ABSTRACT
Intestinal tuft cells have been shown to induce type 2 immune responses during viable parasite infections, but whether oral supplementation with a parasitic exudate is able to promote type 2 immune responses that have been shown to positively regulate obesogenic metabolic processes is yet unresolved. High-fat fed mice were gavaged with pseudocoelomic fluid (PCF) derived from the helminth Ascaris suum or saline thrice a week during weeks 5-9, followed by examination of intestinal tuft cell activity, immune, and metabolic parameters. Helminth PCF upregulated expression of distinct genes in small intestinal tuft cells, including genes involved in regulation of RUNX1 and organic cation transporters. Helminth PCF also enhanced levels of innate lymphoid cells in the ileum, and eosinophils in epididymal white adipose tissue (eWAT). Network analyses revealed two distinct immunometabolic cues affected by oral helminth PCF in high-fat fed mice: one coupling the small intestinal tuft cell responses to the fat-to-lean mass ratio and a second coupling eosinophils in eWAT to general regulation of body fat mass. Our findings point to specific mechanisms by which oral supplementation with helminth PCF may translate into systems-wide effects linking to reduced body and fat mass gain in mice during high-fat feeding.
Subject(s)
Helminths , Immunity, Innate , Mice , Animals , Cues , Lymphocytes , Adipose Tissue , Administration, OralABSTRACT
The objective was to study the effects of weaning in week 5 (W5) vs. week 4 (W4), as well as liquid (LF) vs. dry feed (DF), on growth performance, disaccharidase activity and nutrient transporter expression after weaning. The experiment included 12,923 pigs fed LF or DF in the pre-weaning period and a subpopulation of 15 pigs from each group, W4DF, W4LF, W5DF and W5LF, which were weighed and euthanized five days after weaning. The proximal part of the small intestine was analyzed for maltase, lactase and sucrase activity and the expression of SGLT-1, GLUT-2 and PepT-1. Pigs fed LF displayed less maltase activity (2100 vs. 2729 U/mg protein, p < 0.05) but an increased expression of SGLT-1 (∆Ct: 5.22 vs. 6.21, p = 0.01). Pigs weaned in W5 were heavier than those weaned in W4 (9.35 vs. 7.11 kg BW, p ≤ 0.05), and pigs fed LF were heavier than those fed DF (8.55 vs. 7.91 kg BW, p ≤ 0.05) five days after weaning in the subpopulation. LF pigs (21.8 kg) were heavier than DF pigs (20.6 kg) (SE 0.108, p < 0.0001), and W4 pigs (21.0 kg) were lighter than W5 pigs (21.5 kg) (SE 0.108, p = 0.01) at nine weeks. LF increased weight gain in the early post-weaning period and at nine weeks, although this was apparently not explained by accelerated gut maturation.