Original ResearchFull Report: Basic and Translational—Alimentary TractPaneth Cell Defects Induce Microbiota Dysbiosis in Mice and Promote Visceral Hypersensitivity
Section snippets
Mouse Models
All experimental protocols described in this study were approved by the local Animal Care Use Committee (Comité d'Ethique de Pharmacologie-Toxicologie de Toulouse - Midi-Pyrénées, France) registered as N°86 at the Ministry of Research and Higher Education (N° 0029/SMVT), and conducted in accordance with the European directive 2010/63/UE. All experiments were performed on Day (D) 50 mice. More details are in Supplementary Materials and Methods.
MS Protocol
To minimize cannibalism induced by perinatal stress,
MS in Mice Induced Visceral Hypersensitivity
As a first step in this study, we established a MS model in C3H/HeN mice.
No weight differences were observed among groups of mice from D2 to D50.
The electromyographic (EMG) response to graded colorectal distension was used as an index of visceral sensitivity. MS led to allodynia at day 50 in response to colorectal distension with low volume (P = .028 at 0.02 mL; P = .007 at 0.04 mL; P = .003 at 0.06 mL compared with control; Figure 1A; representative EMG recording is presented in Supplementary
Discussion
Paneth cells producing enteric antimicrobial peptides are important players in small intestine innate immunity. In mice, Paneth cells appear only 2 weeks after birth31, 32, 33, 34 and they are sensitive to environmental factors including enteric infections35, 36 and early life stress.22 Indeed, MS performed in rats decreases epithelial secretory cell lineages number including Paneth cells.22 Furthermore, neonatal MS induces visceral hypersensitivity in adulthood.23 This observation questioned a
Acknowledgments
The authors gratefully acknowledge Yannick Lippi and Claire Naylies from Transcriptomic impact of Xenobiotics platform for technical assistance for microbiota analysis.
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Conflicts of interest The authors disclose no conflicts.