Probiotic therapy for celiac disease.

Celiac disease (CD) is an autoimmune disorder induced by the ingestion of gluten in genetically predisposed individuals who carry the HLA-DQ2 or DQ-8 alleles.1 This autoimmune disorder affects the small bowel and often produces symptoms of diarrhea, malabsorption, and extraintestinal symptoms.1 Although CD was once thought to be a disease manifesting during childhood, studies have shown that the prevalence of CD in adults in the United States ranges from 0.7% to 1.1%.2,3 In addition, several studies have shown that, despite a prevalence comparable to those of European nations, CD remains underdiagnosed in the United States.3–5 At this time, the only treatment for CD is lifelong adherence to a gluten-free diet, which involves the elimination of grains containing gluten, wheat, rye, and barley in addition to food products and additives derived from them.6 Adherence to a gluten-free diet has been shown to improve symptoms, reduce the risk of malignancy, and impart other health benefits such as an improvement in bone mineral density.7–9 However, studies have shown that dietary transgressions in patients with CD are common and can occur anywhere from 32% to 55%.10 Why is it so difficult for patients with CD to adhere to a gluten-free diet? First, the availability of gluten-free products varies among different regions of the United States and the world, especially in developing countries.11,12 Although more widespread than in the past, gluten-free products in the United States tend to be more readily available online and in upscale food stores as compared with regular grocery stores.11 Second, gluten-free products tend to be more expensive than their wheat-containing counterparts, which impacts dietary compliance among patients who cannot afford such a diet.11 Finally, patients who adhere to a gluten-free diet can feel excluded from social activities, such as dining out, travel, and family life, which has a direct negative impact on their quality of life.13 Because of the constraints of a gluten-free diet, alternative therapies for CD are being developed, including agents that prevent gluten uptake into the mucosa, decrease immune activation, and reduce gluten exposure by either binding or degrading gluten in the intestinal lumen.14 Probiotics, which are live microorganisms that confer a health benefit, may offer benefits to patients suffering from intestinal disorders such as irritable bowel syndrome and CD.15 One randomized controlled trial evaluating Bifidobacterium infantis 35624 in patients with irritable bowel syndrome showed a greater reduction in symptom scores for abdominal pain/discomfort, bloating/distention, and bowel movement difficulty compared with placebo.16 This study also showed normalization of peripheral blood mononuclear cell cytokine levels in patients taking B. infantis 35624 but not in those taking Lactobacillus salivarius UCC 4331, indicating a potential anti-inflammatory effect.16 Abnormalities in the intestinal microbiome in patients with CD have prompted consideration of their use as a nondietary therapy. Reduced concentrations of Bifidobacterium species were observed in the feces of untreated CD patients as compared with healthy adults.17 A similar study using PCR to identify gut Bifidobacterium also showed a reduction in Bifidobacterium populations in both active and nonactive CD as compared with healthy controls.18 Some probiotics digest or alter gluten. A specific commercially available probiotic, VSL#3 (containing 8 different bacteria), has been shown to reduce the toxicity of gluten when used in a fermentation process.19 In addition, baked wheat products that are formed by the sourdough fermentation process of wheat gluten by lactobacilli and fungal proteases, are safe for people with CD.20 Several studies have also further expanded on the potential anti-inflammatory effects of B. infantis on CD. The presence of bifidobacterial strains during intestinal digestion was shown to produce different, less toxic, gliadin peptide sequences in vitro, which could modify the proinflammatory cascade triggered by gliadin-derived peptides in addition to protecting