Human Milk Oligosaccharides in Exercise Nutrition: Structure-Specific Evidence, Human Efficacy, and Translational Bottlenecks
- 1School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
- 2National Institute of Biological Sciences, Beijing 102206, China
Abstract
Background/Objectives: Human milk oligosaccharides (HMOs) are structurally diverse bioactive carbohydrates being investigated beyond early-life nutrition. General gut–muscle and short-chain fatty acid (SCFA) frameworks are well described. This review aimed to assess structure-specific evidence for HMO effects on human exercise outcomes and identify the main translational bottlenecks. Methods: This critical translational review systematically searched PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online), Embase, Web of Science Core Collection, Scopus, and SPORTDiscus. Evidence was assigned non-exclusively to Layer A (direct exercise evidence), Layer B (exercise-relevant mechanisms), or Layer C (adult translational evidence). We separately evaluated HMO structure, prespecified human efficacy outcomes, within-model causal support, and distance from healthy human exercise. Results: The five databases yielded 4787 records; 40 reports representing 38 independent studies were included. Several HMOs were tolerated at the doses and durations tested and produced structure-, dose-, and host-dependent microbial responses; limited systemic exposure was documented for selected structures. Some intestinal and disease-model pathways had perturbation, knockout, transfer, or rescue support. However, direct human exercise evidence was sparse and inconsistent: primary or overall interaction tests were generally null, whereas favorable findings were mainly secondary, interim, within-group, or exploratory. No study established the complete sequence from oral exposure to target engagement, healthy skeletal-muscle adaptation, and improved performance. Conclusions: Current evidence supports biological activity and testability of selected HMOs, but not an HMO class effect, a confirmed ergogenic mechanism, or a recommendation for exercise-performance use. Translation is constrained by four unresolved links: structure to exposure, exposure to target engagement, target engagement to muscle phenotype, and muscle phenotype to functional benefit.
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BibTeX
@article{qiao2026human,
title = {{Human Milk Oligosaccharides in Exercise Nutrition: Structure-Specific Evidence, Human Efficacy, and Translational Bottlenecks}},
author = {Chuyuan Qiao and Sitong Guo and Shenglei Yang and Chuwei Yang and Yan Wang},
journal = {Nutrients},
year = {2026},
month = oct,
doi = {10.3390/nu18203417},
url = {https://www.mdpi.com/2072-6643/18/20/3417},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Human Milk Oligosaccharides in Exercise Nutrition: Structure-Specific Evidence, Human Efficacy, and Translational Bottlenecks
AU - Chuyuan Qiao
AU - Sitong Guo
AU - Shenglei Yang
AU - Chuwei Yang
AU - Yan Wang
PY - 2026
DA - 2026/10/18
JO - Nutrients
DO - 10.3390/nu18203417
UR - https://www.mdpi.com/2072-6643/18/20/3417
AB - Background/Objectives: Human milk oligosaccharides (HMOs) are structurally diverse bioactive carbohydrates being investigated beyond early-life nutrition. General gut–muscle and short-chain fatty acid (SCFA) frameworks are well described. This review aimed to assess structure-specific evidence for HMO effects on human exercise outcomes and identify the main translational bottlenecks. Methods: This critical translational review systematically searched PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online), Embase, Web of Science Core Collection, Scopus, and SPORTDiscus. Evidence was assigned non-exclusively to Layer A (direct exercise evidence), Layer B (exercise-relevant mechanisms), or Layer C (adult translational evidence). We separately evaluated HMO structure, prespecified human efficacy outcomes, within-model causal support, and distance from healthy human exercise. Results: The five databases yielded 4787 records; 40 reports representing 38 independent studies were included. Several HMOs were tolerated at the doses and durations tested and produced structure-, dose-, and host-dependent microbial responses; limited systemic exposure was documented for selected structures. Some intestinal and disease-model pathways had perturbation, knockout, transfer, or rescue support. However, direct human exercise evidence was sparse and inconsistent: primary or overall interaction tests were generally null, whereas favorable findings were mainly secondary, interim, within-group, or exploratory. No study established the complete sequence from oral exposure to target engagement, healthy skeletal-muscle adaptation, and improved performance. Conclusions: Current evidence supports biological activity and testability of selected HMOs, but not an HMO class effect, a confirmed ergogenic mechanism, or a recommendation for exercise-performance use. Translation is constrained by four unresolved links: structure to exposure, exposure to target engagement, target engagement to muscle phenotype, and muscle phenotype to functional benefit.
SN - 2072-6643
ER -