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Gut health is "all the rage", lately. So even if it's true that this may be one of the most culpably neglected areas of research in the past century, we should still be careful not to hype the effect of the gut on your physique and health too much.

Well, probiotics and the human microbiome (the one in the gut and elsewhere) are all the rage, these days. Against that background, it's not really surprising that a probiotic supplement and thus a human microbiome modulator made it into the waredownloadsoft news (again). What may be surprising, though, is the fact that casein didn't just do the same, but that its appearance here in the news is not due to its muscle building prowess. Rather than that, casein made the cut, because a recent study by Francois Mariotti, et al. shows that - even in comparison to whey protein - casein attenuates the potentially unhealthy postprandial triglyceride response to a mixed high-fat meal in healthy, overweight men.

• Cheesy! Casein keeps your trigs in check - Due to the interaction between elevated postprandial triglyceride levels, insulin resistance and cardiovascular disease, the results of the previously mentioned study by Mariotti et al. (2015) may be of interest not just for all of us. After all, the proposed mechanism of which the authors, scientists from the AgroParisTech speculate that it is a direct result of the same

  "solubility of casein and its precipitation that forms a gel in the stomach [which have long been] known to influence its rate of absorption and postprandial protein metabolism in the context of regular, low-energy meals" (Mariotti. 2015),

  as the marked effect on the chylomicron kinetics and decrease in postprandial TGs, a risk factor for cardiovascular disease, the French scientists observed in the study at hand.
  

  Figure 1: Area under the curve for triglycerides (did respond), amino acids (didn't respond) and glucose (didn't respond) in 10 overweight subjects after consuming isocaloric high-energy meals with 15% of the energy from protein in form of casein (CAS), whey protein (WHE) or alpha-lactalbumin enriched whey (LAC | Mariotti. 2015)

  As you can see in Figure 1, the proteins which made up exactly 15% of the total energy content of the high-fat meal that was fed to 10 healthy overweight men with an elevated waist circumference (>94 cm) did not affect the subjects' postprandial plasma glucose, amino acids, insulin, or nonesterified fatty acid levels (which would, by the way, suggest that ingesting whey or an alpha-lactalbumin enriched whey protein with a meal ruins its amino acid absorption advantage). The study outcome that did differ, though were the postprandial triglycerides (TGs) levels, where the provision of casein lead to a highly significant 22% (+/- 10%) reduction in the 6-h area under the curve.

• As the authors point out, similar trends were shown for plasma chylomicrons [apolipoprotein (apo)B-48; P < 0.05], yet not for the postprandial oxidative stress (plasma hydroperoxides and malondialdehyde), endothelial dysfunction (salbutamol-induced changes in pulse contour analysis), or low-grade inflammation. This is also why it is as of yet only a logical, but hitherto unsupported hypothesis that consuming casein (micellar casein, not regular sodium or calcium caseinates) would also reduce one's cardiovascular disease risk. Eventually, it does yet appear to be the more reasonable adjunct to a full meal anyway - the purpose of the latter is after all to keep you satiated for a long time; and that's where casein is unquestionably a better choice than whey.
• Probiotics - 0.5% body fat reduction, and a 2.68 cm² reduction in subcutaneous fat area are not much, but they occurred in the absence of diet and exercise - If the trend continued and the 120 nondiabetic and overweight subjects Jung et al. divided into two groups: There was the probiotic group with 60 individuals who consumed 2 g of powder of two probiotic strains, L. curvatus HY7601 and L. plantarum KY1032, each at 2.5 × 109 cfu, twice a day. And there was the and a placebo group, likewise 60 individuals, who consumed the same amount of powder that did not contain any probiotics.
  

  Figure 2: Changes in body composition according to waist measurement and CT scans - All values are relative changes in waist and fat area measure from week 0 to week 12 (Jung. 2015).

  Both groups were advised to take their supplements immediately after breakfast and dinner, but only the probiotic group saw relevant improvements in body fat at slow) pace - albeit a pace at which it would take them "only" 5 years to finally make it into healthy body fat zones.

• Ok, that's painfully slow, but given the fact that the food intake of both groups didn't differ significantly, it is still noteworthy that the 2 g of probiotic powder which contained contained 0.1 g of L. curvatus HY7601, 0.1 g of L. plantarum KY1032, 1.24 g of crystalline cellulose, 0.5 g of lactose, and 0.06 g of blueberry-flavouring agent made the subjects lose significant amounts of body fat, while their peers who received 2 g of a placebo powder that contained 1.34 g of crystalline cellulose, 0.6 g of lactose, and 0.06 g of blueberry-flavouring agent kept gaining.
  

  Figure 3: The provision of the probiotic supplement did also trigger significant improvements in the above markers of cardiovascular disease risk - if it's not the small fat loss, it would thus be the potential CVD risk reduction that makes the use of probiotic supplements attractive especially for overweight individuals (Jung. 2015).

  In conjunction with the likewise statistically significant beneficial effects on health markers like LDL oxidation and LDL particle size which indicate significant improvements in cardiovascular disease risk, this is still the first non-sponsored study (the study was financed by Korean Ministry of Science) that shows that supplementing with commercially available probiotics in man may actually produce health-relevant beneficial effects.

References:

• Jung, Saem, et al. "Supplementation with two probiotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, reduced body adiposity and Lp-PLA 2 activity in overweight subjects." Journal of Functional Foods 19 (2015): 744-752.
• Laugesen, Murray, and R. B. Elliott. "Ischaemic heart disease, Type 1 diabetes, and cow milk A1 β-casein." (2003).
• Mariotti, François, et al. "Casein Compared with Whey Proteins Affects the Organization of Dietary Fat during Digestion and Attenuates the Postprandial Triglyceride Response to a Mixed High-Fat Meal in Healthy, Overweight Men." The Journal of nutrition (2015): jn216812.
• McLachlan, C. N. S. "β-Casein A 1, ischaemic heart disease mortality, and other illnesses." Medical Hypotheses 56.2 (2001): 262-272.

Yogurt does not have to be served this way to be healthy, but I bet many of your friends and relatives would be amazed and much more likely to pass on the cream cake or tiramisu if the option was an appetizing dessert like that.

In a world where being vegan is "the new sexy" and eating animal products "the new smoking", dairy has lost much of its former appeal. I mean, we all remember how the literal "glass of milk" has been marketed as a daily health booster, right? Well, times have changed and that despite the fact that an impartial review of the evidence suggests more benefits than downsides to dairy consumption. Specifically fermented dairy, first and foremost yogurt, but also cheese can, and in the case of yogurt maybe even should be part of your of your diet. And that's not just because both are an often forgotten, but essential part hailed "Mediterranean diet" (Vasilopoulou. 2013). The same diet of which recent studies say that it's associated w/ a -30% reduced CVD risk (Estruch. 2013).
How's that? Well, cheese may be full of saturated fat and cholesterol. In controlled trials, however, even high fat cheese has - in contrast to butter, for example (Hjerpsted. 2011) - no or even beneficial effects on the total and LDL cholesterol levels of otherwise healthy individuals. In addition, real dairy cheese has been found to have neutral effects on body weight when it is consumed as part of an otherwise healthy diet. Some traditional types of cheese even share the anti-hypertensive effects of yogurt, which is still the real star among the fermented dairy products. A star that has been shown to prevent weight gain, reduce cholesterol and more meaningful makers of heart disease risk, to improve glycemia, and to prevent the development and/or progression of type II diabetes in both experimental and observational studies (Tholstrup. 2006; Nestel. 2008; Mozaffarian. 2011, Tapsell. 2015).

Figure 1: A study comparing the effects of getting 13% of one's total daily fat intake from cheese vs. butter on the blood lipids in healthy men and women shows increases in TC and LDL only with butter (Hjerpsted. 2013). In contrast to the total and LDL cholesterol levels, the total / HDL cholesterol ratio wasn't affected sign. by butter though. You can thus expect both forms of high fat dairy having negligible cholesterol mediated effects on the heart health of healthy indiv.

In short, the existing scientific evidence leaves little doubt that yogurt is, maybe next to whey (learn why), the star among the dairy based health foods. Part of its beneficial effects are probably mediated by its ability to improve integrity of our digestive tracts and thus to prevent the influx of pro-inflammatory, obesogenic, and pro-atherogenic endotoxins into the bloodstream. With it being available for almost 10,000 years, yogurt is thus the first and oldest "functional food" to act on the recently discovered link between "leaky gut", obesity and cardiovascular disease (Lam. 2011).

Figure 2: Proposed mechanisms by which yogurt consumption exerts beneficial health effects (Marette. 2015)

Some scientists like Marette & Picard-Deland even go so far as to argue that an early introduction of yoghurt into the diets of children is vital to establish a microbial community that supports long-term health. And while Taspell et al. are right to highlight that "[m]ore research is needed" (Tapsell. 2015). There's little doubt that "yogurt can deliver essential nutrients with high bioavailability and relatively low energy density" (ibid).
The fact pertinent trials still show ambiguous results, when it comes to the effects of yogurt on body weight and composition (Chen. 2012) is mostly a results of the study designs which usually require subjects to simply increase their intake of dairy products, in general, or yogurt, in particular. As Taspell (2015) points out in a recent review this is a problem "if the energy content of the diet is not managed, particularly with high-fat varieties and with added ingredients such as sugar" (ibid). If it is managed, as in habitual consumers, though, high(er) yogurt intakes have been shown to be associated...

• Prevalent Nutrient Deficiencies in the US: More Than 40% are Vitamin A, C, D & E, Calcium or Magnesium Deficient and >90% Don't Get Enough Choline, Fiber & Potassium | read more

  with higher scores for the Dietary Guidelines Adherence Index (DGAI) and higher intakes of key micronutrients, as well as significantly higher potassium and fiber intakes - two nutrients the average Westerner usually doesn't get enough of (Wang. 2013)
• with reduced weight gain in a large US cohort study that tracked the food intake and weight development of 22 557 men and 98 320 women for four years; with R = -0.89 the correlation is similar to the one for the recommended amount of physical activity vs. being sedentary and thus nothing you should ignore as being practically irrelevant
• with reduced inflammation as measured by C-reactive protein, IL-6 and TNF-a in the ATTICA study that involved 3042 healthy Greek adults for whom only 8 servings of dairy products, in general (full fat and low fat!), were linked with already significant reductions in inflammation; since a greater proportion of the cohort reported consumption of fermented dairy foods such as feta cheese (93%), hard yellow cheese (92%) and low-fat yogurt (50%) compared to low-fat milk (46%), we can yet safely assume that many of these anti-inflammatory benefits were actually due to fermented dairy products
• with reduced type II diabetes risk (-12% or both yogurt and cheese) in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct Study (Sluijs. 2012);
  

  Table 1: HRs for risk of type 2 diabetes associated with the substitution of yoghurt (137 ga) for snacks and desserts: EPIC-Norfolk study (n=4,127 | O'Connor. 2014)

  with 28% reduced diabetes risk the results of the EPIC-Norfolk cohort study in the UK were even more impressive (O’Connor. 2014); as you can see in Table 1 the results of this study do yet also underline that the benefits will occur only if yogurt replaces other, less healthier ingredients of ones diet.

References:

• Asemi, Zatollah, et al. "Effects of daily consumption of probiotic yoghurt on inflammatory factors in pregnant women: a randomized controlled trial." Pakistan journal of biological sciences: PJBS 14.8 (2011): 476-482.
• Chen, Mu, et al. "Effects of dairy intake on body weight and fat: a meta-analysis of randomized controlled trials." The American journal of clinical nutrition 96.4 (2012): 735-747.
• de LeBlanc, Alejandra de Moreno, and Gabriela Perdigón. "Yogurt feeding inhibits promotion and progression of experimental colorectal cancer." American Journal of Case Reports 10.4 (2004): BR96-BR104.
• Douglas, Steve M., et al. "Low, moderate, or high protein yogurt snacks on appetite control and subsequent eating in healthy women." Appetite 60 (2013): 117-122.
• Elwood, Peter C., et al. "The consumption of milk and dairy foods and the incidence of vascular disease and diabetes: an overview of the evidence." Lipids 45.10 (2010): 925-939.
• Estruch, Ramón, et al. "Primary prevention of cardiovascular disease with a Mediterranean diet." New England Journal of Medicine 368.14 (2013): 1279-1290.
• Fisberg, Mauro, and Rachel Machado. "History of yogurt and current patterns of consumption." Nutrition reviews 73.suppl 1 (2015): 4-7.
• Hjerpsted, Julie, Eva Leedo, and Tine Tholstrup. "Cheese intake in large amounts lowers LDL-cholesterol concentrations compared with butter intake of equal fat content." The American journal of clinical nutrition 94.6 (2011): 1479-1484.
• Lam, Yan Y., et al. "Role of the gut in visceral fat inflammation and metabolic disorders." Obesity 19.11 (2011): 2113-2120.
• Lithell, H., and B. Zethelius. "Glucose Tolerance and Cardiovascular Mortality." Arch. Intern. Med. 161 (2001): 397.
• Marette, André, and Eliane Picard-Deland. "Yogurt consumption and impact on health: focus on children and cardiometabolic risk." The American journal of clinical nutrition 99.5 (2014): 1243S-1247S.
• Moreno, Aznar LA, et al. "[Scientific evidence about the role of yogurt and other fermented milks in the healthy diet for the Spanish population]." Nutricion hospitalaria 28.6 (2012): 2039-2089.
• Mozaffarian, Dariush, et al. "Changes in diet and lifestyle and long-term weight gain in women and men." New England Journal of Medicine 364.25 (2011): 2392-2404.
• Nestel, Paul J. "Effects of dairy fats within different foods on plasma lipids." Journal of the American College of Nutrition 27.6 (2008): 735S-740S.
• Nestel, Paul J., et al. "Effects of low-fat or full-fat fermented and non-fermented dairy foods on selected cardiovascular biomarkers in overweight adults." British Journal of Nutrition 110.12 (2013): 2242-2249.
• Neyestani, Tirang R., et al. "Improvement of vitamin D status via daily intake of fortified yogurt drink either with or without extra calcium ameliorates systemic inflammatory biomarkers, including adipokines, in the subjects with type 2 diabetes." The Journal of Clinical Endocrinology & Metabolism 97.6 (2012): 2005-2011.
• Nikooyeh, Bahareh, et al. "Daily consumption of vitamin D–or vitamin D+ calcium–fortified yogurt drink improved glycemic control in patients with type 2 diabetes: a randomized clinical trial." The American journal of clinical nutrition 93.4 (2011): 764-771.
• O’Connor, Laura M., et al. "Dietary dairy product intake and incident type 2 diabetes: a prospective study using dietary data from a 7-day food diary." Diabetologia 57.5 (2014): 909-917.
• Ortinau, Laura C., et al. "The effects of increased dietary protein yogurt snack in the afternoon on appetite control and eating initiation in healthy women." Nutr J 12.71 (2013): 10-1186.
• Panagiotakos, Demosthenes B., et al. "Dairy products consumption is associated with decreased levels of inflammatory markers related to cardiovascular disease in apparently healthy adults: the ATTICA study." Journal of the American College of Nutrition 29.4 (2010): 357-364.
• Sluijs, Ivonne, et al. "The amount and type of dairy product intake and incident type 2 diabetes: results from the EPIC-InterAct Study." The American journal of clinical nutrition 96.2 (2012): 382-390.
• Struijk, E. A., et al. "Dairy product intake in relation to glucose regulation indices and risk of type 2 diabetes." Nutrition, Metabolism and Cardiovascular Diseases 23.9 (2013): 822-828.
• Tapsell, Linda C. "Fermented dairy food and CVD risk." British Journal of Nutrition 113.S2 (2015): S131-S135. 
• Tholstrup, Tine. "Dairy products and cardiovascular disease." Current opinion in lipidology 17.1 (2006): 1-10.
• Vasilopoulou, Effie, Vardis Dilis, and Antonia Trichopoulou. "Nutrition claims: a potentially important tool for the endorsement of Greek Mediterranean traditional foods." Mediterranean Journal of Nutrition and Metabolism 6.2 (2013): 105-111.
• Wang, Huifen, et al. "Yogurt consumption is associated with better diet quality and metabolic profile in American men and women." Nutrition Research 33.1 (2013): 18-26.
• Zemel, Michael B., et al. "Calcium and dairy acceleration of weight and fat loss during energy restriction in obese adults." Obesity research 12.4 (2004): 582-590.

With the right diet and lifestyle, stem cell treatments, probiotic supplements or xylose-laden "functional foods" wouldn't be necessary in the first place.

You're probably used to it, but I am in the mood for bragging: The waredownloadsoft is where you'll read about the latest nutrition, exercise and supplement related studies first. In research updates like the one today, I am trying to provide a little more information than in the SV Facebook News, though, where I usually stick only to the main results of studies that have just been published or at least accepted for publication.

In today's installment of what I often call the "Short News", I will discuss three papers that are going to be published in one of the next issues of the peer-reviewed scientific journal Nutrition News.

Studies dealing with a pre-clinical, but promising stem cell therapy for diabetics, the verdict on probiotic supplements (including my evaluation of the scientists' verdict ;-) for weight loss and an update on the effects of the xylitol precursor d-xylose and its effect on mammalian fat cells in vivo.

• Stem Cells as Diabetes Treatment (Xing. 2015) - In software development you'd probably call the latest study from the Cangzhou City Central Hospital an "early alpha version" of an intriguing new way of treating type II diabetes.
  
  In their latest rodent study, Baoheng Xing et al. build on previous experiments in which pancreatic progenitors derived from human embryonic stem cells were shown to be able to effectively treat diabetes in mice (Kroon. 2008). In their study, however, Xing et al. went one step further and developed a system for treating diabetes using human embryonic stem cell–derived pancreatic endoderm in a mouse model of gestational diabetes mellitus.
  

  Figure 1: Glucose (a), insulin (b) and body weight (c) levels of wild type (wt) and treated (db/+PE) vs. untreated (db/+) pregnant mice before and during gestation, as well as Kaplan-Meier survival curves of litters show significant improvement right into the normal range in response to treatment (Xing. 2015)

  To this ends, the researchers had human embryonic stem cells differentiate in vitro into pancreatic endoderm, which were then transplanted into db/+ mice suffering from gestational diabetes mellitus.
  
  As the data in Figure 1 goes to show you, the transplant, of which the researchers expect that it could be used in humans, too, greatly improved the glucose metabolism and reproductive outcome of the treated female rats compared with the control groups. With their results Xing et al. do thus contribute to the growing evidence that diabetes may (sooner or later) be a "curable" disease when we are eventually mastering the use of differentiated human embryonic stem cells for treating general and gestational diabetes mellitus patients.
• Probiotics and weight loss - reviewed (Park. 2015): What's the verdict? You will remember that I am still skeptical with respect to the real world benefits of the new en-vogue supplements that contain billions of life or dead bacteria and promise benefits from increased gut health to... you guessed it, the most marketable of all benefits: weight loss!
  
  A recent systematic review by scientists from the Hoseo University and the Keimyung University in Korea presents the first attempt to summarize and critically evaluate the evidence from clinical trials that have tested the effectiveness of probiotics or foods containing probiotics as a treatment for weight loss. Literature searches of electronic databases such as PubMed, Cochrane Library, and EMBASE were conducted. Methodological quality was assessed using body weight and body mass index (BMI). Initial searches yielded 368 articles. Of these, only 9 met the selection criteria. Because of insufficient data, only 4 of the studies were randomized controlled trials (RCTs) that compared the therapeutic efficacy of probiotics with placebo.
  
  As my skepticism would have made me believe, the meta-analysis of these data showed no significant effect of probiotics on body weight and BMI (body weight, n = 196; mean difference, −1.77; 95% confidence interval, −4.84 to 1.29; P = .26; BMI, n = 154; mean difference, 0.77; 95% confidence interval, −0.24 to 1.78; P = .14).
  

  Figure 3: It's not like there were no benefits. You just have to look at the right parameters to see them. Studies like Kadooka et al. show that the effects on BMI are small compared to those on metabolically more relevant markers like total fat mass, waist circumference and visceral fat (Kadooka. 2015).

  That does not mean that there are no benefits at all, though. I reviewed the few studies that measured not just body weight and BMI, but also the subjects' body fat levels. This is an important difference, because a focus on BMI ignores potentially health relevant changes in body composition. Changes as they were observed by Kadooka et al. (2013; see Figure 3), for example, who found a significant time x group differences for visceral fat, fat percentage, fat mass, and waist circumference with much less pronounced effects on BMI (too low to influence the result of a systematic review significantly) in their 12-week study. In this context, it is also worth mentioning that Sanchez et al. (2014) observed a significant beneficial effect in obese women (but not man) for whom the consumption of 1.6 × 10^8 colony-forming units of LPR/capsule with oligofructose and inulin made it significantly easier to maintain their body weight after a weight loss intervention. Another benefit that must not be ignored.

• Overall, I still feel obliged to repeat what I wrote in my recent article on the effects of sweeteners on the microbiome: We still have to learn very much about the effects of probiotics in general and individual types of gut bacteria, in particular, before we can actually give good strain-specific supplement recommendations. It's after all possible that the same strains that work in the obese subjects of studies like Kadooka (2015) won't work or even do the opposite in lean individuals.
• D-Xylose Exerts Epigenetic Anti-Obesity Effects and Stops Fat Cell Growth (Lim. 2015) - Yes, this is not the first study to show that the provision of D-Xylitol or, as in the case of a 2011 study by Amo,et al., its cousin and "artificial sweetener" xylitol can reduce the weight gain due to obesogenic diets. What makes it interesting, though, is that it involved two different, relatively low dosages of D-xylitol as they could easily be added to our own food chain.
  

  Figure 4: While the effects on body weight and fat gain were significant, the differences (expressed relative to the rodents on regular chow) are still significant, so even if you replace 5-10% of the sugar in your junkfood diet with the low calorie sweetener (2.4kcal/g), you will get fat. If anything it may completely prevent the increase in liver fat - albeit only if the dosage is high enough and the effects are identical in humans (data from Lim. 2015)

  With only 5% and 10% of the sucrose content of the high fat chow of the rodents in Lim et al.'s latest study being replaced by D-Xylose, the scientists observed
  • significant reductions in weight and more importantly fat gain
  • significant reductions in hepatic steatosis (NAFLD),
  • a reduction of the genes that are responsible for the storage of fat to normal (5%) and sub-normal (10% D-Xylose) levels, and
  • significant reductions in total cholesterol and low-density lipoprotein cholesterol, low-/high-density lipoprotein, and the important total cholesterol/high-density lipoprotein ratio.
  In view of the fact that replacing just a relatively small amount of sucrose in our diet with D-Xylose (and probably xylitol) can ameliorate the weight and adipose tissue gain, normalize blood glucose levels and blood lipid profiles and lower the lipid accumulation in the liver by "regulating expression of lipogenesis- and β-oxidation–related genes" (Lim. 2015), it is probably actually warranted to speculate, just like Lim et al., about a "possible application of d-xylose as a dietary supplement for the prevention of obesity-related metabolic disorders" (Lim. 2015) - even though clinical human trials are still warranted.

As read on the SV Facebook: Baking makes gluten resilient to digestion, the presence of protein does the opposite. The food matrix makes the difference.

In view of the fact that "gluten" is or isn't (literally) in everyone's mouth or tummy, I thought that it may make sense to keep you up-to-date on the latest interesting research in the area of non-celiac gluten sensitivity and celiac disease.

Don't worry I am not going to bother you with the typical Internet bogus about how cancer, obesity and everything else we are or are not suffering from (yet) is triggered by gluten. What I will do, though, is to summarize and discuss the results of two recent studies and one review on the connection between our microbiome and our very individual susceptibility to gluten-related health problems

• Celiac disease and non-celiac gluten sensitivity may be all about the microbiome and begin at the very moment you're born via cesarean section and worsen when you're not breastfed - In a soon-to-be-published review in Nutrients Cenit et al. try to elucidate whether gluten intolerance and celiac disease are consequences or triggers of significant imbalances in the bacterial composition of the human microbiome and how one or the other may eventually come about..
  
  As the authors point out, there are in fact studies which suggest that the early colonization of the infant’s gut in conjunction with environmental factors (e.g., breast-feeding, antibiotics, etc.) could influence the development of our kids' oral tolerance to gluten.
  

  Figure 1: Proposed model for celiac disease (CD) pathogenesis. Specific host genetic makeup and environmental factors could promote the colonization of pathobionts and reduce symbionts, thus leading to dysbiosis. Dysbiosis may contribute to disrupting the immune homeostasis and gut integrity, thereby favoring CD onset and aggravating the pathogenesis (Cenit. 2015).

  In that, the early colonization of the intestinal tract is of particular importance, because it programs a normal or abnormal immune reaction to gluten (and other potential allergens). It is thus no wonder that celiac disease and a whole host of other autoimmune diseases have been linked to a lack of, or an improper early colonization of the intestinal tract and the consequential misprogramming of the immune cells. In that, it has been suggested that the resulting dysbiosis may affect autoimmunity by altering the balance between tolerogenic and inflammatory members of the microbiota and, therefore, the host immune response.
  
  Needless to say that the increased risk of autoimmune diseases is a standalone problem. It is after all not a mere reaction to the bacteria, but a bacterially induced phenomenon that involves the epigentic reprogramming of a whole host of genes. This process is however (unfortunately) so complex that we haven't yet fully understood the individual bacteria-gene and gene-gene interactions. Everyone, who tells you otherwise is lying - probably to sell his snake oil or snake oilish lifestyle advise.
  

  Figure 2: While there's one outlier, 3/4 studies on the effects of breastfeeding when the first gluten containing foods are introduced show significantly reduced risks of developing celiac disease (Akobeng. 2006).

  Among the few things we do know, though, is that breastfeeding and the way it promotes the early colonization of the gut with Bifidobacterium spp. is associated with a reduced risk of gluten intolerance. This is particularly true, if gluten containing foods are introduced while the kids are still breastfed (-52% according to a meta-analysis by Akobeng et al. 2006).

• The fact that these benefits do not apply for every breastfed child may be explained by (epi-)genetic polymorphisms of the mother, such as the altered concentration of several immune markers that have been observed by several researchers in the breast milk of mothers with celiac disease (Olivares. 2014). If that's in fact the case, it's hardly astonishing that the number of celiac patients began to rise when the use of formula peaked and is exploding now that more and more women with celiac disease (or non-celiac gluten sensitivity) are feeding their children with "non-protective" breast milk. We must be careful, though, not to jump to conclusions. There are, after all, as Cenit et al. point out "no robust prospective studies revealing how differences in breast milk composition and intestinal microbiota acquisition and evolution early in life might ultimately protect or contribute to CD onset" (Cenit. 2015).
  
  A similar healthy skepticism is necessary with respect to the link of cesarean sections and an increased susceptibility to gluten sensitivity (Dominguez-Bello. 2010). While it would appear logical to assume that the lack of exposure to the vaginal microbiome may contribute to the previously mentioned misprogramming of the immune system, it would be overtly simplistic to assume that gluten wouldn't be a problem if we were all breastfed and born the natural way.
  

  Figure 3: Increases in risk of full-blown celiac, intestinal inflamation and the presence of markers of celiac disease in the blood in subjects with previous exposure to antibiotics; in all fairness it must be said that the risk increase decreased when individuals who were exposed within the last 24m were excluded - even then the reduced 30% increase was statistically significant and practically relevant, though (Mårild. 2013)

  In conjunction with the indisputable link between the (early) use of antibiotics (Mårild. 2013 | see Figure 3) and the first successful efforts to ameliorate the chronic inflammation in celiac guts with prebiotics, there is yet little doubt that the "right" microbial make-up may be what distinguishes celiacs from patients with non-celiac gluten insensitivity and the still large number of people who don't appear to react to gluten at all.
• Study in healthy subjects, celiacs and their relatives suggests that the way your bacteria metabolize gluten may make you sick - From the first study, or rather review, I've analyzed in this feature article we've already learned that the inability to digest or handle gluten may be transmitted via certain immune factors in the breast milk from mother to child. It is thus particularly interesting that scientists from the Universidad de Léon in Spain who compared the stool of sixteen healthy volunteers on normal diet, eleven healthy volunteers on gluten-free diet (GFD), seventy-one relatives of CD patients on normal diet and sixty-nine relatives on GFD for several proteolytic activities, cultivable bacteria involved in gluten metabolism, SCFA and the amount of gluten found that significant differences in how celiac disease patients metabolized gluten.

• Table 1: Cultivable bacteria involved in gluten metabolism isolated from faeces of healthy subjects, active coeliac disease patients and firstdegree relatives (Caminaro. 2015).

  In contrast to healthy volunteers, their feces showed a significantly higher glutenasic activity (FGA), tryptic activity (FTA), SCFA, but lower levels of faecal gluten. That's interesting, yet counter-intuitive. After all, we've previously thought that one of the main problems of celiac disease and non-celiac gluten sensitivity is that the proteins are not broken down. Rather than that the results of the study at hand suggest that celiacs harbour bacteria that generate immunogenic peptides or pro-inflammatory metabolites which are the actual triggers of the problem (otherwise they'd have to poo out at least as much gluten as the other subjects on the gluten-free diets).
  
  Needless to say that this result does, once more, point toward fecal transplants or prebiotics as potential future treatment options celiac disease and non-celiac gluten sensitivity... with the only problem being: We don't know yet which bacteria we want to support and which to annihilate to solve the problem. If you look at the data in Table 1, though, killing the Clostridium and promoting the Lactobacillus population could be a first step to reinstalling a less celiac-prone gut microbiome.
• More 60% of non-celiac gluten patients don't react to gluten in randomized clinical study - That's certainly an impressive number Zanini et al. report in their latest paper in Alimentary Pharmacology and Therapeutics (Zanani. 2015).
  
  

  Let's hope aspergillus niger does not produce the wrong proteins when breaking down gluten otherwise it would make NCGS worse not better. Thus, further studies are needed.

  In the corresponding study the researchers studied 35 non-CD subjects (31 females) that were on a gluten-free diet (GFD), in a double-blind challenge study. Participants were randomised to receive either gluten-containing flour or gluten-free flour for 10 days, followed by a 2-week washout period and were then crossed over. The main outcome measure was their ability to identify which flour contained gluten. Secondary outcome measures of the study from the University and Spedali Civili of Brescia in Italy were based upon Gastrointestinal Symptoms Rating Scale (GSRS) scores (criteria & results see Figure 4).
  
  In contrast to what the Internet experts are trying to make you believe, only 12 and thus hardly more than 34% of the allegedly highly gluten-intolerant patients were able to tell when they were fed gluten-containing flour based on increases in pain, reflux, indigestion, diarrhoea, and constipation.
  

  Figure 4: Increased severity of symptoms according to whether subjects were able to distinguish whether they were fed a gluten-containing or gluten-free diet (Zanani. 2015).

  Seventeen participants (49%), on the other hand, swore black and blue that they had been fed the gluten-containing flour when they were on the gluten-free diet (and if you look at the data in Figure 4, they even felt worse than those who were actually sensitive ;-).
  
  Now, what's most intriguing about this is that the study proves that there's a non-negligible noocebo effect involved, when it comes to non-celiac gluten sensitivity. One that's powerful enough to have people experience real increases in pain, reflux, indigestion, diarrhoea, and constipation... that tells you something about how infections reading too much bogus on the internet is, right?

References:

• Akobeng, Anthony K., et al. "Effect of breast feeding on risk of coeliac disease: a systematic review and meta-analysis of observational studies." Archives of disease in childhood 91.1 (2006): 39-43.
• Caminero, et al. "Differences in gluten metabolism among healthy volunteers, coeliac disease patients and first-degree relatives." British Journal of Nutrition (2015): Ahead of print.
• Dominguez-Bello, Maria G., et al. "Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns." Proceedings of the National Academy of Sciences 107.26 (2010): 11971-11975.
• Mårild, Karl, et al. "Antibiotic exposure and the development of coeliac disease: a nationwide case–control study." BMC gastroenterology 13.1 (2013): 109.
• Newnham, Evan D., et al. "Adherence to the gluten‐free diet can achieve the therapeutic goals in almost all patients with coeliac disease: A five‐year longitudinal study from diagnosis." Journal of gastroenterology and hepatology (2015).
• Olivares, Marta, et al. "Human milk composition differs in healthy mothers and mothers with celiac disease." European journal of nutrition 54.1 (2014): 119-128.
• Özkan, T., T. Özeke, and A. Meral. "Gliadin-specific IgA antibodies in breast milk." Journal of international medical research 28.5 (2000): 234-240.
• Zanetti, et al. "Randomised clinical study: gluten challenge induces symptom recurrence in only a minority of patients who meet clinical criteria for non-coeliac gluten sensitivity." Alimentary Pharmacology and Therapeutics (2015): Ahead of print.