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Leaky gut theory: full of holes?

Nutritional interventions may provide symptom relief despite uncertainty about leaky gut theory.

Lisa Polito

December 21, 2016

6 Min Read
Leaky gut theory: full of holes?

Humans are complex creatures yearning for simple answers. Just as we search for a panacea—that single drug or supplement or food ingredient that will heal all ills (and maybe dodge the effects of aging while we’re at it)—we seek panacea’s disease corollary: that single gene or molecule or biological trigger at the root of all illnesses.

Many believe they have found it: leaky gut syndrome.

Generally, the thin epithelial lining of the intestine takes up large molecules across cells (transcellular) and very small molecules, like water and electrolytes, via the spaces between those cells (paracellular), also known as tight junctions. Abnormal paracellular function allows larger molecules across those tight junctions: the leakiness that is leaky gut. Proponents of the leaky gut syndrome theory hold that this leakiness allows undesirable particles—bacteria, allergens, toxins, food molecules—to enter the bloodstream and or lymphatic system, leading to a cascade of inflammation, systemic immune response and the wreaking all sorts of health havoc: from gastrointestinal disorders and autoimmune conditions to migraines, metabolic disorders and autism.

"It’s a very neat idea," says Eamonn Quigley, MD, head of gastroenterology and hepatology at Houston Methodist Hospital. But that neat idea extrapolates directly from animal models and does so without corresponding evidence that undesirable molecules "leaked" through, he says. Quigley, who is also professor of medicine and internationally recognized researcher in digestive disorders, particularly the microbiome and neurogastroenterology (the relationship between the central nervous system and the gut), explains that while intestinal permeability, and specifically bacterial translocation, is well known to occur in animal models, satisfactory testing for the same mechanism in humans is lacking. 

Without live tissue analysis, detection of abnormal intestinal permeability in humans proves technically challenging, in part because the intestinal barrier is not always a barrier. In fact, Quigley says, it’s not that simple. Information moves back and forth across the epithelial layer: "It is a two-way street, absolutely." Further complicating detection are normal transcellular functions, which can move bacteria and other seemingly undesirable molecules into the intestinal mucosa and beyond, to the submucosa, which holds the intestinal lymphatic system.

Although increased permeability is associated with both severe stress and inflammation, Quigley notes the chicken-and-egg question of primacy: did the permeability cause the disease state, or is it the other way around? "People kind of grabbed onto this theory and applied it to a whole host of illnesses, the most part for which there’s no data," he says.

An alternative perspective

"This is not something that we in integrated medicine or in nutrition just made up," says Liz Lipski, certified nutrition specialist and academic director of nutrition and integrative health, Maryland University of Integrative Health. "It’s real, and it exists. And it contributes to a lot of health issues, including autoimmune disease and so many other things." Lipski, who published her book Leaky Gut Syndrome in 1998, believes the disconnect is a matter of education and perspective within conventional medicine.

"Most [conventional] medicine is aimed at a diagnosis," she says, "and leaky gut is not a disease, so it doesn’t really have a diagnosis, particularly." When encountering a patient with symptoms of leaky gut, she says, "You really want to start looking underneath the hood to figure out why does this person have increased intestinal permeability? Are they under a lot of stress? Are they exposed to toxic overload? Do they have some sort of dysbiosis or infection? Or do they have food sensitivity or undiagnosed celiac disease or all these other things?"

She sees resolution of many problems associated with leaky gut through dietary changes (she favors bone broths, steamed vegetables, vegetable juices, cultured foods and mucous-forming foods) and nutritional supplements (L-glutamine, colostrum, zinc carnosine and quercetin top her list). In her observation, patients have resolved issues with migraine headaches, low energy, depression and anxiety. For people with autoimmune conditions, she says, these nutritional interventions can act like a dimmer switch to bring down the intensity of an immune system flare up.

Going with the gut

An HIV advocacy group is hoping Just Thrive Probiotics might offer such a path to optimizing health and addressing intestinal permeability for HIV patients. After learning of the product in March, the group reached out to Just Thrive in hopes of using the probiotic in clinical trials evaluating treatments for HIV enteropathy, the deterioration of intestinal immune and digestive functions, including barrier function. Unlike many probiotic products, the strains in Just Thrive naturally require no refrigeration, are heat tolerant and survive both gastric system acidity and the presence of antibiotics—significant factors in considering global HIV treatment options. In a matter of months, the company found its probiotic fast-tracked for inclusion in the NIH study, according to Kiran Krishnan, microbiologist and scientific adviser.

The strains in Just Thrive have already been shown to upregulate regulatory T cells that modulate the immune system, and Krishnan believes the product shows great promise for improving intestinal barrier function. In a trial completed earlier this year at the University of North Texas, healthy, symptom-free college students who screened positive for leaky gut consumed an endotoxin-inducing high-calorie, high-fat challenge meal at baseline and again after taking Just Thrive for 30 days. A six- to seven-fold increase of endotoxins in the blood signaled a leaky gut at baseline. Researchers also tracked microbial components and metabolic and inflammatory markers. After probiotic treatment, they expected to see some reduction in the endotoxic load, but Krishnan reports that preliminary data show a 100 percent endotoxemia reduction, as well as drops in other markers, like insulin and ghrelin (the "hunger hormone"). "We were surprised to find that everybody that had endotoxemia from the meal challenge at baseline showed complete reversion."

Most probiotics contain lactobacillus and bifidus strains similar to those found in the gut, but the four bacillus strains in Just Thrive are environmental organisms, which remain in a spore state until reaching the gut. Krishnan postulates that our hunter-gatherer ancestors consumed these endospores with every meal, but our sanitized industrial food system eradicates them along with the bad bacterial players. That absence diminishes the gut microbiome.

"Nature has designed [this] bacteria to act as a probiotic for us," Krishnan says. "[The bacteria] already figured out how to encapsulate themselves to survive the outside environment: the harsh heat, UV radiation, desiccation. And then that same packaging allows them to survive through the gastric system. The moment they get past the gastric system and hit the intestine they come out of that spore packing in about 20 minutes and become a live vegetative probiotic cell in the body."

Whether the probiotics mechanistically strengthen the intestinal barrier or simply improve digestion—thereby reducing the toxic burden on that barrier—likely will not matter to consumers if the end result is symptom reduction and improved health.

Healing the microbiome to heal the human system clearly holds promise, as evidenced by investment in pharmaceutical development of microbe-based treatments. For example, Seres Therapeutics is developing an FDA designated breakthrough drug treatment of recurrent Clostridium difficile infection (despite a recent setback in Phase 2 trial results), but the long view of product development pipeline aims at microbial blends to treat metabolic disorders like liver disease and type 2 diabetes. The idea of healing diabetes with probiotics sounds similar to the disease-remedy theories associated with leaky gut syndrome.

Such targeted treatments are still in discovery phase, but in the meantime, improving digestive function and intestinal tissue health may well take some pressure off the immune system and reduce the endotoxic load in the bloodstream. All that might improve the overall well-being of people who identify with leaky gut symptoms.

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