Impact of Antibiotic Therapies on Resistance Genes Dynamic and Composition of the Animal Gut Microbiota

Antibiotics are major disruptors of the gastrointestinal microbiota, depleting bacterial species beneficial for the host health and favoring the emergence of potential pathogens. Furthermore, the intestine is a reactor of antibiotic resistance emergence, and the presence of antibiotics exacerbates the selection of resistant bacteria that can disseminate in the environment and propagate to further hosts. We reviewed studies analyzing the effect of antibiotics on the intestinal microbiota and antibiotic resistance conducted on animals, focusing on the main food-producing and companion animals. Irrespective of antibiotic classes and animal hosts, therapeutic dosage decreased species diversity and richness favoring the bloom of potential enteropathogens and the selection of antibiotic resistance. These negative effects of antibiotic therapies seem ineluctable but often were mitigated when an antibiotic was administered by parenteral route. Sub-therapeutic dosages caused the augmentation of taxa involved in sugar metabolism, suggesting a link with weight gain. This result should not be interpreted positively, considering that parallel information on antibiotic resistance selection was rarely reported and selection of antibiotic resistance is known to occur also at low antibiotic concentration. However, studies on the effect of antibiotics as growth promoters put the basis for understanding the gut microbiota composition and function in this situation. This knowledge could inspire alternative strategies to antibiotics, such as probiotics, for improving animal performance. This review encompasses the analysis of the main animal hosts and all antibiotic classes, and highlights the future challenges and gaps of knowledge that should be filled. Further studies are necessary for elucidating pharmacodynamics in animals in order to improve therapy duration, antibiotic dosages, and administration routes for mitigating negative effects of antibiotic therapies. Furthermore, this review highlights that studies on aminoglycosides are almost inexistent, and they should be increased, considering that aminoglycosides are the first most commonly used antibiotic family in companion animals. Harmonization of experimental procedures is necessary in this research field. In fact, current studies are based on different experimental set-up varying for antibiotic dosage, regimen, administration, and downstream microbiota analysis. In the future, shotgun metagenomics coupled with long-reads sequencing should become a standard experimental approach enabling to gather comprehensive knowledge on GIM in terms of composition and taxonomic functions, and of ARGs. Decorticating GIM in animals will unveil revolutionary strategies for medication and improvement of animals’ health status, with positive consequences on global health.

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Gut microbiota in a host–brood parasite system: insights from common cuckoos raised by two warbler species

FEMS Microbiology Ecology ◽

10.1093/femsec/fiaa143 ◽

2020 ◽

Vol 96 (9) ◽

Cited By ~ 1

Author(s):

Lucie Schmiedová ◽

Jakub Kreisinger ◽

Milica Požgayová ◽

Marcel Honza ◽

Jean-François Martin ◽

...

Keyword(s):

Environmental Factors ◽

Gut Microbiota ◽

Acrocephalus Arundinaceus ◽

Brood Parasite ◽

Bacterial Strains ◽

Factors Affecting ◽

The Common ◽

Animal Hosts ◽

Bacterial Sources ◽

Selection Of

ABSTRACT An animal's gut microbiota (GM) is shaped by a range of environmental factors affecting the bacterial sources invading the host. At the same time, animal hosts are equipped with intrinsic mechanisms enabling regulation of GM. However, there is limited knowledge on the relative importance of these forces. To assess the significance of host-intrinsic vs environmental factors, we studied GM in nestlings of an obligate brood parasite, the common cuckoo (Cuculus canorus), raised by two foster species, great reed warblers (Acrocephalus arundinaceus) and Eurasian reed warblers (A. scirpaceus), and compared these with GM of the fosterers’ own nestlings. We show that fecal GM varied between cuckoo and warbler nestlings when accounting for the effect of foster/parent species, highlighting the importance of host-intrinsic regulatory mechanisms. In addition to feces, cuckoos also expel a deterrent secretion, which provides protection against olfactory predators. We observed an increased abundance of bacterial genera capable of producing repulsive volatile molecules in the deterrent secretion. Consequently, our results support the hypothesis that microbiota play a role in this antipredator mechanism. Interestingly, fosterer/parent identity affected only cuckoo deterrent secretion and warbler feces microbiota, but not that of cuckoo feces, suggesting a strong selection of bacterial strains in the GM by cuckoo nestlings.

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Potential risks of antibiotic resistant bacteria and genes in bioremediation of petroleum hydrocarbon contaminated soils

Environmental Science Processes & Impacts ◽

10.1039/c9em00606k ◽

2020 ◽

Vol 22 (5) ◽

pp. 1110-1124 ◽

Cited By ~ 2

Author(s):

Colin J. Cunningham ◽

Maria S. Kuyukina ◽

Irena B. Ivshina ◽

Alexandr I. Konev ◽

Tatyana A. Peshkur ◽

...

Keyword(s):

Antibiotic Resistance ◽

Contaminated Soil ◽

Contaminated Soils ◽

Petroleum Hydrocarbon ◽

Resistant Bacteria ◽

Careful Selection ◽

Bacterial Strains ◽

Antibiotic Resistant ◽

Potential Risks ◽

Selection Of

The problems associated with potential risks of antibiotic resistance spreading during bioremediation of oil-contaminated soil are discussed. Careful selection of bacterial strains and pretreatment of organic wastes used as fertilizers are suggested.

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A Microbiome-Based Solution to Address Alarming Levels of Drug-Resistant Bacteria in the Newborn Infant Gut

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2020.1106 ◽

2020 ◽

Vol 41 (S1) ◽

pp. s439-s439

Author(s):

Giorgio Casaburi ◽

Rebbeca Duar ◽

Bethany Henrick ◽

Steven Frese

Keyword(s):

Antibiotic Resistance ◽

Antimicrobial Resistance ◽

Bacterial Species ◽

The United States ◽

Resistant Bacteria ◽

Delivery Mode ◽

Term Infants ◽

Shotgun Metagenomics ◽

Single Strain ◽

Breastfed Infants

Background: Recent studies have focused on the early infant gut microbiome, indicating that antibiotic resistance genes (ARGs) can be acquired in early life and may have long-term sequelae. Limiting the spread of antimicrobial resistance without triggering the development of additional resistance mechanisms would be of immense clinical value. Here, we present 2 analyses that highlight the abundance of ARGs in preterm and term infants and a proof of concept for modulating the microbiome to promote early stabilization and reduction in ARGs in term infants. Methods: Large-scale metagenomic analysis was performed on 2,141 microbiome samples (90% from pre-term infants) from 10 countries; most were from the United States (87%) and were obtained from the Comprehensive Antibiotic Resistance Database (CARD). We assessed the abundance and specific types of ARGs present. In the second study, healthy, breastfed infants were fed B. infantis EVC001 for 3 weeks starting at postnatal day 7. Stool samples were collected at day 21 and were processed utilizing shotgun metagenomics. Selected antimicrobial-resistant bacterial species were isolated, sequenced, and tested for minimal inhibitory concentrations to clinically relevant antibiotics. Results: In the first study, globally, 417 distinct ARGs were identified. The most abundant gene among all samples was annotated as msrE, a plasmid gene known to confer resistance to macrolide-lincosamide-streptogramin B (MLSB) antibiotics. The remaining most-abundant ARGs were efflux-pump genes associated with multidrug resistance. No significant association in antimicrobial resistance was found when considering delivery mode or antibiotic treatment in the first month of life. In the second study, the EVC001-fed group showed a significant decrease (90%) in ARGs compared to controls (P < .0001). ARGs that differed significantly between groups were predicted to confer resistance to β-lactams, fluoroquinolones, or multiple drug classes. Minimal inhibitory concentration assays confirmed resistance phenotypes among isolates Notably, we found resistance to extended-spectrum β-lactamases among healthy, vaginally delivered breastfed infants who had never been exposed to antibiotics. Conclusions: In this study, we show that the term and preterm infant microbiome contains alarming levels of ARGs associated with clinically relevant antibiotics harbored by bacteria commonly responsible for nosocomial infections. Colonization of the breastfed infant gut by a single strain of B. longum subsp infantis had profound impacts on the fecal metagenome, including reduction in ARGs and reduction of potential pathogens. These findings highlight the importance of developing novel approaches to limit the spread of ARGs among clinically relevant bacteria and the relevance of an additional approach in the effort to solve AR globally.Funding: Evolve BioSystems provided Funding: for this study.Disclosures: Giorgio Casaburi reports salary from Evolve BioSystems.

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Incidence of enterococci resistant to clinically relevant antibiotics in environmental waters and in reclaimed waters used for irrigation

Journal of Water and Health ◽

10.2166/wh.2020.020 ◽

2020 ◽

Vol 18 (6) ◽

pp. 911-924

Author(s):

Silvia Monteiro ◽

Ricardo Santos

Keyword(s):

Antibiotic Resistance ◽

Crop Production ◽

Wastewater Treatment Plants ◽

Antibiotic Resistance Genes ◽

Treated Wastewater ◽

Resistant Bacteria ◽

Antibiotic Resistant ◽

Vancomycin Resistant ◽

Wastewater Samples ◽

Selection Of

Abstract Treated wastewater discharged into the environment or reused in different activities can be a major vehicle for the transmission of antibiotic-resistant bacteria and antibiotic-resistance genes. In this study, environmental and wastewater samples, collected at different stages of treatment, were studied to identify the possibility of a positive selection of antibiotic-resistant organisms in wastewater treatment plants (WWTPs). Enterococci were isolated, characterized into the main human species, and subjected to the Kirby–Bauer test using seven antibiotics (five classes): ampicillin, chloramphenicol, ciprofloxacin, gentamicin, linezolid, tetracycline, and vancomycin. Furthermore, vancomycin-resistant enterococci (VRE), a major cause of nosocomial infection, was identified, and the genes vanA and vanB detected directly in the samples and in all confirmed VRE. Data showed that WWTPs were able to reduce the levels of antibiotic resistance, although 72% of the disinfected wastewaters still presented antibiotic-resistant enterococci. VRE were detected in 6% of the samples, including in reclaimed waters. UV disinfection was not effective at removing VRE and multiple antibiotic-resistant (MAR) enterococci, most commonly Enterococcus faecalis. The use of reclaimed water containing VRE and MAR enterococci in crop production, irrigation of urban gardens, and street cleaning increases immensely the potential risk to human health.

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Microbiota restoration reduces antibiotic-resistant bacteria gut colonization in patients with recurrent Clostridioides difficile infection from the open-label PUNCH CD study

Genome Medicine ◽

10.1186/s13073-021-00843-9 ◽

2021 ◽

Vol 13 (1) ◽

Cited By ~ 1

Author(s):

Amy Langdon ◽

◽

Drew J. Schwartz ◽

Christopher Bulow ◽

Xiaoqing Sun ◽

...

Keyword(s):

Antibiotic Resistance ◽

Gut Microbiota ◽

Resistance Gene ◽

Resistance Genes ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Antibiotic Resistant Bacteria ◽

Open Label ◽

Antibiotic Resistant ◽

Clostridioides Difficile

Abstract Background Once antibiotic-resistant bacteria become established within the gut microbiota, they can cause infections in the host and be transmitted to other people and the environment. Currently, there are no effective modalities for decreasing or preventing colonization by antibiotic-resistant bacteria. Intestinal microbiota restoration can prevent Clostridioides difficile infection (CDI) recurrences. Another potential application of microbiota restoration is suppression of non-C. difficile multidrug-resistant bacteria and overall decrease in the abundance of antibiotic resistance genes (the resistome) within the gut microbiota. This study characterizes the effects of RBX2660, a microbiota-based investigational therapeutic, on the composition and abundance of the gut microbiota and resistome, as well as multidrug-resistant organism carriage, after delivery to patients suffering from recurrent CDI. Methods An open-label, multi-center clinical trial in 11 centers in the USA for the safety and efficacy of RBX2660 on recurrent CDI was conducted. Fecal specimens from 29 of these subjects with recurrent CDI who received either one (N = 16) or two doses of RBX2660 (N = 13) were analyzed secondarily. Stool samples were collected prior to and at intervals up to 6 months post-therapy and analyzed in three ways: (1) 16S rRNA gene sequencing for microbiota taxonomic composition, (2) whole metagenome shotgun sequencing for functional pathways and antibiotic resistome content, and (3) selective and differential bacterial culturing followed by isolate genome sequencing to longitudinally track multidrug-resistant organisms. Results Successful prevention of CDI recurrence with RBX2660 correlated with taxonomic convergence of patient microbiota to the donor microbiota as measured by weighted UniFrac distance. RBX2660 dramatically reduced the abundance of antibiotic-resistant Enterobacteriaceae in the 2 months after administration. Fecal antibiotic resistance gene carriage decreased in direct relationship to the degree to which donor microbiota engrafted. Conclusions Microbiota-based therapeutics reduce resistance gene abundance and resistant organisms in the recipient gut microbiome. This approach could potentially reduce the risk of infections caused by resistant organisms within the patient and the transfer of resistance genes or pathogens to others. Trial registration ClinicalTrials.gov, NCT01925417; registered on August 19, 2013.

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Phage Therapy: A Potential Solution for Antibiotic Resistance

10.51627/pghr.2021.08.00071 ◽

2021 ◽

Author(s):

Chirag Choudhary ◽

Keyword(s):

Antibiotic Resistance ◽

Bacterial Infections ◽

Phage Therapy ◽

Biological Agents ◽

Resistant Bacteria ◽

Potential Solution ◽

Antibiotic Resistant Bacteria ◽

Antibiotic Resistant ◽

The Future

The idea of using a virus to kill bacteria may seem counterintuitive, but it may be the future of treating bacterial infections. Before the COVID-19 pandemic, one of the most frightening biological agents were so-called “superbugs” – antibiotic resistant bacteria – which could not be treated with conventional therapeutics. When antibiotics were first developed, they were hailed as a panacea. A panacea they were not.

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Antibiotic Resistance of Staphylococcus spp. Isolated from Sewage in Manaus, Amazonas

European Journal of Medical and Health Sciences ◽

10.24018/ejmed.2021.3.1.597 ◽

2021 ◽

Vol 3 (1) ◽

pp. 134-137

Author(s):

Sabrine P. Nogueira ◽

Suanni L. Andrade ◽

Paulo F. C. Magalhães Jr ◽

Rudi E. L. Procopio

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

Resistant Bacteria ◽

Human Pathogens ◽

Amazonas State ◽

Staphylococcus Spp ◽

The City ◽

Selection Of

Staphylococcus spp. have become important human pathogens in recent decades due to the selection of resistant bacteria and the spread of their resistance genes in the environment. This study aimed to evaluate the resistance of Staphylococcus spp. obtained from sewage in the city of Manaus, Amazonas state, Brazil. The isolates were tested for susceptibility to antimicrobials using the Kirby-Bauer method for ampicillin, azithromycin, ciprofloxacin, clindamycin, chloramphenicol, erythromycin, gentamicin, oxacillin, cefoxitin, linezolid, penicillin, rifampicin, sulfazotrim, tetracycline and vancomycin. Among the strains isolated from sewage, the greatest resistance was observed for penicillin and oxacillin, with 100% of isolates resistant to these antibiotics. Some antibiotics had resistant and sensitive strains (ampicillin, clindamycin, erythromycin, cefoxitin, azithromycin). Staphylococcus spp. were identified as sensitive to ciprofloxacin chloramphenicol gentamicin linezolid sulfazotrim tetracycline, vancomycin, with no strain resistant to these antibiotics.

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Longitudinal effects of antibiotics and fecal transplant on lemur gut microbiota structure, associations, and resistomes

10.1101/2020.11.11.378349 ◽

2020 ◽

Author(s):

Sally L. Bornbusch ◽

Rachel L. Harris ◽

Nicholas M. Grebe ◽

Kimberly Roche ◽

Kristin Dimac-Stohl ◽

...

Keyword(s):

Antibiotic Resistance ◽

Gut Microbiota ◽

Antibiotic Resistance Genes ◽

Microbial Consortia ◽

Negative Consequences ◽

Fecal Transplant ◽

Negative Effects ◽

Beneficial Effects ◽

Integrated Study

AbstractAntibiotics alter the diversity, structure, and dynamics of host-associated microbial consortia, including via development of antibiotic resistance; however, patterns of recovery from dysbiosis and methods to mitigate negative effects, remain poorly understood. We applied an ecological framework via long-term, integrated study of community structure, across scales, to improve understanding of host-microbe symbiosis during dysbiosis and recovery. We experimentally administered a broad-spectrum antibiotic alone or with subsequent fecal transfaunation to healthy, male ring-tailed lemurs (Lemur catta) and longitudinally tracked the diversity, composition, associations, and resistomes of their gut microbiota. Whereas microbial diversity recovered rapidly in lemurs, antibiotics caused long-term instability in community composition – effects that were attenuated by fecal transfaunation. Antibiotic resistance genes, which were universally present, including in treatment-naïve subjects, increased during and persisted after antibiotic treatment. Long-term, integrated study post antibiotic-induced dysbiosis revealed differential, metric-dependent evidence of recovery, beneficial effects of fecal transfaunation, and negative consequences to lemur resistomes.

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The Human Gut Resistome up to Extreme Longevity

mSphere ◽

10.1128/msphere.00691-21 ◽

2021 ◽

Author(s):

Teresa Tavella ◽

Silvia Turroni ◽

Patrizia Brigidi ◽

Marco Candela ◽

Simone Rampelli

Keyword(s):

Antibiotic Resistance ◽

Gut Microbiota ◽

Healthy Aging ◽

Resistant Bacteria ◽

Human Gut ◽

Bacterial Populations ◽

Antibiotic Resistant ◽

Ecological Fitness ◽

Extreme Longevity ◽

Definition Of

Antibiotic resistance is widespread among different ecosystems, and in humans it plays a key role in shaping the composition of the gut microbiota, enhancing the ecological fitness of certain bacterial populations when exposed to antibiotics. A considerable component of the definition of healthy aging and longevity is associated with the structure of the gut microbiota, and, in this regard, the presence of antibiotic-resistant bacteria is critical to many pathologies that come about with aging.

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Antibiotic Administration Routes Significantly Influence the Levels of Antibiotic Resistance in Gut Microbiota

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00670-13 ◽

2013 ◽

Vol 57 (8) ◽

pp. 3659-3666 ◽

Cited By ~ 91

Author(s):

Lu Zhang ◽

Ying Huang ◽

Yang Zhou ◽

Timothy Buckley ◽

Hua H. Wang

Keyword(s):

Antibiotic Resistance ◽

Gut Microbiota ◽

Oral Administration ◽

Oral Exposure ◽

Resistant Bacteria ◽

Gene Pools ◽

Antibiotic Administration ◽

Gi Tract ◽

Content Type ◽

Gene Carriers

ABSTRACTThis 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 oftet(M)-carryingEnterococcusspp. orblaCMY-2-carryingEscherichia coliwere 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.

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