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Hedberg, Maria E.
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Publications (10 of 16) Show all publications
Pietz, G., De, R., Hedberg, M., Sjöberg, V., Sandström, O., Hernell, O., . . . Hammarström, M.-L. (2017). Immunopathology of childhood celiac disease: Key role of intestinal epithelial cells. PLoS ONE, 12(9), Article ID e0185025.
Open this publication in new window or tab >>Immunopathology of childhood celiac disease: Key role of intestinal epithelial cells
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 9, article id e0185025Article in journal (Refereed) Published
Abstract [en]

BACKGROUND & AIMS: Celiac disease is a chronic inflammatory disease of the small intestine mucosa due to permanent intolerance to dietary gluten. The aim was to elucidate the role of small intestinal epithelial cells in the immunopathology of celiac disease in particular the influence of celiac disease-associated bacteria.

METHODS: Duodenal biopsies were collected from children with active celiac disease, treated celiac disease, and clinical controls. Intestinal epithelial cells were purified and analyzed for gene expression changes at the mRNA and protein levels. Two in vitro models for human intestinal epithelium, small intestinal enteroids and polarized tight monolayers, were utilized to assess how interferon-γ, interleukin-17A, celiac disease-associated bacteria and gluten influence intestinal epithelial cells.

RESULTS: More than 25 defense-related genes, including IRF1, SPINK4, ITLN1, OAS2, CIITA, HLA-DMB, HLA-DOB, PSMB9, TAP1, BTN3A1, and CX3CL1, were significantly upregulated in intestinal epithelial cells at active celiac disease. Of these genes, 70% were upregulated by interferon-γ via the IRF1 pathway. Most interestingly, IRF1 was also upregulated by celiac disease-associated bacteria. The NLRP6/8 inflammasome yielding CASP1 and biologically active interleukin-18, which induces interferon-γ in intraepithelial lymphocytes, was expressed in intestinal epithelial cells.

CONCLUSION: A key factor in the epithelial reaction in celiac disease appears to be over-expression of IRF1 that could be inherent and/or due to presence of undesirable microbes that act directly on IRF1. Dual activation of IRF1 and IRF1-regulated genes, both directly and via the interleukin-18 dependent inflammasome would drastically enhance the inflammatory response and lead to the pathological situation seen in active celiac disease.

National Category
Immunology
Identifiers
urn:nbn:se:umu:diva-139860 (URN)10.1371/journal.pone.0185025 (DOI)000411339900076 ()28934294 (PubMedID)
Available from: 2017-09-25 Created: 2017-09-25 Last updated: 2018-06-09Bibliographically approved
Soki, J., Hedberg, M., Patrick, S., Balint, B., Herczeg, R., Nagy, I., . . . Urban, E. (2016). Emergence and evolution of an international cluster of MDR Bacteroides fragilis isolates. Journal of Antimicrobial Chemotherapy, 71(9), 2441-2448
Open this publication in new window or tab >>Emergence and evolution of an international cluster of MDR Bacteroides fragilis isolates
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2016 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, no 9, p. 2441-2448Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to examine the antibiotic resistance profiles, antibiotic resistance mechanisms and possible 'clonal' nature of some MDR Bacteroides fragilis strains that simultaneously harboured cfiA, nimB, IS1186 and IS4351. Antibiotic susceptibilities were determined by Etests and antibiotic resistance genes and different genetic elements were detected by applying PCR methods. The environments of the cfiA and nimB genes were also determined by sequencing. The transferability of the cfiA, nimB and tet(Q) genes was tested by conjugation. The genetic relatedness of the test strains was tested by ERIC-PCR or PFGE. The complete genome sequences of two strains (B. fragilis BF8 and O:21) were determined by next-generation sequencing. Most of the seven B. fragilis strains tested displayed multidrug resistance phenotypes; five strains were resistant to at least five types of antibiotics. Besides the common genetic constitution, ERIC-PCR implied high genetic relatedness. Similarities in some of the antibiotic resistance mechanisms [carbapenems (cfiA) and metronidazole (nimB)] also confirmed their common origin, but some other resistance mechanisms {MLSB [erm(F)] and tetracycline [tet(Q)]} and PFGE typing revealed differences. In B. fragilis BF8 and O:21, erm(F) and tet(X) genes were found with IS4351 borders, thus constituting Tn4351. All the strains were tet(Q) positive and transferred this gene in conjugation experiments, but not the cfiA and nimB genes. An international cluster of MDR B. fragilis strains has been identified and characterized. This 'clone' may have emerged early in the evolution of division II B. fragilis strains, which was suggested by the low-complexity ERIC profiles and differences in the PFGE patterns.

National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-127971 (URN)10.1093/jac/dkw175 (DOI)000383911600011 ()27246231 (PubMedID)
Available from: 2016-12-13 Created: 2016-11-21 Last updated: 2018-06-09Bibliographically approved
Sjöberg, V., Sandström, O., Hedberg, M., Hammarström, S., Hernell, O. & Hammarström, M.-L. (2013). Intestinal T-cell responses in celiac disease: impact of celiac disease associated bacteria. PLoS ONE, 8(1), e53414
Open this publication in new window or tab >>Intestinal T-cell responses in celiac disease: impact of celiac disease associated bacteria
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2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 1, p. e53414-Article in journal (Refereed) Published
Abstract [en]

A hallmark of active celiac disease (CD), an inflammatory small-bowel enteropathy caused by permanent intolerance to gluten, is cytokine production by intestinal T lymphocytes. Prerequisites for contracting CD are that the individual carries the MHC class II alleles HLA-DQ2 and/or HLA-DQ8 and is exposed to gluten in the diet. Dysbiosis in the resident microbiota has been suggested to be another risk factor for CD. In fact, rod shaped bacteria adhering to the small intestinal mucosa were frequently seen in patients with CD during the "Swedish CD epidemic" and bacterial candidates could later be isolated from patients born during the epidemic suggesting long-lasting changes in the gut microbiota. Interleukin-17A (IL-17A) plays a role in both inflammation and anti-bacterial responses. In active CD IL-17A was produced by both CD8(+) T cells (Tc17) and CD4(+) T cells (Th17), with intraepithelial Tc17 cells being the dominant producers. Gluten peptides as well as CD associated bacteria induced IL-17A responses in ex vivo challenged biopsies from patients with inactive CD. The IL-17A response was suppressed in patients born during the epidemic when a mixture of CD associated bacteria was added to gluten, while the reverse was the case in patients born after the epidemic. Under these conditions Th17 cells were the dominant producers. Thus Tc17 and Th17 responses to gluten and bacteria seem to pave the way for the chronic disease with interferon-γ-production by intraepithelial Tc1 cells and lamina propria Th1 cells. The CD associated bacteria and the dysbiosis they might cause in the resident microbiota may be a risk factor for CD either by directly influencing the immune responses in the mucosa or by enhancing inflammatory responses to gluten.

Place, publisher, year, edition, pages
PLoS, Public Library of Science, 2013
National Category
Pediatrics Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-64525 (URN)10.1371/journal.pone.0053414 (DOI)000313551500069 ()23326425 (PubMedID)
Available from: 2013-01-31 Created: 2013-01-31 Last updated: 2018-06-08Bibliographically approved
Hedberg, M. E., Israelsson, A., Moore, E. R. B., Svensson-Stadler, L., Wai, S. N., Pietz, G., . . . Hammarstrom, S. (2013). Prevotella jejuni sp nov., isolated from the small intestine of a child with coeliac disease. International Journal of Systematic and Evolutionary Microbiology, 63(11), 4218-4223
Open this publication in new window or tab >>Prevotella jejuni sp nov., isolated from the small intestine of a child with coeliac disease
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2013 (English)In: International Journal of Systematic and Evolutionary Microbiology, ISSN 1466-5026, E-ISSN 1466-5034, Vol. 63, no 11, p. 4218-4223Article in journal (Refereed) Published
Abstract [en]

Five obligately anaerobic, Gram-stain-negative, saccharolytic and proteolytic, non-spore-forming bacilli (strains CD3 :27, CD3 :28(T), CD3 :33, CD3 :32 and CD3 :34) are described. All five strains were isolated from the small intestine of a female child with coeliac disease. Cells of the five strains were short rods or coccoid cells with longer filamentous forms seen sporadically. The organisms produced acetic acid and succinic acid as major metabolic end products. Phylogenetic analysis based on comparative 16S rRNA gene sequence analysis revealed close relationships between CD3 : 27, CD3 :28(T) and CD3 :33, between CD3 :32 and Prevotella histicola CCUG 55407(T), and between CD3 :34 and Prevotella melaninogenica CCUG 4944B(T). Strains CD3 : 27, CD3 :28(T) and CD3 :33 were clearly different from all recognized species within the genus Prevotella and related most closely to but distinct from P. melaninogenica. Based on 16S rRNA, RNA polymerase) beta-subunit (rpoB) and 60 kDa chaperonin protein subunit (cpn60) gene sequencing, and phenotypic, chemical and biochemical properties, strains CD3 :27, CD3 :28(T) and CD3 :33 are considered to represent a novel species within the genus Prevotella, for which the name Prevotella jejuni sp. nov. is proposed. Strain CD3 : 28(T) (=CCUG 60371(T)=DSM 26989(T)) is the type strain of the proposed novel species. All five strains were able to form homologous aggregates, in which tube-like structures were connecting individual bacteria cells. The five strains were able to bind to human intestinal carcinoma cell lines at 37 degrees C.

National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-84790 (URN)10.1099/ijs.0.052647-0 (DOI)000328666600045 ()
Available from: 2014-01-28 Created: 2014-01-20 Last updated: 2018-06-08Bibliographically approved
Hedberg, M. E., Moore, E. R., Svensson-Stadler, L., Hörstedt, P., Baranov, V., Hernell, O., . . . Hammarström, M.-L. (2012). Lachnoanaerobaculum a new genus in Lachnospiraceae; characterization of Lachnoanaerobaculum umeaense gen. nov., sp. nov., isolated from human small intestine, Lachnoanaerobaculum orale gen. nov., sp. nov., isolated from saliva and reclassification of Eubacterium saburreum (Prevot) Holdeman and Moore 1970 as Lachnoanaerobaculum saburreum comb. nov.. International Journal of Systematic and Evolutionary Microbiology, 62(11), 2685-2690
Open this publication in new window or tab >>Lachnoanaerobaculum a new genus in Lachnospiraceae; characterization of Lachnoanaerobaculum umeaense gen. nov., sp. nov., isolated from human small intestine, Lachnoanaerobaculum orale gen. nov., sp. nov., isolated from saliva and reclassification of Eubacterium saburreum (Prevot) Holdeman and Moore 1970 as Lachnoanaerobaculum saburreum comb. nov.
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2012 (English)In: International Journal of Systematic and Evolutionary Microbiology, ISSN 1466-5026, E-ISSN 1466-5034, Vol. 62, no 11, p. 2685-2690Article in journal (Refereed) Published
Abstract [en]

Two new obligately anaerobic Gram-positive, saccharolytic and non-proteolytic spore-forming bacilli (strain CD3:22 and N1) are described. Strain CD3:22 was isolated from a biopsy of the small intestine of a child with celiac disease and strain N1 from the saliva of a healthy young man. The cells of both strains were observed to be filamentous with lengths of approximately 5 to >20 µm, some of them curving and with swellings. The novel organisms produced H2S, NH3, butyric acid and acetic acid as major metabolic end products. Phylogenetic analyses, based on comparative 16S rRNA gene sequencing, revealed close relationships (98 % sequence similarity) between the two isolates, as well as the type strain of Eubacterium saburreum CCUG 28089T and four other Lachnospiraceae bacterium/E. saburreum-like organisms. This group of bacteria were clearly different from any of the 19 known genera in the family Lachnospiraceae. While Eubacterium spp. are reported to be non-spore-forming, reanalysis of E. saburreum CCUG 28089T confirmed that the bacterium, indeed, is able to form spores. Based on 16S rRNA gene sequencing, phenotypic and biochemical properties, CD3:22 (CCUG 58757T) and N1 (CCUG 60305T) represent new species of a new and distinct genus, named Lachnoanaerobaculum, in the family Lachnospiraceae [within the order Clostridiales, class Clostridia, phylum Firmicutes]. Strain CD3:22 is the type strain of the type species, Lachnoanaerobaculum umeaense gen. nov., sp. nov., of the proposed new genus. Strain N1 is the type strain of the species, Lachnoanaerobaculum orale gen. nov., sp. nov. Moreover, E. saburreum CCUG 28089T is reclassified as Lachnoanaerobaculum saburreum comb. nov.

National Category
Microbiology
Identifiers
urn:nbn:se:umu:diva-51168 (URN)10.1099/ijs.0.033613-0 (DOI)22228654 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 222720Swedish Research Council
Available from: 2012-01-11 Created: 2012-01-11 Last updated: 2018-06-08Bibliographically approved
Hedberg, M., Hammarström, M.-L., Hernell, O., Baranov, V., Wai, S. N., Moore, E. & Hammarström, S. (2010). Clostridiales bacterium CD3:22-an anaerobic spore-forming bacterium isolated from small intestine in a celiac disease patient.
Open this publication in new window or tab >>Clostridiales bacterium CD3:22-an anaerobic spore-forming bacterium isolated from small intestine in a celiac disease patient
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2010 (English)Report (Other academic)
National Category
Clinical Medicine
Identifiers
urn:nbn:se:umu:diva-35386 (URN)
Note
Kompletteras 2012-09Available from: 2010-08-16 Created: 2010-08-16 Last updated: 2018-06-08Bibliographically approved
Hasslöf, P., Hedberg, M., Twetman, S. & Stecksén-Blicks, C. (2010). Growth inhibition of oral mutans streptococci and candida by commercial probiotic lactobacilli: an in vitro study. BMC Oral Health, 10, 18
Open this publication in new window or tab >>Growth inhibition of oral mutans streptococci and candida by commercial probiotic lactobacilli: an in vitro study
2010 (English)In: BMC Oral Health, ISSN 1472-6831, E-ISSN 1472-6831, Vol. 10, p. 18-Article in journal (Refereed) Published
Abstract [en]

The selected probiotic strains showed a significant but somewhat varying ability to inhibit growth of oral mutans streptococci and Candida albicans in vitro.

National Category
Dentistry
Identifiers
urn:nbn:se:umu:diva-40681 (URN)10.1186/1472-6831-10-18 (DOI)000208596700018 ()20598145 (PubMedID)
Available from: 2011-03-05 Created: 2011-03-05 Last updated: 2018-06-08Bibliographically approved
Hedberg, M., Hasslöf, P., Sjöström, I., Stecksén-Blicks, C. & Twetman, S. (2009). In vitro inhibition of mutans streptococci by probiotic lactobacilli.
Open this publication in new window or tab >>In vitro inhibition of mutans streptococci by probiotic lactobacilli
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2009 (English)Report (Other academic)
Identifiers
urn:nbn:se:umu:diva-26497 (URN)
Available from: 2009-10-12 Created: 2009-10-12 Last updated: 2018-06-08
Ou, G., Hedberg, M., Hörstedt, P., Baranov, V., Forsberg, G., Drobni, M., . . . Hammarström, S. (2009). Proximal small intestinal microbiota and identification of rod-shaped bacteria associated with childhood celiac disease. American Journal of Gastroenterology, 104(12), 3058-3067
Open this publication in new window or tab >>Proximal small intestinal microbiota and identification of rod-shaped bacteria associated with childhood celiac disease
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2009 (English)In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 104, no 12, p. 3058-3067Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Alterations in the composition of the microbiota in the intestine may promote development of celiac disease (CD). Using scanning electron microscopy (SEM) we previously demonstrated that rod-shaped bacteria were present on the epithelium of proximal small intestine in children with CD but not in controls. In this study we characterize the microbiota of proximal small intestine in children with CD and controls and identify CD-associated rod-shaped bacteria. METHODS: Proximal small intestine biopsies from 45 children with CD and 18 clinical controls were studied. Bacteria were identified by 16S rDNA sequencing in DNA extracted from biopsies washed with buffer containing dithiothreitol to enrich bacteria adhering to the epithelial lining, by culture-based methods and by SEM and transmission electron microscopy. RESULTS: The normal, mucosa-associated microbiota of proximal small intestine was limited. It was dominated by the genera Streptococcus and Neisseria, and also contained Veillonella, Gemella, Actinomyces, Rothia, and Haemophilus. The proximal small intestine microbiota in biopsies from CD patients collected during 2004-2007 differed only marginally from that of controls, and only one biopsy (4%) had rod-shaped bacteria by SEM (SEM+). In nine frozen SEM+ CD biopsies from the previous study, microbiotas were significantly enriched in Clostridium, Prevotella, and Actinomyces compared with SEM- biopsies. Bacteria of all three genera were isolated from children born during the Swedish CD epidemic. New Clostridium and Prevotella species and Actinomyces graevenitzii were tentatively identified. CONCLUSIONS: Rod-shaped bacteria, probably of the indicated species, constituted a significant fraction of the proximal small intestine microbiota in children born during the Swedish CD epidemic and may have been an important risk factor for CD contributing to the fourfold increase in disease incidence in children below 2 years of age during that time.

Keywords
small intestinal microbiota, identification of rod-shaped bacteria, childhood celiac disease
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-35059 (URN)10.1038/ajg.2009.524 (DOI)19755974 (PubMedID)
Available from: 2010-07-05 Created: 2010-07-05 Last updated: 2018-06-08Bibliographically approved
Hedberg, M. & Nord, C. E. (2008). Anaerobic bacteria (3rded.). In: Antimicrobial therapy and vaccines: volume I: Microbes. New York: Apple Trees Production, LLC
Open this publication in new window or tab >>Anaerobic bacteria
2008 (English)In: Antimicrobial therapy and vaccines: volume I: Microbes, New York: Apple Trees Production, LLC , 2008, 3rdChapter in book (Other academic)
Place, publisher, year, edition, pages
New York: Apple Trees Production, LLC, 2008 Edition: 3rd
Keywords
Anaerobic bacteria, antimicrobial therapy
National Category
Microbiology in the medical area
Research subject
Microbiology
Identifiers
urn:nbn:se:umu:diva-26357 (URN)
Available from: 2009-10-06 Created: 2009-10-06 Last updated: 2018-06-08
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