Biosecurity standards and farming practices have profoundly changed the way domestic animals interact with the environment and themselves. Farm intensification processes resemble the lifestyle changes that humans underwent post industrialization, which have been linked to the occurrence of immune-mediated and metabolic disorders. Modern rearing practices reduce maternal and offspring interactions, promote changes in diet, restrict animals indoors, and rely on the use of antibiotics and vaccines to maintain animal health. These practices may hinder the proper colonization of the gastrointestinal tract with commensal organisms that co-evolved with livestock species. The gut microbiota aids nutrient digestion, stimulates immune and intestinal development and maturation, and promotes the competitive exclusion of pathogens. Microbial colonization in early life is critical for host metabolic and immune programming, and disruptions of gut microbial community stability can lead to development of metabolic and immune disorders seen at later stages of life. Identifying how farming practices influence microbial composition and the potential effects on host physiology, metabolism, and disease resistance is necessary to guide intervention strategies to promote beneficial microbial–host interactions, and improve animal health and performance.

SummaryObjectiveRising worldwide prevalence of obesity and metabolic diseases in children has accentuated the importance of developing prevention and management strategies. The objective of this study was to establish a model for childhood obesity using high‐fat feeding of adolescent pigs, as pigs have a longer developmental period and are physiologically more similar to humans than rodents.MethodsCrossbred pigs were fed a high‐fat diet (HFD) or low‐fat diet (n = 6/treatment) from postnatal day 49 to 84. On postnatal day 84, an oral glucose tolerance test was performed, jugular blood sampled to determine lipopolysaccharide levels and plasma lipids, intestinal digesta collected to characterize microbial and metabolite composition and back fat and intestinal tissue assayed for gene expression.ResultsFive‐week HFD increased weight gain and back fat thickness, caused dyslipidaemia and impaired glucose tolerance and increased expression of genes in back fat suggesting inflammation. HFD pigs had distinct proximal colon microbiota with 48% reduction (P < 0.05) in Bacteroidetes and increased expression of pro‐inflammatory genes interleukin‐18 and tumour necrosis factor in ileum (P < 0.05).ConclusionsThese findings indicate that adolescent pigs should be considered a suitable model for childhood obesity, because short‐term HFD feeding is sufficient to induce obesity and glucose intolerance, recapitulating disease characteristics in adolescent pigs.

No abstract

Neonatal antibiotics administered to human infants initiate gut microbiota dysbiosis that may have long-term effects on body weight (BW) and metabolism. We examined antibiotic-induced adaptations in pancreatic islets of the piglet, a well-accepted model of human infant microbiota and pancreas development. Neonatal piglets randomized to amoxicillin (30mg/kg BW/day; n=7, ANTI) or placebo (vehicle control; n=7, CON) from postnatal day (PND)0-13 were euthanized at PND7, 14 and 49. The metabolic phenotype along with functional, immunohistological and transcriptional phenotypes of the pancreatic islets were studied. The gut microbiome was characterized by 16S sequencing and microbial metabolites and microbiome-sensitive host molecules were measured. Compared with CON, ANTI PND7 piglets had elevated transcripts of genes involved in GLP-1 synthesis or signaling in islets (p<0.05) coinciding with higher plasma GLP-1 (p=0.11), along with increased Tnf (p<0.05) and Npg1 (p<0.05). Antibiotic-induced relative increases in Escherichia, Coprococcus, Ruminoccocus, Dehalobacterium and Oscillospira of the ileal microbiome at PND7 normalized after antibiotic withdrawal. In ANTI islets at PND14, the expression of key regulators Pdx1, Igf2 and Tcf7l2 was down-regulated, preceding a 40% reduction of b-cell area (p<0.01) and islet insulin content at PND49 (p<0.05). At PND49, a 2-fold elevated plasma insulin concentration (p=0.07) was observed in ANTI compared with CON. We conclude that antibiotic treatment of neonatal piglets elicits gut microbial changes accompanied by phasic alterations in key regulatory genes in pancreatic islets at PND7 and 14. By PND49, reduced b-cell area and islet insulin content were accompanied by elevated non-fasted insulin despite normoglycemia, indicative of islet stress.