Birck MM, Nguyen DN, Cilieborg MS, Kamal SS, Nielsen DS, Damborg P, Olsen JE, Lauridsen C, Sangild PT, Thymann T. Enteral but not parenteral antibiotics enhance gut function and prevent necrotizing enterocolitis in formula-fed newborn preterm pigs. Am J Physiol Gastrointest Liver Physiol 310: G323-G333, 2016. First published December 17, 2015 doi:10.1152/ajpgi.00392.2015.-Preterm infants are susceptible to infection and necrotizing enterocolitis (NEC) and are often treated with antibiotics. Simultaneous administration of enteral and parenteral antibiotics during the first days after preterm birth prevents formula-induced NEC lesions in pigs, but it is unknown which administration route is most effective. We hypothesized that only enteral antibiotics suppress gut bacterial colonization and NEC progression in formula-fed preterm pigs. Caesarean-delivered preterm pigs (90 -92% of gestation) were fed increasing amounts of infant formula from birth to day 5 and given saline (CON) or antibiotics (ampicillin, gentamicin, and metronidazole) via the enteral (ENT) or parenteral (PAR) route (n ϭ 16 -17). NEC lesions, intestinal morphology, function, microbiology, and inflammatory mediators were evaluated. NEC lesions were completely prevented in ENT pigs, whereas there were high incidences of mild NEC lesions (59 -63%) in CON and PAR pigs (P Ͻ 0.001). ENT pigs had elevated intestinal weight, villus height/crypt depth ratio, and goblet cell density and reduced gut permeability, mucosal adherence of bacteria, IL-8 levels, colonic lactic acid levels, and density of Gram-positive bacteria, relative to CON pigs (P Ͻ 0.05). Values in PAR pigs were intermediate with few affected parameters (reduced lactic acid levels and density and adherence of Gram-positive bacteria, relative to CON pigs, P Ͻ 0.05). There was no evidence of increased antimicrobial resistance following the treatments. We conclude that enteral, but not parenteral, administration of antibiotics reduces gut bacterial colonization, inflammation, and NEC lesions in newborn, formula-fed preterm pigs. Delayed colonization may support intestinal structure, function, and immunity in the immediate postnatal period of formulafed preterm neonates.

Obese dogs seem to have a different gut microbiome (GM) composition compared to lean dogs, and in humans, GM composition may negatively impact the ability to lose weight in some individuals. The purpose of this study was to investigate the interaction between exercise, weight‐loss and the composition of GM in dogs. Eighteen obese pet dogs were recruited for a 12‐week weight‐loss intervention. All dogs were fed restrictively with a commercial high‐protein/high‐fibre dry diet, and eight of these dogs were enrolled in an exercise program in addition to the diet intervention. Faecal samples were collected and the dogs were weighed at week 0, week 6 and week 12. GM composition was determined using MiSeq‐based tag‐encoded 16S rRNA gene high‐throughput amplicon sequencing, and concentrations of short chain fatty acids (SCFA) by gas‐liquid chromatography. Total weight loss, food allowance and GM were not changed by exercise inclusion. However, Megamonas abundance negatively correlated with weight loss rate and Ruminococcaceae relative abundance was lower at 12 weeks in dogs with a faster weight loss rate (≥1% per week) compared with slower weight loss rate (<1% per week) independent of exercise. Acetic and propionic acid concentrations decreased in the dogs with a faster weight loss rate. Members of Megamonas and Ruminococcaceae produce acetic and propionic acids and we therefore interpret that having a GM that favour SCFA production may negatively affect weight loss rate in dogs. Weight loss rate in dogs may be related to the composition of the GM and its production of metabolites.

Objectives: To asses if administrating mothers giving birth by cesarean delivery prophylactic antibiotics either before skin incision or immediately after cutting the umbilical cord influences gut microbiota colonization and antibiotic susceptibility of the gut bacteria in the newborn. Antibiotics administered before skin incision lowers the risk of surgical site infections for the mothers, but also exposes the fetus to the antibiotic. Methods: Forty-two pregnant women scheduled for elective cesarean section were recruited at Odense University Hospital, Denmark, and randomly assigned to receive cefuroxime either before skin incision or immediately after the umbilical cord was cut. Fecal samples were collected from all infants at age 10 days and 9 months. Composition of the gut microbiota was determined by 16S rRNA gene amplicon high-throughput sequencing. Gram-positive cocci and Enterobacteriaceae were isolated and identified before antimicrobial susceptibility tests were performed by disk diffusion. Results: No clear difference in the composition of the gut microbiota was observed between infants whose mothers received cefuroxime before or after cesarean delivery at neither time point, though surprisingly at 9 months of age, but not at 10 days of age, the number of observed species was higher in infants where mothers received cefuroxime after cord clamping. No differences in antimicrobial susceptibility of Enterobacteriaceae, Enterococcus spp., and Staphylococcus spp. were seen at 10 days. 4 Conclusion: Timing of cefuroxime administration to mothers undergoing cesarean section does not have major effects on gut microbiota and bacterial antibiotic resistance traits in infants. Clinical trials registration: "Antibiotics and Microbiota among newborn Infants", NCT02072798.

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