Abstract
Fecal microbiota transplantation (FMT) is now widely used to treat recurrent Clostridium difficile infection, but has been less studied as a means to restore microbiome diversity and composition following antibiotic or chemotherapy treatments. The purpose of our study was to assess the efficacy of FMT to reverse antibiotic- and chemotherapy-induced gut dysbiosis in a mouse model. C57BL/6J mice were treated with ampicillin for 1 week and/or received a single intraperitoneal injection of 5-Fluorouracil. Fresh stool was collected and analyzed using shotgun metagenomics and the Illumina sequencing platform. Ampicillin caused a significant and immediate decrease in bacterial species richness and diversity that persisted for one week. In mice that received FMT, disruption of the intestinal microbiota was reversed immediately. Antibiotic and chemotherapy administration caused significant alteration in species distribution, including a decrease in the relative proportions of Clostridium scindens and Faecalibacterium prausnitzii, and an increase in known pathogenic species. In mice receiving FMT, we observed a significant increase in species known to exhibit anti-inflammatory properties. Moreover, chemotherapy led to a critical decrease in key ‘health-promoting’ species and to an altered functional profile, especially when chemotherapy was administered in tandem with antibiotics, and that FMT can ameliorate these effects.
Highlights
Cancer patients, especially those with hematological malignancies, receive high doses of chemotherapeutic agents that often cause for gastrointestinal mucositis[1]
A mouse model demonstrated that Fecal microbiota transplantation (FMT) in vancomycin-resistant Enterococcus faecium (VRE)-colonized mice eliminates infection by pathogenic microorganism, and that elimination of this colonization was correlated with restoration of a fecal flora that contains Barnesiella[13]
Principal coordinates analysis (PCoA) of Bray-Curtis dissimilarities showed a profound disruption of the architecture of the intestinal microbiota after antibiotic treatment (ANOSIM Day 1 Abt-Chem and Abt-Chem-FMT groups vs Day 8 Abt-Chem group, p = 0.001), which persisted after chemotherapy administration (ANOSIM Day 1 Abt-Chem and Abt-Chem-FMT groups vs Day 12 Abt-Chem group, p = 0.004) and 1 week after discontinuation of antibiotic and chemotherapy treatment in mice that did not receive FMT (ANOSIM Day 1 Abt-Chem and Abt-Chem-FMT groups vs Day 16 Abt-Chem group, p = 0.007, Fig. 2B)
Summary
Especially those with hematological malignancies, receive high doses of chemotherapeutic agents that often cause for gastrointestinal mucositis[1] This side effect can enable bacterial translocation leading to bloodstream infection (BSI), a major cause of morbidity and mortality in cancer patients[2]. It was previously reported that the intestinal microbiota are drastically altered following chemotherapy, and that intestinal microbiota composition in pretreatment individuals can be used to predict the onset of subsequent bacteremia[6,7]. These authors reported that several taxa, including Barnesiellaceae, Christensenella and Faecalibacterium, were less abundant in patients who developed a subsequent BSI. A mouse model demonstrated that FMT in vancomycin-resistant Enterococcus faecium (VRE)-colonized mice eliminates infection by pathogenic microorganism, and that elimination of this colonization was correlated with restoration of a fecal flora that contains Barnesiella[13]
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