abstract

BACKGROUND

Adiposity rebound (AR) is the point when the BMI begins to rise again during early childhood. Early AR (before age 5) is associated with higher risk of lifelong obesity and metabolic disorders and may be influenced by breastfeeding. Although human milk oligosaccharides (HMOs) in breast milk are crucial for child growth, their association with AR status has not been studied.

OBJECTIVES

This study aimed to explore the association between breast milk HMOs and AR status in children.

METHODS

In this case-control study, we included 184 mother-child pairs from the Tohoku Medical Megabank Project Birth and Three-Generation (TMM BirThree) Cohort Study (93 AR cases, 91 controls). Breast milk was collected 1 mo postpartum, and the concentration of 15 HMO molecules and α-diversity index (Inverse Simpson index) were quantified. Wilcoxon rank-sum test and partial least squares-discriminant analysis identified candidate HMOs, and multivariable logistic regression analysis evaluated associations between candidate HMOs and AR status. Analyses were stratified by maternal secretor status (secretor or nonsecretor).

RESULTS

In secretor mothers, multivariable logistic regression showed that the inverse Simpson index [odds ratio (OR): 0.54; 95% CI: 0.36, 0.82), the sum of sialic acid-bound HMOs (OR: 0.61; 95% CI: 0.41, 0.91), and 3'-sialyllactose (OR: 0.67; 95% CI: 0.46, 0.98) were inversely associated with early AR in the fully adjusted model. A trend of interaction between sialyl-lacto-N-tetraose-a (LSTa) and maternal secretor status regarding AR was observed in the fully adjusted model (P-interaction = 0.051).

CONCLUSIONS

α-Diversity, sialic acid-bound HMOs, and 3'-sialyllactose may involved in inhibiting AR in children of secretor mothers, and a trend of interactive effect between LSTa and maternal secretor status regarding AR is indicated. These findings offer novel perspectives on the associations between breastfeeding and a childhood adiposity as well as potential metabolic disorders later in life. This trial is registered at https://www.umin.ac.jp/ as UMIN000047160.

摘要

背景

肥胖反弹（AR）是指儿童早期身体质量指数（BMI）开始再次上升的时间点。早期肥胖反弹（5岁之前）与终生肥胖和代谢紊乱的较高风险相关，并且可能受到母乳喂养的影响。尽管母乳中的人乳寡糖（HMOs）对儿童生长至关重要，但它们与肥胖反弹状况之间的关联尚未得到研究。

目的

本研究旨在探讨母乳中的人乳寡糖与儿童肥胖反弹状况之间的关联。

方法

在这项病例对照研究中，我们纳入了来自东北医学大数据库项目出生及三代人（TMM BirThree）队列研究的184对母婴（93例肥胖反弹病例，91例对照）。产后1个月收集母乳，并对15种人乳寡糖分子的浓度和α-多样性指数（辛普森逆指数）进行定量分析。采用Wilcoxon秩和检验和偏最小二乘判别分析确定候选的人乳寡糖，并通过多变量逻辑回归分析评估候选的人乳寡糖与肥胖反弹状况之间的关联。分析按母亲分泌型状态（分泌型或非分泌型）进行分层。

结果

在分泌型母亲中，多变量逻辑回归显示，在完全调整模型中，辛普森逆指数[比值比（OR）：0.54；95%置信区间（CI）：0.36，0.82]、唾液酸结合型人乳寡糖总和（OR：0.61；95%CI：0.41，0.91）和3'-唾液酸乳糖（OR：0.67；95%CI：0.46，0.98）与早期肥胖反弹呈负相关。在完全调整模型中观察到唾液酸乳糖-N-四糖-a（LSTa）与母亲分泌型状态在肥胖反弹方面存在交互作用趋势（交互作用P值=0.051）。

结论

α-多样性、唾液酸结合型人乳寡糖和3'-唾液酸乳糖可能参与抑制分泌型母亲的孩子出现肥胖反弹，并且提示LSTa与母亲分泌型状态在肥胖反弹方面存在交互作用趋势。这些发现为母乳喂养与儿童肥胖以及日后潜在的代谢紊乱之间的关联提供了新的视角。本试验在https://www.umin.ac.jp/上注册，注册号为UMIN000047160。