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Commensal bacteria ...
Commensal bacteria weaken the intestinal barrier by suppressing epithelial neuropilin-1 and Hedgehog signaling
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Pontarollo, G. (author)
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Kollar, B. (author)
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Mann, A. (author)
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show more...
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Khuu, M. P. (author)
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Kiouptsi, K. (author)
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Bayer, F. (author)
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Brandao, I. (author)
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Zinina, V. V. (author)
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Hahlbrock, J. (author)
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Malinarich, F. (author)
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Mimmler, M. (author)
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Bhushan, S. (author)
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Marini, F. (author)
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Ruf, W. (author)
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Belheouane, M. (author)
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Baines, J. F. (author)
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Endres, K. (author)
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Reba, S. M. (author)
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Raker, V. K. (author)
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Deppermann, C. (author)
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Welsch, C. (author)
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Bosmann, M. (author)
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Soshnikova, N. (author)
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Chassaing, B. (author)
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- Bergentall, Mattias (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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Sommer, F. (author)
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- Bäckhed, Fredrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Center for Cardiovascular and Metabolic Research (CMR),Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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Reinhardt, C. (author)
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: Nature Metabolism. - 2522-5812. ; 5:7, s. 1174-87
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Abstract
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- The gut microbiota influences intestinal barrier integrity through mechanisms that are incompletely understood. Here we show that the commensal microbiota weakens the intestinal barrier by suppressing epithelial neuropilin-1 (NRP1) and Hedgehog (Hh) signaling. Microbial colonization of germ-free mice dampens signaling of the intestinal Hh pathway through epithelial Toll-like receptor (TLR)-2, resulting in decreased epithelial NRP1 protein levels. Following activation via TLR2/TLR6, epithelial NRP1, a positive-feedback regulator of Hh signaling, is lysosomally degraded. Conversely, elevated epithelial NRP1 levels in germ-free mice are associated with a strengthened gut barrier. Functionally, intestinal epithelial cell-specific Nrp1 deficiency (Nrp1(& UDelta;IEC)) results in decreased Hh pathway activity and a weakened gut barrier. In addition, Nrp1(& UDelta;IEC) mice have a reduced density of capillary networks in their small intestinal villus structures. Collectively, our results reveal a role for the commensal microbiota and epithelial NRP1 signaling in the regulation of intestinal barrier function through postnatal control of Hh signaling. A molecular mechanism is revealed through which commensal bacteria modulate intestinal epithelial barrier function.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Pontarollo, G.
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Kollar, B.
-
Mann, A.
-
Khuu, M. P.
-
Kiouptsi, K.
-
Bayer, F.
-
show more...
-
Brandao, I.
-
Zinina, V. V.
-
Hahlbrock, J.
-
Malinarich, F.
-
Mimmler, M.
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Bhushan, S.
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Marini, F.
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Ruf, W.
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Belheouane, M.
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Baines, J. F.
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Endres, K.
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Reba, S. M.
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Raker, V. K.
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Deppermann, C.
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Welsch, C.
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Bosmann, M.
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Soshnikova, N.
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Chassaing, B.
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Bergentall, Matt ...
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Sommer, F.
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Bäckhed, Fredrik ...
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Reinhardt, C.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Nature Metabolis ...
- By the university
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University of Gothenburg