Short-Term Effect of Antibiotics on Human Gut Microbiota

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.

[1]  J. Jansson,et al.  Long-term ecological impacts of antibiotic administration on the human intestinal microbiota , 2013, The ISME Journal.

[2]  Rafael Bargiela,et al.  Gut microbiota disturbance during antibiotic therapy: a multi-omic approach , 2012, Gut.

[3]  C. Mcnulty,et al.  European Antibiotic Awareness Day 2012: general practitioners encouraged to TARGET antibiotics through guidance, education and tools. , 2012, The Journal of antimicrobial chemotherapy.

[4]  E. Dempsey,et al.  High-Throughput Sequencing Reveals the Incomplete, Short-Term Recovery of Infant Gut Microbiota following Parenteral Antibiotic Treatment with Ampicillin and Gentamicin , 2012, Antimicrobial Agents and Chemotherapy.

[5]  C. Manichanh,et al.  Storage conditions of intestinal microbiota matter in metagenomic analysis , 2012, BMC Microbiology.

[6]  B. Finlay,et al.  Shifting the balance: antibiotic effects on host–microbiota mutualism , 2011, Nature Reviews Microbiology.

[7]  J. Faith,et al.  Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice , 2011, Proceedings of the National Academy of Sciences.

[8]  Christian L. Lauber,et al.  PrimerProspector: de novo design and taxonomic analysis of barcoded polymerase chain reaction primers , 2011, Bioinform..

[9]  R. Guigó,et al.  Reshaping the gut microbiome with bacterial transplantation and antibiotic intake. , 2010, Genome research.

[10]  S. Dasgupta,et al.  Central Nervous System Demyelinating Disease Protection by the Human Commensal Bacteroides fragilis Depends on Polysaccharide A Expression , 2010, The Journal of Immunology.

[11]  William A. Walters,et al.  Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample , 2010, Proceedings of the National Academy of Sciences.

[12]  William A. Walters,et al.  QIIME allows analysis of high-throughput community sequencing data , 2010, Nature Methods.

[13]  Anders F. Andersson,et al.  Short-Term Antibiotic Treatment Has Differing Long-Term Impacts on the Human Throat and Gut Microbiome , 2010, PloS one.

[14]  N. Shime,et al.  Eradication of the commensal intestinal microflora by oral antimicrobials interferes with the host response to lipopolysaccharide , 2010, European Journal of Clinical Microbiology & Infectious Diseases.

[15]  P. Bork,et al.  A human gut microbial gene catalogue established by metagenomic sequencing , 2010, Nature.

[16]  E. P. Dellinger,et al.  Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. , 2010, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[17]  David Artis,et al.  Metagenomic analyses reveal antibiotic-induced temporal and spatial changes in intestinal microbiota with associated alterations in immune cell homeostasis , 2009, Mucosal Immunology.

[18]  D. Foureau,et al.  Role of Gut Commensal Microflora in the Development of Experimental Autoimmune Encephalomyelitis1 , 2009, The Journal of Immunology.

[19]  Hilary G. Morrison,et al.  Reproducible Community Dynamics of the Gastrointestinal Microbiota following Antibiotic Perturbation , 2009, Infection and Immunity.

[20]  Les Dethlefsen,et al.  The Pervasive Effects of an Antibiotic on the Human Gut Microbiota, as Revealed by Deep 16S rRNA Sequencing , 2008, PLoS biology.

[21]  E. Goldstein,et al.  Serum bactericidal activities of moxifloxacin and levofloxacin against aerobic and anaerobic intra-abdominal pathogens. , 2008, Anaerobe.

[22]  G. Blandino,et al.  Antimicrobial Susceptibility and β-Lactamase Production of Anaerobic and Aerobic Bacteria Isolated from Pus Specimens from Orofacial Infections , 2007, Journal of chemotherapy.

[23]  Anne K Camper,et al.  Comparison of propidium monoazide with ethidium monoazide for differentiation of live vs. dead bacteria by selective removal of DNA from dead cells. , 2006, Journal of microbiological methods.

[24]  E. Goldstein,et al.  Fluoroquinolones and anaerobes. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[25]  R. Knight,et al.  UniFrac: a New Phylogenetic Method for Comparing Microbial Communities , 2005, Applied and Environmental Microbiology.

[26]  J. Doré,et al.  Resilience of the Dominant Human Fecal Microbiota upon Short-Course Antibiotic Challenge , 2005, Journal of Clinical Microbiology.

[27]  A. McKenzie,et al.  Development of Allergic Airway Disease in Mice following Antibiotic Therapy and Fungal Microbiota Increase: Role of Host Genetics, Antigen, and Interleukin-13 , 2005, Infection and Immunity.

[28]  G. Woodnutt,et al.  Augmentin (amoxicillin/clavulanate) in the treatment of community-acquired respiratory tract infection: a review of the continuing development of an innovative antimicrobial agent. , 2004, The Journal of antimicrobial chemotherapy.

[29]  K B Holten,et al.  Appropriate prescribing of oral beta-lactam antibiotics. , 2000, American family physician.

[30]  R. Moletta,et al.  Molecular microbial diversity of an anaerobic digestor as determined by small-subunit rDNA sequence analysis , 1997, Applied and environmental microbiology.

[31]  M. Cohen,et al.  Fluoroquinolones: relationships between structural variations, mammalian cell cytotoxicity, and antimicrobial activity. , 1992, Journal of medicinal chemistry.

[32]  Warren W. Esty,et al.  The Efficiency of Good's Nonparametric Coverage Estimator , 1986 .

[33]  R. Rodloff Activities of Quinolones Against Obligately Anaerobic Bacteria , 2007 .

[34]  K. Drlica,et al.  Fluoroquinolones: action and resistance. , 2003, Current topics in medicinal chemistry.

[35]  K. Goa,et al.  Levofloxacin: a review of its use in the treatment of bacterial infections in the United States. , 2003, Drugs.

[36]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[37]  A. Chao Nonparametric estimation of the number of classes in a population , 1984 .