ABSTRACT: It was recently shown that fasting alters the composition of microbial communities residing in the distal intestinal tract of animals representing five classes of vertebrates [i.e., fishes (tilapia), amphibians (toads), reptiles (leopard geckos), birds (quail), and mammals (mice)]. In this study, we tested the hypothesis that the extent of tissue reorganization in the fasted distal intestine was correlated with the observed changes in enteric microbial diversity. Segments of intestine adjacent to those used for the microbiota study were examined histologically to quantify cross-sectional and mucosal surface areas and thicknesses of mucosa, submucosa, and tunica muscularis. We found no fasting-induced differences in the morphology of distal intestines of the mice (3 days), quail (7 days), or geckos (28 days). The toads, which exhibited a general increase in phylogenetic diversity of their enteric microbiota with fasting, also exhibited reduced mucosal circumference at 14 and 21 days of fasting. Tilapia showed increased phylogenetic diversity of their enteric microbiota, and showed a thickened tunica muscularis at 21 days of fasting; but this morphological change was not related to microbial diversity or absorptive surface area, and thus, is unlikely to functionally match the changes in their microbiome. Given that fasting caused significant increases and reductions in the enteric microbial diversity of mice and quail, respectively, but no detectable changes in distal intestine morphology, we conclude that reorganization is not the primary factor shaping changes in microbial diversity within the fasted colon, and the observed modest structural changes are more related to the fasted state. Anat Rec, 300:2208-2219, 2017. © 2017 Wiley Periodicals, Inc.