Perinatal antibiotic treatment of sows affects intestinal barrier and immune system in offspring
Résumé
Maternal environment during pregnancy and lactation influences health of the offspring and its microbiota.
Immune tolerance to dietary and commensal microbiota antigens develops early in life. Our aim was to
investigate intestinal barrier and local immune response to LPS in piglets deriving from sows whose
microbiota was manipulated by antibiotics. Long-term consequences on gut adaptation to a high fat diet were
examined in growing offspring. Sows were given amoxicillin (AMX; 40 mg/kg/d) per os (n=11 AMX) or
not (n=12 CTL) from 10 d before to 21 d after parturition. One piglet per litter was sacrificed at post-natal
day (PND) 14, 21 and after weaning at PND42. The remaining ones were given either a low fat (LF) or a
high fat (HF) diet (to enhance LPS epithelial passage) from PND140 to 169. At PND14, ileal permeability
was greater in AMX than CTL piglets (P<0.05). At PND21, no increase in proliferation of lamina propria
mononuclear cells (LPMCs) in response to LPS was noticed, demonstrating LPMC tolerance in both
groups. Analysis of laser-captured enterocyte transcriptome indicated specific changes in immune response
pathways. Especially differential expression of BFIFB1, HPSE and FSTL4 genes demonstrated stimulation
of proinflammatory activity, corroborating the increased TNFα secretion in response to LPS observed in
LPMCs of AMX piglets. At PND42 gene analysis suggested a repression of the immune response towards
weaning-induced stress in AMX piglets. At PND169, HF diet increased ileal permeability in CTL offspring
only. By contrast, ileal explant sensitivity to LPS was altered in HF pigs, especially in AMX-HF pigs.
Manipulating maternal microbiota modified offspring ileal barrier and immune response to LPS during the
neonatal period. It also influenced the intestinal adaptive response to a HF diet in adult offspring, suggesting
microbiota-related imprinting.