Gut Microbiota vs Hematological Malignancies - What You Might Not Know

Author: Zhou Qinghe This article is published by the author with the authorization of Yimaitong, please do not reprint without authorization
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Regarding the diseases caused by the imbalance of intestinal flora, you may think of digestive system diseases for the first time.
With the continuous in-depth research of medicine, the function of intestinal microorganisms has completely subverted our cognition
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A huge group of bacteria exists in our gut, silently controlling our metabolism and immune system.
Nowadays, gut microbes have become a research hotspot in the field of global cancer.
Relationships are also slowly gaining attention
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Under physiological conditions, the gut microbiota is a highly diverse group of non-pathogenic commensal bacteria, mainly composed of Firmicutes, Bacteroides, Actinomyces, and Proteobacteria
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The gut microbiota acts as a signaling hub that integrates environmental inputs such as diet with genetic and immune signals to influence host responses such as metabolism and immunity
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Under normal circumstances, the intestinal flora maintains a certain steady state, thereby maintaining the integrity and function of the intestinal mucosal barrier.
When the intestinal flora is disturbed, it will affect the permeability of the intestinal mucosa and break the balance, thereby affecting the host's metabolism and metabolism.
Immunity, affecting the occurrence and development of tumor, metabolic and other diseases
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Recent studies have found that gut microbes may induce gene mutations, disrupt the balance of cell proliferation and apoptosis through chronic inflammation, initiate unnecessary innate and adaptive immune responses, etc.
, leading to the occurrence and development of hematological tumors [1]
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For hematological malignancies, repeated chemotherapy, transplantation and frequent use of broad-spectrum antibiotics will break the homeostasis of intestinal flora, affect the diversity of intestinal flora, lead to intestinal flora disorder, and affect the host's immunity.
System and influence on host hematopoietic recovery
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The gut microbiota is a key extrinsic regulator of innate and adaptive immunity and hematopoiesis [2]
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Intestinal microbes mainly exert their immunomodulatory effects through their metabolites, short chain fatty acids (SCFAs).
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Inhibit the proliferation of T and B lymphocytes, SCFA can up-regulate Fas to promote the apoptosis of T lymphocytes and inhibit their accumulation in the inflammatory intestinal mucosa
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Gut microbes and SCFA induce the differentiation and proliferation of intestinal regulatory T cells (Treg) cells by up-regulating intestinal homing molecules and FoxP3 transcription molecules, thereby regulating immunity [3]
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The mechanism by which the host regulates hematopoiesis through gut microbes is that bacterial metabolites enter the bone marrow through the blood to activate the MyD88-dependent TLR pathway and NOD1 pathway, induce bone marrow mesenchymal stem cells to produce interferon, activate the STAT1 signaling pathway, and act on hematopoietic stem/progenitor cells.
, In addition, lipopolysaccharide in metabolites can also directly act on hematopoietic stem/progenitor cells, and jointly inhibit hematopoiesis through these two ways [4]
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Changes in the structure and diversity of intestinal flora in patients with hematological malignancies are mainly manifested in the excessive growth of intestinal Escherichia coli, the reduction or absence of the beneficial bacteria Clostridium tenuva, and the presence of Enterococcus faecalis, Enterococcus sulphur, about Some bacteria in the intestinal tract such as Acinetobacter bacillus exhibit specific growth, which affects the occurrence and development of the disease, and increases the possibility of infection and disease recurrence [5] (see Table 1)
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Table 1 Main characteristics of the microbiota of hematological malignancies For leukemia, the study found that there is an interaction between the intestinal microecology and leukemia treatment.
During chemotherapy, the microbiota will change, and the richness of intestinal microorganisms will gradually decrease, but at the same time the intestinal microbiota will change.
The gut microbiota can in turn influence the efficacy and toxicity of chemotherapy drugs
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Recent studies have found that the diversity and composition of the gut microbiota before chemotherapy can predict the occurrence of chemotherapy-related complications such as gastrointestinal reactions, neutropenia, and bloodstream infections, and that these complications can be affected by modulation of gut microbiota.
be improved [6]
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After hematopoietic stem cell transplantation, the number of Bacteroides decreased, and the microorganisms were mainly Enterococcus.
Enterococcus and its released toxins could aggravate the damage of intestinal mucosal epithelial cells.
In addition, the reduction of the proportion of intestinal commensal bacteria led to the reduction of Treg cell production.
Various factors GVHD is aggravated, and transplant patients who develop intestinal dysbiosis in the early post-transplantation period have an increased risk of developing GVHD and GVHD-related mortality in the later period [7]
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Changes in gut microbiota during transplantation are also considered to be associated with the occurrence of infection and delayed immune reconstitution, and may also be potential targets for therapy
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The current therapeutic strategies to intervene in the intestinal flora mainly include antibiotic application, dietary adjustment, probiotic treatment and fecal microbiota transplantation (FMT)
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In 2020, both the European Society of Blood and Marrow Transplantation and the Chinese Society of Hematology included FMT as one of the treatment options for hormone-resistant acute graft-versus-host disease (aGVHD)
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However, the mechanism of FMT on aGVHD is still unclear.
At present, it is believed that fecal bacteria from healthy donors can restore the imbalance of intestinal flora structure and function in patients with aGVHD, thereby improving related clinical symptoms
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In addition, supplementing intestinal probiotics and their metabolites, regulating intestinal regional and systemic immune responses, and reducing the colonization resistance of bacterial flora may also be the potential mechanisms for FMT to function
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FMT affects the efficacy of tumor immunotherapy by changing the intestinal flora and immune response state
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However, at present, the related research on intestinal flora and FMT in the immunotherapy of hematological tumors is still lacking, and it may become a hot spot of future research
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However, in the face of this special group of patients with blood diseases, there are still many unanswered questions about the safety and efficacy of FMT as a new technology, and long-term, repeated and large-sample clinical trials are still needed to demonstrate [8]
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References: 1.
Yuan L, Wang W, Zhang W, et al.
Gut Microbiota in Untreated Diffuse Large B Cell Lymphoma Patients.
Front Microbiol.
2021, 12:646361.
2.
Wei Tong, Xi Yaming, Mao Xiali, et al.
Research progress on the relationship between intestinal microecology and hematopoiesis[J].
Journal of Clinical Hematology, 2020, 33(3): 229-232.
3.
Mao Dan, Chen Yu, Sheng Lixia, et al.
Research status of the relationship between intestinal microecology and immune function in patients with hematological tumors [J].
International blood transfusion and Journal of Hematology, 2020, 43(5):5.
4.
Hannah Y, Baldridge MT, King K Y.
Hematopoiesis and the bacterial microbiome[J].
Blood, 2021,132(6):559-564.
5.
D'Angelo Christopher R , Sudakaran Sailendharan, Callander Natalie S.
Clinical effects and applications of the gut microbiome in hematologic malignancies[J].
Cancer, 2021,127: 679-687.
6.
Mao Xiali, Xi Yaming, Wei Tong, et al.
Research on intestinal microbiome and leukemia Progress[J].
Chinese Journal of Microecology, 2020,32(12):1476-1481.
7.
Wang Li, Gao Rui, Liu Shufeng, et al.
Research progress on the role of gut microbes in hematopoietic stem cell transplantation[J].
China Experiment Journal of Hematology, 2018, 26(1): 5.
8.
Wu Depei, Zhao Ye.
Pay attention to the value of fecal bacterial transplantation in the treatment of blood system diseases [J].
Chinese Journal of Practical Internal Medicine, 2021, 1(4): 265-267.
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