Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2

Caminero, Alberto; McCarville, Justin L.; Galipeau, Heather J.; Deraison, Céline; Bernier, Steve P.; Constante, Marco; Rolland, Corinne; Meisel, Marlies; Murray, Joseph A.; Yu, Xuechen; Alaedini, Armin; Coombes, Brian K.; Berčík, Přemysl; Southward, Carolyn M.; Ruf, Wolfram; Jabrì, Bana; Chirdo, Fernando Gabriel; Casqueiro, Javier; Surette, Michael G.; Vergnolle, Nathalie; Verdú, Elena F.

doi:10.1038/s41467-019-09037-9

Cited by 115 publications

(117 citation statements)

References 67 publications

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“…In turn, the abundance of potential pathogenic species such as Acinetobacter and Pseudomonas exhibited the opposite pattern. Interestingly, a recent study has reported that Pseudomonas aeruginosa, an opportunistic pathogen from CeD patients, may have proteolytic activity and could trigger a severe intestinal inflammation synergistically with gluten in experimental CeD models (Caminero et al, 2019). All in all, our study provides new insights into the human milk bacterial profile and its potential role in CeD onset in children in a prospective study for the first time.…”

Section: Discussionmentioning

confidence: 68%

Breast-Milk Microbiota Linked to Celiac Disease Development in Children: A Pilot Study From the PreventCD Cohort

et al. 2020

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Celiac disease (CeD) is an immune-mediated disorder triggered by exposure to dietary gluten proteins in genetically predisposed individuals. In addition to the host genome, the microbiome has recently been linked to CeD risk and pathogenesis. To progress in our understanding of the role of breast milk microbiota profiles in CeD, we have analyzed samples from a subset of mothers (n = 49) included in the PreventCD project, whose children did or did not develop CeD. The results of the microbiota data analysis indicated that neither the BMI, HLA-DQ genotype, the CeD condition nor the gluten-free diet of the mothers could explain the human milk microbiota profiles. Nevertheless, we found that origin country, the offspring's birth date and, consequently, the milk sampling date influenced the abundance and prevalence of microbes in human milk, undergoing a transition from an anaerobic to a more aerobic microbiota, including potential pathogenic species. Furthermore, certain microbial species were more abundant in milk samples from mothers whose children went on to develop CeD compared to those that remained healthy. These included increases in facultative methylotrophs such as Methylobacterium komagatae and Methylocapsa palsarum as well as in species such as Bacteroides vulgatus, that consumes fucosylated-oligosaccharides present in human milk, and other breast-abscess associated species. Theoretically, these microbiota components could be vertically transmitted from mothers-to-infants during breastfeeding, thereby influencing CeD risk.

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Section: Discussionmentioning

confidence: 68%

Breast-Milk Microbiota Linked to Celiac Disease Development in Children: A Pilot Study From the PreventCD Cohort

et al. 2020

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“…Perturbations of the gut microbiota (dysbiosis) and viral infections have been suggested to trigger the first hit of mucosal inflammation [20,21]. In this regard, a series of elegant experiments has provided some mechanistic insights showing that both gluten-and amylase-trypsin inhibitor-derived peptides generated by pathobiont species, such as Pseudomonas aeriginosa, are able to disrupt the epithelial barrier, to activate protease-activated receptors-2 signalling, and to recruit intraepithelial lymphocytes in sensitized mice with a susceptible genetic background [22,23]. Nonetheless, gut mucosa may also harbour gluten-degrading bacteria, such as Rothia spp.…”

Section: Discussionmentioning

confidence: 99%

Comparative Study of Salivary, Duodenal, and Fecal Microbiota Composition Across Adult Celiac Disease

Panelli

Capelli

Lupo

et al. 2020

JCM

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Background: Growing evidence suggests that an altered microbiota composition contributes to the pathogenesis and clinical features in celiac disease (CD). We performed a comparative analysis of the gut microbiota in adulthood CD to evaluate whether: (i) dysbiosis anticipates mucosal lesions, (ii) gluten-free diet restores eubiosis, (iii) refractory CD has a peculiar microbial signature, and (iv) salivary and fecal communities overlap the mucosal one. Methods: This is a cross-sectional study where a total of 52 CD patients, including 13 active CD, 29 treated CD, 4 refractory CD, and 6 potential CD, were enrolled in a tertiary center together with 31 controls. A 16S rRNA-based amplicon metagenomics approach was applied to determine the microbiota structure and composition of salivary, duodenal mucosa, and stool samples, followed by appropriate bioinformatic analyses. Results: A reduction of both α- and β-diversity in CD, already evident in the potential form and achieving nadir in refractory CD, was evident. Taxonomically, mucosa displayed a significant abundance of Proteobacteria and an expansion of Neisseria, especially in active patients, while treated celiacs showed an intermediate profile between active disease and controls. The saliva community mirrored the mucosal one better than stool. Conclusion: Expansion of pathobiontic species anticipates villous atrophy and achieves the maximal divergence from controls in refractory CD. Gluten-free diet results in incomplete recovery. The overlapping results between mucosal and salivary samples indicate the use of saliva as a diagnostic fluid.

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“…Lactobacilli can hydrolase shorter peptides (Francavilla et al 2017); however, bacilli and clostridia can destruct also larger molecules. The degradation products have to be carefully considered as it has been shown that proteases produced by some bacteria increase the immunogenicity of gluten peptides (Nistal et al 2016;Caminero et al 2019).…”

Section: Discussionmentioning

confidence: 99%

Microbiome of root vegetables—a source of gluten-degrading bacteria

Kõiv

Adamberg

et al. 2020

Appl Microbiol Biotechnol

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Gluten is a cereal protein that is incompletely digested by human proteolytic enzymes that create immunogenic peptides that accumulate in the gastrointestinal tract (GIT). Although both environmental and human bacteria have been shown to expedite gluten hydrolysis, gluten intolerance is a growing concern. Here we hypothesize that together with food, we acquire environmental bacteria that could impact our GIT with gluten-degrading bacteria. Using in vitro gastrointestinal simulation conditions, we evaluated the capacity of endophytic bacteria that inhabit root vegetables, potato (Solanum tuberosum), carrot (Daucus sativus), beet (Beta vulgaris), and topinambur (Jerusalem artichoke) (Helianthus tuberosus), to resist these conditions and degrade gluten. By 16S rDNA sequencing, we discovered that bacteria from the families Enterobacteriaceae, Bacillaceae, and Clostridiaceae most effectively multiply in conditions similar to the human GIT (microoxic conditions, 37 °C) while utilizing vegetable material and gluten as nutrients. Additionally, we used stomach simulation (1 h, pH 3) and intestinal simulation (1 h, bile salts 0.4%) treatments. The bacteria that survived this treatment retained the ability to degrade gluten epitopes but at lower levels. Four bacterial strains belonging to species Bacillus pumilus, Clostridium subterminale, and Clostridium sporogenes isolated from vegetable roots produced proteases with postproline cleaving activity that successfully neutralized the toxic immunogenic epitopes. Key points • Bacteria from root vegetables can degrade gluten. • Some of these bacteria can resist conditions mimicking gastrointestinal tract.

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Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2

Cited by 115 publications

References 67 publications

Breast-Milk Microbiota Linked to Celiac Disease Development in Children: A Pilot Study From the PreventCD Cohort

Breast-Milk Microbiota Linked to Celiac Disease Development in Children: A Pilot Study From the PreventCD Cohort

Comparative Study of Salivary, Duodenal, and Fecal Microbiota Composition Across Adult Celiac Disease

Microbiome of root vegetables—a source of gluten-degrading bacteria

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