The study I’m going to cover today came out several weeks ago, but in draft form with watermarks splashed across its pages. (1) As I wanted to display some of the charts, I thought it best to wait until the finalized version was made available before blogging about it.
This study was a randomized, clinically controlled trial conducted at the Mayo Clinic which sought to determine whether a gluten-free diet would help alleviate symptoms in those suffering from diarrhea-specific irritable bowel syndrome (IBS-D). Participants were recruited from a database of more than 800 patients with confirmed IBS. Of these, 307 with known IBS-D were contacted to take part.
The three main exclusion criteria were: being gluten-free immediately before the start of the study, any history of gluten-free dieting and any clinical evidence of celiac disease. Volunteers were also excluded if they had used tobacco products in the past six months, were using non-steroidal anti-inflammatory drugs or aspirin (these drugs increase gut leakiness), used artificial sweeteners in the two days prior to study commencement (to avoid interfering with gut permeability tests), used any drugs that would impact intestinal transit time or were using any medications that increased the risk of bleeding from gut biopsies.
Ultimately, 45 participants were chosen. IBS-D is heavily represented among women so the majority of volunteers were female. Of the 45 selected, 28 agreed to undergo upper-gastrointestinal endoscopy and sigmoidoscopy for further evaluation.
Participants were randomized into two groups, a gluten-containing diet group (GCD) numbering 22 people and a gluten-free group (GFD) numbering 23. There were no significant differences in age, gender, BMI or levels of anxiety or depression between groups.
As planned, all volunteers had eaten gluten-containing foods to various degrees before taking part in this study. 90% were eating between one and 4.4 servings of gluten-containing food a day. Two participants were ingesting fifteen gluten-containing servings a day.
Holy Bundt cake, Batman!
Americans do love their
opioids wheat after all! Bless their little gut-trashed hearts.
Prior to randomization, participants were screened for genetic vulnerability to celiac disease. Persons most at risk for this autoimmune disorder have at least one of two genetic markers: HLA-DQ2 or HLA-DQ8. In persons with either risk factor, receptors formed by these genes bind to gliadin peptides and activate inflammatory immune responses that can attack the absorptive surfaces of the small intestine and result in celiac disease.
Note the word, “can”. Not everyone with this genetic predisposition goes on to develop full-blown celiac. Nevertheless, as you’ll soon see, they are at elevated risk for increased intestinal permeability and the endotoxemia that results from this.
Estimates are 40% to 50% of the U.S. population carries either HLA-DQ2 or HLA-DQ8 but no one, including anyone in the medical community, knows the real figure as it isn’t routinely screened for. That inconvenient fact, of course, doesn’t prevent armies of delusional health “experts” from touting the supposedly wondrous benefits of eating whole-wheat grains or stop them from labeling as a faddist anyone warning against gluten consumption. But I digress.
Of the 22 members of the gluten-containing group, 11 tested positive for either genetic marker and 11 tested negative. In the gluten-free group, 12 tested positive and 11 tested negative.
Both groups were instructed to eat their prepared meals at the Mayo Clinical Research Unit. Participants were also provided snacks and advised only to eat those foods provided by study dietitians for the 4-week duration of the trial.
Macronutrient composition of both diets was identical and consisted of the following: 20% protein, 30% fat and 50% carbohydrate. Caloric intake was adjusted for physical activity to ensure no one gained or lost weight during the month. No mention was made of how caloric intake was increased in the gluten group to compensate for running sprints to the toilet to avert the soiling of undies:
These graphs illustrate average daily bowel movements between groups. Lines beginning and ending in open symbols represent participants who tested negative for either HLA-DQ2 or HLA-DQ 8 whereas solid symbols are those that tested positive.
With the exception of two people, all participants experienced decreases in bowel frequency in the gluten-free group with none having more than 4.5 bowel movements during the day. Those who were HLA-DQ2 or HLA-DQ8 positive showed the most improvement.
The gluten-containing group was not as fortunate, although some people in this group did experience some improvement. I would suspect this was because they were unable to eat crap loads (pun intended) of processed wheat junk food.
My heart goes out to the HLA-DQ2/HLA-DQ8-negative soul represented by the top line in the gluten group. Six to seven bowel movements a day?!?! This person really needs to stop eating wheat and read this blog.
Many of these folks are at increased risk for developing diverticulitis. A recent study found that people experiencing more than 15 bowel movements in a week ran a 70% higher chance of developing this disorder. (2)
There were no significant differences in stool formation in either group with or without HLA-DQ2 or HLA-DQ8. In other words, stools didn’t get any closer to type 4 on the Bristol Stool Chart.
Type 4 stools resemble a smooth, brown sausage and should sink to the bottom of the toilet bowel leaving very little to no residue after flushing. This, my faithful readers, is the Holy Grail of healthy poop!
There was no difference in stomach emptying or transit time between either group nor was there any significant difference noted in ease of passage. However, given that no attempt was made to correct the gut dysbiosis causing this mayhem, that isn’t too shocking.
Neither upper-gastrointestinal endoscopy nor sigmoidoscopy revealed any differences between the twenty-eight patients randomized to either group who underwent these procedures. No evidence of villous atrophy was found confirming the absence of celiac disease.
Small bowel permeability, aka “leaky gut”, was greater in the gluten-eating group. No surprise here given what we know about gluten’s effect on intestinal tight junctions. Unsurprisingly, gut permeability was even greater in the group genetically predisposed to developing celiac disease as these people experience increased and sustained zonulin release after gluten exposure:
These sets of graphs plot urine excretion of both mannitol and lactulose and serve as a measurement of gut permeability and by extension, endotoxemia. Mannitol excretion was most evident in the gluten group (GCD) between hours zero and two after eating, but not so much between hours eight and twenty-four. As for lactulose, the gluten-free group actually outpaced the gluten-containing group up to hour two. Hmm, small intestinal bacterial overgrowth (SIBO) anyone?
However, the gluten group soon caught up and surpassed this cohort between hours eight and twenty-four. What we see graphically displayed here are some seriously leaky guts from both groups.
Expression of the tight-junction proteins, ZO-1, occludin and claudin-1 were lower in the gluten group. This was especially true for expression of these proteins in the colon and probably accounts for the higher lactulose readings at the eight to twenty-four hour mark in this cohort.
Increased permeability in the small intestine is bad enough without adding a leaky colon to the mix, especially one that is no doubt brimming with lipopolysaccharide-rich, gram-negative gut pathogens as a consequence of colonic dysbiosis. I pity the poor livers and cardiovascular systems of these people!
Here’s a “fun” series of graphs. After drawing blood from each participant, peripheral blood mononuclear cells (PBMCs) were subjected to both rice and gluten to gauge immune reactions. PBMCs are blood cells containing a round nucleus and form part of the immune system. Monocytes, macrophages and lymphocytes are PBMCs for example.
Here we see increases in the anti-inflammatory cytokine interleukin 10 (IL-10) when these cells were exposed to gluten in vitro. Not surprising as this cytokine is typically elevated as a counterbalance to inflammatory cytokines, in this case tumor necrosis factor alpha (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF is a cytokine that stimulates white-cell growth and is part of the inflammatory cascade.
Now I’m sure you’re all thinking that those participants who were HLA-DQ2 and HLA-DQ8 positive were the ones most likely to show increases in inflammatory markers when their blood cells were tested this way. Alas, you’d be wrong. Regardless of genetic predisposition, PBMCs from all volunteers showed this pronounced response testifying to gluten’s universal property of triggering inflammatory immune responses in anyone who eats it.
While some may note that rice also provoked an immune response, albeit muted compared to gluten, please keep in mind that when you have a leaky gut, your immune system will form antigens to a variety of foods simply because food molecules that should never enter the portal vein to liver do so. I receive many emails from readers who have been reduced to eating a very restricted diet because they react to many foods. How could it be otherwise when your gut wall has more holes in it than a slice of Swiss cheese?
There is no indication in this paper that any of these volunteers were screened for SIBO. Nor is there any hint they were checked for an overgrowth of Candida in their GI tracts. I assume they were given stool tests at one point to check for parasites, but given the emails I receive from people at their wit’s end with the medical establishment, failure to test for this wouldn’t surprise me in the least.
It’s blatantly obvious that these IBS patients were suffering from some nasty gut dysbiosis. Nevertheless, as this study makes clear, banishing gluten from the diet will certainly offer symptom relief, especially if the person tests positive for HLA-DQ2 or HLA-DQ8.
However, going gluten-free has no magical ability to eradicate pathogenic bacterial biofilms, tame an overgrowth of Candida in the intestines, kill parasites or replenish what are assuredly depleted colonies of beneficial lactobacillus and bifidobacteria. Many recently diagnosed celiacs soon learn that going gluten-free is but only a first step to healing and sealing their guts.
Ultimately, antibacterial, antifungal (and perhaps antiparasitic) medication, pharmaceutical or herbal, will have to be taken along with probiotics and prebiotics to conquer IBS and many other intestinal issues. What this study makes clear is that keeping gluten in your diet is not a wise decision when battling gut issues.