Digestive Health

Lactobacillus Combo Delays Celiac Onset In At-Risk Children

By Kristen Schepker, Assistant Editor

Lactobacillus Plantarum 660x330Lactobacillus plantarum, one of two probiotic organisms shown to avert the onset of celiac disease in at-risk children. Findings from a new study on celiac disease challenge the prevailing belief that strict gluten avoidance is the only effective approach to managing the condition.

Researchers at Sweden's Lund University showed that certain strains of probiotic bacteria have a suppressive effect on celiac autoimmunity that can delay the onset of the disease in at-risk children.

The investigators found that daily supplementation with a multi-strain lactobacillus probiotic significantly reduced the levels of celiac-related antibodies in kids with genetic predispositions to the disease -- despite their continued consumption of foods containing gluten.

For the estimated three million Americans living with celiac disease (CD), these promising results could shape the future of not only celiac disease treatment, but of prevention as well.

"To our knowledge, this is the first time a probiotic study has been performed on this specific population," said Lund University's Daniel Agardh, MD, PhD, who headed the research team. The data, which they presented in September, at the International Celiac Disease Symposium in New Delhi, India, "show immune-supporting properties of these probiotics as well as a potential preventive effect on the development of CD," he added.  

Agardh's group looked at the effects of two proprietary strains, Lactobacillus plantarum Heal 9 and Lactobacillus paracasei 8700:2, produced by Swedish supplement company Probi AB, on celiac disease autoimmunity. The randomized, double-blind, placebo-controlled trial involved 78 asymptomatic children aged three to seven years, who were deemed to be at increased risk for developing celiac disease owint to the presence of autoimmune markers associated with the disorder.

Much of the research on probiotics in celiac disease focuses on their potential as a therapy to manage existing disease symptoms. The Lund trial is the first to suggest the possibility that probiotics can be used to prevent celiac disease.

All of the kids had two consecutive blood samples that tested positive for tissue transglutaminase autoantibodies (tTGA), taken at least three months apart. They were randomized to take either a probiotic delivering both Lactobacillus strains or a placebo once daily for six months. They did not make any dietary changes, and were encouraged to continuing to eat their usual gluten-containing diets.

Celiac Antibodies Decline

Prior data from both human and animal studies showed that the selected bacterial strains support immune system health and confer "synergistic effects on reducing pro-inflammatory responses in vivo" at doses of 109 CFUs, explained Gun-Britt Fransson, PhD, Vice President Research & Development at Probi. Notably, the present study is the only one as of yet designed to test a larger dose of 1010 CFUs, Fransson added.

The researchers found that over the course of the study, celiac disease-related antibody levels (tTGA-IgA and tTGA-IgG) dropped significantly in children in the probiotic group, but increased significantly in the placebo group.

"The interpretation of this finding is that the probiotics can delay the onset of celiac disease -- and may even prevent from the development of the disease," Fransson proposed. 

Currently, the sole approach known to lessen celiac disease symptoms is a stringent, life-long, gluten-free diet, which, Fransson stated, "seriously affects and complicates everyday life." Therefore, she argued, "giving clinically documented probiotics as a prevention to anyone at risk for developing the disease, which is easy and not too costly, would be highly beneficial." 

Not long ago, scientists first hypothesized that the intestinal microbiota has an influence on celiac disease etiology, leading to the theory that probiotics can serve as a useful adjuvant in the management of gluten intolerance. Today, that theory is gaining traction -- not just within medical research circles, but among key supplement industry players as well.

"We see a growing interest in children’s probiotics," said Probi CEO Peter Nählstedt. The Lund University study, he says, supports the use of probiotics to lower celiac risk, and will, "enable Probi to build a product platform for children."

The Dysbiosis Factor

Several other recent studies further highlight the potential utility of probiotics as a celiac disease therapy.

A 2016 paper in the journal, Digestive Diseases and Sciences, showed that when compared to healthy subjects, patients with celiac disease have reduced levels of beneficial bacteria and elevated amounts of potentially pathogenic microorganisms in their intestinal microbiota.

As a group, celiac sufferers generally exhibit gut dysbiosis, increased intestinal permeability, and immune system disorders. While going gluten-free alleviates gut dysbiosis in some patients, many others will continue to experience symptoms of dysbiosis even after removing grains and other gluten-containing products from their diets. The authors argue that the intestinal microbiota likely plays a significant and independent role in celiac disease pathogenesis (Marasco, G. et al. Dig Dis & Sci. 2016; 61(6): 1461–1472). 

For individuals with celiac disease, certain microorganisms appear to be more efficacious than others in balancing the intestinal flora. There is evidence that species belonging to the genera Lactobacillus and Bifidobacterium in particular convey protective benefits to celiac patients. They exert anti-inflammatory effects as well as "protective properties on epithelial cells from damage caused by gliadin" (Morales, L. et al. Clin Microbiol Rev. 2014; 27(3): 482-489).

In a 2017 literature review of studies exploring probiotics to treat celiac disease, Coqueiro and colleagues note that the "therapeutic effects of probiotics in celiac disease are associated with an improvement in the intestinal microbiota and inflammatory conditions, attenuating the immune response and, generally promoting intestinal health."

Bearing in mind that the amount of scientific data on this subject is fairly limited, the research that does exist shows that using probiotics and enzymes in food production also benefits patients by reducing gluten toxicity, allowing celiac patients to consume foods that would otherwise trigger symptoms. However, the authors stress that probiotics "should be applied as an adjunct in celiac disease treatment." They are not a substitute for a gluten-free diet, which remains essential to effectively treat the condition (Coqueiro, A. et al. Int J Probi & Prebi. 2017; 12(1): 23-32).

Much of the research on probiotics in celiac disease focuses on their potential as a therapy to manage existing disease symptoms. The Lund trial, which has not yet been published, is the first to suggest the possibility that probiotics can be used to prevent celiac disease. Clearly more research is needed, but the initial signals are promising.

Practitioners looking to recommend probiotics to celiac patients should seek out products with documented clinical benefits for human health. "I would look for a probiotic shown to strengthen the intestinal barrier function, strengthen the immune system and reduce the pro-inflammatory response," urged Probi's Fransson.

If current research trends continue, we will likely see the emergence of probiotic supplements designed specifically to prevent celiac disease.


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The "Wheat Zoomer"--A Game-Changer for Gluten Testing?

By Madiha Saeed, MD, Contributing Writer

A new suite of antigen tests collectively called the Wheat Zoomer is being forwarded as a definitive tool to help clinicians figure out if a patient truly is--or is not--sensitive to gluten and other grain-based proteins. Is the Zoomer all that it's cracked up to be? Experts share their views.

Endomicroscopy Offers Insight on Leaky Gut Syndrome

By Isaac Eliaz, MD, Contributing Writer

Confocal laser endomicroscopy (CLE) enables direct visualization of cellular and subcellular changes in the intestinal lining of a living patient. This new imaging technique gives the ability to detect subtle inflammatory changes and epithelial gap formations in patients with intolerance to specific food group, providing objective evidence to support the controversial concept of "leaky gut syndrome."

Probiotics Research Update: Glucose Control, Obesity Prevention & Ulcer Remedy

By Kristen Schepker, Assistant Editor

The recent explosion in human microbiome research and its increasing coverage in the media, has made "probiotics" a household word. While many people understand that beneficial bacteria are a crucial component of digestive health, scientists continue to uncover the myriad ways in which probiotics promote good health far beyond the GI tract.

Following are reviews of some of the latest probiotics studies highlighting the roles that gut flora play in regulating blood sugar levels, influencing obesity, and combating H. pylori infection.

How To Restore Gut Flora After Antibiotics

By Kristen Schepker, Assistant Editor

Antibiotics eradicate pathogenic infections and save lives -- but in doing so, they also disrupt the integrity of the intestinal microbiome. While many physicians recognize the need for restoring a patient's microbial balance following a course of antibiotic therapy, far fewer understand how to do this effectively.

According to Amie Skilton, ND, restoration of gut flora is both art and science. Done well, it can make a world of difference for patients. In some cases, it can even help patients overcome the illnesses for which the antibiotics were initially prescribed.

But it takes more than just recommending an off-the-shelf probiotic and hoping for the best.

The Centers for Disease Control reported last Spring that of the 154 million prescriptions for antibiotics written in doctor’s offices and emergency departments each year, 30 percent are unnecessary. Most of the extraneous prescriptions, the CDC found, were doled out for respiratory conditions caused by viruses like common colds, viral sore throats, bronchitis, and sinus and ear infections, which do not respond to antibiotics. Use of these drugs "put patients at needless risk for allergic reactions or the sometimes deadly diarrhea, Clostridium difficile.”

Further complicating the picture is the reality that antibiotics aren't only dispersed from doctor's offices; they're also fed liberally to livestock and sprayed extensively on produce, leaving minute but biologically active traces in the foods that humans then consume.

Dose, Timing Determine Impactantibiotics pills

As antibiotics kill off infection-causing microorganisms, they also non-selectively destroy communities of beneficial gut bacteria, weakening the stability of the intestinal microbiome. This wholesale destruction can be massive; experimental data collected from a study using qPCR indicate up to a 10-fold reduction in bacterial isolates immediately after treatment with antibiotics (Panda, S. et al. PLoS One. 2014; 9(4): e95476).

"It's truly a decimating effect," says Dr. Skilton, a naturopathic physician and herbalist at the Elysium Clinic of Natural Medicine, Sydney, NSW, Australia.

In a webinar sponsored by Holistic Primary Care and Bioceuticals, she outlined the myriad impacts of antibiotics on the human microbiome, noting that not all antibiotics are equally destructive to gut bacteria. 

The degree to which these drugs damage intestinal microbiota depends on drug type, treatment duration, and frequency of use, Skilton said. Certain antibiotics, for instance, trigger a greater release of endotoxins and cytokines than others. Higher daily doses are more impactful. Prolonged use of high-dose antibiotics can cause extreme damage to the microbiome that may take years of restorative therapy to reverse, if it can be reversed at all.

And contrary to common belief, intravenous antibiotics can have the same negative impact on gut flora as oral drugs. "For a long time it was thought that IV drugs would bypass the gut and not have the same impact. We now know this is not true."

The timing of antibiotic delivery also makes a difference. Individuals who frequently use antibiotics early in life are more vulnerable to many types of illness as they age. In a paper published earlier this year, researchers demonstrated an association between antibiotic use during infancy and subsequent poor neurocognitive outcomes, suggesting that antibiotic consumption in a patient's first year of life was associated with small but statistically significant differences in cognitive, behavioral, and mood measures during childhood (Slykerman, R. et al. Acta Paediatr. 2017; 106(1): 87–94). 

Others have linked fetal and early childhood antibiotic exposure to the subsequent development of asthma later in life (Örtqvist, A. et al. Brit Med J. 2014; 349. doi: https://doi.org/10.1136/bmj.g6979). Antibiotics have also been associated with obesity and weight gain in children as well adults (Million, M. et al. Clin Microbiol & Infec. 2013; 19(4): 305–313). Researchers attribute these changes to the altered gut microbial composition.

Antibiotics can trigger the release of toxic lipopolysaccharides (LPS), large molecules found in the outer membranes of pathogenic Gram-negative bacteria. Some suggest that antibiotic-induced LPS release may contribute to the development of septic shock in patients treated for severe infections caused by Gram-negative bacteria. Others have demonstrated that LPS triggers an immune response by releasing inflammatory cytokines, a problem that worsens after antibiotic treatment, noted Skilton in her webinar (Wu, T. et al. Toxicol Lett. 2009; 191(2-3): 195-202).

From a pathogen's point of view, production of LPS is a survival strategy. These molecules interact on cell surfaces to form a barrier, preventing the antibiotics and other hydrophobic compounds from entering and allowing Gram-negative bacteria to live even in harsh environments (Zhang, G. et al. Curr Opin Microbiol. 2013; 16(6): 779–785).

How to Restore the Flora

Probiotics are one aspect in a comprehensive strategy to restore gut flora following antibiotics. Given the microbial diversity of a healthy gut ecosystem, Skilton recommends using products that contain many different species of beneficial microbes rather than "monocropping" with one or two single strains.

As a general rule, she advises one month of probiotic treatment for every week that a patient was on antibiotics. Those who have been on prolonged continuous antibiotic regimens, will likewise need long-term restoration. She stressed that for most people,  there are no health risks associated with extended probiotic supplementation.

Patients receiving IV antibiotics should also take commensal probiotics. Some clinicians who are aware of this issue will start the probiotics as early as four hours after a dose of IV antibiotics.

Rebuilding the Glycocalyx

People who have been on long-term or multiple courses of antibiotics typically show a severe erosion of the glycocalyx that normally coats the  intestinal microvilli. This is usually accompanied by a loss of brush borders and a marked reduction in secretory IgA production.

GlycocalyxIn some cases, these changes are caused by the effects of antibiotics themselves. In others, they reflect the impact of the infection for which the antibiotics were prescribed. Either way, the effect is the same: establishment of a microenvironment that is hospitable to opportunistic pathogens like Candida, but increasingly difficult for normal commensal bacteria.

Fungal infections are almost always accompanied by insufficient IgA production, as Candida consumes both glycocalyx and sIgA as fuels. It becomes a vicious cycle: low IgA begets Candida which further depletes IgA. Chronic urinary tract infections, and mucosal infections like thrush are red flags for low sIgA production, Skilton pointed out.

Without a healthy glycocalyx, organisms like Lactobacilli and Bifidobacilli have great difficulty establishing themselves. In this context, supplementation with ordinary probiotics will usually fail.

"Even if you recommend the best probiotics in the world, theres’ no way for them to stick and colonize if the glycocalyx is eroded," Dr. Skilton explained. "You can actually exaggerate the GI symtoms by giving probiotics, if the there's loss of ability to produce glycocalyx."

To restore a healthier microenvironment in these cases, you need to leverage the unique characteristics of Saccharomyces boulardii, an antibiotic-resistant, probiotic yeast originally isolated from lychee fruit in Indochina. Though not a true commensal organism, S. boulardii is a potent inducer of glycocalyx production and IgA secretion. It also stimulates brush border enzymes, and promotes polyamine production, which feeds the intestinal microvilli and can be helpful for healing ulcerative colitis, Crohn’s disease, and irritable bowel syndrome.

S. boulardii is able to work in the context of highly pathogenic antibiotic-resistant bacteria like Clostridium difficile and has actually been used as a preventive therapy against C. difficile–associated diarrhea (Goldstein, E. et al. Clin Infect Dis. 2015; 60 (suppl_2): S148-S158). S. boulardii may reduce some of the toxic effects of enterotoxin A by inhibiting toxin A-receptor binding and preventing the formation of enterotoxin B.

But the most remarkable thing is it's ability to quickly colonize the damaged endothelium and displace pathogenic yeasts while simutaneously creating a healthier microenvironment for commensal bacteria. "S. boulardii actually forces a physical evacuation of the Candida," said Dr. Skilton noting that it is specifically active against 7 out of the 8 most common pathogenic Candida species. The one exception is C. tropicalis.

"Think of the situation like the aftermath of a hurricane hitting a village. The antibiotics are the hurricane. S. boulardii is like the contractor that comes in and repairs the damage to the village. You can then repopulate the village with commensals."

BioCeuticals, an Australian practitioner-only nutraceutical company, recently introduced a product called SB Floractiv, providing 250 mg S. boulardii (also called S. cereviciae) per capsule.

For patients who've been on long-term antibiotics, begin slowly with one capsule (250 mg) per day for 3-4 days, then increase to two per day for another 3-4 days, and then increase in a similar step-wise pattern up to four per day (1000 mg) that should be continued for the remainder of a 4 week period.

S. boulardii is very safe, and the only true contraindication is in patients with true IgE-mediated reactions to yeasts, manifesting as anaphylaxis or Saccharomyceshives. That said, it is important to be aware that in the first few days of taking S. boulardii, some patients may experience a noticeable "bowel flush" as the probiotic yeast displaces the Candida species. Candidal die-off can also make people feel ill. It is best to advise patients of these possibilities beforehand, so they're not surprised if they occur.

According to Dr. Skelton, in 9 out of 10 patients, four weeks of intensive S. boulardii supplementation is siffucient to restore a healthy glycocalyx layer and induce adequate IgA secretion. This then sets the stage for a much more effective round of restoration with a multi-strain probiotic.

Bioceuticals has designed a product specifically for use after antibiotics. Called BioFloractiv 500, it contains 500 billion CFUs, 12 species, and 14 strains of beneficial bacteria. Dr. Skilton recommends a maximum of 14 days, though one week of daily therapy is sufficient for most, according to Skilton.

Patients with irritable bowel syndrome or Crohn’s disease, however, may need longer-term support to rebuild a healthy microbiome after taking antibiotics.

A Comprehensive Approach

Probiotics are just one part of the picture. And if a patient cannot tolerate any type of probiotic, its a red flag that a patient's immune system is not functioning properly.

"You first need to address any aspects of the nervous system, especially sympathetic dominance, that may be affecting the digestive tract," said Dr. Skilton. She has found fish oil, zinc, vitamin A, and colostrum to be of value in many cases. The latter, "is really good for restoring sIgA. Do this for a week or so before even trying probiotics." Slippery Elm and glutamine supplements can also be helpful in some cases.

Plant-based medicnes like oregano oil, tea tree oil, or pau d'arco extract may be helfpul in ridding the GI tract of pathogenic yeast. But Dr. Skilton stressed that these will do nothing to stimulate sIgA production, and chronic yeast infections are almost always associated with low IgA.  These natural yeast-busters should never be used at the same time as S. boulardii; this "friendly" yeast is just as vulnerable to things like oregano and tea tree as the pathogenic yeasts.

A number of probiotic and prebiotic foods can aid the process of gut restoration. Tom O'Bryan, DC, founder of the Gluten Summit and the Certified Gluten Practitioner training program, recommends several foods to eat -- and several to avoid -- when rebuilding the gut after antibiotic treatment.

"When your gut has been compromised, you don’t want to tax your gut," O’Bryan says. "Taxing" foods include wheat, dairy, sugar, unhealthy fats, and fried items. These foods, he notes, "throw gasoline on the fire" of a recovering intestinal system. 

On the other hand, one should eat plenty of foods that promote the growth of healthy commensal organisms. O'Bryan recommends organic stewed apples, cooked until soft and shimmery, as one good option. Cooking apples, he explains, releases pectin -- a soluble fiber that provides fuel for beneficial bacteria.

The pectin present in stewed apples can also help to heal a damaged intestinal lining and seal off the tears in a leaky gut, preventing large food molecules from slipping through.

Similarly, collagen helps to seal a leaky gut. O'Bryan also encourages patients recovering from antibiotic treatment to eat chicken bone broth, a good source of collagen, which also acts as a natural prebiotic, feeding the healthy bacteria in the gut.

Butyrate -- a natural substance made in the intestine -- is another important player in gut bacteria restoration. O'Bryan explains that the cells lining the inside of the gut reproduce rapidly and that butyrate fuels the rebuilding of new cells. Insufficient butyrate production and a slow turnover of intestinal cells make the body more vulnerable to the development of cancer cells, resulting in a higher risk of colon cancer.

An array of prebiotic fruits and vegetables, including foods bananas, sweet potatoes and other tubers help to rebuild the gut microbiome, providing insoluble fiber that feeds good -- but not harmful -- bacteria.

Fermented, unpasteurized vegetables like sauerkraut, kimchi, and fermented beets, are another excellent source of natural probiotics. Every vegetable produces different families of beneficial bacteria during fermentation, O’Bryan notes, encouraging patients to eat one forkful of fermented vegetables twice a day. "The key to health in your gut is the diversity of your microbiome," he argues, pointing out that thousands of different families of bacteria live and interplay in the gut with wide-ranging impacts on our health.

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Stop Fighting, Start Restorative Healing: A Functional Approach to SIBO

By By Russell Jaffe, MD, Contributing Writer

The key to helping people dealing with small intestinal bacterial overgrowth (SIBO) is to initiate restorative healing of the affected tissues. We need to shift physiology so that the internal environment no longer favors the overgrowth of hostile bacteria in the small intestine. If we fail to do that, treatments aimed at eradicating the bugs will have little long-term efficacy

Probiotics: Benefits Beyond Gut Health

By Kristen Schepker, Assistant Editor

Probiotics are widely touted for their capacity to improve digestive function and strengthen gastrointestinal health. But according to new research, the effects of beneficial bacteria extend far beyond the gut alone.

Low FODMAP Diet Offers Road to Relief for IBS

By Kristen Schepker

When it comes to treating irritable bowel syndrome (IBS), prevailing wisdom encourages eating more dietary fiber to help manage unpleasant digestive symptoms. But new research indicates that a group of fermentable carbohydrates referred to as FODMAPs -- found in many high-fiber foods -- might actually make IBS symptoms worse.

Why Probiotics Don’t Always Work

By Zach Bush, MD, Contributing Writer

The optimally healthy human gut should contain between 20,000 and 30,000 species of bacteria. Variety is key. The greater the diversity, the healthier the microbiome. Zealous use of probiotics, while reflecting a positive trend overall, could be causing problems by "monocropping" the GI tract with a relatively small number of species at the expense of ecosystem diversity.