Short-chain fatty acids are key mediators of the favorable effects of the Mediterranean diet on intestinal barrier integrity, 2022, Seethaler et al

Andy

Retired committee member
ABSTRACT

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.

Open access, https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqac175/6687830
 
Is the Mediterranean diet high-fibre? I never thought it qualified for that. AFAIK, it's the fibre that feeds/supports the bacteria that produce the SCFAs. Hmmm, isn't SCFA production mostly in the colon, while intestinal permeability problems generally occur further upstream? My off-the-cuff guess is that they did their study, then mined it for random correlations that would be newsworthy. Maybe they're depending on the reluctance of researchers to do follow-up studies that might show that the correlations are just random chance.
 
I mention omega-3 because the Mediterranean diet is comprised of the foods that provide the highest amounts of this fatty acid (fish, seeds, nuts, leafy veg and some oils), so it could be tricky to distinguish between SCFAs and omega-3s as the source of the improvement in intestinal permeability markers.
 
The mediterranean diet is typically considered "high fibre", but there are >30 indexes to measure adherence to this diet.. For example some use a threshold value for the amount of fibre or vegetables to be included in a diet for a participant to be seen as "adhering" to the diet, others use quartiles so that those in the top quartile is seen as adhering and the others not. The quartiles will obviously vary between populations studied so when comparing studies on "mediterranean diet" the actual diets can be quite different.
I mention omega-3 because the Mediterranean diet is comprised of the foods that provide the highest amounts of this fatty acid (fish, seeds, nuts, leafy veg and some oils), so it could be tricky to distinguish between SCFAs and omega-3s as the source of the improvement in intestinal permeability markers.
There could also be synergistic effects :) Omega-3 intake is quite visible in blood samples so if one bothers to look it should be possible to control for it.
 
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