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König, Julia
Publications (10 of 13) Show all publications
König, J., Siebenhaar, A., Högenauer, C., Arkkila, P., Nieuwdorp, M., Norén, T., . . . Brummer, R. J. (2017). Consensus report: Faecal microbiota transfer - clinical applications and procedures. Alimentary Pharmacology and Therapeutics, 45(2), 222-239.
Open this publication in new window or tab >>Consensus report: Faecal microbiota transfer - clinical applications and procedures
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2017 (English)In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 45, no 2, p. 222-239Article in journal (Refereed) Published
Abstract [en]

Background: Faecal microbiota transplantation or transfer (FMT) aims at replacing or reinforcing the gut microbiota of a patient with the microbiota from a healthy donor. Not many controlled or randomised studies have been published evaluating the use of FMT for other diseases than Clostridium difficile infection, making it difficult for clinicians to decide on a suitable indication.

Aim: To provide an expert consensus on current clinical indications, applications and methodological aspects of FMT.

Methods: Well-acknowledged experts from various countries in Europe have contributed to this article. After literature review, consensus has been achieved by repetitive circulation of the statements and the full manuscript among all authors with intermittent adaptation to comments (using a modified Delphi process). Levels of evidence and agreement were rated according to the GRADE system. Consensus was defined a priori as agreement by at least 75% of the authors.

Results: Key recommendations include the use of FMT in recurrent C. difficile infection characterised by at least two previous standard treatments without persistent cure, as well as its consideration in severe and severe-complicated C. difficile infection as an alternative to total colectomy in case of early failure of antimicrobial therapy. FMT in inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS) and metabolic syndrome should only be performed in research settings.

Conclusions: Faecal microbiota transplantation or transfer is a promising treatment for a variety of diseases in which the intestinal microbiota is disturbed. For indications other than C. difficile infection, more evidence is needed before more concrete recommendations can be made.

Place, publisher, year, edition, pages
Hoboken, USA: Wiley-Blackwell Publishing Inc., 2017
National Category
Gastroenterology and Hepatology Pharmacology and Toxicology
Identifiers
urn:nbn:se:oru:diva-53881 (URN)10.1111/apt.13868 (DOI)000389441900003 ()27891639 (PubMedID)2-s2.0-85002170778 (Scopus ID)
Note

Funding Agencies:

Seres Therapeutics

AbbVie

Astellas

Biogen

Janssen

MSD

Mundipharma

Takeda Summit Therapeutics

FalkFoundation

Takeda

Available from: 2016-12-12 Created: 2016-12-12 Last updated: 2018-01-13Bibliographically approved
König, J., Holster, S., Maaike, B. & Brummer, R. J. (2017). Randomized clinical trial: Effective gluten degradation by Aspergillus niger-derived enzyme in a complex meal setting. Scientific Reports, 7(13100).
Open this publication in new window or tab >>Randomized clinical trial: Effective gluten degradation by Aspergillus niger-derived enzyme in a complex meal setting
2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, no 13100Article in journal (Refereed) Published
Abstract [en]

The Aspergillus niger-derived prolyl endoprotease (AN-PEP) has previously been shown to degrade gluten in healthy subjects when added to an intragastrically infused meal. The current study investigated the efficacy of AN-PEP in a physiological meal setting. In this randomized placebo-controlled crossover study, 18 gluten-sensitive subjects consumed a porridge containing 0.5 g gluten together with two tablets either containing a high or low dose of AN-PEP, or placebo. Gastric and duodenal content was sampled over 180 minutes, and areas under the curve of gluten concentrations were calculated. The primary outcome, i.e. success rate of high dose AN-PEP defined as at least 50% gluten degradation compared to placebo in the duodenum, was achieved in 10 of 13 comparisons. In the stomach, gluten levels were reduced from 176.9 (median, interquartile range 73.5–357.8) to 22.0 (10.6–50.8, p = 0.001) in the high dose and to 25.4 μg × min/ml (16.4–43.7, p = 0.001) in the low dose. In the duodenum, gluten levels were reduced from 14.1 (8.3–124.7) in the placebo to 6.3 (3.5–19.8, p = 0.019) in the high dose and to 7.4 μg × min/ml in the low dose (3.8–12.0, p = 0.015). Thus even in a physiological meal setting, AN-PEP significantly degraded most gluten in the stomach before it entered the duodenum.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017
Keyword
Gluten
National Category
Nutrition and Dietetics
Research subject
Nutrition
Identifiers
urn:nbn:se:oru:diva-61493 (URN)10.1038/s41598-017-13587-7 (DOI)000412950900035 ()29026170 (PubMedID)2-s2.0-85031294461 (Scopus ID)
Note

Funding Agency:

DSM

Available from: 2017-10-12 Created: 2017-10-12 Last updated: 2017-11-10Bibliographically approved
König, J., Wells, J., Cani, P. D., García-Ródenas, C. L., MacDonald, T., Mercenier, A., . . . Brummer, R.-J. (2016). Human Intestinal Barrier Function in Health and Disease. Clinical and Translational Gastroenterology, 7(10), Article ID e196.
Open this publication in new window or tab >>Human Intestinal Barrier Function in Health and Disease
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2016 (English)In: Clinical and Translational Gastroenterology, ISSN 2155-384X, E-ISSN 2155-384X, Vol. 7, no 10, article id e196Article, review/survey (Refereed) Published
Abstract [en]

The gastrointestinal tract consists of an enormous surface area that is optimized to efficiently absorb nutrients, water, and electrolytes from food. At the same time, it needs to provide a tight barrier against the ingress of harmful substances, and protect against a reaction to omnipresent harmless compounds. A dysfunctional intestinal barrier is associated with various diseases and disorders. In this review, the role of intestinal permeability in common disorders such as infections with intestinal pathogens, inflammatory bowel disease, irritable bowel syndrome, obesity, celiac disease, non-celiac gluten sensitivity, and food allergies will be discussed. In addition, the effect of the frequently prescribed drugs proton pump inhibitors and non-steroidal anti-inflammatory drugs on intestinal permeability, as well as commonly used methods to assess barrier function will be reviewed.

Place, publisher, year, edition, pages
New York: Nature Publishing Group, 2016
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-53247 (URN)10.1038/ctg.2016.54 (DOI)000391816200003 ()27763627 (PubMedID)
Note

Funding Agency:

ILSI Europe Probiotics Task Force

Available from: 2016-10-25 Created: 2016-10-24 Last updated: 2017-11-29Bibliographically approved
König, J., Ganda-Mall, J.-P., Rangel, I., Edebol-Carlman, H. & Brummer, R. J. (2015). The Role of the Gut Microbiota in Brain Function. In: Koen Venema & Ana Paula do Carmo (Ed.), Probiotics and Prebiotics: Current Research and Future Trends. Poole, UK: Caister Academic Press.
Open this publication in new window or tab >>The Role of the Gut Microbiota in Brain Function
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2015 (English)In: Probiotics and Prebiotics: Current Research and Future Trends / [ed] Koen Venema & Ana Paula do Carmo, Poole, UK: Caister Academic Press, 2015Chapter in book (Refereed)
Place, publisher, year, edition, pages
Poole, UK: Caister Academic Press, 2015
National Category
Medical and Health Sciences Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:oru:diva-39860 (URN)978-1-910190-09-8 (ISBN)
Available from: 2014-12-17 Created: 2014-12-17 Last updated: 2017-10-17Bibliographically approved
König, J. & Brummer, R.-J. (2014). Alteration of the intestinal microbiota as a cause of and a potential therapeutic option in irritable bowel syndrome. Beneficial Microbes, 5(3), 247-261.
Open this publication in new window or tab >>Alteration of the intestinal microbiota as a cause of and a potential therapeutic option in irritable bowel syndrome
2014 (English)In: Beneficial Microbes, ISSN 1876-2883, E-ISSN 1876-2891, Vol. 5, no 3, p. 247-261Article, review/survey (Refereed) Published
Abstract [en]

The intestinal microbiota forms a complex ecosystem that is in close contact with its host and has an important impact on health. An increasing number of disorders are associated with disturbances in this ecosystem. Also patients suffering from irritable bowel syndrome (IBS) show an altered composition of their gut microbiota. IBS is a multifactorial chronic disorder characterised by various abdominal complaints and a worldwide prevalence of 10-20%. Even though its aetiology and pathophysiology are complex and not well understood, it is widely accepted that aberrations along the microbe-gut-brain axis are involved. In this review, it will be discussed how exogenous factors, e.g. antibiotics, can cause disbalance in the intestinal microbiota and thereby contribute to the development of IBS. In addition, several new IBS treatment options that aim at re-establishing a healthy, beneficial ecosystem will be described. These include antibiotics, probiotics, prebiotics and faecal transplantation.

Place, publisher, year, edition, pages
Wageningen Academic Publishers, 2014
Keyword
gut microbiota, antibiotics, probiotics, prebiotics, faecal transplantation
National Category
Nutrition and Dietetics Microbiology in the medical area
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-35263 (URN)10.3920/BM2013.0033 (DOI)000347675000003 ()24583610 (PubMedID)2-s2.0-84904070878 (Scopus ID)
Available from: 2014-06-05 Created: 2014-06-05 Last updated: 2018-01-11Bibliographically approved
König, J., Lang, I., Siwetz, M., Fröhlich, J. & Huppertz, B. (2014). Amnion-derived mesenchymal stromal cells show a mesenchymal-epithelial phenotype in culture.. Cell and Tissue Banking, 15(2), 193-198.
Open this publication in new window or tab >>Amnion-derived mesenchymal stromal cells show a mesenchymal-epithelial phenotype in culture.
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2014 (English)In: Cell and Tissue Banking, ISSN 1389-9333, E-ISSN 1573-6814, Vol. 15, no 2, p. 193-198Article in journal (Refereed) Published
Abstract [en]

The amnionic membrane is a rich source of multipotent mesenchymal stromal cells (hAMSC), which are readily available and show a potential use in regenerative medicine and tissue engineering. Before these cells can be applied clinically, careful characterization is necessary, especially as primary cells are known to change their phenotype in culture. We analyzed the mesenchymal phenotype of hAMSC at different stages after isolation using immunohistochemistry. Shortly after isolation (1 day), 92 % (±7 %) of the hAMSC expressed the mesenchymal marker vimentin, 2 % (±1 %) stained for the epithelial marker cytokeratin-7 and 5 % (±4 %) co-expressed these markers. After 5 days, the double positive cells slightly increased to 7 % (±3 %), while exclusive expression of cytokeratin-7 or vimentin remained unchanged (1 % ± 2 % and 92 % ± 1 %, respectively). After the first passage, all attached cells were vimentin-positive, while 54 % (±9 %) co-expressed cytokeratin-7 and vimentin. Thus, we conclude that under culture, hAMSC adopt a hybrid mesenchymal-epithelial phenotype. It is also essential to perform microscopical examination during the first days after isolation to detect contaminations with human amnion-derived epithelial cells in cultures of hAMSC.

Place, publisher, year, edition, pages
Dordrecht: Springer Netherlands, 2014
Keyword
Amnion; Placenta; Mesenchymal stromal cells; Cytokeratin; Vimentin
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-33863 (URN)10.1007/s10561-013-9415-8 (DOI)000337051300003 ()24326460 (PubMedID)2-s2.0-84902551356 (Scopus ID)
Note

Funding Agencies:

Franz-Lanyar-Foundation 339 349

Medical University of Graz

Available from: 2014-02-20 Created: 2014-02-20 Last updated: 2017-12-06Bibliographically approved
Kinzer, M., Hingerl, K., König, J., Reinisch, A., Strunk, D., Huppertz, B. & Lang, I. (2014). Mesenchymal stromal cells from the human placenta promote neovascularization in a mouse model in vivo.. Placenta, 35(7), 517-519.
Open this publication in new window or tab >>Mesenchymal stromal cells from the human placenta promote neovascularization in a mouse model in vivo.
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2014 (English)In: Placenta, ISSN 0143-4004, E-ISSN 1532-3102, Vol. 35, no 7, p. 517-519Article in journal (Refereed) Published
Abstract [en]

Cell transplantation is a promising strategy in regenerative medicine for revascularization of ischemic tissues. Based on our observation that placental mesenchymal stromal cells (PMSC) enhance endothelial cell viability in vitro via secretion of angiogenic factors, we asked whether PMSC support vascular growth in vivo. PMSC were isolated from amnion and placental endothelial cells (PLEC) from chorion and either separately or co-transplanted subcutaneously into immune-deficient mice. Co-transplantation resulted in a higher number of perfused human vessels (CD31+/vimentin+) containing mouse glycophorin A+ erythrocytes. Results indicate positive effects of PMSC on neovascularization in vivo, making them attractive candidates to create autologous PMSC/PLEC pairs for research and transplantation.

Place, publisher, year, edition, pages
London: W. B. Saunders Co Ltd, 2014
Keyword
Human placenta; Mesenchymal stromal cells; Vascularization; Angiogenesis; Mouse model
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-35282 (URN)10.1016/j.placenta.2014.04.004 (DOI)000337999500014 ()24814611 (PubMedID)2-s2.0-84902174777 (Scopus ID)
Available from: 2014-06-10 Created: 2014-06-10 Last updated: 2017-12-05Bibliographically approved
König, J. & Brummer, R.-J. (2014). Modulation of the gut ecosystem in irritable bowel syndrome. In: Gert Folkerts, Johan Garssen (Ed.), Pharma-Nutrition: an overview (pp. 55-73). Springer International Publishing.
Open this publication in new window or tab >>Modulation of the gut ecosystem in irritable bowel syndrome
2014 (English)In: Pharma-Nutrition: an overview / [ed] Gert Folkerts, Johan Garssen, Springer International Publishing , 2014, p. 55-73Chapter in book (Refereed)
Place, publisher, year, edition, pages
Springer International Publishing, 2014
Series
AAPS Advances in the Pharmaceutical Sciences Series, ISSN 2210-7371 ; 12
National Category
Pharmacology and Toxicology
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-38897 (URN)10.1007/978-3-319-06151-1_4 (DOI)000343292300004 ()978-3-319-06151-1 (ISBN)978-3-319-06150-4 (ISBN)
Available from: 2014-11-24 Created: 2014-11-21 Last updated: 2018-01-11Bibliographically approved
König, J., Weiss, G., Rossi, D., Wankhammer, K., Reinisch, A., Kinzer, M., . . . Lang, I. (2014). Placental Mesenchymal Stromal Cells Derived from Blood Vessels or Avascular Tissues: What Is the Better Choice to Support Endothelial Cell Function?. Stem Cells and Development, 24(1), 115-131.
Open this publication in new window or tab >>Placental Mesenchymal Stromal Cells Derived from Blood Vessels or Avascular Tissues: What Is the Better Choice to Support Endothelial Cell Function?
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2014 (English)In: Stem Cells and Development, ISSN 1547-3287, E-ISSN 1557-8534, Vol. 24, no 1, p. 115-131Article in journal (Refereed) Published
Abstract [en]

Mesenchymal stromal cells (MSCs) are promising tools for therapeutic revascularization of ischemic tissues and for support of vessel formation in engineered tissue constructs. Recently, we could show that avascular-derived MSCs from placental amnion release soluble factors that exhibit survival-enhancing effects on endothelial cells (ECs). We hypothesize that MSCs derived from placental blood vessels might have even more potent angiogenic effects. Therefore, we isolated and characterized MSCs from placental chorionic blood vessels (bv-MSCs) and tested their angiogenic potential in comparison to amnion-derived avascular MSCs (av-MSCs). bv-MSCs express a very similar surface marker profile compared with av-MSCs and could be differentiated toward the adipogenic and osteogenic lineages. bv-MSCs exert immunosuppressive properties on peripheral blood mononuclear cells, suggesting that they are suitable for cell transplantation settings. Conditioned medium (Cdm) from av-MSCs and bv-MSCs significantly enhanced EC viability, whereas only Cdm from bv-MSCs significantly increased EC migration and network formation (Matrigel assay). Angiogenesis array analysis of av- and bv-MSC-Cdm revealed a similar secretion pattern of angiogenic factors, including angiogenin, interleukins-6 and -8, and tissue inhibitors of matrix metalloproteinase-1 and 2. Enzyme-linked immunosorbent assay analysis showed that, in contrast to av-MSCs, bv-MSCs secreted vascular endothelial growth factor. In direct coculture with bv-MSCs, ECs showed a significantly increased formation of vessel-like structures compared with av-MSCs. With regard to therapeutic treatment, bv-MSCs and particularly their Cdm might be valuable to stimulate angiogenesis especially in ischemic tissues. av-MSCs and their Cdm could be beneficial in conditions when it is required to promote the survival and stabilization of blood vessels without the risk of unmeant angiogenesis.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:oru:diva-38531 (URN)10.1089/scd.2014.0115 (DOI)000346839900010 ()25244528 (PubMedID)2-s2.0-84919794448 (Scopus ID)
Available from: 2014-11-11 Created: 2014-11-11 Last updated: 2017-09-27Bibliographically approved
König, J., Rangel, I. & Brummer, R. J. (2013). The Role of Lactic Acid Bacteria in the Pathophysiology and Treatment of Irritable Bowel Syndrome (IBS). Food and Nutrition Sciences, 4(11), 27-39.
Open this publication in new window or tab >>The Role of Lactic Acid Bacteria in the Pathophysiology and Treatment of Irritable Bowel Syndrome (IBS)
2013 (English)In: Food and Nutrition Sciences, ISSN 2157-944X, E-ISSN 2157-9458, Vol. 4, no 11, p. 27-39Article in journal (Refereed) Published
Abstract [en]

Irritable bowel syndrome (IBS) is a multifactorial chronic disorder characterized by various abdominal complaints and a worldwide prevalence of 10% - 20%. Although its etiology and pathophysiology are complex and still not completely understood, aberrations along the microbe-gut-brain axis are known to play a central role. IBS is characterized by inter-related alterations in intestinal barrier function, gut microbe composition, immune activation, afferent sensory signaling and brain activity. Pharmaceutical treatment is generally ineffective and, hence, most therapeutic strategies are based on non-drug approaches. A promising option is the administration of probiotics, in which lactic acid bacteria strains are considered specifically beneficial. This review aims to provide a concise, although comprehensive, overview of the role of lactic acid bacteria in the pathophysiology and treatment of IBS.

Keyword
Irritable Bowel Syndrome (IBS); Probiotics; Lactic Acid Bacteria; Gut-Brain Axis
National Category
Pharmacology and Toxicology
Research subject
Medicine; Medicine
Identifiers
urn:nbn:se:oru:diva-33871 (URN)10.4236/fns.2013.411A005 (DOI)
Available from: 2014-02-20 Created: 2014-02-20 Last updated: 2018-01-11Bibliographically approved
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