Changes in Human Fecal Microbiota Due to Chemotherapy Analyzed by TaqMan-PCR, 454 Sequencing and PCR-DGGE Fingerprinting

• Published in: PloS one Vol. 6; no. 12; p. e28654
• Main Authors: Zwielehner, Jutta, Lassl, Cornelia, Hippe, Berit, Pointner, Angelika, Switzeny, Olivier J., Remely, Marlene, Kitzweger, Elvira, Ruckser, Reinhard, Haslberger, Alexander G.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.12.2011; Public Library of Science (PLoS)
• Subjects: Aged; Analysis; Anti-Bacterial Agents - pharmacology; Antibiotics; Bacteria; Bacterial infections; Bacteroides; Bacteroides - drug effects; Bacteroides - genetics; Bifidobacterium - drug effects; Bifidobacterium - genetics; Biology; Breastfeeding & lactation; Cancer; Case-Control Studies; Chemotherapy; Cloning; Clostridium; Clostridium - drug effects; Clostridium - genetics; Clostridium - growth & development; Clostridium difficile; Clusters; Colonization; Colony Count, Microbial; Denaturing Gradient Gel Electrophoresis - methods; DNA Fingerprinting - methods; Drug-Related Side Effects and Adverse Reactions; E coli; Ecosystem biology; Ecosystems; Escherichia coli; Fatty acids; Fecal microflora; Feces; Feces - microbiology; Fingerprinting; Gel electrophoresis; Genes; Genetic Variation; Health; High-Throughput Nucleotide Sequencing; Humans; Institutionalization; Intestinal microflora; Medicine; Metagenome - genetics; Microbiota; Microbiota (Symbiotic organisms); Middle Aged; Mitigation; Neoplasms - genetics; Neoplasms - microbiology; Next-generation sequencing; Phylogeny; Polymerase chain reaction; Polymerase Chain Reaction - methods; Principal components analysis; Probiotics; RNA; RNA, Ribosomal, 16S - genetics; rRNA 16S; Sequence Analysis, DNA - methods; Stem cells; Taq Polymerase - metabolism
• DOI: 10.1371/journal.pone.0028654
• ISSN: 1932-6203

We investigated whether chemotherapy with the presence or absence of antibiotics against different kinds of cancer changed the gastrointestinal microbiota. Feces of 17 ambulant patients receiving chemotherapy with or without concomitant antibiotics were analyzed before and after the chemotherapy cycle at four time points in comparison to 17 gender-, age- and lifestyle-matched healthy controls. We targeted 16S rRNA genes of all bacteria, Bacteroides, bifidobacteria, Clostridium cluster IV and XIVa as well as C. difficile with TaqMan qPCR, denaturing gradient gel electrophoresis (DGGE) fingerprinting and high-throughput sequencing. After a significant drop in the abundance of microbiota (p = 0.037) following a single treatment the microbiota recovered within a few days. The chemotherapeutical treatment marginally affected the Bacteroides while the Clostridium cluster IV and XIVa were significantly more sensitive to chemotherapy and antibiotic treatment. DGGE fingerprinting showed decreased diversity of Clostridium cluster IV and XIVa in response to chemotherapy with cluster IV diversity being particularly affected by antibiotics. The occurrence of C. difficile in three out of seventeen subjects was accompanied by a decrease in the genera Bifidobacterium, Lactobacillus, Veillonella and Faecalibacterium prausnitzii. Enterococcus faecium increased following chemotherapy. Despite high individual variations, these results suggest that the observed changes in the human gut microbiota may favor colonization with C. difficile and Enterococcus faecium. Perturbed microbiota may be a target for specific mitigation with safe pre- and probiotics.