This article, published in the esteemed journal Blood Science, highlights the intricate role of gut microbiota in hematopoiesis, encompassing its influence on both benign and malignant conditions. As a peer-reviewed platform at the forefront of clinical and experimental hematology, Blood Science is recognized for its impact on advancing our understanding of molecular biology, physiology, and clinical applications. Authored by Professor Tao Cheng from the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Med-ical College, Professor Hui Cheng from the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Med-ical College and Professor Pengxu Qian from the First Affiliated Hospital, Zhejiang University School of Medicine，this work provides crucial insights into the therapeutic implications of gut microbiota for hematological health and disease management.The gut microbiota, a dynamic ecosystem primarily composed of bacteria, significantly impacts metabolic, immune, and hematopoietic processes. Dysbiosis, or disruption in the balance of gut microbiota, has been implicated in various systemic diseases, including those affecting hematopoiesis. This article synthesizes findings from recent experimental and clinical research to explore the mechanisms through which microbial metabolites, inflammatory pathways, and targeted interventions like fecal microbiota transplantation (FMT) and probiotics influence hematological outcomes.
Figure 1. Mechanisms of gut microbiota in the regulation of hematopoie- sis. FoxO = Forkhead box O, HSC = hematopoietic stem cell, IFN = inter- feron, LPS = lipopolysaccharides, ROS = reactive oxygen species, STAT = signal transducer and activator of transcription, TLR4 = Toll-like receptor 4, TRIF = TIR domain -containing adaptor inducing interferon-b.
Gut microbiota plays an essential role in maintaining hematopoietic homeostasis. Microbial metabolites such as short-chain fatty acids (SCFAs) enhance the self-renewal and differentiation of hematopoietic stem cells (HSCs), while lactate stimulates bone marrow stromal cells to secrete cytokines that support erythropoiesis. However, certain bacterial components, such as lipopolysaccharides (LPS), activate toll-like receptor 4 (TLR4) on HSCs, leading to inflammation and impaired regeneration. Age-related gut dysbiosis further exacerbates these effects, reducing microbiota diversity and increasing systemic inflammation, which compromises HSC function. Remarkably, studies demonstrate that FMT from young to aged mice can rejuvenate HSCs, restoring hematopoietic capacity by alleviating inflammation and enhancing signaling pathways.
In hematologic malignancies, dysbiosis has profound effects on disease progression and treatment outcomes. In acute myeloid leukemia (AML), dysbiosis accelerates disease development in animal models, but interventions like probiotics and FMT have shown promise in mitigating these effects and reducing chemotherapy complications. In lymphoma, microbial diversity correlates strongly with disease severity and prognosis, with tools like the SRI index emerging as valuable biomarkers. Similarly, in multiple myeloma (MM), gut microbiota profiles are linked to tumor progression and minimal residual disease (MRD) status. Specific bacterial species, such as Veillonella, have been associated with inflammatory pathways that drive disease progression in myeloproliferative neoplasms (MPN).
Non-malignant hematological disorders also exhibit a strong relationship with gut dysbiosis. In anemia, disruptions in gut microbiota impair iron metabolism and increase SCFA concentrations. This suggests that tailored iron supplementation strategies could serve as potential therapies, although excessive iron may exacerbate dysbiosis and inflammation. In aplastic anemia (AA), elevated levels of pro-inflammatory bacterial species activate immune pathways, influencing disease progression. Microbiota-targeted treatments have shown potential in enhancing outcomes, particularly in refractory cases. Similarly, in immune thrombocytopenia (ITP), altered gut microbiota compositions correlate with platelet counts and disease severity, offering novel avenues for diagnosis and therapy.
In conclusion, the gut microbiota is a critical regulator of hematopoiesis and hematological diseases, affecting disease progression, therapeutic responses, and overall prognosis. Emerging interventions, such as microbiota-based therapies and biomarker development, hold promise for advancing personalized medicine in hematology. However, large-scale clinical trials and detailed mechanistic studies are necessary to validate these approaches and facilitate their integration into clinical practice. As big data analytics evolve, they will further refine our understanding of the microbiota-hematology axis, paving the way for innovative treatments.
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