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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

Léa Siegwald, Anna Cherta-Murillo, Stefan Christen, C. L. Boulangé, C. Chou, Francis Foata, A. Lahiry, A. Frézal et al.

Current Developments in Nutrition, 2025

26 participants · 3 citations

Abstract

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,…

How strong is the evidence?

Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 26 participants or records.

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