Fetal exposure to maternal inflammation does not affect postnatal development of genetically-driven ileitis and colitis.
BACKGROUND
Chronic inflammatory disorders have been increasing in incidence over the past decades following geographical patterns of industrialization. Fetal exposure to maternal inflammation may alter organ functions and the offspring's disease risk. We studied the development of genetically-driven ileitis and colitis in response to maternal inflammation using mouse models.


METHODS
Disease susceptible (TnfΔARE/+ and IL10-/-) and disease-free (Tnf+/+ and IL10-/+) offspring were raised in inflamed and non-inflamed dams. Ileal, caecal and colonic pathology was evaluated in the offspring at 8 or 12 weeks of age. Ly6G-positive cells in inflamed sections from the distal ileum and distal colon were analysed by immunofluorescence microscopy. Gene expression of pro-inflammatory cytokines was measured in whole tissue specimens by quantitative PCR. Microarray analyses were performed on laser microdissected intestinal epithelium. Caecal bacterial communities were assessed by Illumina sequencing of 16S rRNA amplicons.


RESULTS
Disease severity, the number of infiltrated neutrophils as well as Tnf and Il12p40 mRNA expression were independent of maternal inflammation in the offspring of mouse models for ileitis (TnfΔARE/+) and colitis (IL10-/-). Although TNF-driven maternal inflammation regulated 2,174 (wild type) and 3,345 (TnfΔARE/+) genes in the fetal epithelium, prenatal gene expression patterns were completely overwritten after birth. In addition, co-housing experiments revealed no change in phylogenetic diversity of the offspring's caecal microbiota in response to maternal inflammation. This is independent of the offspring's genotype before and after the onset of tissue pathology.


CONCLUSIONS
Disease risk and activity in mouse models of chronic ileitis and colitis was independent of the fetal exposure to maternal inflammation. Likewise, maternal inflammation did not alter the diversity and composition of offspring's caecal microbiota, clearly demonstrating that changes of the gene expression program in the fetal gut epithelium were not relevant for the development of chronic inflammatory disorders in the gut.
Chair of Nutrition and Immunology, Technische Universität München, Freising- Weihenstephan, Bavaria, Germany; ZIEL - Research Center for Nutrition and Food Sciences, Freising-Weihenstephan, Bavaria, Germany.
Jana
J
Hemmerling
Chair of Nutrition and Immunology, Technische Universität München, Freising- Weihenstephan, Bavaria, Germany; ZIEL - Research Center for Nutrition and Food Sciences, Freising-Weihenstephan, Bavaria, Germany.
Katharina
K
Heller
Chair of Nutrition and Immunology, Technische Universität München, Freising- Weihenstephan, Bavaria, Germany; ZIEL - Research Center for Nutrition and Food Sciences, Freising-Weihenstephan, Bavaria, Germany.
Gabriele
G
Hörmannsperger
Chair of Nutrition and Immunology, Technische Universität München, Freising- Weihenstephan, Bavaria, Germany; ZIEL - Research Center for Nutrition and Food Sciences, Freising-Weihenstephan, Bavaria, Germany.
Monika
M
Bazanella
Chair of Nutrition and Immunology, Technische Universität München, Freising- Weihenstephan, Bavaria, Germany; ZIEL - Research Center for Nutrition and Food Sciences, Freising-Weihenstephan, Bavaria, Germany.
Thomas
T
Clavel
Biomedical Sciences Research Centre, Institute for Immunology, Alexander Fleming, Vari, Athens, Greece.
George
G
Kollias
Chair of Nutrition and Immunology, Technische Universität München, Freising- Weihenstephan, Bavaria, Germany; ZIEL - Research Center for Nutrition and Food Sciences, Freising-Weihenstephan, Bavaria, Germany.
Dirk
D
Haller
D000818:Animals; D003092:Colitis / Q000235:genetics* / Q000473:pathology*; D017931:DNA Primers; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007079:Ileitis / Q000235:genetics* / Q000473:pathology*; D007249:Inflammation / Q000473:pathology*; D016753:Interleukin-10 / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012336:RNA, Ribosomal, 16S / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D017931:DNA Primers; D012336:RNA, Ribosomal, 16S; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10