ABSTRACT
Coprophagia by suckling rabbits, i.e. ingestion of feces from their mother, reduces mortality after weaning. We hypothesized that this beneficial effect of coprophagia is immune-mediated at the intestinal level. Therefore, this study investigated immune development after weaning by analyzing the ileal transcriptome at day 35 and 49 in rabbits with differential access to coprophagia in early life. Rabbit pups had access between day 1 and 15 to (i) no feces (NF) or (ii) feces from unrelated does (Foreign Feces, FF) or (iii) feces from unrelated does treated with antibiotics (FFab). 350 genes were differentially expressed between day 35 and day 49 in suckling rabbits with access to coprophagia. These genes coded for antimicrobial peptides, a mucin, cytokines and chemokines, pattern recognition receptors, proteins involved in immunoglobulin A secretion and in interferon signaling pathway. Strikingly, prevention of coprophagia or access to feces from antibiotic-treated does in early life blunted immune development between day 35 et 49 in the ileum of rabbits. Thus, coprophagia might be crucial for the maturation of intestinal immunity in rabbits and could explain why this behavior improves survival.
Subject(s)
Coprophagia , Ileum , Animals , Rabbits , Weaning , Feces , Anti-Bacterial AgentsABSTRACT
Neonatal period is characterized by an immature intestinal barrier. Scattered evidence suggests that early life stressful events induce long lasting alterations of intestinal homeostasis mimicking Irritable Bowel Syndrome (IBS). Those observations highlighting defect of intestinal barrier by early life stress questioned its potential role as a risk factor for gastrointestinal disorders such as colitis and infections. In this study, we aimed to analyze if maternal separation (MS) in mice mimicks IBS main features. We next addressed whether MS could trigger or exacerbate colitis in genetically predisposed mice and/or enhance susceptibility to gastrointestinal infections in wild type mice. MS induced main features of IBS in adult wild type male mice i.e. intestinal hyperpermeability, visceral hypersensitivity, microbiota dysbiosis, bile acid malabsorption and low grade inflammation in intestine associated with a defect of Paneth cells and the ILC3 population. This breach in mucosal barrier functions in adults was associated with a systemic IgG response against commensal E. coli and increased IFNγ secretion by splenocytes. However, in IL10-/- mice, MS did not trigger nor worsen colitis. Furthermore, wild type mice submitted to MS did not show increase susceptibility to gastrointestinal infections (S. Typhimurium, L. monocytogenes or T. gondii) compared to controls. Altogether, our results identify MS in mice as a good experimental model for IBS mimicking all the main features. In addition, early life stress, even though it has long lasting consequences on intestinal homeostasis, does not constitute a facilitating factor to colitis in predisposed individuals nor to gastrointestinal infections in wild type mice.
Subject(s)
Irritable Bowel Syndrome/metabolism , Stress, Psychological/metabolism , Animals , Colitis/etiology , Colitis/pathology , Disease Models, Animal , Dysbiosis , Escherichia coli/pathogenicity , Gastrointestinal Diseases/microbiology , Gastrointestinal Diseases/physiopathology , Gastrointestinal Microbiome/physiology , Genetic Predisposition to Disease/genetics , Inflammation , Intestinal Mucosa/microbiology , Intestinal Mucosa/physiology , Intestines/microbiology , Intestines/physiology , Irritable Bowel Syndrome/physiopathology , Male , Maternal Deprivation , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Microbiota/physiology , Stress, Psychological/physiopathologyABSTRACT
O gênero Croton possui seiscentas espécies e é originário de regiões tropicais. Croton gnaphelil é conhecida no sul do Brasil como infalivina, sendo utilizada popularmente nos distúrbios hepáticos. A substância majoritária presente nas partes aéreas desta planta foi isolada e identificada através de métodos espectroscópicos, sendo identificada como um glicosídeo acilado, o canferol‑3‑O‑(6"‑O‑p‑cumaroil)‑β‑D‑glicopyranose, também chamado de tilirosídeo.
Croton genus comprises six hundred species being native in tropical forests. Croton gnaphalliis popularly known as "infalivina" in South of Brazil and it is traditionally used for hepatic disorders. The major compound from aerial parts of this plant was isolated and its structure elucidated through spectroscopic analysis. It was identified as an acylglycoside, kaempferol‑3‑O‑(6"‑O‑p‑coumaroyl)‑ β ‑D‑glucopyranoside, known as tiliroside.
