Breastfeeding, the gut microbiome, and growth among infants in Lusaka, Zambia

Background: In low- and middle-income countries (LMICs), ~250 million young children are at risk of not reaching their full growth and developmental potential. Early-life gut microbiota is increasingly recognized as a key factor influencing long-term growth and development, yet data from LMICs, including Zambia, remain limited.Objective: This sub-study, nested within a 2x2 cluster-randomized trial (NCT05120427) in Lusaka, Zambia, aimed to characterize early-life gut microbiota composition and diversity; examine associations with breastfeeding status, nutritional status, and maternal HIV status; and explore links between the microbiome and child growth and development.Methods: Anthropometry and participant characteristics were assessed at baseline (2-11 months) and after 18 months of intervention; child development was measured at endline using the Global Scales for Early Development. Rectal swab stool samples were collected from a sub-sample of 247 infants at baseline and profiled via 16S rRNA gene sequencing. Microbial abundances were visualized with stacked bar plots and Uniform Manifold Approximation and Projection for dimensionality reduction. Beta diversity and its associations with explanatory variables were analyzed using distance-based redundancy analysis and non-metric multidimensional scaling. Multivariate linear models evaluated genus-level associations with growth indicators, while random forest regression and partial least squares regression identified predictors of endline growth and development outcomes.Results: We found that breastfeeding and nutritional status showed significant associations with microbiota composition and diversity. However, early microbiota features, even combined with anthropometry, were weak predictors of later growth and development.Conclusions: Overall, further research is needed to clarify early microbiome drivers and their impact on child outcomes, particularly in LMIC settings.

背景：在中低收入国家（low- and middle-income countries, LMICs），约2.5亿幼儿面临无法充分发挥生长与发育潜能的风险。生命早期肠道菌群日益被视为影响长期生长发育的关键因素，但包括赞比亚在内的中低收入国家相关数据仍较为匮乏。
研究目标：本子研究嵌套于赞比亚卢萨卡开展的一项2×2整群随机对照试验（NCT05120427），旨在阐明生命早期肠道菌群的组成与多样性特征，探究其与母乳喂养状态、营养状况及母体HIV感染状态的关联，并剖析菌群与儿童生长发育之间的联系。
研究方法：研究在基线（2~11月龄）与干预18个月后评估了人体测量学指标及受试者特征；采用《全球早期发育量表》（Global Scales for Early Development）在随访终点评估儿童发育情况。我们从基线时的247名婴幼儿亚样本中采集直肠拭子粪便样本，并通过16S rRNA基因测序进行菌群分析。菌群丰度以堆叠柱状图可视化，并采用均匀流形近似与投影（Uniform Manifold Approximation and Projection, UMAP）进行降维分析。基于距离的冗余分析与非度量多维标度法用于分析β多样性及其与解释变量的关联。采用多变量线性模型评估菌属水平指标与生长指标的关联；同时借助随机森林回归与偏最小二乘回归识别随访终点生长与发育结局的预测因子。
研究结果：本研究发现，母乳喂养状态与营养状况与菌群组成及多样性存在显著关联。然而，即便结合人体测量学指标，早期菌群特征对后续生长与发育的预测能力仍较弱。
研究结论：综上，未来仍需开展进一步研究，以阐明生命早期菌群的驱动因素及其对儿童结局的影响，尤其在中低收入国家场景中。