Alterations of gut microbiome accelerate multiple myeloma progression by increasing the relative abundances of nitrogen-recycling bacteria
Authors: Wen Zhou
Jian Ouyang
Yinghong Zhu
Jian Li
Lu Xie
Guancheng Li
Jingyu Zhang
Yanjuan He
Wei Jia
Lugui Qiu
Jingchao Lin
Minghua Wu
Jiliang Xia
Jiaojiao Guo
Yongjun Guan
Mingming Su
Xingxing Jian
Yihui Wang
Jinuo Wang
Qian Lei
Juanjuan Xiang
Journal: Microbiome (2020)
Discipline: MICROBIOLOGY
Keywords: Fecal microbiota transplantation; Gut microbiome; Multiple myeloma; Nitrogen-recycling bacteria.
Affiliations: State Key Laboratory of Experimental Hematology, Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China., Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of Health, China-Africa Research Center of Infectious Deseases, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China., Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, Shanghai, China., Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Metabo-Profile Biotechnology (Shanghai) Co. Ltd., Shanghai, China., State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China., School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China., State Key Laboratory of Experimental Hematology, Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China. ., Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of Health, China-Africa Research Center of Infectious Deseases, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China. .

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. Video abstract. 

Retracted: No

PubPeer comments:
 Fig 5B, 5E. ![file] Black rectangle: compare with Fig 5A B of [Li et al (2017)] . ![] Violet: Compare with Fig 4C D from [Zhou et al (2016)] . ![file] Grey and bright green: Compare with Figs 6A,E of [Liu et al (2017)] . ![file] Brown: Fig 7B from Liu et al. ![file] , 
 Figs 6C, 7A. ![file] For comparison: Fig 6B from [Zhou et al (2017)] ; Figs 7A,B, 9B from [Liu et al (2017)] ; Figs 3B, 4B from [Dang et al (2017)] ; Fig 4A from [Jiang et al (2017)] . ![file] Figs 3H, 4A B from [Zhou et al (2016)] ; Fig 4C D from [Zhou et al (2016)] . ![file] , 
 Fig 6C. The loading control appears to be recycled from Fig 1B of [Cheng et al (2014)] (there identified as actin). ![file] ![file] UPDATE: Other sightings include *[left]* Fig 6B from [Ying et al (2017)] .  The expression of Wnt5a, b-catenin, and pGSK3b protein was measured by Western blot after the indicated treatment and quantified . ![] Fig 1B from [Wang et al (2017)] ,  western blot analysis were performed to determine the ... protein levels of STMN1 in four osteosarcoma cell lines (HOS, Saos-2, U-2OS and MG-63, as well as normal osteoblast cell line hFOB1.19). ![] ,