Short-Term Effect of Antibiotics on Human Gut Microbiota

PLOS ONE, Dec 2019

From birth onwards, the human gut microbiota rapidly increases in diversity and reaches an adult-like stage at three years of age. After this age, the composition may fluctuate in response to external factors such as antibiotics. Previous studies have shown that resilience is not complete months after cessation of the antibiotic intake. However, little is known about the short-term effects of antibiotic intake on the gut microbial community. Here we examined the load and composition of the fecal microbiota immediately after treatment in 21 patients, who received broad-spectrum antibiotics such as fluoroquinolones and β-lactams. A fecal sample was collected from all participants before treatment and one week after for microbial load and community composition analyses by quantitative PCR and pyrosequencing of the 16S rRNA gene, respectively. Fluoroquinolones and β-lactams significantly decreased microbial diversity by 25% and reduced the core phylogenetic microbiota from 29 to 12 taxa. However, at the phylum level, these antibiotics increased the Bacteroidetes/Firmicutes ratio (p = 0.0007, FDR = 0.002). At the species level, our findings unexpectedly revealed that both antibiotic types increased the proportion of several unknown taxa belonging to the Bacteroides genus, a Gram-negative group of bacteria (p = 0.0003, FDR<0.016). Furthermore, the average microbial load was affected by the treatment. Indeed, the β-lactams increased it significantly by two-fold (p = 0.04). The maintenance of or possible increase detected in microbial load and the selection of Gram-negative over Gram-positive bacteria breaks the idea generally held about the effect of broad-spectrum antibiotics on gut microbiota.

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Short-Term Effect of Antibiotics on Human Gut Microbiota

Citation: Panda S, El khader I, Casellas F, Lo pez Vivancos J, Garca Cors M, et al. ( Short-Term Effect of Antibiotics on Human Gut Microbiota Suchita Panda 0 Ismail El khader 0 Francesc Casellas 0 Josefa Lo pez Vivancos 0 Montserrat Garca Cors 0 Alba Santiago 0 Silvia Cuenca 0 Francisco Guarner 0 Chaysavanh Manichanh 0 Paul D. Cotter, Teagasc Food Research Centre, Ireland 0 1 Digestive System Research Unit, Vall d'Hebron Research Institute , Barcelona , Spain , 2 Centro de Investigacio n Biome dica en Red en el A rea tema tica de Enfermedades Hepa ticas y Digestivas (CIBERehd), Instituto de Salud Carlos III , Madrid , Spain , 3 Internal Medicine Department, Capio Hospital General de Catalunya, Universitat Internacional de Catalunya , Barcelona , Spain From birth onwards, the human gut microbiota rapidly increases in diversity and reaches an adult-like stage at three years of age. After this age, the composition may fluctuate in response to external factors such as antibiotics. Previous studies have shown that resilience is not complete months after cessation of the antibiotic intake. However, little is known about the short-term effects of antibiotic intake on the gut microbial community. Here we examined the load and composition of the fecal microbiota immediately after treatment in 21 patients, who received broad-spectrum antibiotics such as fluoroquinolones and b-lactams. A fecal sample was collected from all participants before treatment and one week after for microbial load and community composition analyses by quantitative PCR and pyrosequencing of the 16S rRNA gene, respectively. Fluoroquinolones and b-lactams significantly decreased microbial diversity by 25% and reduced the core phylogenetic microbiota from 29 to 12 taxa. However, at the phylum level, these antibiotics increased the Bacteroidetes/ Firmicutes ratio (p = 0.0007, FDR = 0.002). At the species level, our findings unexpectedly revealed that both antibiotic types increased the proportion of several unknown taxa belonging to the Bacteroides genus, a Gram-negative group of bacteria (p = 0.0003, FDR,0.016). Furthermore, the average microbial load was affected by the treatment. Indeed, the b-lactams increased it significantly by two-fold (p = 0.04). The maintenance of or possible increase detected in microbial load and the selection of Gram-negative over Gram-positive bacteria breaks the idea generally held about the effect of broad-spectrum antibiotics on gut microbiota. - Funding: This work was funded in part by the Fondo de Investigacio n Sanitaria, Ministerio de Ciencia e Innovacion, Spain (PI10/00902 grant) and in part by HENUFOOD (CEN-20101016). Ciberehd is funded by the Instituto de Salud Carlos III. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Clinicians commonly prescribe antibiotics to treat infections. The choice of antibiotic is well indicated in clinical guidelines for targeting specific pathogens, Gram-positive or Gram-negative bacteria [1]. However, little is known about the effects of antibiotics on the whole composition and load of the gut microbiota immediately after treatment. Human fecal microbiota is composed of four main groups of bacteria (phyla), namely Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria [2], the first two phyla accounting for more than 80% of the microbiota. Firmicutes comprise mostly Grampositive bacteria with a DNA that has a low G+C content, but also include Gram-negative bacteria. Bacteroidetes include Gramnegative bacteria, which are represented mainly by the Bacteroides genus in the human gut. Proteobacteria consist of Gram-negative bacteria and include a wide variety of well-studied pathogens. Actinobacteria are a group of Gram-positive bacteria with a DNA that has a high G+C content. Since the introduction of antibiotics in the 1940s, the short-term effect of these drugs on gut microbiota has been mainly documented on the basis of culture methods. However, given the difficulty in developing cultures for most gut bacteria [3], the information gathered from this technique is insufficient to understand the full targets of antibiotics. A few recent studies have used high-throughput sequencing technology to deeply characterize the long-term effect of antibiotics [4,5,6,7]. These studies have shown that treatment is followed by a significant alteration of the gut microbiota composition and a decrease between one-fourth to one-third of the microbial diversity in the digestive tract [4,8]. The microbiota is relatively resilient and returns to the pre-treatment state several weeks after drug cessation [9]. However, other recent studies on the long-term effects of antibiotic intake have shown that microbiota does not show complete resilience three months after treatment cessation [4,5,9,10,11]. Variations in the resilienc (...truncated)


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Suchita Panda, Ismail El khader, Francesc Casellas, Josefa López Vivancos, Montserrat García Cors, Alba Santiago, Silvia Cuenca, Francisco Guarner, Chaysavanh Manichanh. Short-Term Effect of Antibiotics on Human Gut Microbiota, PLOS ONE, 2014, 4, DOI: 10.1371/journal.pone.0095476