Alterations of Gut Microbiome Accelerate Multiple Myeloma Progression By Increasing the Relative Abundances of Nitrogen Recycling Bacteria

Background: Gut microbiome alterations are closely related to human health and linked to a variety of diseases. Although great efforts have been made to understand the risk factors for multiple myeloma (MM), little is known about the role of the gut microbiome and alterations of its metabolic functions in the development of MM patients. Materials and Methods: From a cohort of 19 newly diagnosed patients with MM and 18 gender- and age-matched healthy controls (HCs), fresh fecal samples and fasting serum samples were collected, respectively, for metagenomic sequencing and metabolomic detection. Subsequently, the high-quality reads were used for taxonomic classification using Kraken and for functional annotation using MetaCV, and metabolic profiling was statistically analyzed using SIMCA-P. On the R platform, bacterial diversity was analyzed using vegan package and differential taxa were identified using DESeq2 package. In addition, we performed fecal microbiota transplantation (FMT) experiments in C57BL/KaLwRij mice which can be artificially induced to develop MM by injecting 5TGM1 MM cells. Results: Here, significant differences in bacterial composition between MM and HC were first discovered (PERMANOVA, P=0.001), and greater bacterial richness in MM was evaluated by Shannon index (P=0.045). Several species with significant difference between the two groups were further confirmed by using qPCR of 16S rDNA V1-V2 regions in an expend cohort. Specifically, short-chain-fatty-acid producing bacteria such as Clostridium butyrate were substantially shrunk, while nitrogen recycling bacteria such as Klebsiella sp. were significantly enriched in MM. And, the MM-enriched bacteria showed higher abundance in MM patients with ISS-Ⅲ than those of MM patients with ISS-Ⅱ. We measured much more urea in the serum of MM than those in HC (P