Siegwald Léa, Cherta-Murillo Anna, Christen Stefan, Boulangé Claire L, Chou Chieh J, Foata Francis, Lahiry Anirban, Frézal Adrien, Giner Maria Pilar, Godin Jean-Philippe, Sakwinska Olga
Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland.
Nestlé Institute of Food Safety and Analytical Sciences, Nestlé Research, Lausanne, Switzerland.
Curr Dev Nutr. 2025 Jul 24;9(9):107506. doi: 10.1016/j.cdnut.2025.107506. eCollection 2025 Sep.
Galacto-oligosaccharides (GOS) intake has been linked to health benefits via modulation of the gut microbiome. Milk, where the majority of lactose is enzymatically converted to GOS (called here Novel or "N milk"), retains milk's nutritional value with reduced lactose and a high amount of prebiotic GOS.
The aim of this study was to investigate the effect of N milk on the gut microbiome and related changes in health-related biomarkers, complemented by ex vivo fermentation experiments.
In a 2-arm crossover, double-blind, randomized controlled clinical trial, 26 healthy adults consumed either N milk (containing 9 g GOS and 1.7 g of lactose per serving) or lactose-free milk (control), for 2 wk with a 2-wk washout period. Stool and fasting blood samples were collected at the start and the end of the intervention periods. Gut microbiome was analyzed using shotgun metagenomics, and metabolites using both targeted and untargeted methods. In addition, we tested lactose-free milk, N milk, and GOS in ex vivo colonic fermentation to obtain insights into the bacterial processing of substrates.
N milk intake led to a 3-fold increase in median gut bifidobacteria ( < 0.0001) and significant increases in plasma acetate, octanoic acid, β-alanine, and nicotinamide (all < 0.05). Untargeted plasma metabolomics revealed a shift in amino acid metabolism, with an increase in 3-indole propionate, accompanied by a decrease in 2 uremic toxins, p-cresol sulfate, and indoxyl-sulfate ( < 0.05 without false discovery rate adjustment). Ex vivo fermentation experiments supported the results of the clinical study, whereby N milk increased bifidobacteria accompanied by higher production of short-chain fatty acids and a shift in microbial tryptophan metabolism, and indicated unique effects of N milk compared with GOS.
N milk resulted in a significant increase in gut bifidobacteria, along with changes in plasma metabolites previously associated with immune and metabolic health benefits.This study was registered at clinicaltrials.gov as NCT05207839.
摄入低聚半乳糖（GOS）可通过调节肠道微生物群对健康产生益处。牛奶中大部分乳糖会被酶转化为GOS（此处称为新型或“N牛奶”），它保留了牛奶的营养价值，同时乳糖含量降低，且含有大量益生元GOS。
本研究旨在通过体外发酵实验，探究N牛奶对肠道微生物群的影响以及与健康相关生物标志物的相关变化。
在一项双臂交叉、双盲、随机对照临床试验中，26名健康成年人分别饮用N牛奶（每份含9克GOS和1.7克乳糖）或无乳糖牛奶（对照），为期2周，中间有2周的洗脱期。在干预期开始和结束时收集粪便和空腹血样。使用鸟枪法宏基因组学分析肠道微生物群，使用靶向和非靶向方法分析代谢物。此外，我们在体外结肠发酵中测试了无乳糖牛奶、N牛奶和GOS，以深入了解底物的细菌加工过程。
摄入N牛奶使肠道双歧杆菌中位数增加了3倍（<0.0001），血浆乙酸、辛酸、β-丙氨酸和烟酰胺显著增加（均<0.05）。非靶向血浆代谢组学显示氨基酸代谢发生变化，3-吲哚丙酸增加，同时两种尿毒症毒素对甲酚硫酸盐和吲哚酚硫酸盐减少（未经错误发现率调整时<0.05）。体外发酵实验支持了临床研究结果，即N牛奶增加了双歧杆菌，同时短链脂肪酸产量更高，微生物色氨酸代谢发生变化，并表明N牛奶与GOS相比具有独特作用。
N牛奶使肠道双歧杆菌显著增加，同时血浆代谢物发生变化，这些变化之前与免疫和代谢健康益处相关。本研究已在clinicaltrials.gov上注册，注册号为NCT05207839。
