Tier 4 — mechanistic

Molecular weight and gut microbiota determine the bioavailability of orally administered hyaluronic acid

Matěj Šimek, Kristýna Turková, Martin Schwarzer, Kristina Nešporová, Lukáš Kubala, Martina Hermannová, Tereza Foglová, Barbora Šafránková, Martin Šindelář, Dagmar Šrůtková, Sofia Chatzigeorgiou, Tereza Novotná, Tomáš Hudcovic, Vladimír Velebný
Carbohydrate Polymers 2023 313:120880

Bibliography

PubMed
PMID 37182970
DOI
10.1016/j.carbpol.2023.120880
Competing interests
The authors declared no competing interests; several authors were affiliated with Contipro a.s.

Study snapshot

DesignMechanistic isotope-tracing study in germ-free and conventional mice
ModelGerm-free and conventional wild-type mice
SampleAnimal experiment
InterventionOrally administered 13C-labeled hyaluronic acid of differing molecular weights
DurationAcute absorption and metabolism experiment
EndpointsHA digestion; Microbiome-dependent cleavage; Intestinal absorption; Systemic bioavailability; Short-chain fatty acid metabolism

What the study showed, in plain terms

This mechanistic study used isotope-labeled hyaluronic acid in mice to investigate what happens after oral ingestion.

Bacteroides species were important for breaking HA into small oligosaccharides, some of which crossed the intestinal wall. Most remaining fragments were metabolized further, and estimated systemic bioavailability of intact/traceable HA-related material was low, around 0.2%.

The findings argue against simplistic claims that an oral HA capsule simply reaches the skin or joints intact. They support a more complex microbiome- and metabolite-mediated mechanism, but they do not test clinical efficacy in humans.

Key findings

  • Gut Bacteroides were important for HA cleavage and absorption.
  • HA was cleaved into oligosaccharides smaller than 3 kDa, some of which were absorbed.
  • Estimated oral bioavailability was low, around 0.2%, suggesting indirect regulatory mechanisms may matter.

What this study can and cannot tell us

  • Animal study, not a human pharmacokinetic trial.
  • Bioavailability estimates from mice cannot be directly converted into human supplement absorption percentages.
  • Mechanistic findings do not establish skin or joint efficacy.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology