Hematological malignancies are diverse, with high malignancy characteristics, poor prognoses, and high mortality rates. The development of hematological malignancies is driven by genetic factors, tumor microenvironment factors, or metabolic factors; however, even when considering all of these factors, one still cannot fully estimate the risk of hematological malignancies. Several recent studies have demonstrated an intimate connection between intestinal microbes and the progression of hematological malignancies, and gut microbes play a primary role in the initiation and progression of hematological tumors through direct and indirect mechanisms. Thus, we summarize the correlation between intestinal microbes and hematological malignancies’ onset, progression, and therapeutic effect in order to better understand how intestinal microbes affect their initiation and progression, especially in leukemia, lymphoma, and multiple myeloma, which may provide potential therapeutic targets for improving the survival of patients with hematological malignancies.

In this study, we explored the effect of semaphorin5A (SEMA5A) on RA pathogenesis and its specific TSP1 domain on pannus formation. The expression of SEMA5A was detected in the synovium, the fibroblast-like synoviocytes (FLSs) and the SF of RA patients and healthy controls (HCs) by real-time quantitative PCR (q-PCR), immunohistochemistry staining, western blot and ELISA. SEMA5A-mAb intervention was performed to appraise the severity of joints in the CIA model. Transcriptome sequencing and bioinformatics analysis in SEMA5A-transfected FLSs from HCs were performed to screen differentially expressed genes after SEMA5A overexpression. An MTT assay in RA-FLSs, a chicken embryo allantoic membrane experiment and a tube formation experiment were used to clarify the influence of SEMA5A on cell proliferation and angiogenesis. Furthermore, a rescue experiment verified the function of the TSP1 domain of SEMA5A in the progress of RA with Sema5a^−/− CIA mice. The expression of SEMA5A increased in RA compared with that in HCs. Simultaneously, SEMA5A-mAbs significantly attenuated joint injury and the inflammatory response in CIA models. In addition, transcriptome sequencing and angiogenesis-related experiments verified the ability of SEMA5A to promote FLS proliferation and angiogenesis. Moreover, TSP1 was proved to be an essential domain in SEMA5A-induced angiogenesis in vitro. Additionally, rescue of TSP1-deleted SEMA5A failed to reduce the severity of arthritis in a CIA model constructed with Sema5a ^−/− mice. In summary, upregulation of SEMA5A was first confirmed in pathological lesions of RA patients. Furthermore, treatment with SEMA5A-mAbs attenuated the progress of RA in the CIA model. Moreover, TSP1 was indicated as the key domain of SEMA5A in the promotion of pannus formation in RA. Graphical Abstract

Although novel therapies have dramatically improved outcomes for multiple myeloma (MM) patients, relapse is inevitable and overall outcomes are heterogeneous. The gut microbiota is becoming increasingly recognized for its influence on host metabolism. To date, evidence has suggested that the gut microbiota contributes to MM, not only via the progressive activities of specific bacteria but also through the influence of the microbiota on host metabolism. Importantly, the abnormal amino acid metabolism, as well as the altered microbiome in MM, is becoming increasingly apparent, as is the influence on MM progression and the therapeutic response. Moreover, the gut-microbiota–host-amino-acid metabolism interaction in the progression of MM has been highlighted. Modulation of the gut microbiota (such as fecal microbiota transplantation, FMT) can be modified, representing a new angle in MM treatment that can improve outcomes. In this review, the relationship between gut microbiota, metabolism, and MM, together with strategies to modulate the microbiota, will be discussed, and some unanswered questions for ongoing and future research will be presented.

Pneumonia accounts for a significant cause of morbidity and mortality in multiple myeloma (MM) patients. It has been previously shown that intestinal Klebsiella pneumonia (K. pneumonia) enriches in MM and promotes MM progression. However, what role the altered gut microbiota plays in MM with pneumonia remains unknown. Here, we show that intestinal K. pneumonia is significantly enriched in MM with pneumonia. This enriched intestinal K. pneumonia links to the incidence of pneumonia in MM, and intestinal colonization of K. pneumonia contributes to pneumonia in a 5TGM1 MM mice model. Further targeted metabolomic assays reveal the elevated level of glutamine, which is consistently increased with the enrichment of K. pneumonia in MM mice and patients, is synthesized by K. pneumonia, and leads to the elevated secretion of TNF-α in the lung normal fibroblast cells for the higher incidence of pneumonia. Inhibiting glutamine synthesis by establishing glnA-mutated K. pneumonia alleviates the incidence of pneumonia in the 5TGM1 MM mice model. Overall, our work proposes that intestinal K. pneumonia indirectly contributes to pneumonia in MM by synthesizing glutamine. Altogether, we unveil a gut–lung axis in MM with pneumonia and establish a novel mechanism and a possible intervention strategy for MM with pneumonia.