Early life antibiotic exposure affects pancreatic islet development and metabolic regulation

Abstract

Childhood antibiotic exposure has been recently linked with increased risk of metabolic disease later in life. A better understanding of this association would potentially provide strategies to reduce the childhood chronic disease epidemic. Therefore, we explored the underlying mechanisms using a swine model that better mimics human infants than rodents, and demonstrated that early life antibiotic exposure affects glucose metabolism 5 weeks after antibiotic withdrawal, which was associated with changes in pancreatic development. Antibiotics exerted a transient impact on postnatal gut microbiota colonization and microbial metabolite production, yet changes in the expression of key genes involved in short-chain fatty acid signaling and pancreatic development were detected in later life. These findings suggest a programming effect of early life antibiotic exposure that merits further investigation.

Long‐term effect of early antibiotic exposure on amino acid profiles and gene expression of transporters and receptors in the small intestinal mucosa of growing pigs with different dietary protein levels

“…In mice, some previous studies have indicated that low‐dose antibiotic exposure in early life may have a long‐term effect on host metabolism . In pigs, antibiotic exposure in early life altered glucose metabolism 35 days after antibiotic withdrawal . Our studies also showed that in‐feed antibiotics treatment in early life had a long‐term effect on serum urea level and fecal AA fermentation products .…”

Establishing a model for childhood obesity in adolescent pigs

“…cDNA was synthesized using Maxima First Strand cDNA Synthesis Kit (Thermo Fisher Scientific). Quantitative real‐time polymerase chain reaction (PCR) was performed as previously described using primers listed in Table S2. Data were analysed using the comparative CT (2 −ΔΔCT ) method as described previously using glyceraldehyde phosphate dehydrogenase as the housekeeping gene.…”

“…On the other hand, increased propensity for obesity and metabolic disease is now associated with early life antibiotics . In a previous study, early life antibiotic exposure in piglets altered metabolic regulation with a standard diet, however failed to change fat deposition . It was expected that the lack of difference in adiposity was due to the absence of a dietary challenge.…”

Prevotella in Pigs: The Positive and Negative Associations with Production and Health

“…Perturbation of well-balanced (homeostatic) microbial populations is known to have long-term adverse effects on host physiology [ 4 , 5 , 6 , 7 ]. For example, antibiotic perturbation of the piglet GIT microbiota in early life has been shown to be associated with impaired gut microbiome development and altered metabolic regulation later in life [ 8 ]. Furthermore, compromised resistance against infectious agents has been reported in pigs raised under more hygienic and controlled conditions [ 9 ].…”