ABSTRACT
BACKGROUND: We investigated whether chemotherapy with the presence or absence of antibiotics against different kinds of cancer changed the gastrointestinal microbiota. METHODOLOGY/PRINCIPAL FINDINGS: 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 (pâ=â0.037) 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. CONCLUSIONS/SIGNIFICANCE: 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.
Subject(s)
DNA Fingerprinting/methods , Denaturing Gradient Gel Electrophoresis/methods , Drug-Related Side Effects and Adverse Reactions , Feces/microbiology , Metagenome/genetics , Polymerase Chain Reaction/methods , Sequence Analysis, DNA/methods , Aged , Anti-Bacterial Agents/pharmacology , Bacteroides/drug effects , Bacteroides/genetics , Bifidobacterium/drug effects , Bifidobacterium/genetics , Case-Control Studies , Clostridium/drug effects , Clostridium/genetics , Clostridium/growth & development , Colony Count, Microbial , Genetic Variation , Health , High-Throughput Nucleotide Sequencing , Humans , Middle Aged , Neoplasms/genetics , Neoplasms/microbiology , Phylogeny , RNA, Ribosomal, 16S/genetics , Taq Polymerase/metabolismABSTRACT
The gastrointestinal microbiota produces short-chain fatty acids, especially butyrate, which affect colonic health, immune function and epigenetic regulation. To assess the effects of nutrition and aging on the production of butyrate, the butyryl-CoA:acetate CoA-transferase gene and population shifts of Clostridium clusters lV and XlVa, the main butyrate producers, were analysed. Faecal samples of young healthy omnivores (24 ± 2.5 years), vegetarians (26 ± 5 years) and elderly (86 ± 8 years) omnivores were evaluated. Diet and lifestyle were assessed in questionnaire-based interviews. The elderly had significantly fewer copies of the butyryl-CoA:acetate CoA-transferase gene than young omnivores (P=0.014), while vegetarians showed the highest number of copies (P=0.048). The thermal denaturation of the butyryl-CoA:acetate CoA-transferase gene variant melting curve related to Roseburia/Eubacterium rectale spp. was significantly more variable in the vegetarians than in the elderly. The Clostridium cluster XIVa was more abundant in vegetarians (P=0.049) and in omnivores (P<0.01) than in the elderly group. Gastrointestinal microbiota of the elderly is characterized by decreased butyrate production capacity, reflecting increased risk of degenerative diseases. These results suggest that the butyryl-CoA:acetate CoA-transferase gene is a valuable marker for gastrointestinal microbiota function.
Subject(s)
Acyl Coenzyme A/metabolism , Bacteria/enzymology , Bacterial Proteins/genetics , Butyrates/metabolism , Coenzyme A-Transferases/genetics , Adult , Age Factors , Aged , Aged, 80 and over , Bacteria/genetics , Bacteria/isolation & purification , Bacteria/metabolism , Bacterial Proteins/metabolism , Clostridium/enzymology , Clostridium/genetics , Clostridium/isolation & purification , Clostridium/metabolism , Coenzyme A-Transferases/metabolism , Diet , Feces/chemistry , Feces/microbiology , Female , Gastrointestinal Tract/microbiology , Humans , Life Style , Male , Young AdultABSTRACT
AIMS: This study aimed at determining ageing-related shifts in diversity and composition of key members of the fecal microbiota by comparing institutionalized elderly (n = 17, 78-94 years) and young volunteers (n = 17, 18-31 years). METHODS AND RESULTS: A combination of molecular methods was used to characterize the diversity and relative abundance of total gastro-intestinal flora, along with relevant subsets within the genera Bacteroides, bifidobacteria and Clostridium cluster IV. The institutionalized elderly harbored significantly higher numbers of Bacteroides cells than control (28.5 +/- 8.6%; 21.4 +/- 7.7%; p = 0.016) but contained less bifidobacteria (1.3 +/- 0.9, 2.7 +/- 3.2%, p = 0.026) and Clostridium cluster IV (26.9 +/- 11.7%, 36.36 +/- 11.26%, p = 0.036). The elderly also displayed less total Bacteria diversity and less diversity with the Clostridium cluster IV (p < 0.016) and Bacteroides. CONCLUSION: Despite high individual variations, our analyses indicate the composition of microbiota in the elderly comprises a less diverse subset of young healthy microbiota. SIGNIFICANCE AND IMPACT OF THE STUDY: A better understanding of the individual composition of the human microbiota and the effects of ageing might result in the development of specifically targeted supplementation for elderly citizens in order to support healthy ageing.
