低乳糖高半乳糖低聚糖牛奶对健康成人肠道微生物组和血浆代谢组的影响：一项随机、双盲、对照临床试验，并辅以离体实验

IF 3.2 Q2 NUTRITION & DIETETICS

Current Developments in Nutrition Pub Date : 2025-07-24 DOI:10.1016/j.cdnut.2025.107506

Léa Siegwald , Anna Cherta-Murillo , Stefan Christen , Claire L Boulangé , Chieh J Chou , Francis Foata , Anirban Lahiry , Adrien Frézal , Maria Pilar Giner , Jean-Philippe Godin , Olga Sakwinska

{"title":"低乳糖高半乳糖低聚糖牛奶对健康成人肠道微生物组和血浆代谢组的影响：一项随机、双盲、对照临床试验，并辅以离体实验","authors":"Léa Siegwald , Anna Cherta-Murillo , Stefan Christen , Claire L Boulangé , Chieh J Chou , Francis Foata , Anirban Lahiry , Adrien Frézal , Maria Pilar Giner , Jean-Philippe Godin , Olga Sakwinska","doi":"10.1016/j.cdnut.2025.107506","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Objectives</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>N milk intake led to a 3-fold increase in median gut bifidobacteria (<em>P</em> < 0.0001) and significant increases in plasma acetate, octanoic acid, β-alanine, and nicotinamide (all <em>P</em> < 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 (<em>P</em> < 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.</div></div><div><h3>Conclusions</h3><div>N milk resulted in a significant increase in gut bifidobacteria, along with changes in plasma metabolites previously associated with immune and metabolic health benefits.</div><div>This study was registered at <span><span>clinicaltrials.gov</span><svg><path></path></svg></span> as NCT05207839.</div></div>","PeriodicalId":10756,"journal":{"name":"Current Developments in Nutrition","volume":"9 9","pages":"Article 107506"},"PeriodicalIF":3.2000,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Impact of Low-Lactose, High Galacto-Oligosaccharides Milk on Gut Microbiome and Plasma Metabolome in Healthy Adults: A Randomized, Double-Blind, Controlled Clinical Trial Complemented by Ex Vivo Experiments\",\"authors\":\"Léa Siegwald , Anna Cherta-Murillo , Stefan Christen , Claire L Boulangé , Chieh J Chou , Francis Foata , Anirban Lahiry , Adrien Frézal , Maria Pilar Giner , Jean-Philippe Godin , Olga Sakwinska\",\"doi\":\"10.1016/j.cdnut.2025.107506\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>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.</div></div><div><h3>Objectives</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>N milk intake led to a 3-fold increase in median gut bifidobacteria (<em>P</em> < 0.0001) and significant increases in plasma acetate, octanoic acid, β-alanine, and nicotinamide (all <em>P</em> < 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 (<em>P</em> < 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.</div></div><div><h3>Conclusions</h3><div>N milk resulted in a significant increase in gut bifidobacteria, along with changes in plasma metabolites previously associated with immune and metabolic health benefits.</div><div>This study was registered at <span><span>clinicaltrials.gov</span><svg><path></path></svg></span> as NCT05207839.</div></div>\",\"PeriodicalId\":10756,\"journal\":{\"name\":\"Current Developments in Nutrition\",\"volume\":\"9 9\",\"pages\":\"Article 107506\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-07-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current Developments in Nutrition\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2475299125029671\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"NUTRITION & DIETETICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Developments in Nutrition","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2475299125029671","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}

引用次数: 0

摘要

半乳糖低聚糖（GOS）的摄入通过调节肠道微生物群与健康益处有关。牛奶中的大部分乳糖被酶转化为GOS（这里称为Novel或“N牛奶”），通过减少乳糖和大量益生元GOS保留了牛奶的营养价值。本研究的目的是通过体外发酵实验，研究N乳对肠道微生物组的影响以及与健康相关的生物标志物的相关变化。方法在一项两组交叉、双盲、随机对照的临床试验中，26名健康成年人在2周的时间内饮用N牛奶（每份含有9 g GOS和1.7 g乳糖）或不含乳糖的牛奶（对照组），并进行2周的洗脱期。在干预期开始和结束时采集粪便和空腹血液样本。使用散弹枪宏基因组学分析肠道微生物组，使用靶向和非靶向方法分析代谢物。此外，我们在离体结肠发酵中测试了无乳糖牛奶、N牛奶和GOS，以深入了解细菌对底物的处理。结果n牛奶摄入导致肠道双歧杆菌中位数增加3倍（P < 0.0001），血浆乙酸、辛酸、β-丙氨酸和烟酰胺显著增加（P < 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2种尿毒症毒素、对甲酚硫酸盐和吲哚基硫酸盐减少（P < 0.05，未调整错误发现率）。体外发酵实验支持了临床研究的结果，即N乳增加了双歧杆菌，同时增加了短链脂肪酸的产量，并改变了微生物色氨酸代谢，与GOS相比，N乳具有独特的作用。结论牛奶导致肠道双歧杆菌的显著增加，同时血浆代谢物的变化也与免疫和代谢健康益处相关。本研究在clinicaltrials.gov注册为NCT05207839。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

The Impact of Low-Lactose, High Galacto-Oligosaccharides Milk on Gut Microbiome and Plasma Metabolome in Healthy Adults: A Randomized, Double-Blind, Controlled Clinical Trial Complemented by Ex Vivo Experiments

Background

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.

Objectives

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.

Methods

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.

Results

N milk intake led to a 3-fold increase in median gut bifidobacteria (P < 0.0001) and significant increases in plasma acetate, octanoic acid, β-alanine, and nicotinamide (all P < 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 (P < 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.

Conclusions

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.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊