The Gluten Solution: Aspergillus Niger-Derived Enzyme May Make "Gluten-Free" Redundant - Enzyme Supplementation Reduces the Amount of Gliadin in the Duodenum by 80-90%

Can a pill simulate "gluten-free"?

The problem with gluten (if there is one, after all we are not all suffering from coeliac disease) is that its proline-peptides cannot be digested by any of the enzymes in the human intestinal tract. Therefore, the long proline-rich gluten peptides reach the small intestine intact after ingestion where they are the driving motors of coeliac disease in 1% of the population, in whom the specific amino acid sequences of such poorly digested proline-rich gluten peptides triggers an abnormal immune response.

More recently, though, studies have shown that less pronounced adverse reactions to gluten consumption can occur even in subjects who don't suffer from coeliac disease. As Salden et al. point out, "[p]resently non-coeliac gluten sensitivity has been clinically recognised as a separate condition in which neither allergic nor autoimmune mechanisms are involved" (Salden. 2015). Accordingly, the results of the latest study from the Maastricht University Medical Center are relevant for much more than just 1% of the population (West. 2003; Mäki. 2003; Fasano. 2003; Bingley. 2004).

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Now I got you curious, right? Ok, here's what the Dutch scientists did: In their randomized, double-blind, placebo-controlled, cross-over study 12 healthy volunteers attended to four test days with at least one week washout in-between. On day 2-3, a liquid low or high calorie meal (4 g gluten) with Aspergillus niger prolyl endoprotease (AN-PEP | 6.1 mL of AN-PEP corresponding with 1.600.000 Protease in a total of 100 mL water) or placebo was administered into the stomach.

Table 1: Recipe and nutritional composition of the low and high calorie test meal per 300 g portion (Salden. 2015).

Table 1 shows the composition of the meals. All test meals contained 5.2 g of gluten powder, of which 4.0 g was gluten protein (Syral, Aalst, Belgium). Encapsulated refined olive oil powder (VanaGrasa 80B; FrieslandCampina, Kievit B.V., Meppel, The Netherlands) was used as fat source for the meals and together with maltodextrin as additional energy source for the high calorie meal, and sodium caseinate (DMV, Veghel, The Netherlands) was used to match both meals for protein content. The dry meal powders were dissolved in a total volume of 300 mL tap water of 40 °C by stirring with a spoon and subsequently mixing with a Turrax (Ultra Turrax T25; IKA, Staufen, Germany). Low and high caloric meals were not blinded to the investigator.

The gastric emptying was tracked with acetaminophen and a triple-lumen catheter was used to get the gastric and duodenal samples that were used to calculate the 240-min area under the curve (AUC0–240 min) of α-gliadin concentrations.

Figure 1: Total alpha-gliadin in the duodenum (µg x min | left) and western blot showing degradation of water-insoluble gliadin over time in the stomach and duodenum in low and high calorie meals with and without AN-PEP (Salden. 2015).

As you can see in Figure 1, the addition of the Aspergillus niger prolyl endoprotease worked it's magic on the indigestible gluten peptides and reduced the amount of potentially pro-inflammatory alpha-gliadin that made it into the duodenum by 91% and 81% depending on the size of the meal. That's huge and as the scientists point out the first time that someone observed in vivo that the AN-PEP enzyme efficiently degrades gluten from a meal in the stomach of human subjects.

Is Noneliac Gluten Sensitivity Legit? A Review of the Latest Scientific Evidence on NCGS by Alex Leaf (Guestpost) | more

Bottom line: You probably already realized why the results of the study at hand are important. If one could add sufficient amounts of AN-PEP to gluten-containing products and / or take a supplement that contains Aspergillus niger prolyl endoprotease (AN-PEP) with every gluten-containing meal, we could minimize, probably even totally prevent any pro-inflammatory effects of gluten in both coeliac patients and subjects with non-coeliac gluten intolerance.

Ok, it's questionable whether it's feasible to put a gliadin digesting enzyme into goods without impairing their quality (gluten is after all added for its ability to "glue" things together; putting AN-PEP into the dough may thus ruin it).

A pill with Aspergillus niger prolyl endoprotease (AN-PEP), on the other hand, could make the life of people who risk developing diarrhea or other symptoms of gluten intolerance whenever they eat out significantly easier... ah, and it could be big business in view of the contemporary gluten-scare, which brings me to the sponsors of the study (DSM Nutritional Products AG) who are about to use the study to advertise their AN-PEP products which have already been approved by the French Agency for Food, Environmental and Occupational Health & Safety | Comment on Facebook!

References:

• Bingley, Polly J., et al. "Undiagnosed coeliac disease at age seven: population based prospective birth cohort study." Bmj 328.7435 (2004): 322-323.
• Fasano, Alessio, et al. "Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study." Archives of internal medicine 163.3 (2003): 286-292.
• Mäki, Markku, et al. "Prevalence of celiac disease among children in Finland." New England Journal of Medicine 348.25 (2003): 2517-2524.
• Piper, Justin L., Gary M. Gray, and Chaitan Khosla. "Effect of prolyl endopeptidase on digestive-resistant gliadin peptides in vivo." Journal of Pharmacology and Experimental Therapeutics 311.1 (2004): 213-219.
• Salden et al. "Randomised clinical study: Aspergillus niger-derived enzyme digests gluten in the stomach of healthy volunteers." Alimentary Pharmacology and Therapeutics (2015): Accepted manuscript.
• West, J., et al. "Seroprevalence, correlates, and characteristics of undetected coeliac disease in England." Gut 52.7 (2003): 960-965.

Forget the Blood Type Diet, Embrace the Gut Type Diet: Eating According to the Likes or Dislikes of Your Bacterial Subtenants Could Keep You Healthy, Lean & Sane.

Image 1: You better feed them right, or your gut bacteria could will disbehave just like the Alien in Ellen Ripley (Sigourney Weaver) in Alien 3 (20th Century Fox).

Eating right for your type, probably is not what it takes to have dietary success. Scientists from the US and Brazil have now found that eating according to the likes an dislikes of your bacterial subtenants seems to could eventually have a much greater potential (Wu. 2011) in keeping you healthy and, as the results of the joint research efforts of Canadian and Irish scientists shows, psychologically sane (Bravo. 2011).

Scientists estimate that the genome of the sum of our gut microbia is about 100x more complex than our own gene-sequence and the type and ratio of the 300-1000 different species within your intestinal tract have a major impact not only on how you digest your food, but also on how you look, feel and perform. It is therefore particularly interesting that Gary D. Wu and his colleagues established (for the first time) the existence of a stable microbiome composition that appears to be specialize to strive on a specific diet.

Note: Currently, the data is still too scarce and the variety of gut microbia, as well as their interactions too complex, for any reliable conclusions on whether it is "optimal" to eat according to your current gut biome or whether and in which way it would benefit your health, performance or body composition to modify / tweak the composition of the latter by dietary strategies and/or supplements or even medications. Even the idea of "optimizing" the microbial composition of our guts for "optimal" macro-nutrient usage is illusive, as it could well be that the specialization of our gut bacteria, i.e. their efficiency in using only little of the dietary energy for themselves and redirecting the rest to us, could theoretically be among the reasons for the obesity epidemic, as well.

In a preliminary analysis Wu et al. had established that in 98 healthy volunteers, whose stool they had analyzed for its individual microbiome composition there was a high correlation between habitual diets (measured by dietary questionnaires; data cf. figure 1, below) and the predominant type of bacteria.

Bacteroide enterotype was highly associated with animal protein, a variety of amino acids, and saturated fats, suggesting that meat consumption as in a Western diet characterized this enterotype. [...] The Prevotella enterotype, [...] was associated with [...] high values for carbohydrates and simple sugars, indicating association with a carbohydrate-based diet more typical of agrarian societies.

As one would expect, "self-reported vegetarians (n = 11) showed enrichment in the Prevotella
enterotype (27% Prevotella enterotype vs. 10% Bacteriodes enterotype; p = 0.13)" and the one self-reported vegan was in the Prevotella enterotype group, as well.

Image 2: Prevotella histicola is a major driving force of tooth decay (King's College). Its relatives in the gut, on the other hand, have been found to be implicated in insulin resistance and infertility due to endotoxin-related inflammation.

Now, if you are a dentist or did some research in the area of "caries" for whatever reason, the name "Prevotella" will probably sound remotely familiar. After all, the Prevotella species has been found to be associated with severe early childhood caries (e.g. Tanner. 2011). These are also the guys, whose poisonous lipolysaccharide dung increases the synthesis of the inflammatory cytokine TNF-alpha (Kim. 2007), which, in turn, has long been known to induce insulin resistance (Hotamisligil. 1999) - quite smart from the bacteria, isn't it? After all, if your body does not suck up the glucose the Prevotella will have more sugar to feed on. What may be less smart, though ,is that the endotoxin (lipolysaccharides are considered endotoxins) induced inflammation will also compromise testicular function on multiple levels, which in turn would deprive future generations of bacteria of their hosts.

Figure 1: Associations (Spearman correlation; -1: max neg. / +1 max pos.) between habitual dietary intake of sugars, vitamins & minerals, fats, amino acids, proteins and micronutrients and bacterial composition, where enterotype 1 is bacteriode dominant, and enterotype 2 is prevotella dominant (data adapted from Wu. 2011)

The polysaccharide A (PSA) produced by Bacteroides, an even larger class of bacteria which obviously strives on a high fat, high protein diet (or rather what mainstream dietitians call "high protein"), on the other hand, has recently been implicated in beneficial modulations of the immune system (Troy. 2010) and apparently even protects the nerves from he central nervous system from demyelation (Ochoa-Repáraz. 2010), i.e. the destruction of the insulating myelin layer. There is however a broad variety among the Bacteroides and as Wexler in his aptly titled paper "Bacteroides: the good, the bad, and the nitty-gritty." points out (Wexler. 2010):

The bacteria maintain a complex and generally beneficial relationship with the host when retained in the gut, but when they escape this environment they can cause significant pathology, including bacteremia and abscess formation in multiple body sites.

Based on the results of Wu's study, which also showed that a short-term dietary intevention (10 days) could not change the Bacteriode dominance of the 10 subjects who had been randomly assigned to high fat/low or a low fat/high fiber diets, we can thus only say that we probably are "optimized" for a certain macronutrient composition. Whether this is a beneficial or detrimental adaptation has still to be determined. What has however been established (in a rat model) is that chronic treatment with the probiotic bacteria Lactobacillus rhamnosus

[...] induced region-dependent alterations in GABAB1b mRNA in the brain [, ...] reduced GABAAα2 mRNA expression in the prefrontal cortex and amygdala, but increased GABAAα2 in the hippocampus [and] reduced stress-induced corticosterone and anxiety- and depression-related behavior.

Bravo et al. ascribe these beneficial psycho-physiological effects to the "modulatory constitutive communication pathway between the bacteria exposed to the gut and the brain". And highlight the "bidirectional communication of the gut–brain axis" as a possible target to treat stress-related disorders.

Image 3: The antibiotic vancomycin could potentially induce obesity month after treatment.

Did you know that Thuny et al. clearly showed that (Thuny. 2010) combined treatment with vancomycin-plus-gentamycin in patients with infective endocarditis was associated with a significant gain in BMI of +2.3kg/m² in the first year after discharge from hospital. For a man of 180cm this would be ~7.5kg. Vancomycin, by the way happens to be the cousin of Avoparcin an antimicribial growth promoter that has been used in the EU for fattening animals for about a year before it was prohibited in 1997.

In defense of "antibiotics" and as a word of caution against exuberant enthusiasm for all bacteria it should yet be mentioned that alternative antibiotics did not exhibit the same profound effects in the Thuny study. Moreover, observations in germ-free mice suggest that (Bäckhed. 2006)

[germ-free] animals are protected from diet-induced obesity by two complementary but independent mechanisms that result in increased fatty acid metabolism: (i) elevated levels of Fiaf, which induces Pgc-1α; and (ii) increased AMPK activity.

In view of the ever increasing resistance towards antibiotics, it is however unrealistic to assume that we will see similar effects in humans after the administration of individual or even combined high-dose antibiotics.

Moreover, more and more scientists argue that, based on the growth-promoting effects of antibiotics in food animals (Linn. 2011), it is more than likely that the long thought of relation between gut microbiota and the human obesity epidemic is real and that research into the detailed working principles of antimicrobial growth promoters (AGP) in animals may reveal hitherto overlooked underpinnings of obesity an respective treatment strategies.

We will see what future research will bring. Yet, while you are waiting for me to keep you on par with the results, I suggest you better stay away from growth or non-growth promoting antibiotics if you want to stay healthy, sane and slim.

AKG as in Arginine Alpha-Ketoglutarate for GI Health

For many of us, our gut is like our feet. We ignore it as long as it appears to be working properly. I think, I do not have to tell you that this is a mistake. Just like you cannot run without healthy feed, you cannot digest and use all the good food and supplements you consume without a healthy gut. This is why you should be interested in the findings of a recent review by scientists from the Hubei key Laboratory of Animal Nutrition and Feed Science in Wuhan 430023, China (Hou. 2011).


The scientists evaluation of related studies lead them to conclude that the conversion of Alpha-ketoglutarate (AKG), which is an intermediate of the Krebs cycle and bridges amino acid metabolism with glucose oxidation, into glutamate in the gastrointestinal tract of humans and animals is of particular interest in view of overall gastric functioning, "including regulation of cell function, neurotransmission, and gastric emptying".

Translating the basic research into practice, results of recent studies indicate that dietary supplementation with AKG alleviates oxidative stress and injury in intestinal mucosal cells, while improving intestinal mucosal integrity and absorption of nutrients in endotoxin-challenged pigs.

If you do not find that exciting, you might be interested in AKG's effect on mTOR-signaling (largely regarded as one of the fundamental triggers of protein synthesis and "muscle growth"):

The beneficial effects of AKG are associated with increased activation of the mTOR signaling pathway and net protein synthesis.

So, in view of the disappointing news on the inability of Arginine-AKG to raise nitric oxide levels, it may come as a surprise that it may have a distinct value far apart from muscle pumps and popping veins.