title: Stereomicroscopic 3D-pattern profiling of murine and human intestinal inflammation reveals unique structural phenotypes.
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.
authors.affiliation: Division of Gastroenterology and Liver Disease, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Rodriguez-Palacios
authors.affiliation: Division of Gastroenterology and Liver Disease, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kodani
authors.affiliation: Division of Gastroenterology and Liver Disease, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Kaydo
authors.affiliation: Division of Gastroenterology and Liver Disease, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Davide
authors.initials: D
authors.lastname: Pietropaoli
authors.affiliation: Division of Gastroenterology and Liver Disease, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Daniele
authors.initials: D
authors.lastname: Corridoni
authors.affiliation: Department of Visual Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Howell
authors.affiliation: 1] Division of Gastroenterology and Liver Disease, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA [2] Department of Digestive Health Institute, University Hospitals Case Medical Center, Cleveland, Ohio 44106, USA.
authors.forename: Jeffry
authors.initials: J
authors.lastname: Katz
authors.affiliation: 1] Department of Digestive Health Institute, University Hospitals Case Medical Center, Cleveland, Ohio 44106, USA [2] Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Xin
authors.affiliation: 1] Division of Gastroenterology and Liver Disease, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA [2] Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Theresa T
authors.initials: TT
authors.lastname: Pizarro
authors.affiliation: 1] Division of Gastroenterology and Liver Disease, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA [2] Department of Digestive Health Institute, University Hospitals Case Medical Center, Cleveland, Ohio 44106, USA [3] Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Fabio
authors.initials: F
authors.lastname: Cominelli
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D007410:Intestinal Diseases / Q000139:chemically induced / Q000235:genetics / Q000382:microbiology / Q000473:pathology*; D007413:Intestinal Mucosa / Q000473:pathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008853:Microscopy / Q000379:methods*