Goldfish
The editor randomly investigated recent articles in the three top journals of CNS, but found the treasure. The cliché microorganism and tumors became treasures in the palm! shows that research on microorganisms and human health is unstoppable! Search for more than 3,000 published articles in Pubmed with the keyword "(microbiome) AND (cancer)". Without further ado, follow the editor to experience the charm of microorganisms!
PART1Tumor microorganism research status
Early: High stage: High stage clinical research on the effect of microorganisms on cancer began in 1868, and William Busch reported spontaneous tumor regression in patients with Streptococcus pyogenes infected. In 1911, Rolls sarcoma virus (RSV) was discovered to convert the benign tissues of poultry into malignant tumors. For the next few decades, people have been searching for virus behind every cancer, but it ended in failure.
Modern: Currently, this field advocates the importance of microorganisms (including bacteria and fungi) in cancer and cancer treatment. rarely has microorganisms that directly cause cancer, but many microorganisms appear to be complicit in cancer growth, usually working through the host's immune system . The mechanism analysis of the intestinal microbiology-immune system interaction shows that by regulating primary and secondary lymphoid tissue activity against cancer and tumor immune surveillance, it has a powerful impact on innate and adaptive immunity. in preclinical model , microbial metabolites can regulate the phenotype of tumor somatic mutations and the efficacy of immune checkpoint inhibitors. Despite a large amount of preclinical evidence, methods that translate microbiota regulation methods into humans have not yet been widely commercialized. However, engineered bacterial cancer therapy has been applied in preclinical and clinical trials.
PART2 Effect of microorganisms on TME
Intestinal microbiota Effect of intestinal bacterial flora on TME
Home 1Intestinal ecosystem can affect tumor occurrence by affecting the immune environment of proximal and distant tumors, the influx of myeloid and lymphocytes and as well as inflammation and metabolic patterns. The secretory components of the intestinal flora are equally important, such as outer membrane vesicles (OMVs) that can reprogram tumor microenvironment (TME) into the pto-TH1 mode (CXCL10, IFNγ), metabolites including butyric acid and niacin mediate Gpr109a-dependent IL-18 induction in the colon epithelium, inhibiting colitis and colon cancer .
Effect of intratumoral microbial flora on TME
The mechanism of intratumoral microbial flora on different tumor types has been limited, especially outside the respiratory and digestive tract, but their impact on TME seems to inhibit local anti-tumor immunity. In addition, microorganisms in the tumor have been reported to have specific effects on the tumor. Immunologically, microorganisms in tumors usually generate drug resistance programming by connecting low proportions of TILs through PRR, including CD8+ T cells, CD4+ CD25+ FoxP3+ Tregs, which is observed in colorectal cancer, pancreatic cancer , breast cancer and lung cancer.
Figure 1: Microorganisms and TME
PART3 Application of microbiome
Diagnostic use of microbiome data
HD As both host tissue and microbiome are affected by carcinogenic effects, the genetic heterogeneity of microorganisms may provide opportunities for the diagnosis and localization of diseases . For example, a TP53 gene mutation from blood origin can indicate the cancer status of the host, and more than 25 cancer types will have the above changes. Microbiologically based diagnosis presents many challenges, including low biomass relative to the host and the confounding of reagents or environmental contaminants.
Almost all microbial-based cancer diagnosis is based on sequencing and is concentrated on tumors in the digestive tract, such as colorectal, pancreatic , and lung cancer. It was not until recently that cancer types outside the airway, such as breast or brain cancer, may also contain a uniquely composed microbiome. However, compared with cancer cells, the abundance of microbial cells in the tumor is lower, and knowledge of their functions and potential remains limited. Its universality and impact need to be further verified in different cohorts and treatment contexts.
Prognostic use of microbiome data
The role of microorganisms in cancer formation, diagnosis, prognosis and treatment has been controversial for centuries. In some cancers, tumor gene expression can predict the patient's prognosis. study shows that tumor microbial abundance, alone or in combination with tumor gene expression, can predict cancer prognosis and drug response to to a certain extent.
Microbiome and cancer treatment
Currently, there are many ways to treat cancer, including chemotherapy, radiation therapy, microbial transplantation, probiotic therapy, microbial targeted tumors, post-biological therapy, antibiotic therapy, phage therapy , etc. Among them, the common one is chemotherapy, and the more characteristic one is phage therapy.
engineering exogenous bacteria and viral preparations for cancer treatment have made significant progress. Currently, the US FDA has approved two similar drugs: oncolytic virus therapy for treating advanced melanoma with T-VEC, and bacterial cancer therapy (BCT) with the attenuated vaccine Mycobacterium bovine tuberculosis (BCG vaccine).
Although bacterial cancer therapy has been historically controversial, BCT is regaining attention through the synthetic biology technology, which can programmatically limit the systemic toxicity of BCT while enhancing regional anti-tumor immunity. The regulatory challenges for BCT drugs are considerable, and although clinical trials are underway, no commercial breakthrough has been made.
Figure 2: Microorganisms and cancer
PART4Microorganisms and non-tumor diseases
More than 90% of human diseases are related to microorganisms. The above mainly introduces the relationship between tumors and microorganisms. So which non-tumor diseases are related to human microorganisms? Let me introduce to you several diseases with complex causes and high correlation with microorganisms:
① Rheumatoid arthritis (RA)
Rheumatoid arthritis is a long-term persistent disease that mainly affects joints. The cause is unknown, but it is related to genetic and environmental factors. Human microorganisms may interact with host genes and environmental factors, increasing the risk of RA. metagenome association analysis (Metagenome-Wide Association Study (MWAS) found that human oral flora and intestinal flora are correlated. Some common microbial species in the oral and intestinal microbial populations in patients with RA will increase simultaneously, such as Lactobacillus salivarius.
② Type 2 diabetes (Type 2 diabetes, T2D)
Type 2 diabetes is a complex endocrine disease caused by genetic and environmental factors. The cause and pathogenesis are relatively complex, and it is currently considered to be a heterogeneous disease with multiple genes and multiple factors. Metagenomic association analysis of type 2 diabetes is the first successful example of metagenomic association analysis of intestinal microorganisms in the world. MWAS study found that there are major differences in the structure and function of intestinal microbiota between healthy people and T2D patients.
③ Atherosclerosis (atherosclerosis, AS)
Infection is related to the development of cardiovascular disease and atherosclerosis. Research from the past decade has found that microbial ecosystems in different parts of the human body can lead to metabolic and cardiovascular-related diseases.Local or distant infections can lead to harmful inflammatory responses that aggravate plaque formation or trigger plaque rupture. The metabolism of cholesterol and lipid by the intestinal microbiota will affect the formation of atherosclerotic plaques. Specific components of diet and intestinal microbial metabolism have different effects on atherosclerosis. For example, dietary fiber is beneficial, while bacterial metabolite trimethylamine-N-oxide is considered harmful.
④ Liver disease
The liver is the organ that is most in contact with the intestine and is exposed to a large number of bacterial components and metabolites. Various liver diseases, such as alcoholic liver disease , non-alcoholic liver disease and primary sclerotic cholangitis , are all related to changes in the microbiota. Fungal disorders may affect the extent of liver steatosis, inflammation and fibrosis in through multiple interactions with the host immune system and other cell types.
Figure 3: Microorganisms and non-tumor diseases
PART5 Summary
The editor’s nagging about microorganisms has come to an end. Since it has been so popular recently and there are many related diseases, Shengxinren has also prepared personalized topic designs for everyone about microbial hot topics. You can pay attention to it. Recently, Shengxinren has become less and less. One is less.
