Putative intestinal stem cell density in controls and in CD patients. a 71% of non-coeliac subjects had one CD133+ epithelial cell every two crypts and 29% had one CD133+ cell per crypt; similar results were obtained for Lgr5+ intestinal cells. Therefore, we defined as “normal” a putative ISC density of 0.5–1 CD133+ or Lgr5+ cell/crypt. b At baseline, 55% of CD patients presented with reduced CD133+ and Lgr5+ intestinal cells (less than one every two crypts), whereas only 45% had a normal CD133/Lgr5+ representation. We defined as “ISC depletion” an ISC density <0.5 CD133+/Lgr5+ cell/crypt. Upon dietary intervention, the number of CD133+ and Lgr5+ epithelial cells significantly increased at 6 months and reached a peak at 12 months of GFD, when in some patients the putative ISC density was augmented versus controls. We defined a density >1 cell/crypt as “ISC amplification”. After 24 months of GFD, the CD133/Lgr5+ cell density was similar in patients and controls. Panels c through f show representative immunohistochemistry pictures for CD133+ putative ISC (arrows) in CD patients at baseline (c, higher magnification in d), at 12 months (e) and at 24 months (f) of GFD.