José M. Ruiz de Morales

Differences of small intestinal bacteria populations in adults and children with/without celiac disease: Effect of age, gluten diet, and disease

Background: Scientific evidence has revealed microecological changes in the intestinal tract of celiac infants. The objective of this work is the study of bacterial differences in the upper small intestine in both adults (healthy, untreated celiac disease [CD], and CD treated with a gluten‐free diet) and children (healthy and untreated CD). Methods: Intestinal bacterial communities were identified by 16S rRNA gene sequencing of DNA extracted from duodenal biopsies. Results: Analysis of the sequences from adults and children showed that this niche was colonized by bacteria affiliated mainly with three phyla: Firmicutes, Proteobacteria, and Bacteroidetes. In total, 89 different genera were identified in adults and 46 in children. Bacterial richness was significantly lower in the children than in the adults. A global principal component analysis of the bacterial communities of both healthy and untreated CD patient groups (including both children and adults) revealed a strong effect of age in principal component 1—clustering all adults and children separately—and a possible effect of the disease in adults with untreated patients clustering separately. Conclusions: There are bacterial differences in the upper small intestine between untreated children CD patients and untreated CD adults due to age. There are bacterial differences in the upper small bacteria microbiota between treated and untreated CD adults due to treatment with a gluten‐free diet. (Inflamm Bowel Dis 2011;)

Diversity of the cultivable human gut microbiome involved in gluten metabolism: isolation of microorganisms with potential interest for coeliac disease

Gluten, a common component in the human diet, is capable of triggering coeliac disease pathogenesis in genetically predisposed individuals. Although the function of human digestive proteases in gluten proteins is quite well known, the role of intestinal microbiota in the metabolism of proteins is frequently underestimated. The aim of this study was the isolation and characterisation of the human gut bacteria involved in the metabolism of gluten proteins. Twenty-two human faecal samples were cultured with gluten as the principal nitrogen source, and 144 strains belonging to 35 bacterial species that may be involved in gluten metabolism in the human gut were isolated. Interestingly, 94 strains were able to metabolise gluten, 61 strains showed an extracellular proteolytic activity against gluten proteins, and several strains showed a peptidasic activity towards the 33-mer peptide, an immunogenic peptide in patients with coeliac disease. Most of the strains were classified within the phyla Firmicutes and Actinobacteria, mainly from the genera Lactobacillus, Streptococcus, Staphylococcus, Clostridium and Bifidobacterium. In conclusion, the human intestine exhibits a large variety of bacteria capable of utilising gluten proteins and peptides as nutrients. These bacteria could have an important role in gluten metabolism and could offer promising new treatment modalities for coeliac disease.

Human recombinant anti-transglutaminase antibody testing is useful in the diagnosis of silent coeliac disease in a selected group of at-risk patients.

Background Functional dyspepsia, unexplained chronic hypertransaminasaemia (CHT) and hepatitis C virus (HCV) are common gastrointestinal situations that have been related to coeliac disease. Antibodies to tissue transglutaminase (tTG) have been claimed recently to be highly effective as a screening method for coeliac disease. Aim To assess the prevalence of coeliac disease by means of detection of antibodies against human tTG in the abovementioned groups of patients. Patients and methods A control group consisted of 165 normal blood donors. Patient groups comprised 90 CHT patients, 102 HCV patients and 92 functional dyspepsia patients. All patients were tested for anti‐tTG (immunoglobulin A, IgA) antibodies. Anti‐endomysium (IgA) antibodies (AEA) and antigliadin (IgA) antibodies (AGA) and antigliadin (immunoglobulin G, IgG) antibodies (AGG) were also tested. When anti‐tTG or AEA was positive, a duodenal biopsy was recommended. Results One of 165 blood donors, three of 92 functional dyspepsia patients, four of 90 CHT patients and none of 102 HCV patients were positive for anti‐tTG antibodies. In the anti‐tTG‐positive group, all but one were AEA‐positive. There were no AEA‐ or AGA IgA‐positives that revealed a negative anti‐tTG test. Duodenal biopsy confirmed a diagnosis of coeliac disease in all the cases. Statistically significant differences were found between the controls and the functional dyspepsia group and between the controls and the CHT group, but not between the controls and the HCV group. Conclusions Both CHT and functional dyspepsia may represent a true oligosymptomatic form of coeliac disease. In such conditions, the detection of anti‐tTG antibodies is useful as a screening method. Coeliac disease is not an autoimmune manifestation of HCV, so screening for coeliac disease in HCV patients cannot be recommended.

Differences in gluten metabolism among healthy volunteers, coeliac disease patients and first-degree relatives.

Coeliac disease (CD) is an immune-mediated enteropathy resulting from exposure to gluten in genetically predisposed individuals. Gluten proteins are partially digested by human proteases generating immunogenic peptides that cause inflammation in patients carrying HLA-DQ2 and DQ8 genes. Although intestinal dysbiosis has been associated with patients with CD, bacterial metabolism of gluten has not been studied in depth thus far. The aim of this study was to analyse the metabolic activity of intestinal bacteria associated with gluten intake in healthy individuals, CD patients and first-degree relatives of CD patients. Faecal samples belonging to twenty-two untreated CD patients, twenty treated CD patients, sixteen healthy volunteers on normal diet, eleven healthy volunteers on gluten-free diet (GFD), seventy-one relatives of CD patients on normal diet and sixty-nine relatives on GFD were tested for several proteolytic activities, cultivable bacteria involved in gluten metabolism, SCFA and the amount of gluten in faeces. We detected faecal peptidasic activity against the gluten-derived peptide 33-mer. CD patients showed differences in faecal glutenasic activity (FGA), faecal tryptic activity (FTA), SCFA and faecal gluten content with respect to healthy volunteers. Alterations in specific bacterial groups metabolising gluten such as Clostridium or Lactobacillus were reported in CD patients. Relatives showed similar parameters to CD patients (SCFA) and healthy volunteers (FTA and FGA). Our data support the fact that commensal microbial activity is an important factor in the metabolism of gluten proteins and that this activity is altered in CD patients.

Enfermedad celíaca refractaria

Resumen La principal causa de falta de respuesta a la dieta sin gluten es la ingestion continuada y generalmente inadvertida de gluten. El diagnostico de enfermedad celiaca refractaria se establece tras la exclusion de otras enfermedades, ante la persistencia de malabsorcion y atrofia vellositaria. Comprende un heterogeneo grupo de afecciones, en general en pacientes adultos, y afortunadamente se manifiestan de forma infrecuente (

Gluten Metabolism in Humans: Involvement of the Gut Microbiota

Abstract Gluten proteins are the major storage proteins that are deposited in the starchy endosperm cells of developing wheat grain. These proteins have the capacity to form a viscoelastic network, and thus wheat is used in numerous processed foods. Therefore, a large amount of gluten protein is ingested by humans. However, because of their high proline and glutamine content, gluten peptides are relatively resistant to complete digestion by human digestive proteases because those enzymes are deficient in prolyl endopeptidasic activity. The incomplete digestion of gluten proteins generates high molecular weight oligopeptides that remain in the lumen of the small intestine; some of these are capable of triggering the inflammatory process associated with celiac disease (CD). Nevertheless, there are several reasons why gut microbiota should be taken into account when considering the metabolism of proteins in the human intestine. For example, there are bacteria in the oral cavity that have the ability to hydrolyze gluten peptides, and there are bacteria in the large intestine with the ability to digest gliadin peptides. These bacteria could generate different digestion processes for gluten proteins in CD patients and in healthy people. Therefore, this review examines gluten metabolism throughout the gastrointestinal tract, and the role of the gut microbiota in this process.Gluten proteins are the major storage proteins that are deposited in the starchy endosperm cells of developing wheat grain. These proteins have the capacity to form a viscoelastic network, and thus wheat is used in numerous processed foods. Therefore, a large amount of gluten protein is ingested by humans. However, because of their high proline and glutamine content, gluten peptides are relatively resistant to complete digestion by human digestive proteases because those enzymes are deficient in prolyl endopeptidasic activity. The incomplete digestion of gluten proteins generates high molecular weight oligopeptides that remain in the lumen of the small intestine; some of these are capable of triggering the inflammatory process associated with celiac disease (CD). Nevertheless, there are several reasons why gut microbiota should be taken into account when considering the metabolism of proteins in the human intestine. For example, there are bacteria in the oral cavity that have the ability to hydrolyze gluten peptides, and there are bacteria in the large intestine with the ability to digest gliadin peptides. These bacteria could generate different digestion processes for gluten proteins in CD patients and in healthy people. Therefore, this review examines gluten metabolism throughout the gastrointestinal tract, and the role of the gut microbiota in this process.

Efficacy and safety of immunomodulatory drugs in patients with anterior uveitis: A systematic literature review

Background: To assess the efficacy and safety of immunomodulatory drugs in patients with noninfectious anterior uveitis (AU). Methods: Systematic review of studies were retrieved from Medline (1961 to March 2016), Embase (1961 to March 2016), and Cochrane Library (up to March 2016), and a complementary hand search was also performed. The selection criteria were as follows: (population) noninfectious AU patients, adults; (intervention) immunomodulatory drugs (any dose, regimen, route of administration, duration of treatment); (outcome) control of inflammation, steroid-sparing effect, AU flares, adverse events, and so on; (study design) systematic literature reviews, randomized controlled trials, and observational studies. The study quality was assessed using the Jadad scale and according to The Oxford Centre for Evidence-based Medicine (update 2009). Results: We included 13 studies of moderate-poor quality, with a mean duration from 5 months to 20 years, and number of AU patients ranging from 9 to 274. Patients demographic and clinical characteristics were very heterogeneous. In most cases, uveitis anatomic classification criteria and outcomes definitions were unclear. Some of the studies only included AU patients with a systemic disease associated, mostly spondyloarthritis, others, mixed populations (idiopathic and systemic disease associated patients), and in some articles this data is not described. We found that methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might prevent AU flares, improve ocular inflammation and visual acuity, and decrease systemic steroids doses. Conclusions: Although there is a lack of robust evidence, methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might be effective in AU patients.

Documento de recomendaciones de tratamiento de la uveítis anterior no infecciosa

BACKGROUND AND OBJECTIVE To develop recommendations on the use of immunodepressors in patients with non-infectious, non-neoplastic anterior uveitis (AU) based on best evidence and experience. MATERIAL AND METHODS A multidisciplinary panel of five experts was established, who, in the first nominal group meeting defined the scope, users, and chapters of the document. A systematic literature review was performed to assess the efficacy and safety of immunosuppressors in patients with non-infectious, non-neoplastic AU. All the above was discussed in a second nominal group meeting and 33 recommendations were generated. Through the Delphi methodology, the degree of agreement with the recommendations was tested also by 25 more experts. Recommendations were voted on from one (total disagreement) to 10 (total agreement). We defined agreement if at least 70% voted ≥7. The level of evidence and degree of recommendation was assessed using the Oxford Centre for Evidence-based Medicines Levels of Evidence. RESULTS The 33 recommendations were accepted. They include specific recommendations on patients with non-infectious, non-neoplastic AU, as well as different treatment lines. CONCLUSIONS In patients with non-infectious, non-neoplastic AU, these recommendations on the use of immunosuppressors might be a guide in order to help in the treatment decision making, due to the lack of robust evidence or other globally accepted algorithms.