scholarly journals A Pathogen-Selective Antibiotic Minimizes Disturbance to the Microbiome

2016 ◽  
Vol 60 (7) ◽  
pp. 4264-4273 ◽  
Author(s):  
Jiangwei Yao ◽  
Robert A. Carter ◽  
Grégoire Vuagniaux ◽  
Maryse Barbier ◽  
Jason W. Rosch ◽  
...  

ABSTRACTBroad-spectrum antibiotic therapy decimates the gut microbiome, resulting in a variety of negative health consequences. Debio 1452 is a staphylococcus-selective enoyl-acyl carrier protein reductase (FabI) inhibitor under clinical development and was used to determine whether treatment with pathogen-selective antibiotics would minimize disturbance to the microbiome. The effect of oral Debio 1452 on the microbiota of mice was compared to the effects of four commonly used broad-spectrum oral antibiotics. During the 10 days of oral Debio 1452 treatment, there was minimal disturbance to the gut bacterial abundance and composition, with only the unclassified S24-7 taxon reduced at days 6 and 10. In comparison, broad-spectrum oral antibiotics caused ∼100- to 4,000-fold decreases in gut bacterial abundance and severely altered the microbial composition. The gut bacterial abundance and composition of Debio 1452-treated mice were indistinguishable from those of untreated mice 2 days after the antibiotic treatment was stopped. In contrast, the bacterial abundance in broad-spectrum-antibiotic-treated mice took up to 7 days to recover, and the gut composition of the broad-spectrum-antibiotic-treated mice remained different from that of the control group 20 days after the cessation of antibiotic treatment. These results illustrate that a pathogen-selective approach to antibiotic development will minimize disturbance to the gut microbiome.

2018 ◽  
Vol 154 (6) ◽  
pp. S-643 ◽  
Author(s):  
Daniel Laubitz ◽  
Monica Midura-Kiela ◽  
Fayez K. Ghishan ◽  
Pawel R. Kiela

2021 ◽  
Author(s):  
Evangelia Stavroulaki ◽  
Jan S. Suchodolski ◽  
Rachel Pilla ◽  
Geoffrey T. Fosgate ◽  
Chi-Hsuan Sung ◽  
...  

Antibiotic treatment in early life influences gastrointestinal (GI) microbial composition and function. In humans, the resultant intestinal dysbiosis is associated with an increased risk for certain diseases later in life. The objective of this study was to determine the temporal effects of antibiotic treatment on the GI microbiome of young cats. Fecal samples were collected from cats randomly allocated to receive either amoxicillin/clavulanic acid (20 mg/kg q12h) for 20 days (AMC group; 15 cats) or doxycycline (10 mg/kg q24h) for 28 days (DOX group;15 cats) as part of the standard treatment of upper respiratory tract infection. In addition, feces were collected from healthy control cats (CON group;15 cats). All cats were approximately two months of age at enrolment. Samples were collected on days 0 (baseline), 20 or 28 (AMC and DOX, respectively; last day of treatment), 60, 120, and 300. DNA was extracted and sequencing of the 16S rRNA gene and qPCR assays were performed. Fecal microbial composition was different on the last day of treatment for AMC cats, and 1 month after the end of antibiotic treatment for DOX cats, compared to CON cats. Species richness was significantly greater in DOX cats compared to CON cats on the last day of treatment. Abundance of Enterobacteriales was increased, and that of Erysipelotrichi was decreased in cats of the AMC group on the last day of treatment compared to CON cats. The abundance of the phylum Proteobacteria was increased in cats of the DOX group on days 60 and 120 compared to cats of the CON group. Only minor differences in abundances between the treatment groups and the control group were present on day 300. Both antibiotics appear to delay the developmental progression of the microbiome, and this effect is more profound during treatment with amoxicillin/clavulanic acid and one month after treatment with doxycycline. Future studies are required to determine if these changes influence microbiome function and whether they have possible effects on disease susceptibility in cats.


2013 ◽  
Vol 41 (2) ◽  
pp. 149-155 ◽  
Author(s):  
Grégory Dubourg ◽  
Jean-Christophe Lagier ◽  
Fabrice Armougom ◽  
Catherine Robert ◽  
Gilles Audoly ◽  
...  

2020 ◽  
Author(s):  
Daniela Gaio ◽  
Matthew Z DeMaere ◽  
Kay Anantanawat ◽  
Graeme J Eamens ◽  
Michael Liu ◽  
...  

Abstract BackgroundEarly weaning and intensive farming practices predispose piglets to the development of infectious and often lethal diseases, against which antibiotics are used. Besides contributing to the build-up of antimicrobial resistance, antibiotics are known to modulate the gut microbial composition. Studies have previously investigated the effects of probiotics as alternatives to antibiotic treatment for the prevention of post-weaning diarrhea. In order to describe the post-weaning gut microbiota, and the effects of two probiotics formulations and of intramuscular antibiotic treatment on the gut microbiota, we processed over 800 faecal time-series samples from 126 piglets and 42 sows, generating over 8Tbp of metagenomic shotgun sequence data. Here we describe the animal trial procedures, the generation of our metagenomic dataset and the analysis of the microbial community composition using a phylogenetic framework.ResultsFactors such as age, litter effects, and breed, by significantly correlating with gut microbial community shifts, can be major confounding factors in the assessment of treatment effects. Intramuscular antibiotic treatment and probiotic treatments were found to correlate with alpha and beta diversity, as well as with a transient establishment of Mollicutes and Lactobacillales, respectively. We found the abundance of certain taxa to correlate with weight gain.ConclusionsOur findings demonstrate that breed, litter, and age, are important contributors to variation in the community composition, and that treatment effects of the antibiotic and probiotic treatments were subtle, while host age was the dominant factor in shaping the gut microbiota of piglets after weaning. The current study shows, by means of a phylogenetic diversity framework, that the post-weaning pig gut microbiome appears to follow a highly structured developmental program with characteristic post-weaning changes that can distinguish hosts that were born as little as two days apart in the second month of life.


Author(s):  
Xing Heng ◽  
Yuanhe Jiang ◽  
Weihua Chu

Antibiotics which can treat or prevent infectious diseases play an important role in medical therapy. However, the use of antibiotics has potential negative effects on the health of the host. For example, antibiotics use may affect the host's immune system by altering the gut microbiota. Therefore, the aim of the study was to investigate the influence of antifungal (fluconazole) treatment on gut microbiota and immune system of mice. Results showed that gut microbial composition of mice receiving fluconazole treatment was significantly changed after the trial. Fluconazole did not affect the relative abundance of bacteria but significantly reduced the diversity of bacterial flora. In the Bacteriome, Firmicutes and Proteobacteria significantly increased, while Bacteroidetes, Deferribacteres, Patescibacteria, and Tenericutes showed a remarkable reduction in fluconazole treated group in comparison with the control group. In the mycobiome, the relative abundance of Ascomycota was significantly decreased and Mucoromycota was significantly increased in the intestine of mice treated with fluconazole compared to the control group. RT-qPCR results showed that the relative gene expression of ZO-1, occludin, MyD88, IL-1β, and IL-6 was decreased in fluconazole-treated group compared to the control. Serum levels of IL-2, LZM and IgM were significantly increased, while IgG level had considerably down-regulated in the fluconazole-treated compared to the control. These results suggest that the administration of fluconazole can influence the gut microbiota and that a healthy gut microbiome is important for the regulation of the host immune responses.


Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 467 ◽  
Author(s):  
Yanbei Wu ◽  
Robert Li ◽  
Haiqiu Huang ◽  
Arnetta Fletcher ◽  
Lu Yu ◽  
...  

Accumulated evidence suggests that the cruciferous vegetables-derived compound indole-3-carbinol (I3C) may protect against prostate cancer, but the precise mechanisms underlying its action remain unclear. This study aimed to verify the hypothesis that the beneficial effect of dietary I3C may be due to its modulatory effect on the gut microbiome of mice. Athymic nude mice (5–7 weeks old, male, Balb c/c nu/nu) with established tumor xenografts were fed a basal diet (AIN-93) with or without 1 µmoles I3C/g for 9 weeks. The effects of dietary I3C on gut microbial composition and microbial species interactions were then examined by 16s rRNA gene-based sequencing and co-occurrence network analysis. I3C supplementation significantly inhibited tumor growth (p < 0.0001) and altered the structure of gut microbiome. The abundance of the phylum Deferribacteres, more specifically, Mucispirillum schaedleri, was significantly increased by dietary I3C. Additionally, I3C consumption also changed gut microbial co-occurrence patterns. One of the network modules in the control group, consisting of seven bacteria in family S-27, was positively correlated with tumor size (p < 0.009). Moreover, dietary I3C disrupted microbial interactions and altered this association between specific microbial network and tumor development. Our results unraveled complex relationships among I3C ingestion, gut microbiota, and prostate tumor development and may provide a novel insight into the mechanism for the chemopreventive effect of dietary I3C on prostate cancer.


PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0161654 ◽  
Author(s):  
Tine D. Clausen ◽  
Thomas Bergholt ◽  
Olivier Bouaziz ◽  
Magnus Arpi ◽  
Frank Eriksson ◽  
...  

2015 ◽  
Vol 37 (3) ◽  
pp. 319-326 ◽  
Author(s):  
Jonathan D. Grein ◽  
Katherine L. Kahn ◽  
Samantha J. Eells ◽  
Seong K. Choi ◽  
Marianne Go-Wheeler ◽  
...  

BACKGROUNDAntibiotic treatment for asymptomatic bacteriuria (ASB) is prevalent but often contrary to published guidelines.OBJECTIVETo evaluate risk factors for treatment of ASB.DESIGNRetrospective observational study.SETTINGA tertiary academic hospital, county hospital, and community hospital.PATIENTSHospitalized adults with bacteriuria.METHODSPatients without documented symptoms of urinary tract infection per Infectious Diseases Society of America (IDSA) criteria were classified as ASB. We examined ASB treatment risk factors as well as broad-spectrum antibiotic usage and quantified diagnostic concordance between IDSA and National Healthcare Safety Network criteria.RESULTSAmong 300 patients with bacteriuria, ASB was present in 71% by IDSA criteria. By National Healthcare Safety Network criteria, 71% of patients had ASB; within-patient diagnostic concordance with IDSA was moderate (kappa, 0.52). After excluding those given antibiotics for nonurinary indications, antibiotics were given to 38% (62/164) with ASB. Factors significantly associated with ASB treatment were elevated urine white cell count (65 vs 24 white blood cells per high-powered field, P<.01), hospital identity (hospital C vs A, odds ratio, 0.34 [95% CI, 0.14–0.80], P =.01), presence of leukocyte esterase (5.48 [2.35–12.79], P<.01), presence of nitrites (2.45 [1.11–5.41], P=.03), and Escherichia coli on culture (2.4 [1.2–4.7], P=.01). Of patients treated for ASB, broad-spectrum antibiotics were used in 84%.CONCLUSIONSASB treatment was prevalent across settings and contributed to broad-spectrum antibiotic use. Associating abnormal urinalysis results with the need for antibiotic treatment regardless of symptoms may drive unnecessary antibiotic use.Infect. Control Hosp. Epidemiol. 2016;37(3):319–326


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