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Antibiotic administration routes significantly influence the levels of antibiotic resistance in gut microbiota.

ABSTRACT: This study examined the impact of oral exposure to antibiotic-resistant bacteria and antibiotic administration methods on antibiotic resistance (AR) gene pools and the profile of resistant bacteria in host gastrointestinal (GI) tracts using C57BL/6J mice with natural gut microbiota. Mice inoculated with a mixture of tet(M)-carrying Enterococcus spp. or blaCMY-2-carrying Escherichia coli were treated with different doses of tetracycline hydrochloride (Tet) or ampicillin sodium (Amp) and delivered via either feed or intravenous (i.v.) injection. Quantitative PCR assessment of mouse fecal samples revealed that (i) AR gene pools were below the detection limit in mice without prior inoculation of AR gene carriers regardless of subsequent exposure to corresponding antibiotics; (ii) oral exposure to high doses of Tet and Amp in mice inoculated with AR gene carriers led to rapid enrichment of corresponding AR gene pools in feces; (iii) significantly less or delayed development of AR in the GI tract of the AR carrier-inoculated mice was observed when the same doses of antibiotics were administered via i.v. injection rather than oral administration; and (iv) antibiotic dosage, and maybe the excretion route, affected AR in the GI tract. The shift of dominant AR bacterial populations in the gut microbiota was consistent with the dynamics of AR gene pools. The emergence of endogenous resistant bacteria in the gut microbiota corresponding to drug exposure was also observed. Together, these data suggest that oral administration of antibiotics has a prominent effect on AR amplification and development in gut microbiota, which may be minimized by alternative drug administration approaches, as illustrated by i.v. injection in this study and proper drug selection.

SUBMITTER: Zhang L

PROVIDER: S-EPMC3719697 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Antibiotic administration routes significantly influence the levels of antibiotic resistance in gut microbiota.

Zhang Lu L Huang Ying Y Zhou Yang Y Buckley Timothy T Wang Hua H HH

Antimicrobial agents and chemotherapy 20130520 8

This study examined the impact of oral exposure to antibiotic-resistant bacteria and antibiotic administration methods on antibiotic resistance (AR) gene pools and the profile of resistant bacteria in host gastrointestinal (GI) tracts using C57BL/6J mice with natural gut microbiota. Mice inoculated with a mixture of tet(M)-carrying Enterococcus spp. or blaCMY-2-carrying Escherichia coli were treated with different doses of tetracycline hydrochloride (Tet) or ampicillin sodium (Amp) and delivered ...[more]

PMID: 23689712

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Project description:Previous studies have identified oral administration of antibiotics and gut-impacting drugs as critical drivers for fecal antibiotic resistance (AR) and microbiome disruption in lab mice, but the practical implications of these findings have yet to be validated in hosts nurtured in conventional environment. Using ampicillin (Amp) as a way to extrapolate the general effect of antibiotics, this project examined the impact of drug administration routes on fecal microbiota and resistome using poultry raised in a teaching farm. AR genes were found to be abundant in the feces of young Leghorn chicks without previous antibiotic treatment. In chickens seeded with bla CMY-2 + Escherichia coli, 300 mg/kg body weight of Amp was orally administered for 5 days. This led to the fecal microbiota switching from Firmicutes occupied (95.60 ± 2.62%) and Lactobacillus rich, to being dominated by Proteobacteria (70.91 ± 28.93%), especially Escherichia/Shigella. However, when Amp was given via muscle injection, Firmicutes was mostly retained (i.e., from 83.6 ± 24.4% pre- to 90.4 ± 15.2% post-treatment). In control chickens without seeding with bla CMY-2 + E. coli, oral Amp also led to the increase of Proteobacteria, dominated by Klebsiella and Escherichia/Shigella, and a reduction of Firmicutes. Specifically within Firmicutes, Enterococcus, Clostridium, etc. were enriched but Lactobacillus was diminished. The fecal resistome including Ampr genes was more abundant in chickens receiving oral Amp than those treated with muscle injection, but the difference was primarily within 1 log. The data illustrated that both drug administration routes and pre-existing gut microbiota have profound impacts on gut microbiome disruption when antibiotic treatment is given. In hosts nurtured in a conventional environment, drug administration route has the most evident impact on gut microbiota rather than the size of the targeted bla CMY-2 + gene pool, likely due to the pre-existing bacteria that are (i) less susceptible to Amp, and/or (ii) with Ampr- or multidrug resistance-encoding genes other than bla CMY-2 +. These results demonstrated the critical interplay among drug administration routes, microbiota seeded through the gastrointestinal tract, AR, gut microbiota disruption, and the rise of common opportunistic pathogens in hosts. The potential implications in human and animal health are discussed.

Project description:BackgroundPreterm children with their aberrant gut microbiota and susceptibility to infections and inflammation constitute a considerable target group for probiotic therapy to generate the age-appropriate healthy microbiota.Methods68 preterm neonates were randomized into five intervention groups: Beginning from the median age of 3 days, 13 children received Lactobacillus rhamnosus GG (LGG) directly orally, and 17 via the lactating mother. 14 children received LGG with Bifidobacterium lactis Bb-12 (Bb12) orally, and 10 via the lactating mother. 14 children received placebo. The children's faecal microbiota was assessed at the age of 7 days by 16S rRNA gene sequencing.ResultsThe gut microbiota compositions of the children directly receiving the probiotic combination (LGG + Bb12) were significantly different from those of the children receiving the other intervention modes or placebo (p = 0.0012; PERMANOVA), the distinction being due to an increase in the relative abundance of Bifidobacterium animalis (P < 0.00010; ANCOM-BC), and the order Lactobacillales (P = 0.020; ANCOM-BC).ConclusionThe connection between aberrant primary gut microbiota and a heightened risk of infectious and non-communicable diseases invites effective microbiota modulation. We show that the direct, early, and brief probiotic intervention of LGG + Bb12 109 CFU each, is sufficient to modulate the gut microbiota of the preterm neonate.ImpactPreterm children have a higher risk of several health problems partly due to their aberrant gut microbiota. More research is needed to find a safe probiotic intervention to modify the gut microbiota of preterm children. The maternal administration route via breast milk might be safer for the newborn. In our study, the early and direct administration of the probiotic combination Lactobacillus rhamnosus GG with Bifidobacterium lactis Bb-12 increased the proportion of bifidobacteria in the preterm children's gut at the age of 7 days, but the maternal administration route was not as effective.

Project description:Oral antibiotics are a critical tool for fighting bacterial infections, yet their use can have negative consequences, such as the disturbance of healthy gut bacterial communities and the dissemination of antibiotic residues in feces. Altering antibiotic administration route may limit negative impacts on intestinal microbiota and reduce selective pressure for antimicrobial resistance genes (ARG) persistence and mobility. Thus, a study was performed in pigs to evaluate route of therapeutic oxytetracycline (oxytet) administration, an antibiotic commonly used in the U.S. swine industry, on intestinal microbial diversity and ARG abundance. Given that oral antibiotics would be in direct contact with intestinal bacteria, we hypothesized that oral administration would cause a major shift in intestinal bacterial community structure when compared to injected antibiotic. We further postulated that the impact would extend to the diversity and abundance of ARG in swine feces. At approximately 3 weeks-of-age, piglets were separated into three groups (n = 21-22 per group) with two groups receiving oxytet (one via injection and the second via feed) and a third non-medicated group. Oxytet levels in the plasma indicated injected antibiotic resulted in a spike 1 day after administration, which decreased over time, though oxytet was still detected in plasma 14 days after injection. Conversely, in-feed oxytet delivery resulted in lower but less variable oxytet levels in circulation and high concentrations in feces. Similar trends were observed in microbial community changes regardless of route of oxytet administration; however, the impact on the microbial community was more pronounced at all time points and in all samples with in-feed administration. Fecal ARG abundance was increased with in-feed administration over injected, with genes for tetracycline and aminoglycoside resistance enriched specifically in the feces of the in-feed group. Sequencing of plasmid-enriched samples revealed multiple genetic contexts for the resistance genes detected and highlighted the potential role of small plasmids in the movement of antibiotic resistance genes. The findings are informative for disease management in food animals, but also manure management and antibiotic therapy in human medicine for improved antibiotic stewardship.

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Antibiotic administration routes significantly influence the levels of antibiotic resistance in gut microbiota.

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Antibiotic administration routes significantly influence the levels of antibiotic resistance in gut microbiota.

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