TY - JOUR
T1 - Alterations of gut microbiome accelerate multiple myeloma progression by increasing the relative abundances of nitrogen-recycling bacteria
AU - Jian, Xingxing
AU - Zhu, Yinghong
AU - Ouyang, Jian
AU - Wang, Yihui
AU - Lei, Qian
AU - Xia, Jiliang
AU - Guan, Yongjun
AU - Zhang, Jingyu
AU - Guo, Jiaojiao
AU - He, Yanjuan
AU - Wang, Jinuo
AU - Li, Jian
AU - Lin, Jingchao
AU - Su, Mingming
AU - Li, Guancheng
AU - Wu, Minghua
AU - Qiu, Lugui
AU - Xiang, Juanjuan
AU - Xie, Lu
AU - Jia, Wei
AU - Zhou, Wen
N1 - Funding Information:
This work was supported by the Ministry of Science and Technology of China (2018YFA0107800), National Natural Science Foundation of China (31900102, 81974010, 81570205, 81630007, and 81800209), China Postdoctoral Science Foundation (2019 M652792), “111” project (111-2-12), Strategic Priority Research Program of Central South University (ZLXD2017004), SKLEH-Pilot Research Grant (ZK16-04), Postdoctoral Fund of Central South University, and Fundamental Research Fund for Graduate of Central South University (2018zzts079).
PY - 2020/5/28
Y1 - 2020/5/28
N2 - 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.].
AB - 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.].
KW - Fecal microbiota transplantation
KW - Gut microbiome
KW - Multiple myeloma
KW - Nitrogen-recycling bacteria
UR - http://www.scopus.com/inward/record.url?scp=85085635633&partnerID=8YFLogxK
U2 - 10.1186/s40168-020-00854-5
DO - 10.1186/s40168-020-00854-5
M3 - Journal article
C2 - 32466801
AN - SCOPUS:85085635633
SN - 2049-2618
VL - 8
JO - Microbiome
JF - Microbiome
IS - 1
M1 - 74
ER -