Exploratory, Randomized, Double-blind, Placebo-controlled Study on the Effects of Bifidobacterium infantis Natren Life Start Strain Super Strain in Active Celiac Disease

Background/Aims: The aim of this exploratory trial was to establish if the probiotic Bifidobacterium natren life start (NLS) strain strain may affect the clinical course and pathophysiological features of patients with untreated celiac disease (CD). Positive findings would be helpful in directing future studies. Methods: Twenty-two adult patients having 2 positives CD-specific tests were enrolled. Patients were randomized to receive 2 capsules before meals for 3 weeks of either Bifidobacterium infantis natren life start strain super strain (Lifestart 2) (2×109 colony-forming units per capsule) (n=12) or placebo (n=10), whereas they also consumed at least 12 g of gluten/day. A biopsy at the end of the trial confirmed CD in all cases. The primary outcome was intestinal permeability changes. Secondary endpoints were changes in symptoms and the Gastrointestinal Symptom Rating Scale, and in immunologic indicators of inflammation. Results: The abnormal baseline intestinal permeability was not significantly affected by either treatment. In contrast to patients on placebo, those randomized to B. infantis experienced a significant improvement in Gastrointestinal Symptom Rating Scale (P=0.0035 for indigestion; P=0.0483 for constipation; P=0.0586 for reflux). Final/baseline IgA tTG and IgA DGP antibody concentration ratios were lower in the B. infantis arm (P=0.055 for IgA tTG and P=0.181 for IgA DGP). Final serum macrophage inflammatory protein-1&bgr; increased significantly (P<0.04) only in patients receiving B. infantis. The administration of B. infantis was safe. Conclusions: The study suggests that B. infantis may alleviate symptoms in untreated CD. The probiotic produced some immunologic changes but did not modify abnormal intestinal permeability. Further studies are necessary to confirm and/or expand these observations.

[1]  A. Caminero,et al.  Differences of small intestinal bacteria populations in adults and children with/without celiac disease: Effect of age, gluten diet, and disease , 2012, Inflammatory bowel diseases.

[2]  C. Pert,et al.  Attenuation of rodent neuropathic pain by an orally active peptide, RAP-103, which potently blocks CCR2- and CCR5-mediated monocyte chemotaxis and inflammation , 2012, PAIN.

[3]  L. Laghi,et al.  Duodenal and faecal microbiota of celiac children: molecular, phenotype and metabolome characterization , 2011, BMC Microbiology.

[4]  J. Ludvigsson,et al.  Clinical management of coeliac disease , 2011, Journal of internal medicine.

[5]  R. Ffrench,et al.  A Phase I Study to Determine Safety, Tolerability and Bioactivity of Nexvax2® in HLA DQ2+ Volunteers With Celiac Disease Following a Long-Term, Strict Gluten-Free Diet , 2011 .

[6]  J. Fox,et al.  TLR2-dependent pathway of heterologous down-modulation for the CC chemokine receptors 1, 2, and 5 in human blood monocytes. , 2011, Blood.

[7]  E. Smecuol,et al.  Long-term deterioration of quality of life in adult patients with celiac disease is associated with treatment noncompliance. , 2010, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[8]  E. Smecuol,et al.  Dynamics of celiac disease-specific serology after initiation of a gluten-free diet and use in the assessment of compliance with treatment. , 2010, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[9]  Y. Sanz,et al.  Pivotal Advance: Bifidobacteria and Gram‐negative bacteria differentially influence immune responses in the proinflammatory milieu of celiac disease , 2010, Journal of leukocyte biology.

[10]  E. Ricca,et al.  Modulation of the immune response by probiotic strains in a mouse model of gluten sensitivity. , 2009, Cytokine.

[11]  G. Rubin,et al.  Systematic review: adherence to a gluten‐free diet in adult patients with coeliac disease , 2009, Alimentary pharmacology & therapeutics.

[12]  J. Murray,et al.  Between Celiac Disease and Irritable Bowel Syndrome: The “No Man's Land” of Gluten Sensitivity , 2009, The American Journal of Gastroenterology.

[13]  James Versalovic,et al.  Targeting the human microbiome with antibiotics, probiotics, and prebiotics: gastroenterology enters the metagenomics era. , 2009, Gastroenterology.

[14]  Y. Sanz,et al.  Imbalances in faecal and duodenal Bifidobacterium species composition in active and non-active coeliac disease , 2008, BMC Microbiology.

[15]  Y. Sanz,et al.  Bifidobacterium strains suppress in vitro the pro-inflammatory milieu triggered by the large intestinal microbiota of coeliac patients , 2008, Journal of Inflammation.

[16]  K. Madsen,et al.  Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function. , 2008, American journal of physiology. Gastrointestinal and liver physiology.

[17]  K. Kaukinen,et al.  Live probiotic Bifidobacterium lactis bacteria inhibit the toxic effects induced by wheat gliadin in epithelial cell culture , 2008, Clinical and experimental immunology.

[18]  A. Fasano,et al.  The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT‐1001 in coeliac disease subjects: a proof of concept study , 2007, Alimentary pharmacology & therapeutics.

[19]  Andrew G. Spencer,et al.  Combination enzyme therapy for gastric digestion of dietary gluten in patients with celiac sprue. , 2007, Gastroenterology.

[20]  P. Whorwell,et al.  Efficacy of an Encapsulated Probiotic Bifidobacterium infantis 35624 in Women with Irritable Bowel Syndrome , 2006, The American Journal of Gastroenterology.

[21]  U. Chattopadhyay,et al.  Macrophage inflammatory protein (MIP)1α and MIP1β differentially regulate release of inflammatory cytokines and generation of tumoricidal monocytes in malignancy , 2006, Cancer Immunology, Immunotherapy.

[22]  M. Gobbetti,et al.  Proteolytic activity and reduction of gliadin‐like fractions by sourdough lactobacilli , 2005, Journal of applied microbiology.

[23]  A. Zinsmeister,et al.  A randomized controlled trial of a probiotic combination VSL# 3 and placebo in irritable bowel syndrome with bloating , 2005, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[24]  M. Bauserman,et al.  The use of Lactobacillus GG in irritable bowel syndrome in children: a double-blind randomized control trial. , 2005, The Journal of pediatrics.

[25]  D. Schuppan,et al.  Celiac disease: epidemiology, pathogenesis, diagnosis, and nutritional management. , 2005, Nutrition in clinical care : an official publication of Tufts University.

[26]  S. James.  National Institutes of Health Consensus Development Conference Statement on Celiac Disease, June 28-30, 2004. , 2005, Gastroenterology.

[27]  F. Shanahan,et al.  Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. , 2005, Gastroenterology.

[28]  W. Karpus,et al.  CCR5 Regulates High Dose Oral Tolerance by Modulating CC Chemokine Ligand 2 Levels in the GALT1 , 2004, The Journal of Immunology.

[29]  L. Greco,et al.  Sourdough Bread Made from Wheat and Nontoxic Flours and Started with Selected Lactobacilli Is Tolerated in Celiac Sprue Patients , 2004, Applied and Environmental Microbiology.

[30]  R. Di Cagno,et al.  Proteolysis by Sourdough Lactic Acid Bacteria: Effects on Wheat Flour Protein Fractions and Gliadin Peptides Involved in Human Cereal Intolerance , 2002, Applied and Environmental Microbiology.

[31]  A. Fasano,et al.  Current approaches to diagnosis and treatment of celiac disease: an evolving spectrum. , 2001, Gastroenterology.

[32]  M. Horton,et al.  Distinct Requirements for C-C Chemokine and IL-2 Production by Naive, Previously Activated, and Anergic T Cells , 2000, The Journal of Immunology.

[33]  D. Goeddel,et al.  Human macrophage inflammatory protein alpha (MIP-1 alpha) and MIP-1 beta chemokines attract distinct populations of lymphocytes , 1993, The Journal of experimental medicine.

[34]  Govind Bhagat,et al.  Serum cytokine elevations in celiac disease: association with disease presentation. , 2010, Human immunology.

[35]  J. Laparra,et al.  Bifidobacteria inhibit the inflammatory response induced by gliadins in intestinal epithelial cells via modifications of toxic peptide generation during digestion , 2010, Journal of cellular biochemistry.

[36]  V. Gonzalez,et al.  Quality of life in celiac disease patients: prospective analysis on the importance of clinical severity at diagnosis and the impact of treatment. , 2009, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[37]  A. Fasano,et al.  A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease. , 2007, The American journal of clinical nutrition.

[38]  T. Schall,et al.  Human Macrophage Inflammatory Protein cr ( MIP-lc ~ ) and MIPI ~ Chemoklnes Attract Distinct Populations of Lymphocytes , 2003 .

[39]  B. V. von Blomberg,et al.  Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac disease: disappointing in clinical practice , 1999, American Journal of Gastroenterology.