Bifidobacterium longum and microbiome maturation modify a nutrient intervention for stunting in Zimbabwean infants.

IF 9.7 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL EBioMedicine Pub Date : 2024-10-01 Epub Date: 2024-09-27 DOI:10.1016/j.ebiom.2024.105362
Ethan K Gough, Thaddeus J Edens, Lynnea Carr, Ruairi C Robertson, Kuda Mutasa, Robert Ntozini, Bernard Chasekwa, Hyun Min Geum, Iman Baharmand, Sandeep K Gill, Batsirai Mutasa, Mduduzi N N Mbuya, Florence D Majo, Naume Tavengwa, Freddy Francis, Joice Tome, Ceri Evans, Margaret Kosek, Andrew J Prendergast, Amee R Manges
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Abstract

Background: Small-quantity lipid-based nutrient supplements (SQ-LNS), which has been widely tested to reduce child stunting, has largely modest effects to date, but the mechanisms underlying these modest effects are unclear. Child stunting is a longstanding indicator of chronic undernutrition and it remains a prevalent public health problem. The infant gut microbiome may be a key contributor to stunting; and mother and infant fucosyltransferase (FUT) phenotypes are important determinants of infant microbiome composition.

Methods: We investigated whether mother-infant FUT status (n = 792) and infant gut microbiome composition (n = 354 fecal specimens from 172 infants) modified the impact of an infant and young child feeding (IYCF) intervention, that included SQ-LNS, on stunting at age 18 months in secondary analysis of a randomized trial in rural Zimbabwe.

Findings: We found that the impact of the IYCF intervention on stunting was modified by: (i) mother-infant FUT2+/FUT3- phenotype (difference-in-differences -32.6% [95% CI: -55.3%, -9.9%]); (ii) changes in species composition that reflected microbiome maturation (difference-in-differences -68.1% [95% CI: -99.0%, -28.5%); and (iii) greater relative abundance of B. longum (differences-in-differences 49.1% [95% CI: 26.6%, 73.6%]). The dominant strains of B. longum when the intervention started were most similar to the proficient milk oligosaccharide utilizer subspecies infantis, which decreased with infant age and differed by mother-infant FUT2+/FUT3- phenotypes.

Interpretation: These findings indicate that a persistently "younger" microbiome at initiation of the intervention reduced its benefits on stunting in areas with a high prevalence of growth restriction.

Funding: Bill and Melinda Gates Foundation, UK DFID/Aid, Wellcome Trust, Swiss Agency for Development and Cooperation, US National Institutes of Health, UNICEF, and Nutricia Research Foundation.

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长双歧杆菌和微生物组的成熟改变了对津巴布韦婴儿发育迟缓的营养干预。
背景:小量脂质营养补充剂(SQ-LNS)已被广泛测试用于减少儿童发育迟缓,但迄今为止,这种补充剂的效果并不明显,而产生这种微弱效果的机制尚不清楚。儿童发育迟缓是慢性营养不良的一个长期指标,也是一个普遍存在的公共卫生问题。婴儿肠道微生物组可能是导致发育迟缓的一个关键因素;而母亲和婴儿的岩藻糖基转移酶(FUT)表型是婴儿微生物组组成的重要决定因素:我们调查了母婴岩藻糖基转移酶状态(n = 792)和婴儿肠道微生物组组成(n = 来自 172 名婴儿的 354 份粪便标本)是否会改变包括 SQ-LNS 在内的婴幼儿喂养(IYCF)干预措施对 18 个月大婴儿发育迟缓的影响:我们发现,"养育子女干预措施 "对发育迟缓的影响受以下因素影响(i) 母婴 FUT2+/FUT3- 表型(差异-32.6% [95% CI: -55.3%, -9.9%]);(ii) 反映微生物组成熟的物种组成变化(差异-68.1% [95% CI: -99.0%, -28.5%]);(iii) B. longum 的相对丰度增加(差异 49.1% [95% CI: 26.6%, 73.6%])。干预开始时,长鼻杆菌的优势菌株与精通牛奶寡糖利用的婴儿亚种最为相似,随着婴儿年龄的增长,优势菌株减少,母婴FUT2+/FUT3-表型也有所不同:这些研究结果表明,在生长受限高发地区,干预开始时持续 "年轻化 "的微生物群降低了干预对发育迟缓的益处:比尔及梅林达-盖茨基金会、英国国际发展部/援助署、惠康基金会、瑞士发展与合作署、美国国立卫生研究院、联合国儿童基金会和Nutricia研究基金会。
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来源期刊
EBioMedicine
EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
17.70
自引率
0.90%
发文量
579
审稿时长
5 weeks
期刊介绍: eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.
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