Mangia!  Mangia!


Today I want to write about an Italian study that sought to find out if adding the prebiotic inulin to pasta would have any effect on intestinal permeability. In other words, would the augmentation of beneficial gut flora lessen a leaky gut? (1)

Now, before I twirl my fork around this tasty morsel of scientific research, I can just hear my “Paleo diet” readers snicker at the absurdity of it all. Don’t these researchers know that completely abstaining from gluten would reduce intestinal permeability caused by eating pasta in the first place?

Maybe they do or maybe they don’t. Nowhere in this paper is the work of Alessio Fasano referenced. I found this a bit odd as he is originally from Italy and the foremost researcher on zonulin’s effect on intestinal tight junctions.

But let’s face facts here. All the blog posts and scientific research in the world will have but a small impact on wheat consumption. The reality is that the majority of the world’s population will never give up eating gluten grains.

To paraphrase Thomas Moffet, we humans are quite adept at digging our own graves with our teeth. I seriously doubt that is going to change in my lifetime.

It’s not surprising that this study was conducted in Italy. Can anyone imagine the average Italian without their lasagna or spaghetti alla puttanesca?

However, Italy is not the only country in love with wheat.

The Chinese and their steamed buns, the Australians and their Vegemite-slathered toast, the French and their baguettes, the Belgians and their waffles, the Austrians and their pastries, the Germans and their beer, and the Americans and their….well, pretty much everything. Wheat is the world champ of edible grasses.

But enough of stating the obvious. Let’s dive right into this steaming, al dente, and aromatic pile of research and see if augmenting beneficial gut flora through prebiotic supplementation can lessen intestinal permeability in those eating wheat.

Twenty healthy men with an average age of 18.8 years were enrolled in this study. Average BMI was 22.8. None had any gastrointestinal complaints or were on any medications.

These strapping young bucks were free of any of the following habits or medical conditions: having a BMI outside of the range of 20 to 25, drinking more than 30 grams of alcohol daily, smoking, hypertension, diabetes, systemic or hormonal disease, skin disease, familial hypercholesterolemia or high triglyceride levels.

Our young Italian men had also been screened against the use of any of the following in the six months prior to the start of the study: vitamin and mineral supplements, non-steroidal anti-inflammatory drugs, antibiotics, antacids, proton-pump inhibitors, ulcer medication and other gastric medications.

During the first two weeks (the run-in period), all subjects consumed an identical diet containing the same amount of soluble and insoluble fiber, but with no added inulin.

After this period was over, half the participants were fed regular wheat pasta and the other half fed wheat pasta enriched with inulin. The standard pasta (spaghetti and rigatoni) was made from 100% durum wheat. The prebiotic-enriched pasta contained 11% inulin derived from chicory. Both pastas were the same in taste and appearance.

Apart from the difference in pastas, all participants were fed the following identical macronutrient ratios: 20% simple carbohydrates, mainly from fruit, 30% complex carbohydrates, mainly bread, potatoes and pasta, and 35% fat, mainly in the form of butter, cheese and meat.

Meals were consumed three times a day and cooked by the kitchen staff where this study was conducted. All subjects were instructed to write down any extra food they ate apart from these three meals.

After the first five weeks of the prebiotic intervention, both groups went back to eating the control diet for 8 weeks to return all participants to baseline values. This was followed by another 5 weeks where the group that had eaten the 100% wheat pasta was now fed the inulin-enriched pasta, and the group that had eaten the prebiotic pasta now ate the standard pasta.

This trial, by the way, is called a double-blind, crossover study because both groups undergo the intervention. This type of study reduces confounding variables even more so than a typical randomized, placebo-controlled trial where only one group is subjected to the intervention or treatment.

During the two, 5-week intervention arms of this study, intestinal permeability was measured by detecting the presence of ingested lactulose and mannitol in urine. As mentioned in the previous post, this sugar and sugar alcohol should not be able to freely cross the gut barrier unless intestinal permeability exists.

Serum and fecal levels of zonulin, the intestinal tight-junction protein, were also measured. Also measured was glucagon-like peptide 2 (GLP-2). GLP-2 is a gut hormone secreted by the L cells of the small and large intestine and is thought to play a role in tight junction regulation.


Courtesy: Inulin-enriched pasta improves intestinal permeability and modifies the circulating levels of zonulin and glucagon-like peptide in healthy young volunteers

Courtesy: Inulin-enriched pasta improves intestinal permeability and modifies the circulating levels of zonulin and glucagon-like peptide in healthy young volunteers


As can be seen in this chart, no significant difference in energy, macronutrient or fiber intake was noted between groups during either 5-week diet period.



Click to enlarge


Here are graphed the detectable levels of lactulose and mannitol in urine. While there was no significant difference seen in urine levels of mannitol, this was not the case with lactulose.

Lactulose excretion was significantly lower in the inulin-consuming group, although not zero, which isn’t surprising given their continued intake of wheat.

Finally, when compared to the baseline measurement and the levels seen when consuming the control pasta, the combined lactulose and mannitol excretion was much lower in the inulin group.




Here we see levels of zonulin, a marker of increased intestinal permeability. While fecal zonulin showed no statistical difference, serum zonulin levels were lower in the group eating pasta with inulin.




Finally, these graphs show levels of fasting GLP-2 and the rate of its release (AUC of plasma) during the observation period. While AUC levels were unaffected, fasting levels of GLP-2 were higher in the inulin group.

As I wrote in this post,

“Glucagon-like peptides (GLPs) are also released by healthy L-cells of the small intestine and colon, and the alpha cells of the pancreas. These hormones influence insulin and glucagon secretion and their dysregulation may be a contributing factor in insulin resistance. These hormones reduce appetite and the rate of stomach emptying making you feel full.”

Delaying the rate of stomach emptying and feeling full are important factors when trying to control appetite and caloric intake. Disturbed gut flora will always negatively impact the production of gut hormones, including those that signal satiety to the brain.

In the discussion section of this paper the authors note:

“Studies in vitro and on animal models have previously connected an altered microbiota composition with the development of obesity, insulin resistance, and diabetes in the host. There are several possible mechanisms for this result, including the modulation of intestinal barrier integrity by GLP-2 secretions.

Recently, Cani et al assessed the effect of oligofructose on gut microbiota, IP [intestinal permeability], and hepatic [liver] and systemic inflammation in ob/ob mice. The prebiotic enriched diet increased intestinal lactobacilli and bifidobacteria and preserved intestinal barrier function. These effects were related to increased production of intestinal GLP-2. This result suggests that GLP-2 might mediate the benefits of prebiotics.”

Admittedly, this is a small study conducted exclusively in healthy men. I would like to see larger studies of this type, but with the inclusion of women and a gluten-free cohort serving as the baseline. That said, the fact that this was a placebo-controlled, crossover trial speaks to its strengths.

So what can we conclude from this?

Pretty much what many other trials have already confirmed. Beneficial gut flora are vital for maintaining intestinal barrier function even in the presence of foods that work in the opposite direction.

Just as beneficial bacteria can protect, although never entirely mitigate, against the ill effects of binge drinking, both probiotics and prebiotics can also help moderate the effects of eating gluten in non-celiac populations.

However, as I’ve mentioned elsewhere, I doubt that solely augmenting gut flora populations can fully compensate for the negative impact on intestinal peristalsis caused by gluten opioids and adenosine. The risk of developing small intestinal bacterial overgrowth will still be present.

But yes, apparently you can eat your pasta and have it too, if only up to a point.

In a world in love with its wheat, supplementing with probiotics and prebiotics is as good as it’s likely to get for millions of my fellow gluten-eating human beings.

Alla prossima volta (see you next time)!


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