Alterations of gut microbiome accelerate multiple myeloma progression by increasing the relative abundances of nitrogen-recycling bacteria

Xingxing Jian, Yinghong Zhu, Jian Ouyang, Yihui Wang, Qian Lei, Jiliang Xia, Yongjun Guan, Jingyu Zhang, Jiaojiao Guo, Yanjuan He, Jinuo Wang, Jian Li, Jingchao Lin, Mingming Su, Guancheng Li, Minghua Wu, Lugui Qiu, Juanjuan Xiang, Lu Xie, Wei JIAWen Zhou*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

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. Results: Here, in a cohort of newly diagnosed patients with MM and healthy controls (HCs), significant differences in metagenomic composition were discovered, for the first time, with higher bacterial diversity in MM. Specifically, nitrogen-recycling bacteria such as Klebsiella and Streptococcus were significantly enriched in MM. Also, the bacteria enriched in MM were significantly correlated with the host metabolome, suggesting strong metabolic interactions between microbes and the host. In addition, the MM-enriched bacteria likely result from the regulation of urea nitrogen accumulated during MM progression. Furthermore, by performing fecal microbiota transplantation (FMT) into 5TGM1 mice, we proposed a mechanistic explanation for the interaction between MM-enriched bacteria and MM progression via recycling urea nitrogen. Further experiments validated that Klebsiella pneumoniae promoted MM progression via de novo synthesis of glutamine in mice and that the mice fed with glutamine-deficient diet exhibited slower MM progression. Conclusions: Overall, our findings unveil a novel function of the altered gut microbiome in accelerating the malignant progression of MM and open new avenues for novel treatment strategies via manipulation of the intestinal microbiota of MM patients. [MediaObject not available: see fulltext.].

Original languageEnglish
Article number74
JournalMicrobiome
Volume8
Issue number1
DOIs
Publication statusPublished - 28 May 2020

Scopus Subject Areas

  • Microbiology
  • Microbiology (medical)

User-Defined Keywords

  • Fecal microbiota transplantation
  • Gut microbiome
  • Multiple myeloma
  • Nitrogen-recycling bacteria

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