Role of Intestinal Bacteria in Gliadin-Induced Changes in Intestinal Mucosa: Study in Germ-Free Rats

10 pages, 6 figures.[Background and Aims]: Celiac disease (CD) is a chronic inflammatory disorder of the small intestine that is induced by dietary wheat gluten proteins (gliadins) in genetically predisposed individuals. The overgrowth of potentially pathogenic bacteria and infections has been suggested to contribute to CD pathogenesis. We aimed to study the effects of gliadin and various intestinal bacterial strains on mucosal barrier integrity, gliadin translocation, and cytokine production.[Methodology/Principal Findings]: Changes in gut mucosa were assessed in the intestinal loops of inbred Wistar-AVN rats that were reared under germ-free conditions in the presence of various intestinal bacteria (enterobacteria and bifidobacteria isolated from CD patients and healthy children, respectively) and CD-triggering agents (gliadin and IFN-γ) by histology, scanning electron microscopy, immunofluorescence, and a rat cytokine antibody array. Adhesion of the bacterial strains to the IEC-6 rat cell line was evaluated in vitro. Gliadin fragments alone or together with the proinflammatory cytokine interferon (IFN)-γ significantly decreased the number of goblet cells in the small intestine; this effect was more pronounced in the presence of Escherichia coli CBL2 and Shigella CBD8. Shigella CBD8 and IFN-γ induced the highest mucin secretion and greatest impairment in tight junctions and, consequently, translocation of gliadin fragments into the lamina propria. Shigella CBD8 and E. coli CBL2 strongly adhered to IEC-6 epithelial cells. The number of goblet cells in small intestine increased by the simultaneous incubation of Bifidobacterium bifidum IATA-ES2 with gliadin, IFN-γ and enterobacteria. B. bifidum IATA-ES2 also enhanced the production of chemotactic factors and inhibitors of metalloproteinases, which can contribute to gut mucosal protection.[Conclusions]: Our results suggest that the composition of the intestinal microbiota affects the permeability of the intestinal mucosa and, consequently, could be involved in the early stages of CD pathogenesis.This work was supported by grants 310/07/0414, 303/08/0367, P304/10/P406 of the Grant Agency of the Czech Republic; IAA500200801, IAA500200710, KJB50020094 of the Academy of Sciences; AV CR-C.S.I.C. 09/10, Project 2B06155 of the Ministry of Education; and Institutional Research Concept AVOZ50200510. This work was also supported by grants 2006CZ0030 and 2008CZ0023 from Consejo Superior de Investigaciones Científicas (CSIC, Spain) and AGL2008-01440/ALI and Consolider Fun-C-Food CSD2007-00063 from the Spanish Ministry of Science and Innovation. The scholarship to G. De Palma from Junta de Ampliación de Estudios - Consejo Superior de Investigaciones Científicas (JAE-CSIC; Spain) is fully acknowledged.Peer reviewe

Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138242/1/imr12567.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138242/2/imr12567_am.pd

Rozhovor Britských listů 315. Bezbariérový přístup nemáme. Na invalidy se kašle [Britské listy Interview 315. We do not have access for the disabled people. Everyone ignores them here.]

"In every high rise here at this housing estate, there lives at least one disabled person consigned to a wheelchar. And these are people who have been living here for years," says Marie Cinová from the North Bohemian border town of Šluknov, Czech Republic. Ms. Cinová has a disabled son. She herself is disabled, as is her husband, a cardiac waiting for a heart operation in hospital now. Ms Cinová washes her son at the sink in the kitchen because the wheelchair will not fit through the bathroom door. She needs the door to be re-built but no one will help her - nor will help come for the other disabled people. Maybe her fellow citizens should help her financially? But should they be doing what is undoubtedly the duty of the state? Her account is IBAN CZ752700 0000 0021 1375 4545. This interview was broadcast by the Czech cable TV station Regionalnitelevize.cz from Friday 4th September 2020

Pivotal Advance: Bifidobacteria and Gram-negative bacteria differentially influence immune responses in the proinflammatory milieu of celiac disease

Abstract Immunomodulatory effects of intestinal bacteria under the immune (IFN-γ) and environmental triggers (gliadins) of celiac disease on peripheral blood mononuclear cells. CD is a chronic inflammatory disorder of the small intestine that presents in genetically predisposed individuals following gluten consumption. In this study, the effects of Bifidobacterium (Bifidobacterium bifidum IATA-ES2 and Bifidobacterium longum ATCC15707) and Gram-negative bacteria (Bacteroides fragilis DSM2451, Escherichia coli CBL2, and Shigella CBD8 isolated from CD patients), alone and in the presence of CD triggers (gliadins and/or IFN-γ) on surface marker expression and cytokine production by PBMCs, were determined. These effects were also evaluated in cocultures of PBMCs and Caco-2 cells. The Gram-negative bacteria induced higher secretion of Th1-type proinflammatory cytokines (IL-12 and/or IFN-γ) than the Bifidobacterium strains. Shigella CBD8 and E. coli CBL2 up-regulated mainly HLA-DR and CD40 expression involved in Th1 activation, and Bifidobacterium strains up-regulated CD83 expression. Specific interactions among the studied bacteria, gliadins, and IFN-γ, which favored the CD immune features, were also detected. Therefore, intestinal bacteria could be additional factors that regulate the ability of monocytes recruited to the mucosa to respond to gliadins and IFN-γ in CD patients, influencing the course of the disease.</jats:p

Postawy pacjentów chorych na cukrzycę wobec ich choroby

Background. Education of diabetic patients is integral to effective treatment. Material and methods. In the presented work, we studied Eastern Slovakian patients with diabetes type 2 with or without insulin treatment. We focused on their diabetic self-care and compared their attitudes, education on their disease, and treatment provided by professionals. There were 411 patients in the insulin-treated group. We used the standardized Diabetes Care Profile questionnaire (DCP). Results. The groups had very different attitudes toward diabetic self-care. Patients with provided professional self-care education scored higher in all areas of diabetic care. Appropriate education influenced knowledge and consequently the management and attitudes of diabetic patients toward their disease. Educated patients scored higher in the categories ‘Self-care ability’, ‘Importance of care’, ‘Self-care adherence’, ‘Diet adherence’, ‘Medical barriers’, ‘Exercise barriers’, ‘Monitoring barriers’ and ‘Understanding practice’ (p < 0.01). Patients who had not received diabetes education presented higher scores in emotional areas, i.e., negative and positive attitudes toward diabetes mellitus (p < 0.01). Conclusions. We concluded that it is beneficial for a structured e ducational process to be integrated in diabetes treatment.Wprowadzenie. Edukacja pacjentów chorych na cukrzycę stanowi integralną część ich skutecznego leczenia. Materiał i metody. W prezentowanym badaniu porównano postawy w zakresie samodzielnej profilaktyki cukrzycy w dwóch grupach pacjentów cierpiących na cukrzycę typu 2, która wymaga insulinoterapii, w odniesieniu do szkoleń edukacyjnych dotyczących ich choroby oraz leczenia prowadzonego przez specjalistów. Badaną grupę stanowiło 411 pacjentów cierpiących na cukrzycę typu 2 leczoną za pomocą insuliny, którzy pochodzą ze wschodniej części Słowacji. Zastosowano standardowy kwestionariusz DCP (ang. Diabetes Care Profile), wykorzystywany do oceny czynników społecznych i psychologicznych wśród cukrzyków. Wyniki. Postawy dwóch porównywanych grup pacjentów wobec cukrzycy różniły się istotnie w zakresie samodzielnej profilaktyki. Pacjenci z zapewnionym profesjonalnym szkoleniem dotyczącym samodzielniej profilaktyki uzyskiwali wyższe oceny we wszystkich obszarach związanych z monitorowaniem i leczeniem cukrzycy. Prawidłowy proces edukacyjny ma wpływ na poziom wiedzy, a tym samym na działania podejmowane przez pacjentów i ich postawy wobec choroby. Pacjenci, którzy otrzymali odpowiednie przeszkolenie, lepiej kontrolowali sfery takie jak „Umiejętności dot. samodzielnej profilaktyki”, „Znaczenie samodzielnej profilaktyki”, „Przestrzeganie zasad samodzielnej profilaktyki”, „Przestrzeganie diety”, „Ograniczenia natury medycznej”, „Ograniczenia w wykonywaniu ćwiczeń”, „Ograniczenia w monitorowaniu” oraz „Rozumienie procedur” (p < 0,01). Z kolei pacjenci nieposiadający odpowiedniej wiedzy prezentowali lepsze wyniki w obszarach związanych ze sferą emocjonalną – negatywnym i pozytywnym nastawieniu do cukrzycy (p < 0,01). Wnioski. W kontekście uzyskanych wyników, zintegrowanie ustrukturyzowanego procesu edukacyjnego z leczeniem osób chorujących na cukrzycę wydaje się konieczne

Modulation of phenotypic and functional maturation of dendritic cells by intestinal bacteria and gliadin: relevance for celiac disease

Abstract Bifidobacteria and enterobacteria influence phenotypic and functional maturation of DCs differently, which together with gliadin, could define the role of DCs in celiac disease progression. DC maturation and functions are influenced by microbial and environmental stimuli, which could contribute to immune dysfunction. Here, we have investigated the role of enterobacteria (Escherichia coli CBL2 and Shigella CBD8) isolated from CD patients, bifidobacteria (Bifidobacterium longum CECT 7347 and Bifidobacterium bifidum CECT 7365), and gliadins on phenotypic and functional features of MDDCs and in coculture with Caco-2 cells. The ultimate goal of our study is to understand the roles played by specific components of the gut microbiota in CD. Enterobacteria induced marked alterations in MDDC morphology, inducing podosome dissolution and dendrites, and activated MDDC adhesion and spreading. Enterobacteria also induced inflammatory cytokine production (IFN-γ, TNF-α, and IL-12), partially resembling the gliadin-induced Th1-type cytokine profile. B. longum CECT 7347 and B. bifidum CECT 7365 induced minor MDDC morphological changes and activated adhesion and spreading and inflammatory cytokine production to a lesser extent compared with enterobacteria. B. longum CECT 7347 also induced lower CD86 and CD40 expression on MDDCs than the two enterobacteria. The aforementioned bifidobacterial strain also reduced gliadin-induced IFN-γ production and increased IL-10 secretion when both stimuli were combined. Similar trends were detected for MDDCs cocultured with Caco-2 cells. B. longum CECT 7347 reversed the gliadin-reduced ZO-1 expression in Caco-2 cells. Thus, our results suggest that specific components of the gut microbiota may influence phenotypic and functional maturation of DCs differently and their interactions with epithelial cells. This could ultimately define the role of DCs in CD progression.</jats:p

lfex/ltest: 0.13.6

&lt;h2&gt;What's Changed&lt;/h2&gt; &lt;ul&gt; &lt;li&gt;Compile ltest using rebar3 LFE plugin by @John-Goff in https://github.com/lfex/ltest/pull/76&lt;/li&gt; &lt;/ul&gt; &lt;h2&gt;New Contributors&lt;/h2&gt; &lt;ul&gt; &lt;li&gt;@John-Goff made their first contribution in https://github.com/lfex/ltest/pull/76&lt;/li&gt; &lt;/ul&gt; &lt;p&gt;&lt;strong&gt;Full Changelog&lt;/strong&gt;: https://github.com/lfex/ltest/compare/0.13.5...0.13.6&lt;/p&gt

Mucin production by goblet cells in rat intestinal loops.

<p>Mucin production after application of <i>B. bifidum</i> IATA-ES2 (A), IFN-γ (B), gliadin+IFN-γ+ <i>B. bifidum</i> IATA-ES2 (C), <i>E. coli</i> CBL2+gliadin+IFN-γ D), <i>E. coli</i> BL2+gliadin+ IFN-γ+<i>B. bifidum</i> IATA-ES2 (E) and <i>Shigella</i> CBD8+gliadin+IFN-γ (F). Bacteria were applied at 10⁶/loop. The samples were coated with gold and examined by Aquasem electron microscopy (Tescan, Czech Republic) in the SEM mode. Scale bar, 20 µm.</p