Abstract
Recent findings have revealed that gut microbiota plays a substantial role in modulating diseases such as autism, rheumatoid arthritis, allergies, and cancer that occur at sites distant to the gut. Athymic nude mice have been employed for tumorigenic research for decades; however, the relationships between the gut microbiome and host’s response in drug treatment to the grafted tumors have not been explored. In this study, we analyzed the fecal microbiome of nonxenograft and xenograft nude mice treated with phytosaponins from a popular medicinal plant, Gynostemma pentaphyllum (Gp). Analysis of enterobacterial repetitive intergenic consensus (ERIC)-PCR data showed that the microbiota profile of xenograft mice departed from that of the nonxenograft mice. After ten days of treatment with Gp saponins (GpS), the microbiota of the treated mice was closer to the microbiota at Day 0 before the implantation of the tumor. Data obtained from 16S pyrosequencing of fecal samples reiterates the differences in microbiome between the nonxenograft and xenograft mice. GpS markedly increased the relative abundance of Clostridium cocleatum and Bacteroides acidifaciens, for which the beneficial effects on the host have been well documented. This study, for the first time, characterizes the properties of gut microbiome in nude mice responding to tumor implant and drug treatment. We also demonstrate that dietary saponins such as GpS can potentially regulate the gut microbial ecosystem by increasing the number of symbionts. Interestingly, this regulation of the gut ecosystem might, at least in part, be responsible for or contribute to the anticancer effect of GpS.
Highlights
Accumulated evidence shows that the efficacy of drug treatments varies greatly from individual to individual, possibly influenced by the genetic polymorphism of individuals
Significant alteration in the gut microbiota of xenograft nude mice To investigate whether a tumor implanted in the flank of a mouse would affect microbiota in the gut, fecal samples were collected from mice at Days 0, 5 and 10
Inter-animal variation in microbial profile appeared at Day 0, a clear separation between the samples from Day 10 normal and tumor-bearing mice appears in the Partial least squares discriminant analysis (PLS-DA) plot (Fig 1E) and in the correlation coefficient plot (Fig 1F)
Summary
Accumulated evidence shows that the efficacy of drug treatments varies greatly from individual to individual, possibly influenced by the genetic polymorphism of individuals. It is well recognized that factors such as nutrition, age, overall health, and gut bacterial distribution, influence the drug metabolism of an individual. Microbes can influence the bioavailability and bioactivity of ingested products, including functional foods and herbal medicines [4, 5] as well as the host’s metabolic phenotypes [6]. Accumulating evidence shows that the gut microbiota can influence diseases found in organs or tissues distant from the gut, such as obesity [2, 3], diabetes [7, 8], autism [9, 10], rheumatoid arthritis [11], allergies [12, 13], and chronic liver disease [14]
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