Celiac disease prevalence in patients with idiopathic inflammatory myopathies, a cross-sectional study.

Up to 30% of patients with celiac disease (CD) suffer from concurrent autoimmune disease, compared to 3% of the general population. The association between CD and the current clinical phenotypes of inflammatory myopathies (IIM) patients has not been thoroughly addressed. Assess the CD features among patients with IIM and their relationship with the clinical phenotype and the myositis specific (MSA) and associated antibodies (MAA). For this cross-sectional study, we recruited 99 adult patients classified as IIM from a tertiary center in Mexico. We assessed serum MSA, MAA, and CD-associated autoantibodies (IgA anti-tissue transglutaminase (tTG) and both IgA and IgG anti-deaminated gliadin peptide (DGP)). Patients with highly suggestive serology for CD were then tested for IgG anti-endomysium antibodies, and a duodenal biopsy was performed. 70.7% of patients were positive for at least one antibody. Nine duodenal biopsies were taken, revealing findings compatible with celiac disease in two cases. Subjects with anti-MDA5 antibodies were more likely to have positive anti-tTG IgA antibodies (OR 6.76, 95% CI 1.85-24.62, P = 0.013) and suggestive CD serology (OR 6.41, 95% CI 1.62-25.29, P = 0.009). Patients with anti-Mi2 antibodies were more likely to have positive anti-DGP IgG antibodies (OR 3.35, 95% CI 1.12-9.96, P = 0.039), while positivity for these autoantibodies was less frequent in patients with anti-NXP2 antibodies (OR 0.22, 95% CI 0.06-0.80, P = 0.035). There is a higher prevalence of serologic and definite CD in patients with IIM compared to the general population. Identifying this subgroup of patients may have prognostic and therapeutic implications. Key points • The study estimated a serological celiac disease (CD) prevalence of 70.7% in patients with idiopathic inflammatory myopathies (IIM) and a biopsy-confirmed prevalence of 2%, suggesting that IIM patients should be considered a high-risk population for CD. • We identified a significant association between serological CD and the presence of anti-MDA5 and anti-Mi2 antibodies, suggesting a potential justification for celiac disease screening in this specific subgroup of patients. • The impact of gluten-free diets on IIM patients with serological markers of CD remains untested and warrants further investigation through prospective, randomized studies.

Molecular and Structural Parallels between Gluten Pathogenic Peptides and Bacterial-Derived Proteins by Bioinformatics Analysis.

Gluten-related disorders (GRDs) are a group of diseases that involve the activation of the immune system triggered by the ingestion of gluten, with a worldwide prevalence of 5%. Among them, Celiac disease (CeD) is a T-cell-mediated autoimmune disease causing a plethora of symptoms from diarrhea and malabsorption to lymphoma. Even though GRDs have been intensively studied, the environmental triggers promoting the diverse reactions to gluten proteins in susceptible individuals remain elusive. It has been proposed that pathogens could act as disease-causing environmental triggers of CeD by molecular mimicry mechanisms. Additionally, it could also be possible that unrecognized molecular, structural, and physical parallels between gluten and pathogens have a relevant role. Herein, we report sequence, structural and physical similarities of the two most relevant gluten peptides, the 33-mer and p31-43 gliadin peptides, with bacterial pathogens using bioinformatics going beyond the molecular mimicry hypothesis. First, a stringent BLASTp search using the two gliadin peptides identified high sequence similarity regions within pathogen-derived proteins, e.g., extracellular proteins from Streptococcus pneumoniae and Granulicatella sp. Second, molecular dynamics calculations of an updated α-2-gliadin model revealed close spatial localization and solvent-exposure of the 33-mer and p31-43 peptide, which was compared with the pathogen-related proteins by homology models and localization predictors. We found putative functions of the identified pathogen-derived sequence by identifying T-cell epitopes and SH3/WW-binding domains. Finally, shape and size parallels between the pathogens and the superstructures of gliadin peptides gave rise to novel hypotheses about activation of innate immunity and dysbiosis. Based on our structural findings and the similarities with the bacterial pathogens, evidence emerges that these pathologically relevant gluten-derived peptides could behave as non-replicating pathogens opening new research questions in the interface of innate immunity, microbiome, and food research.

Immune profiling of breast milk from mothers with treated celiac disease.

BACKGROUND: The protective effect of breastfeeding on celiac disease (CD) onset is controversial. We studied a wide range of milk components in milk produced by celiac mothers following long-term gluten-free diet (GFD) in comparison to milk produced by healthy mothers. METHODS: Breast-milk samples from celiac (n = 33) and healthy (n = 41) mothers were obtained during the first year of lactation. A panel of bioactive components was analyzed by enzyme-linked immunosorbent assay in the aqueous fraction. We studied molecules involved in defenses, immunoregulation, and strengthening of the gut-epithelial barrier. RESULTS: During late lactation (from 6 to 12 months after delivery), the content of total immunoglobulin A (IgA) and IgM was significantly lower in the milk produced by celiac patients. Nevertheless, gliadin (GFD)-specific IgA relative contribution was higher in this group, in contrast to tetanus toxoid-specific antibodies. The balance between pro-inflammatory and anti-inflammatory molecules was different. While interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 were most frequently found in samples from celiac mothers, soluble Toll-like receptor-2 prevalence was lower. CONCLUSIONS: We describe differences between the innate and adaptive immune profile of milk produced by celiac and healthy mothers. These results might explain previous controversial reports about breastfeeding and CD protection. IMPACT: In spite of a long-term adherence to GFD, the milk produced by mothers with CD exhibit a different immune profile, in relation with some immunoregulatory factors and antibody content. This work shows a more comprehensive characterization of milk from celiac mothers, including macronutrients, lysozymes, growth factors, and immunoregulatory components that had not been studied before. The present study widens the available data regarding the characteristics of human milk of celiac mothers following GFD. Further follow-up studies of the health of children who were breastfed by celiac mothers will be necessary in order to also estimate the impact of the present results therein.

Digestion of Intact Gluten Proteins by Bifidobacterium Species: Reduction of Cytotoxicity and Proinflammatory Responses.

Celiac disease (CD) is a chronic illness characterized by an inflammatory process triggered by gluten protein intake. Recent evidence has suggested that the lower relative abundance of bifidobacteria in the intestinal lumen may be associated with CD. Herein, we assessed the effect of the Bifidobacterium species Bifidobacterium bifidum, Bifidobacterium longum, Bembidion breve, Bifidobacterium animalis alone, and also a Bifidobacterium consortium on the digestion of intact gluten proteins (gliadins and glutenins) and the associated immunomodulatory responses elicited by the resulting peptides. The cytotoxicity and proinflammatory responses were evaluated through the activation of NF-kB p65 and the expression of cytokines TNF-α and IL-1ß in Caco-2 cell cultures exposed to gluten-derived peptides. The peptides induced a clear reduction in cytotoxic responses and proinflammatory marker levels compared to the gluten fragments generated during noninoculated gastrointestinal digestion. These results highlight the possible use of probiotics based on bifidobacteria as a prospective treatment for CD.

Structural conformation and self-assembly process of p31-43 gliadin peptide in aqueous solution. Implications for celiac disease.

Celiac disease (CeD) is a highly prevalent chronic immune-mediated enteropathy developed in genetically predisposed individuals after ingestion of a group of wheat proteins (called gliadins and glutenins). The 13mer α-gliadin peptide, p31-43, induces proinflammatory responses, observed by in vitro assays and animal models, that may contribute to innate immune mechanisms of CeD pathogenesis. Since a cellular receptor for p31-43 has not been identified, this raises the question of whether this peptide could mediate different biological effects. In this work, we aimed to characterize the p31-43 secondary structure by different biophysical and in silico techniques. By dynamic light scattering and using an oligomer/fibril-sensitive fluorescent probe, we showed the presence of oligomers of this peptide in solution. Furthermore, atomic force microscopy analysis showed p31-43 oligomers with different height distribution. Also, peptide concentration had a very strong influence on peptide self-organization process. Oligomers gradually increased their size at lower concentration. Whereas, at higher ones, oligomers increased their complexity, forming branched structures. By CD, we observed that p31-43 self-organized in a polyproline II conformation in equilibrium with ß-sheets-like structures, whose pH remained stable in the range of 3-8. In addition, these findings were supported by molecular dynamics simulation. The formation of p31-43 nanostructures with increased ß-sheet structure may help to explain the molecular etiopathogenesis in the induction of proinflammatory effects and subsequent damage at the intestinal mucosa in CeD.

IgA anti-tissue transglutaminase antibodies and IgG antibodies against deamidated gliadin peptides as predictors of celiac disease. / Anticuerpos antitransglutaminasa tisular IgA y contra péptidos de gliadina desaminados IgG como predictores de enfermedad celíaca.

OBJECTIVE: To compare the performance of IgA anti-tissue transglutaminase antibodies (IgA anti-tTG), IgA anti-endomysial antibodies (IgA EMA), and IgA/IgG antibodies against deamidated gliadin peptides (IgA/IgG anti-DGP) for the diagnosis of celiac disease. METHODS: Descriptive study in patients with celiac disease. Anti-DGP (IgA/IgG), IgA EMA, IgA anti-tTG antibodies were measured and an intestinal biopsy was done. Sex: female (61 %). Median age: 78.4 months old. RESULTS: A total of 136 children were included; 108 had high IgA anti-DGP titers; 124, increased IgG anti-DGP titers; 128, positive IgA EMA titers; and 130, increased IgA anti-tTG titers. High IgG anti-DGP titers were observed in 4/6 patients with negative IgA anti-tTG antibodies. The combination of IgG anti-DGP + IgA anti-tTG antibodies showed a positive correlation in 134 patients and the IgG anti-DGP + EMA combination was positive in 133 children. CONCLUSION: IgA EMA, IgA anti-tTG, and IgG anti-DGP antibodies exhibited an adequate specificity and sensitivity. The IgG anti-DGP/anti-tTG combination showed a 98-99 % sensitivity and a 100 % specificity. The anti-tTG and IgG anti-DGP option yields excellent results, with a low cost and independence from the observer.

Objetivo. Comparar el rendimiento de anticuerpos antitransglutaminasa IgA (anti-TG2 IgA), antiendomisio IgA (EMA IgA) y antigliadina desaminada IgA/IgG (AGADGP IgA/IgG) para el diagnóstico de enfermedad celiaca. Métodos. Estudio descriptivo en pacientes con enfermedad celíaca. Se dosaron anticuerpos: AGADGP (IgA/IgG), EMA IgA, anti-TG2 IgA y biopsia intestinal. Sexo: mujeres (61 %). Mediana de edad: 78,4 meses. Resultados. Se incluyeron 136 niños; 108 presentaron AGADGP IgA elevado; 124, AGADGP IgG aumentado; 128, EMA IgA positivo; 130, anti-TG2 IgA aumentado. Cuatro de 6 pacientes con anti-TG2 IgA negativos tenían AGADGP IgG elevado. La combinación de los anticuerpos AGADGP IgG + anti-TG2 IgA tuvo una correlación positiva en 134 pacientes y la combinación AGADGP IgG + EMA fue positiva en 133 niños. Conclusión. Se demostró la buena especificidad y sensibilidad de EMA IgA, anti-TG2 IgA y AGADGP IgG. La combinación AGADGP IgG/anti-TG2 mostró sensibilidad del 98-99 % y especificidad del 100 %. La elección de anti-TG2 y AGADGP IgG da excelentes resultados, con bajo costo y no depende del operador.

Celiac Disease: Historical Standpoint, New Perspectives of Treatments and Contemporary Research Techniques.

Celiac disease (CD) is an inflammatory syndrome that affects mainly the intestine, but also other organs. This ailment is also affected by the physicochemical behavior of gluten as such. From the medical standpoint, this pathology results from a combination of genetic and environmental factors. At the same time, gliadin (the alcohol-soluble fraction of gluten) along with other related oligomers, such as 33-gliadin, present high immunogenicity and are responsible for triggering of this disease. Within CD characterization, there are mainly two different approaches to carry out this study; one focuses on its chronic phase, while the other deals with its initial stages. Although the chronic phase of CD has been well characterized, the initiation of the inflammatory process is still unclear. As this process is apparently related to the aggregation of the oligomers involved in CD, the initiation of the disease could be explained by means of clarifying their self-assembly behavior. Thus, this work addresses the clinical explanation, within the chronic approach, attempting to combine it with the physicochemical techniques used for characterization of proteins aggregates as well.

Text Message Intervention (TEACH) Improves Quality of Life and Patient Activation in Celiac Disease: A Randomized Clinical Trial.

OBJECTIVE: To determine the impact of the Text Message Educational Automated Compliance Help (TEACH) text message intervention as a pragmatic approach for patient engagement among adolescents with celiac disease (CD) as measured by gluten-free diet (GFD) adherence, patient activation, and quality of life (QOL). STUDY DESIGN: Randomized controlled trial with patient recruitment at a pediatric, university-based hospital and through social media; 61 participants ages 12-24 years with CD diagnosed at least 1 year were enrolled. The TEACH intervention cohort received 45 unique text messages over a 3-month study period while the control group received standard of care treatment. Primary outcome measures included objective markers of GFD adherence included serum tissue transglutaminase IgA and deamidated gliadin peptide IgA levels. Secondary patient-reported outcomes collected via online survey included the Celiac Dietary Adherence Test, National Institutes of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS) Global Short Form measure of QOL, Celiac Symptom Index, and Patient Activation Measure. All measures were assessed at enrollment and after the 3-month study period. Statistical analysis performed using the 2-tailed paired Student t test. RESULTS: Among the TEACH intervention group, there was significant improvement comparing enrollment scores with 3-month follow-up scores in patient activation (Patient Activation Measure score 63.1 vs 72.5, P?=?.01) and QOL (NIH PROMIS Global Mental Health 50.8 vs 53.3, P?=?.01 and NIH PROMIS Global Physical Health 50.8 vs 57.7, P?=?.03). There was no statistically significant difference in patient-reported or objectively measured GFD adherence. CONCLUSIONS: TEACH is an effective intervention among patients with CD to improve patient activation and QOL, even among a cohort with GFD adherence at baseline. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02458898.

Celiac Disease and Cystic Fibrosis: Challenges to Differential Diagnosis.

Cystic fibrosis and celiac disease were considered a single clinical entity for many years. Differentiation between the diseases occurred some time in the 1930s of the 20th Century. Both diseases may present the intestinal malabsorption syndrome and similar clinical manifestations that contribute to difficulties with clinical distinction. We describe a report of two patients with initial diagnosis of cystic fibrosis, who were subsequently diagnosed with celiac disease. These case reports emphasize the possibility of false positivity being shown in the sweat test in CD, which may result in delayed diagnosis and inadequate management of this disease.

[Cereal-dependent exercise-induced anaphylaxis]. / Anafilaxia dependiente de cereales inducida por ejercicio.

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is increasing. In vitro test such as omega-5-gliadin levels are useful in the diagnosis, while oral single blind challenge tests (OCT) with wheat plus exercise continuous being the gold standard diagnostic method. This paper reports the case of a 38-year-old woman, with several episodes of anaphylaxis after eating different foods and doing exercise after ingestion. An allergy study was performed with positive skin prick tests for wheat, barley and rye. Total IgE 238.0KU/L, positive specific IgE (>100KU/L) to wheat, barley and rye, and negative to rTri-a-19 omega-5 gliadin. OCT with bread and exercise was positive. In this case of wheat-dependent exerciseinduced anaphylaxis (WDEIA) with negative serum specific IgE to omega-5-gliadin, negative results with gamma, alpha, bheta y omega-gliadin doesn't exclude the diagnosis of WDEIA.

La anafilaxia inducida por ejercicio dependiente de trigo (WDEIA por sus siglas en inglés de wheat-dependent-exercise-induced-anaphylaxis) es una entidad cada vez más frecuente. La detección de IgE frente a omega-5-gliadina in vitro se usa como método diagnóstico, pero la provocación oral controlada simple ciego (POC) con el alimento, junto con la realización de ejercicio físico, es el método diagnóstico patrón de referencia. Se comunica el caso de una paciente de 38 años de edad, con antecedente de episodios de anafilaxia relacionados con la ingestión de alimentos y la realización de actividad física. Se realizó un estudio alergológico. Las pruebas cutáneas fueron positivas a harina de trigo, cebada y centeno. IgE total: 238.0 kU/L, IgE específica positiva (mayor de 100 kU/L) a trigo, cebada, centeno y negativa a rTri-a-19omega-5 gliadina. La provocación oral controlada con pan de trigo y ejercicio físico fue positiva. En este caso con anafilaxia inducida por ejercicio dependiente de trigo sin sensibilización omega-5 gliadina la ausencia de IgE frente gamma, alfa, beta yomega-gliadina no excluiría el diagnóstico de esta enfermedad.

Prevalence of celiac disease and celiac autoimmunity in the Toba Native Amerindian community of Argentina.

BACKGROUND: Celiac disease (CD) is mostly recognized among subjects with a Caucasian ethnic ancestry. No studies have explored conditions predisposing Amerindians to CD. OBJECTIVE: To prospectively assess environmental, genetic and serological conditions associated with CD among members of the Toba native population attending a multidisciplinary sanitary mission. METHODS: An expert nutritionist determined daily gluten intake using an established questionnaire. Gene typing for the human leukocyte antigen (HLA) class II alleles was performed on DNA extracted from peripheral blood (HLA DQ2/DQ8 haplotype). Serum antibodies were immunoglobulin (Ig) A tissue transglutaminase (tTG) and the composite deamidated gliadin peptides/tTG Screen test. Positive cases were tested for IgA endomysial antibodies. RESULTS: A total of 144 subjects (55% female) were screened. The estimated mean gluten consumption was 43 g/day (range 3 g/day to 185 g/day). Genetic typing showed that 73 of 144 (50.7%) subjects had alleles associated with CD; 69 (94.5%) of these subjects had alleles for HLA DQ8 and four had DQ2 (5.5%). Four and six subjects had antibody concentrations above the cut-off established by the authors' laboratory (>3 times the upper limit of normal) for IgA tTG and deamidated gliadin peptides/tTG screen, respectively. Four of these had concomitant positivity for both assays and endomysial antibodies were positive in three subjects who also presented a predisposing haplotype. CONCLUSION: The present study was the first to detect CD in Amerindians. The native Toba ethnic population has very high daily gluten consumption and a predisposing genetic background. We detected subjects with persistent CD autoimmunity and, at least, three of them fulfilled serological criteria for CD diagnosis.

Clinical, serologic, and histologic features of gluten sensitivity in children.

OBJECTIVE: To describe the clinical, serologic, and histologic characteristics of children with gluten sensitivity (GS). STUDY DESIGN: We studied 15 children (10 males and 5 females; mean age, 9.6 ± 3.9 years) with GS who were diagnosed based on a clear-cut relationship between wheat consumption and development of symptoms, after excluding celiac disease (CD) and wheat allergy, along with 15 children with active CD (5 males and 10 females; mean age, 9.1 ± 3.1 years) and 15 controls with a functional gastrointestinal disorder (6 males and 9 females; mean age, 8.6 ± 2.7 years). All children underwent CD panel testing (native antigliadin antibodies IgG and IgA, anti-tissue transglutaminase antibody IgA and IgG, and anti-endomysial antibody IgA), hematologic assessment (hemoglobin, iron, ferritin, aspartate aminotransferase, erythrocyte sedimentation rate), HLA typing, and small intestinal biopsy (on a voluntary basis in the children with GS). RESULTS: Abdominal pain was the most prevalent symptom in the children with GS (80%), followed by chronic diarrhea in (73%), tiredness (33%), bloating (26%), limb pain, vomiting, constipation, headache (20%), and failure to thrive (13%). Native antigliadin antibodies IgG was positive in 66% of the children with GS. No differences in nutritional, biochemical, or inflammatory markers were found between the children with GS and controls. HLA-DQ2 was found in 7 children with GS. Histology revealed normal to mildly inflamed mucosa (Marsh stage 0-1) in the children with GS. CONCLUSION: Our findings support the existence of GS in children across all ages with clinical, serologic, genetic, and histologic features similar to those of adults.

[Study of prevalence of celiac disease in children with type 1 diabetes mellitus: result of 10 years of follow-up]. / Estudo da prevalência da doença celíaca em crianças e adolescentes com diabetes melito tipo 1: resultado de 10 anos de acompanhamento.

OBJECTIVE: To estimate the prevalence of celiac disease (CD) in children and adolescents with type 1 diabetes mellitus (T1DM) treated in the Children's Division of Endocrinology, at the Universidade Federal de Minas Gerais Hospital das Clínicas. SUBJECTS AND METHODS: Children and adolescents diagnosed with T1DM, aged 0 to 18 year, were included in this study performed from March 1999 to April 2009. All patients were screened for CD at their first visit and, again, annually. The investigation was performed through the measurement of IgA (AGAA) and IgG (AGAG) antigliadin antibodies. Patients with values of AGAA and/or AGAG above two times the cutoff mark undertook intestinal biopsy. RESULTS: A group of 21 patients were excluded from the initial total of 384 patients. Out of the remaining, 50 patients had positive serology and 29 underwent intestinal biopsy. The prevalence index was 3.1%. CONCLUSION: The periodic screening of CD in diabetic patients should be encouraged, due to its high prevalence.

Estudo da prevalência da doença celíaca em crianças e adolescentes com diabetes melito tipo 1: resultado de 10 anos de acompanhamento / Study of prevalence of celiac disease in children with type 1 diabetes mellitus: result of 10 years of follow-up

OBJETIVO: Avaliar a prevalência da doença celíaca (DC) em crianças e adolescentes com diabetes melito tipo 1 (DM1) atendidos no Serviço de Endocrinologia Pediátrica do Hospital das Clínicas da Universidade Federal de Minas Gerais. SUJEITOS E MÉTODOS: Incluídos no estudo crianças e adolescentes com diagnóstico prévio de DM1 acompanhadas no serviço no período de março de 1999 a abril de 2009, com idades entre zero e 18 anos. Todos foram rastreados para DC na primeira consulta e anualmente. A investigação foi realizada por meio da dosagem dos anticorpos da classe IgA (AGAA) e IgG (AGAG) antigliadina. Os pacientes com AGAA e/ou AGAG acima de duas vezes o valor de referência foram submetidos à biópsia intestinal. RESULTADOS: Foram excluídos 21 pacientes do total inicial de 384. Destes, 50 tiveram a sorologia positiva e 29 foram submetidos à biópsia intestinal. A prevalência encontrada foi de 3,1%. CONCLUSÃO: O rastreamento periódico da DC nos pacientes diabéticos deve ser encorajado, dada sua alta prevalência.

OBJECTIVE: To estimate the prevalence of celiac disease (CD) in children and adolescents with type 1 diabetes mellitus (T1DM) treated in the Children's Division of Endocrinology, at the Universidade Federal de Minas Gerais Hospital das Clínicas. SUBJECTS AND METHODS: Children and adolescents diagnosed with T1DM, aged 0 to 18 year, were included in this study performed from March 1999 to April 2009. All patients were screened for CD at their first visit and, again, annually. The investigation was performed through the measurement of IgA (AGAA) and IgG (AGAG) antigliadin antibodies. Patients with values of AGAA and/or AGAG above two times the cutoff mark undertook intestinal biopsy. RESULTS: A group of 21 patients were excluded from the initial total of 384 patients. Out of the remaining, 50 patients had positive serology and 29 underwent intestinal biopsy. The prevalence index was 3.1%. CONCLUSION: The periodic screening of CD in diabetic patients should be encouraged, due to its high prevalence.

Isolation and phylogenetic analysis of novel γ-gliadin genes in genus Dasypyrum.

As the most ancient member of the wheat gluten family, the γ-gliadin genes are suitable for phylogenetic analysis among wheat and related species. Species in the grass genus Dasypyrum have been widely used for wheat cross breeding. However, the genomic relationships among Dasypyrum species have been little studied. We isolated 22 novel γ-gliadin gene sequences, among which 10 are putatively functional. The open reading frame lengths of these sequences range from 642 to 933 bp, and these putative proteins consist of five domains. Phylogenetic analyses showed that all Dasypyrum γ-gliadin gene sequences clustered in a large group; D. villosum and tetraploid D. breviaristatum γ-gliadin gene sequences clustered in a subgroup, while diploid D. breviaristatum γ-gliadin gene sequences clustered at the edge of the subgroup. All of the Dasypyrum γ-gliadin gene sequences were absent in three major T cell-stimulatory epitopes binding to HLA-DQ2/8 in celiac disease patients. Based on the phylogenetic analyses, we suggest that D. villosum and tetraploid D. breviaristatum evolved in parallel from a diploid ancestor D. breviaristatum.

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) (2×10(9) 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-1ß 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.