
Alterations of gut microbiome accelerate multiple myeloma progression by increasing the relative abundances of nitrogen-recycling bacteria.
Jian Xingxing,Zhu Yinghong,Ouyang Jian,Wang Yihui,Lei Qian,Xia Jiliang,Guan Yongjun,Zhang Jingyu,Guo Jiaojiao,He Yanjuan,Wang Jinuo,Li Jian,Lin Jingchao,Su Mingming,Li Guancheng,Wu Minghua,Qiu Lugui,Xiang Juanjuan,Xie Lu,Jia Wei,Zhou Wen
Microbiome
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.
10.1186/s40168-020-00854-5
Autophagy, cell death, and cytokines in infection: therapeutic perspectives.
Emerging microbes & infections
is a notorious nosocomial pathogen causing a wide range of infections. The increasing trend of antimicrobial resistance obtained by the species immensely highly challenges the clinical treatment, representing a large threat to the global health care network. In particular, the recent convergence of multidrug resistance and hypervirulence in further worsens clinical outcomes, resulting in high mortality. Developments of new therapeutics become urgent, and immunotherapy based on antagonizing the anti-immune strategies of pathogens is a promising strategy, which requires the understanding of immune evasion mechanism in the context of the host-pathogen interactions. However, the underlying mechanisms employed by to counteract host immune responses, especially autophagy and cell death, have not been systematically reviewed and discussed yet. This review aims to summarize the tremendous progress that has been made to illuminate the landscape of cell signalling triggered by infection, especially in aspects of manipulating autophagy, cell death, and cytokine production.
10.1080/22221751.2022.2140607