Antibiotic treatment of rat dams affects bacterial colonization and causes decreased weight gain in pups.

Intergenerational transmission of bacteria during birth initiates the natural successional development of the intestinal microbiota in mammals. This process can be disrupted by antibiotic exposure, potentially affecting early-life microbiota-dependent metabolic programming. In the present study, we specifically investigate the metabolic consequences of exposing neonate Wistar rats to an antibiotic-perturbed low-diversity microbiota from birth until weaning, without exposing the pups directly to antibiotics. Here, we show that pups born from both amoxicillin and vancomycin-treated dams gain less weight than controls. This was concordant with lower feed intake as well as increased colonic expression of the PYY satiety hormone gene at weaning. The weight difference persists into adulthood even though the initial differences in gut microbiota subsided. Our results demonstrate that early-life exposure to an antibiotic-perturbed low-diversity microbiota is sufficient to cause changes in body weight persisting into adulthood.

Antibiotic Treatment Affects Intestinal Permeability and Gut Microbial Composition in Wistar Rats Dependent on Antibiotic Class.

Antibiotics are frequently administered orally to treat bacterial infections not necessarily related to the gastrointestinal system. This has adverse effects on the commensal gut microbial community, as it disrupts the intricate balance between specific bacterial groups within this ecosystem, potentially leading to dysbiosis. We hypothesized that modulation of community composition and function induced by antibiotics affects intestinal integrity depending on the antibiotic administered. To address this a total of 60 Wistar rats (housed in pairs with 6 cages per group) were dosed by oral gavage with either amoxicillin (AMX), cefotaxime (CTX), vancomycin (VAN), metronidazole (MTZ), or water (CON) daily for 10-11 days. Bacterial composition, alpha diversity and caecum short chain fatty acid levels were significantly affected by AMX, CTX and VAN, and varied among antibiotic treatments. A general decrease in diversity and an increase in the relative abundance of Proteobacteria was observed for all three antibiotics. Additionally, the relative abundance of Bifidobacteriaceae was increased in the CTX group and both Lactobacillaceae and Verrucomicrobiaceae were increased in the VAN group compared to the CON group. No changes in microbiota composition or function were observed following MTZ treatment. Intestinal permeability to 4 kDa FITC-dextran decreased after CTX and VAN treatment and increased following MTZ treatment. Plasma haptoglobin levels were increased by both AMX and CTX but no changes in expression of host tight junction genes were found in any treatment group. A strong correlation between the level of caecal succinate, the relative abundance of Clostridiaceae 1 family in the caecum, and the level of acute phase protein haptoglobin in blood plasma was observed. In conclusion, antibiotic-induced changes in microbiota may be linked to alterations in intestinal permeability, although the specific interactions remain to be elucidated as changes in permeability did not always result from major changes in microbiota and vice versa.