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

Department of Nutritional Sciences, Vienna, Austria.
PLoS ONE (Impact Factor: 3.53). 12/2011; 6(12):e28654. DOI: 10.1371/journal.pone.0028654
Source: PubMed

ABSTRACT 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.

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    • "The microbiota and their corresponding genomes, collectively termed microbiome, can be quantitatively assessed by the use of modern sequencing platforms and their respective bioinformatics systems, which are focused primarily on 16S ribosomal RNA [48]. The microbiome of the GI tract, for instance, is very sensitive to a host of environmental factors; in particular diet [49], age and geography [50] [51], antibiotics [52], and other chemotherapeutic agents [53] [54], as well as many other factors that add to the complexity of environmental interactions [55] [56]. It is not surprising that disturbances of the microbiota, termed dysbiosis [43], are associated "
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    • "Based on this study, we cannot determine whether lower diversity contributed to the immune perturbations that underlie AYAHL risk, or was merely a consequence of the disease and its treatment. Two small studies suggest that various chemotherapy regimens immediately reduce and alter the composition of the gut microbiota (van Vliet et al, 2009; Zwielehner et al, 2011). However, these observations were partially confounded by antibiotic use, and long-term studies are lacking. "
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