Short-chain fatty acids are key mediators of the favorable effects of the Mediterranean diet on intestinal barrier integrity: data from the randomized controlled LIBRE trial
Open accessAbstract
Background The Mediterranean diet is associated with the prevention of diabetes, cardiovascular disease, and cancer, all of which are linked to intestinal barrier impairment.Objectives Here, we hypothesize that the Mediterranean diet, possibly via the induction of short-chain fatty acids (SCFAs), improves intestinal barrier integrity. Furthermore, we aim to establish novel personalized nutrition advice based on machine learning algorithms.Methods We studied 260 women with intestinal barrier impairment. The women were allocated to follow either a Mediterranean diet or a control diet for 3 mo. Intestinal permeability was assessed by measuring lipopolysaccharide binding protein (LBP) in plasma and zonulin in feces. SCFA concentrations were analyzed in feces. Bi- and multivariate analyses and machine learning algorithms (random forest classification) were conducted.Results Particularly in the intervention group, adherence to the Mediterranean diet increased, whereas plasma LBP and fecal zonulin concentrations decreased (all q < 0.001 for the intervention group, all q < 0.1 for control group). In the intervention group, fecal SCFA concentrations increased (propionate + 19%; butyrate + 44%; both q < 0.001). Multivariate analyses showed that adherence to the Mediterranean diet was associated with SCFA concentrations (all q < 0.001) and inversely associated with LBP and zonulin concentrations (all q < 0.02). Mediation analyses identified propionate and butyrate as the key mechanistic link between diet and intestinal permeability integrity. Accordingly, using baseline SCFA data, we could predict the effect of the Mediterranean diet on intestinal permeability using a machine learning algorithm (receiver operating characteristic AUC: 0.78-0.96).Conclusions Our data suggest that SCFAs are key mediators for the relation between diet and gut health. Assessment of SCFAs may form a basis for personalized nutrition in future clinical care. These results need to be verified in larger studies powered for this purpose, comprising different study populations. The trial was registered at clinicaltrials.gov as NCT02087592 and NCT02516540.
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The barrier-stabilizing effect of the Mediterranean diet was mediated by propionate and butyrate.
“the barrier-stabilizing effect of the Mediterranean diet was mediated by the propionate and butyrate.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [639]
A 3-month high-fiber intervention with a Mediterranean diet greatly reduced plasma LBP and fecal zonulin concentrations in women with an impaired intestinal barrier.
“a recent randomized clinical trial reported that a 3-month high-fiber intervention with a Mediterranean diet greatly reduced plasma lipopolysaccharide-binding protein (LBP) and fecal zonulin concentrations in women with an impaired intestinal barrier.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [639]
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
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- Authors
- Seethaler, B., Nguyen, N. K., Basrai, M., Kiechle, M., Walter, J., Delzenne, N. M., & Bischoff, S. C.
- Affiliations
- University of Hohenheim (DE)
- TUM Klinikum (DE)
- University College Cork (IE)
- UCLouvain (BE)
- Corresponding author
- Bischoff, Stephan C
- ORCID
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2022-10
- Volume
- 116
- Issue
- 4
- Pages
- 928-942
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W4294543685
- Cited by
- 179
- References
- 53
- Citations by year
- 2026: 46 · 2025: 61 · 2024: 47 · 2023: 23 · 2022: 2
- FWCI
- 10.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Libraries (submittedVersion, other-oa)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Funders
- Federal Ministry of Education and Research (01EA1701)
- German Cancer Aid (110013, 111888)
- Senator Rösner Foundation
- Waltraut Bergmann Foundation
- Sphingotec GmbH
- Science Foundation Ireland (APC/SFI/12/RC/2273_P2, 19/RP/6853)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- Mediterranean diet, short-chain fatty acids, intestinal barrier integrity, intestinal permeability, butyrate, propionate, lipopolysaccharide-binding protein, zonulin, personalized nutrition, dietary adherence, gut health, women
- MeSH terms
- Butyrates, Fatty Acids, Volatile, Feces, Female, Humans, Lipopolysaccharides, Propionates, Diet, Mediterranean
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