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The editor casually researched the recent articles of the three top journals of CNS, but found that the treasure, the cliché microorganisms and tumors have become treasures in the palm of your hand! It can be seen that the research on the relationship between microorganisms and human health is unstoppable! Search for more than 3,000 articles published in Pubmed in 2022 alone with the keyword "(microbiome) AND (cancer)", not to mention follow the editor to feel the charm of microorganisms!
Microbiome biopsy idea
scan code consultation PART
01 tumor microbial research status
Early: Clinical research into the effects of microbes on cancer began in 1868, when William Busch reported spontaneous tumor regression
in patients infected with Streptococcus pyogenes.
In 1911, it was discovered that Rouse sarcoma virus (RSV) transforms benign tissue from poultry into malignant tumors
.
For decades, people searched for the virus behind every cancer, but ultimately failed
.
Modern: Currently, the field advocates the importance of
microorganisms, including bacteria and fungi, in cancer and cancer treatment.
Few microbes directly cause cancer, but many appear to be complicit in cancer growth, often acting
through the host's immune system.
Mechanistic analysis of gut microbiome-immune system interactions has shown powerful effects
on innate and adaptive immunity by modulating primary and secondary lymphoid tissue activity against cancer and tumor immune surveillance.
In preclinical models, microbial metabolites modulate the phenotype of tumor somatic mutations and the efficacy
of immune checkpoint inhibitors.
Despite a large body of preclinical evidence, methods for translating microbiota regulation methods into humans have not yet been widely commercialized
.
However, engineered bacterial cancer therapies are used
in preclinical and clinical trials.
02 INFLUENCE OF MICROORGANISMS ON TME The influence of intestinal flora on tme
The gut ecosystem can influence tumorigenesis
by influencing the immune environment of proximal and distant tumors, the influx of myeloid and lymphocytes, and inflammatory and metabolic patterns.
Equally important are the secretory components of the gut microbiota, such as outer membrane vesicles (OMVs) that can reprogram the tumor microenvironment (TME) to the pto-TH1 model (CXCL10,
IFNγ), metabolites including butyric acid and niacin mediate Gpr109a-dependent IL-18 induction in colonic epithelium, inhibiting colitis and colon cancer
.
Effect of intratumoral flora on TME
Mechanistic studies of viable microbiota within different tumor types have been limited, especially outside the respiratory and digestive tracts, but their effects on TME appear to inhibit local anti-tumor immunity
.
In addition, intratumoral microorganisms have been reported to have a specific effect
on tumors.
Immunology, intratumor-based microbes typically mount a low proportion of TILs via PRR to produce drug-resistant programming, including CD8+ T cells, CD4+ CD25+ FoxP3+Tregs, which has been
observed in colorectal, pancreatic, breast, and lung cancers.
Figure 1: Microorganisms and TME
OF MICROBIOME TO
DIAGNOSTIC USES OF MICROBIOME DATA
Because host tissues and microbiota are both affected by carcinogenicity, genetic heterogeneity of microorganisms may provide opportunities for diagnosing and localizing disease.
For example, a mutation in the TP53 gene of blood origin can indicate the cancer status of the host, and more than 25 cancer types have these changes
.
Microbial-based diagnostics present many challenges, including low biomass relative to the host and confounding
of reagents or environmental contaminants.
Almost all microbiome-based cancer diagnoses are sequence-based and focus on tumors within the digestive tract, such as colorectal, pancreas, lung cancer
.
It has only recently been suggested that types of cancer outside the airways, such as breast or brain cancer, may also contain a unique composition of the microbiome
.
However, compared with cancer cells, the abundance of microbial cells in tumors is low, and their function and potential are still poorly
understood.
Further validation of its prevalence and impact
is needed across different cohort and treatment settings.
Prognostic use of microbiome data
The role of microbes in cancer formation, diagnosis, prognosis, and treatment has been controversial
for centuries.
In some cancers, tumor gene expression can predict a patient's prognosis
.
Studies have shown that tumor microbial abundance, alone or in combination with tumor gene expression, can predict cancer prognosis and drug response
to some extent.
The microbiome and cancer treatment
At present, there are various methods of microbial treatment of cancer, including chemotherapy, radiation therapy, microbial transplantation, probiotic therapy, microbial targeted tumors, post-biological therapy, antibiotic therapy, bacteriophage therapy, etc.
, among which the common is chemotherapy, and the more characteristic is phage therapy
.
Significant progress
has been made in engineering exogenous bacterial and viral agents for cancer treatment.
At present, the US FDA has approved two similar drugs: oncolytic virus therapy for advanced melanoma with T-VEC, and bacterial cancer therapy for high-risk, non-muscle-invasive bladder cancer with the attenuated vaccine Mycobacterium bovis tuberculosis (BCG vaccine).
therapies, BCT）
。
Although bacterial cancer therapies have historically been controversial, BCT is regaining attention through synthetic biology techniques that 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, there has been no commercial breakthrough
.
PART
04 Microorganisms and Non-Oncological Diseases
More than 90% of human diseases are related to microorganisms, and the above mainly introduces the relationship between tumors and microorganisms, so which non-tumor diseases are related to human microorganisms? Here are several diseases with complex etiology and high correlation with microorganisms:
(1) Rheumatoid arthritis (RA)
Rheumatoid arthritis is a long-term persistent disease
that primarily affects the joints.
The cause is unknown, but it is related to
genetic and environmental factors.
Human microbes may interact with host genes and environmental factors, increasing the risk of
RA.
Metagenome-Wide Association Study (MWAS) found that there is a correlation
between the human oral microbiota and the gut microbiota.
Some common microbial species in the oral and gut flora of RA patients are increased simultaneously, such as Lactobacillus
salivarius
。
(2) Type 2 diabetes (T2D)
Type 2 diabetes is a complex endocrine disease
caused by a combination of genetic and environmental factors.
Its etiology and pathogenesis are complex, and it is currently considered to be a multi-genetic, multifactorial heterogeneous disease
.
Metagenomic association analysis of type 2 diabetes is the world's first successful example
of metagenomic association analysis of gut microbes.
The MWAS study found that healthy people and T2D patients had large differences
in the structure and function of the gut microbiota.
(3) atherosclerosis (AS)
Infection is associated with
cardiovascular diseases and the development of atherosclerosis.
Research over the past decade has found that microbial ecosystems in different parts of the human body contribute to metabolic and cardiovascular-related diseases
.
Local or distant infection can lead to a harmful inflammatory response that can exacerbate plaque formation or trigger plaque rupture
.
The metabolism of cholesterol and lipids by the gut microbiota affects the formation
of atherosclerotic plaques.
Specific components of diet and gut microbial metabolism have different effects
on atherosclerosis.
For example, dietary fiber is beneficial, while the bacterial metabolite trimethylamine-N-oxide is considered harmful
.
(4) Liver disease
The liver is the organ most in contact with the intestines and is exposed to a large number of bacterial components and metabolites
.
Various liver diseases, such as alcoholic liver disease, nonalcoholic liver disease, and primary sclerosing cholangitis, are associated
with changes in the microbiota.
Microbiosis may affect the degree of steatosis, inflammation, and fibrosis of
the liver through multiple interactions with the host immune system and other cell types.
PART
05
Since it has been so hot recently, and there are many diseases related to it, so Shengxin people have also prepared personalized subject design related to microbial hot spots for everyone, you can pay attention to the fact that recently the hot spots of biobiology are becoming less and less, do one less, and watch the code of interest first
Scan code consultation
END
Don't want to miss the daily hot spots and technologies welcome everyone to add a letter to write for the star recommendation▎Goldfish typesetting ▎XX
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