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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.

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).
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.
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.

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.

You will find dozens of ginger + lemon water recipes on the internet - all of them can pimp your peri-workout drinks and make your tummies "exercise proof".

As a regular here at the waredownloadsoft you know about the beneficial health effects of ginger. It has potent anti-oxidant and anti-inflammatory effects without the usual side-effects of COX-inhibitors (Mashhadi. 2013), has been shown to have anti-cancer effect on it's own (Kim. 2005), as well as to be a perfect adjunct for conventional cancer therapy (Sontakke. 2003).

Ginger has also been shown to exert cardioprotective effects (Ghayur. 2005; Singletary. 2010), strengthens the immune system (Butt. 2011) and significant beneficial effects on the health of the digestive system - including the make-up of your microbiome (Sutherland. 2009).
Now, it is out of question almost all of these effects would be beneficial to athletes, too. The one I want to focus on, today, though, is directly related to the last-mentioned effect: the beneficial effect on the gut. It is well-known that athletes, in general, and endurance athletes, in particular, are having a hard time keeping their tummy from "leaking" (learn more about the link between exercise and leaky gut). With ginger - that's at least what a recent study from the School of Life Sciences at the Heriot-Watt University in Edinburgh suggests. The scientists went from the observations that

1. the frequency of upper and lower gastrointestinal disturbance as a function of exercise is reported to be between 30 and 70%
2. the severity of symptoms ranging from mild stomach discomfort to severe diarrhoea and 
3. the consumption of beverages either before or during exercise may increase the incidence rate by over 25%

to the hypothesis that spiking said beverages with an agent that has previously been shown to reduce the symptoms of nausea and vomiting could be of great benefit for athletes.
In the present study, this agent was ginger that was added to an isotonic beverage 40 recreational athletes (23 male, 17 female) who had volunteered to participate in the study consumed on one out of three test drinks containing 450 ml of either water or beverage A or beverage B in two 225ml servings before and after their workout:

• Study Underlines Real World Benefits of 2g/day of Ginger for Type II Diabetics - Effects Almost on Par W/ Metformin | more

  Beverage A contained 7·5% glucose, 10 mM NaCl, citric acid, K sorbate and 62·5 ml of ginger root extract per 1 L.
• Beverage B was identical to beverage A but the ginger was replaced with 62·5 ml of carrot extract. 
• The control drink contained nothing but plain water.

"Section 1 addressed upper abdominal problems (reflux / heartburn, belching, bloating, stomach cramps/pain, nausea, vomiting); section 2 addressed lower abdominal problems (intestinal/lower abdominal cramps, flatulence, urge to defecate, side ache/stitch, loose stool, diarrhea, intestinal bleeding); and section 3 addressed systemic problems (dizziness, headache, muscle cramp, urge to urinate)" (Pfeiffer. 2012). 

References:

• Ball, D., G. Ashley, and H. Stradling. "Exercise-induced gastrointestinal disturbances: potential amelioration with a ginger containing beverage." Proceedings of the Nutrition Society 74.OCE3 (2015): E186.
• Boppel, B. "[Lead-and cadmium-content of foodstuffs 1. Lead-and Cadmium-content of spices and table salt (author's transl)]." Zeitschrift Fur Lebensmittel-Untersuchung Und-Forschung 160.3 (1975): 299-302.
• Butt, Masood Sadiq, and M. Tauseef Sultan. "Ginger and its health claims: molecular aspects." Critical reviews in food science and nutrition 51.5 (2011): 383-393.
• Ghayur, Muhammad Nabeel, and Anwarul Hassan Gilani. "Ginger lowers blood pressure through blockade of voltage-dependent calcium channels." Journal of cardiovascular pharmacology 45.1 (2005): 74-80.
• Kim, Eok-Cheon, et al. "[6]-Gingerol, a pungent ingredient of ginger, inhibits angiogenesis in vitro and in vivo." Biochemical and biophysical research communications 335.2 (2005): 300-308.
• Mashhadi, Nafiseh Shokri, et al. "Anti-oxidative and anti-inflammatory effects of ginger in health and physical activity: review of current evidence." International journal of preventive medicine 4.Suppl 1 (2013): S36.
• Singletary, Keith. "Ginger: An Overview of health benefits." Nutrition Today 45.4 (2010): 171-183.
• Sontakke, S., V. Thawani, and M. S. Naik. "Ginger as an antiemetic in nausea and vomiting induced by chemotherapy: a randomized, cross-over, double blind study." Indian journal of pharmacology 35.1 (2003): 32-36.
• Srivastava, L. P., Roli Budhwar, and R. B. Raizada. "Organochlorine pesticide residues in Indian spices." Bulletin of environmental contamination and toxicology 67.6 (2001): 856-862.
• Sullivan, James H. "Pesticide residues in imported spices. A survey for chlorinated hydrocarbons." Journal of agricultural and food chemistry 28.5 (1980): 1031-1034.

2/3 of this can may suffice to make a difference. Whether this difference is (a) relevant or (b) irrelevant is yet as questionable as whether the changes the scientists observed will (i) have a negative (ii) a positive or (iii) no effect.

As a waredownloadsoft user you know that the whole craze about aspartam and sucralose is overblown. You will also know that any potential "pro-insulinogenic" effects occurred only in less than a handful of human studies. If they did, though, they occurred in response to the ingestion of artificial sweeteners and glucose or other insulinogenic carbohydrate sources (learn more). Against that background it's also not surprising that in clinical trials vs. observational bogus, artificial sweeteners have been shown to help people with weight problems lose body fat (learn more).

The one thing about the myth of the bad sweetener that has yet not been completely debunked, though, revolves around their negative effects on the human gut microbiome.
You will remember from my previous post on this topic that - as (unfortunately) usual - all empirically valid data we have is based on rodent trials. In our mammalian cousins, the consumption of artificially sweetened products on top of an obesogenic diet has in fact been shown to have an additional effect on the modulation of the gut bacteria that appears to make turn an already "bad" diet into a nightmare (learn more). It is yet still very questionable, which part of the research can be translated to humans and to which subgroup of the population this would apply. Even if we assume a 1:1 translation from rodent to human, we would after all have to exclude most of you, because none of you will be consuming a hypercaloric, hyper-processed high fat + high carbohydrate diet (at least that's what I'd hope).

If we trust the results of a soon-to-be-published observational study from the George Mason University, though, our gut microbiomes could be in danger - although no one knows for sure.
In their thorough, but small scale (N=31) analysis, Cara L. Frankenfeld and her colleagues analysed the fecal sample of their subjects using Multitag Pyrosequencing. This allowed them to compare the bacterial abundance and bacterial diversityacross consumers and non-consumers of aspartame and acesulfame-K using non-parametric statistics and UniFrac analysis, respectively.

To predict some of the consequences of possible difference in the bacterial make-up Frankenfeld et al. applied a phylogenetic investigation of the communities by reconstruction of unobserved states (PICRUSt) in order to predict mean relative abundance of gene function.

Table 1: There were no sign. differences in BMI, energy intake, total carbohydrate and added sugar intake or the "quality" of the diet (as assessed on the Healthy Eating Index) between AS consumers and non-consumers (Frankenfeld. 2015)

Thus, the results of the gene function analysis must be met with a healthy degree of skepticism, because unlike the bacterial counts and diversity, which was also just estimated based on what "left" the subjects in form of feces, the gene assay is a model-based result... think of it like the weather forecast, one of which studies say it's relatively reliable (Langille. 2013).
Among the seven aspartame consumers and seven acesulfame-K consumers (some consumed both), the researchers did indeed find some significant differences in the bacterial make-up compared to those subjects who had abstained from consuming sweeteners in the four days before the fecal samples were collected. I quote from the FT (Frankenfeld. 2015):

• Bacteriodetes and Firmicutes had the highest median abundances and together accounted for the majority of the bacterial class representation in all individuals. 
• The median Bacteriodetes:Firmcutes ratio did not significantly differ across aspartame non-consumers (0.96, range: 0.15-2.97) and consumers (1.08, range: 0.69-1.87), (median test p-value=0.60). 
• There was no overall visual clustering of individuals by acesulfame-K consumption . 
• Overall bacterial diversity evaluated with UniFrac analysis was different across consumers and non-consumers, but there were no significant differences in relative abundance of gene function across consumers and non-consumers (Figure 3).
• There were no observable difference in the three individuals who consumed both aspartame and acesulfame-K (Supplemental Figure 1). 

So, let's briefly sum this up. In line with the overall hysteria about sweeteners, the changes were more significant in the aspartame group (p<0.01) than they were in the acesulfame-K group (p=0.03), but this could be explained by the simple fact that the subjects consumed significantly more aspartame (one can of diet coke contains 150mg, by the way) than acesulfam-K (5.3 mg/day to 112 mg/day vs. 1.7 mg/day to 33.2 mg/day).

Figure 1: Yes, there were differences in the bacterial make-up of the gut microbiome of the four groups, but no one can tell you what these or the vast individual differences in the groups mean for your health (Frankenfeld. 2015) !

Against that background, the "aspartame is the worst" hypothesis could neither be refuted nor supported based on the study at hand, even if the results would signify overall ill-health effects. With all three potentially important markers remaining unchanged, though, this is not the case:

• the ratio of mostly "bad" gram-negative bacteriodetes and "good" gram positive bacteria remained the same - it's thus hard to argue that the subjects who consumed artificial sweeteners had an unhealthier gut microbiome
• there was no general reduction in gut bacteria, which would indicate a general anti-microbial effect of artificial sweeteners as it occurs with antibiotics - it's thus hard to argue that the anti-microbial effects (which don't exist) of artificial sweeteners would leave you similarly defenseless and open to colonization with "bad" bacteria as antibiotics.
• the gene essays say that despite the differences in the numbers of certain bacteria, the gene expression is the same - it's thus hard to argue that there was an epigenetic effect of artificial sweeteners that precipitates us to obesity or even makes us sick / diabetic / whatever