The cultivable human oral gluten-degrading microbiome and its potential implications in coeliac disease and gluten sensitivity

Fernandez-Feo, Martin; Wei, Guoxian; Blumenkranz, Gabriel; Dewhirst, Floyd E.; Schuppan, Detlef; Oppenheim, Frank G.; Helmerhorst, Eva J.

doi:10.1111/1469-0691.12249

Cited by 99 publications

(97 citation statements)

References 30 publications

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“…It is noteworthy, however, that using this method reported here, we identified two bacterial species previously reported by Fernandez-Feo et al 13 and Zamakhchari et al…”

supporting

confidence: 49%

“…There are manufactures who have developed gluten-containing agar plates to identify bacteria which can tolerate gluten. 13,14 The disadvantage of these plates is that further assays are needed to determine if the gluten tolerant bacteria can also digest gluten. However, we modified the Kirby-Bauer agar diffusion assay 15 and developed an agar plate that could not only isolate bacteria which can tolerate gluten but which could also identify bacteria which can digest gluten.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Rapid isolation of gluten-digesting bacteria from human stool and saliva by using gliadin-containing plates

Berger¹,

Sarantopoulos²,

Ongchangco³

et al. 2014

Exp Biol Med (Maywood)

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The number of individuals with gluten intolerance has increased dramatically over the last years. To date, the only therapy for gluten intolerance is the complete avoidance of dietary gluten. To sustain a strictly gluten-free diet, however, is very challenging. Therefore, there is need for a non-dietary therapy. Any such treatment must appreciate that the immunogenic part of gluten are gliadin peptides which are poorly degraded by the enzymes of the gastrointestinal tract. Probiotic therapy and oral enzyme therapy containing gluten-degrading bacteria (GDB) and their gliadin-digesting enzymes are possible new approaches for the treatment of gluten intolerance, however effectively isolating GDB for these treatments is problematic. The goal of this study was to develop an easy technique to isolate GDB rapidly and efficiently with the hope it might lead to newer ways of developing either probiotics or traditional medicines to treat gluten intolerance. Several researchers have already isolated successfully GDB by using gluten minimal or limited agar plates. Although these plates can be used to isolate bacteria which can tolerate gluten, further assays are needed to investigate if the same bacteria can also digest gluten. The agar plates we developed can detect bacteria which cannot only tolerate gluten but are able to digest it as well. Therefore, we were able to combine two steps into one step. Using such technologies, we were able to isolate five GDB from saliva and stool, and identified three bacterial reference strains with gluten-degrading activity. The technique we developed to isolate bacteria with gluten-degrading activity is fast, effective, and easy to use. The GDB isolated by our technology could have potential as part of a probiotic or enzymatic therapy for people with gluten intolerance.

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“…It is noteworthy, however, that using this method reported here, we identified two bacterial species previously reported by Fernandez-Feo et al 13 and Zamakhchari et al…”

supporting

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Rapid isolation of gluten-digesting bacteria from human stool and saliva by using gliadin-containing plates

Berger¹,

Sarantopoulos²,

Ongchangco³

et al. 2014

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

show abstract

“…Although some infections by R. mucilaginosa have been described, this species is considered a harmless colonizer of the oral cavity (68). Recently, it was hypothesized that some species of the Rothia genus, including R. mucilaginosa, are involved in gluten degradation (69,70).…”

Section: Discussionmentioning

confidence: 99%

Salivary Microbiota and Metabolome Associated with Celiac Disease

Francavilla

Ercolini

Piccolo

et al. 2014

Appl Environ Microbiol

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e This study aimed to investigate the salivary microbiota and metabolome of 13 children with celiac disease (CD) under a glutenfree diet (treated celiac disease [T-CD]). The same number of healthy children (HC) was used as controls. The salivary microbiota was analyzed by an integrated approach using culture-dependent and -independent methods. Metabolome analysis was carried out by gas chromatography-mass spectrometry-solid-phase microextraction. Compared to HC, the number of some cultivable bacterial groups (e.g., total anaerobes) significantly (P < 0.05) differed in the saliva samples of the T-CD children. As shown by community-level catabolic profiles, the highest Shannon's diversity and substrate richness were found in HC. Pyrosequencing data showed the highest richness estimator and diversity index values for HC. Levels of Lachnospiraceae, Gemellaceae, and Streptococcus sanguinis were highest for the T-CD children. Streptococcus thermophilus levels were markedly decreased in T-CD children. The saliva of T-CD children showed the largest amount of Bacteroidetes (e.g., Porphyromonas sp., Porphyromonas endodontalis, and Prevotella nanceiensis), together with the smallest amount of Actinobacteria. T-CD children were also characterized by decreased levels of some Actinomyces species, Atopobium species, and Corynebacterium durum. Rothia mucilaginosa was the only Actinobacteria species found at the highest level in T-CD children. As shown by multivariate statistical analyses, the levels of organic volatile compounds markedly differentiated T-CD children. Some compounds (e.g., ethyl-acetate, nonanal, and 2-hexanone) were found to be associated with T-CD children. Correlations (false discovery rate [FDR], <0.05) were found between the relative abundances of bacteria and some volatile organic compounds (VOCs). The findings of this study indicated that CD is associated with oral dysbiosis that could affect the oral metabolome.

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“…Indeed, gluten-degrading bacteria have been isolated from the gastrointestinal tracts of humans and pigs (21)(22)(23)(24)(25). Previously, it was shown that Lactobacillus rhamnosus GG improves the intestinal permeability of Caco-2 cells when exposed to gliadin peptides (26).…”

mentioning

confidence: 99%

Selected Probiotic Lactobacilli Have the Capacity To Hydrolyze Gluten Peptides during Simulated Gastrointestinal Digestion

Francavilla

Angelis

Rizzello

et al. 2017

Appl Environ Microbiol

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The aim of this study was to demonstrate the capacity of probiotic lactobacilli to hydrolyze immunogenic gluten peptides. Eighteen commercial strains of probiotic lactobacilli with highly variable peptidase activity (i.e., aminopeptidase N, iminopeptidase, prolyl endopeptidyl peptidase, tripeptidase, prolidase, prolinase, and dipeptidase), including toward Pro-rich peptides, were tested in this study. Ten probiotic strains were selected on the basis of their specific enzyme activity. When pooled, these 10 strains provided the peptidase portfolio that is required to completely degrade the immunogenic gluten peptides involved in celiac disease (CD). The selected probiotic mixture was able to completely hydrolyze well-known immunogenic epitopes, including the gliadin 33-mer peptide, the peptide spanning residues 57 to 68 of the ␣9-gliadin (␣9-gliadin peptide 57-68), A-gliadin peptide 62-75, and ␥-gliadin peptide 62-75. During digestion under simulated gastrointestinal conditions, the pool of 10 selected probiotic lactobacilli strongly hydrolyzed the wheat bread gluten (ca. 18,000 ppm) to less than 10 ppm after 360 min of treatment. As determined by multidimensional chromatography (MDLC) coupled to nanoelectrospray ionization (nano-ESI)-tandem mass spectrometry (MS/MS), no known immunogenic peptides were detected in wheat bread that was digested in the presence of the probiotics. Accordingly, the level of cytokines (interleukin 2 [IL-2], IL-10, and interferon gamma [IFN-␥]) produced by duodenal biopsy specimens from CD patients who consumed wheat bread digested by probiotics was similar to the baseline value (negative control). Probiotics that specifically hydrolyze gluten polypeptides could also be used to hydrolyze immunogenic peptides that contaminate gluten-free products. This could provide a new and safe adjunctive therapy alternative to the gluten-free diet (GFD).IMPORTANCE This study confirmed that probiotic Lactobacillus strains have different enzymatic abilities for hydrolyzing polypeptides, including the Pro-rich epitopes involved in the pathology of CD. Ten lactobacilli with complementary peptidase activities that hydrolyze gluten peptides during simulated gastrointestinal digestion were selected and tested. The results collected showed the potential of probiotic formulas as novel dietary treatments for CD patients.KEYWORDS celiac disease, probiotic lactobacilli, peptidases, gluten immunogenic peptides, cytokines C eliac disease (CD) is an immune-mediated enteropathy that is triggered by the ingestion of gluten (in genetically susceptible individuals) and that results from the interaction between gluten and immune, genetic, and environmental factors (1). The prevalence of CD is as high as 1% in European countries (2), and its clinical

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The cultivable human oral gluten-degrading microbiome and its potential implications in coeliac disease and gluten sensitivity

Cited by 99 publications

References 30 publications

Rapid isolation of gluten-digesting bacteria from human stool and saliva by using gliadin-containing plates

Rapid isolation of gluten-digesting bacteria from human stool and saliva by using gliadin-containing plates

Salivary Microbiota and Metabolome Associated with Celiac Disease

Selected Probiotic Lactobacilli Have the Capacity To Hydrolyze Gluten Peptides during Simulated Gastrointestinal Digestion

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