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Stereomicroscopic 3D-pattern profiling of murine and human intestinal inflammation reveals unique structural phenotypes

Alex Rodriguez-Palacios (), Tomohiro Kodani, Lindsey Kaydo, Davide Pietropaoli, Daniele Corridoni, Scott Howell, Jeffry Katz, Wei Xin, Theresa T. Pizarro and Fabio Cominelli ()
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Alex Rodriguez-Palacios: Case Western Reserve University School of Medicine
Tomohiro Kodani: Case Western Reserve University School of Medicine
Lindsey Kaydo: Case Western Reserve University School of Medicine
Davide Pietropaoli: Case Western Reserve University School of Medicine
Daniele Corridoni: Case Western Reserve University School of Medicine
Scott Howell: Case Western Reserve University School of Medicine
Jeffry Katz: Case Western Reserve University School of Medicine
Wei Xin: University Hospitals Case Medical Center
Theresa T. Pizarro: Case Western Reserve University School of Medicine
Fabio Cominelli: Case Western Reserve University School of Medicine

Nature Communications, 2015, vol. 6, issue 1, 1-16

Abstract: Abstract Histology is fundamental to assess two-dimensional intestinal inflammation; however, inflammatory bowel diseases (IBDs) are often indistinguishable microscopically on the basis of mucosal biopsies. Here, we use stereomicroscopy (SM) to rapidly profile the entire intestinal topography and assess inflammation. We examine the mucosal surface of >700 mice (encompassing >16 strains and various IBD-models), create a profiling catalogue of 3D-stereomicroscopic abnormalities and demonstrate that mice with comparable histological scores display unique sub-clusters of 3D-structure-patterns of IBD pathology, which we call 3D-stereoenterotypes, and which are otherwise indiscernible histologically. We show that two ileal IBD-stereoenterotypes (‘cobblestones’ versus ‘villous mini-aggregation’) cluster separately within two distinct mouse lines of spontaneous ileitis, suggesting that host genetics drive unique and divergent inflammatory 3D-structural patterns in the gut. In humans, stereomicroscopy reveals ‘liquefaction’ lesions and hierarchical fistulous complexes, enriched with clostridia/segmented filamentous bacteria, running under healthy mucosa in Crohn’s disease. We suggest that stereomicroscopic (3D-SMAPgut) profiling can be easily implemented and enable the comprehensive study of inflammatory 3D structures, genetics and flora in IBD.

Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8577

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DOI: 10.1038/ncomms8577

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