The mechanism of oral bacteria promoting bowel cancer has been found!

In order to keep your mouth clean and prevent periodontitis, you brush your teeth every day
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But, did you know that, in fact, while maintaining healthy teeth, you might also reduce your chances of developing colorectal cancer invisibly? As the most upstream of the digestive tract, the oral cavity is the front line between the human body and the outside world
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Nearly 700 kinds of microorganisms colonize the oral cavity, constituting the second largest human flora after the intestinal flora [1]
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And every day, many bacteria from the oral cavity flow down with the swallowing, breaking through the interception of gastric acid, and successfully landing in the intestinal tract, which affects intestinal health
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Recently, Wang Zhi and Cheng Bin’s team from the Affiliated Dental Hospital of Sun Yat-sen University published an important research result in the top international journal Cancer Research [2]-Porphyromonas gingivalis, a pathogen of periodontitis, After colonization of colorectal tissue, it can recruit myeloid immune cells to activate the inflammasome NLRP3, thereby promoting the occurrence and development of colorectal cancer
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Colorectal cancer seriously endangers human health
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Globally, the incidence of colorectal cancer ranks third and the mortality rate ranks second in the ranking of malignant tumor killers
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In China alone, on average, more than 1,000 people are diagnosed with colorectal cancer every day, and more than 500 people die of colorectal cancer [3]
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What evil is Porphyromonas gingivalis? As a gram-negative anaerobic bacteria, Porphyromonas gingivalis is one of the most murderous bacteria in the oral cavity.
In addition to causing periodontitis and swelling of the gums, it also includes cardiovascular disease, diabetes and Alzheimer’s.
Murder disease and other systemic diseases are closely related [4]
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In colorectal cancer, researchers at Sun Yat-sen University were surprised to find that Porphyromonas gingivalis, which originally existed in the oral cavity, was also significantly enriched in the patient's feces
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Subsequently, colorectal cancer tissues were tested and found that Porphyromonas gingivalis was also present in large numbers in cancer tissues compared to normal tissues
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The consistently prosperous Porphyromonas gingivalis accidentally appeared in colorectal cancer, which gave researchers an unknown premonition: Could it be a "suspect" that promotes the onset of colorectal cancer? Porphyromonas gingivalis is enriched in colorectal cancer tissues (Normal: normal tissue; Adenoma: adenoma; CRC: colorectal cancer).
Subsequently, the researchers investigated the enrichment of Porphyromonas gingivalis in colorectal cancer tissues The relationship between abundance and the prognosis of patients, it is found that the higher the content of Porphyromonas gingivalis, the worse the prognosis of patients
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At this time, Porphyromonas gingivalis and colorectal cancer really have a relationship
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After locking the bacteria, the research team conducted animal experiments and successively selected APCmin/+ mice that can spontaneously form tumors, and xenograft tumor-forming subcutaneous and orthotopic rectal cancer mice as early and late animal models of colorectal cancer, respectively , Treat with Porphyromonas gingivalis (experimental group), streptococcus without cancer risk (negative control group) or broth for culturing bacteria (blank control group)
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After 8 weeks of tumor formation cycle, the mice were dissected to observe the tumor formation of colorectal cancer.
It was found that compared with the two control groups, the number of tumors in the experimental group treated with Porphyromonas gingivalis was more numerous and larger
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Porphyromonas gingivalis promotes the occurrence and development of colorectal cancer
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Mouse tumor formation experiment (Control: broth; S.
mutans: Streptococcus; P.
gingivalis: Porphyromonas gingivalis) tumorigenesis is a multi-factor, multi-step and multi-stage process
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Some tumors are closely related to bacterial infections.
For example, the infamous Helicobacter pylori is the culprit leading to gastric cancer.

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In recent years, researches on the digestive tract flora represented by the intestinal flora theory have sprung up, gradually revealing the inextricably dangerous relationship between digestive tract bacteria and digestive tract tumors
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So, how does Porphyromonas gingivalis promote the occurrence and development of colorectal cancer? After obtaining rectal cancer tissues of orthotopic transplantation tumor-forming mice, the researchers compared the differences in the composition of tumor immune cells between the experimental group and the blank control group, and found that after treatment with Porphyromonas gingivalis, the infiltrated CD11b positive cells, giant cells Myeloid immune cells such as phages and DC cells increased significantly, accompanied by increased levels of inflammatory cytokines IL1β, TNFα, and IL6, while CD4+T cells, CD8+T cells and NK cells had no significant changes
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This indicates that Porphyromonas gingivalis in the intestine creates a pro-inflammatory tumor microenvironment enriched with myeloid cells for colorectal cancer cells
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The immune microenvironment of Porphyromonas gingivalis enriched with myeloid cells and inflammatory cytokines.
However, how can Porphyromonas gingivalis recruit myeloid cells and promote the expression of IL1β and other inflammatory factors? As the dominant inflammatory cytokine in innate immunity, it can also activate the release of other pro-inflammatory cytokines such as TNF and IL-6.
IL1β was selected as the breakthrough point for the research
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It is well known that IL1β needs to be lysed by caspase 1 to mature before secretion.
The activation of caspase 1 is induced by NLRP3 inflammasome, and the assembly of NLRP3 inflammasome complex requires bacteria and other microorganisms to stimulate immune cells [5]
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Following this clue, the researchers first detected the expression of NLRP3 inflammasomes in the rectal cancer tissues of mice with tumor in situ, and indeed found that the expression of NLRP3 inflammasomes in the experimental group treated with Porphyromonas gingivalis was up-regulated.

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Subsequent in vitro co-culture of macrophages and in vivo experiments in NLRP3 knock-out colorectal cancer mice have verified that Porphyromonas gingivalis activates NLRP3 inflammasomes by stimulating myeloid cells, and upregulates IL1β, etc.
Expression of inflammatory factors to promote tumor occurrence and development
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Schematic diagram of the mechanism Although NLRP3 is mainly present in myeloid cells, it is also expressed in epithelial cells
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In order to exclude the influence of intestinal epithelial cells, the researchers constructed a chimeric mouse model of conditional knockout of hematopoietic cells NLRP3.
After feeding with Porphyromonas gingivalis, they found mouse rectal cancer tumors deficient in hematopoietic cells NLRP3 It is smaller and lighter than mice with normal NLRP3 hematopoietic cells, and the enrichment of myeloid cells in the tumor disappears, which means that the NLRP3 inflammasome activated by Porphyromonas gingivalis is derived from myeloid cells
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The researcher, in the form of an imperial gift, peeled off the cocoon from the outside to the inside, revealing another unknown evil of Porphyromonas gingivalis, and also showing the gap between the oral flora and the dark part of the digestive tract tumor.
Interactive
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The research on the intestinal flora is constantly in the sky, attracting countless light, while the oral flora is often overlooked under the cover of its light
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But as a unified whole, the human body has always moved the whole body.
A small mouth can have a great influence on the health of the whole body
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So, what are you waiting for? To prevent colorectal cancer, you may wish to broaden and broaden your thinking, starting with "tooth"
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References: [1] Zhang Y, Wang X, Li H, Ni C, Du Z, Yan F.
Human oral microbiota and its modulation for oral health.
Biomed Pharmacother.
2018;99:883-893.
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biopha.
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146【2】Wang X, Jia Y, Wen L, et al.
Porphyromonas gingivalis Promotes Colorectal Carcinoma by Activating the Hematopoietic NLRP3 Inflammasome.
Cancer Res.
2021;81(10):2745-2759.
doi:10.
1158 /0008-5472.
CAN-20-3827【3】Zheng RS, Sun KX, Zhang SW, et al.
Zhonghua Zhong Liu Za Zhi.
2019;41(1):19-28.
doi:10.
3760/cma.
j.
issn.
0253-3766.
2019.
01.
005【4】Zhang Z, Liu D, Liu S, Zhang S, Pan Y.
The Role of Porphyromonas gingivalis Outer Membrane Vesicles in Periodontal Disease and Related Systemic Diseases.
Front Cell Infect Microbiol.
2021;10: 585917.
Published 2021 Jan 28.
doi:10.
3389/fcimb.
2020.
585917【5】McGettrick AF, O'Neill LA.
NLRP3 and IL-1β in macrophages as critical regulators of metabolic diseases.
Diabetes Obes Metab.
2013;15 Suppl 3:19-25.
doi:10.
1111/dom.
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