Gut: Don't smoke! Yu Jun's team at Chinese University of Hong Kong found that cigarette smoke can promote colorectal cancer

Smoking is a major risk factor
for colorectal cancer (CRC).
The study aimed to investigate whether cigarette smoke promotes colorectal cancer
by altering the gut microbiota and associated metabolites.

On April 6, 2022, Yu Jun's team at Chinese University of Hong Kong published a research paper entitled "Cigarette smoke promotes colorectal cancer through modulation of gut microbiota and related metabolites online" in Gut (IF=32), which studied azomethane-treated C57BL/6 mice 2 per day hours of exposure to cigarette smoke or clean air for 28 weeks
.
The study found a significant increase
in tumor incidence and cell proliferation in mice exposed to cigarette smoke compared to control mice that did not smoke.
Dysbiosis of the gut microbiome was observed in mice exposed to smoke, with significant differences in the abundance of bacterial species, including enrichment of Eggerthella lenta and depletion
of Parabacteroides distasonis and Lactobacillus spp.
Metabolomic analysis showed an increase in bile acid metabolites, particularly taurodeoxycholic acid (TDCA),
in the colons of mice exposed to smoke.
The study found that E.
lenta had the most positive association
with TDCA in mice exposed to smoke.

In addition, mice exposed to smoke exhibited enhanced oncogenic MAPK/ERK signaling (a downstream target of TDCA) and impaired
intestinal barrier function.
In addition, colon cells from germ-free mice transplanted with feces from smoke-exposed mice (GF-AOMS) increased
proliferation.
Similarly, GF-AOMS shows increased abundance of intestinal E.
coli and TDCA, and damage
to the intestinal barrier that activates the MAPK/ERK pathway and colonic epithelium.

In conclusion, the study found that intestinal dysbacteriosis caused by cigarette smoke has a pro-tumor effect
in colorectal cancer.
Intestinal dysbacteriosis caused by smoke alters intestinal metabolites and impairs intestinal barrier function, which may activate oncogenic MAPK/ERK signaling
in the colonic epithelium.
 

Colorectal cancer (CRC) is one of the
most common cancers worldwide.
Although there are many strategies for early CRC screening and prevention, the burden is expected to increase
further.
There is evidence to support an association
between lifestyle such as diet, smoking, obesity, and exercise, and CRC.

Smoking increases the risk of lung cancer, and about 80% of primary lung cancers can be attributed to smoking
.
Smoking also increases the risk of cancer in other organs that are not directly exposed to cigarette smoke, such as the colon, rectum, pancreas, and kidneys
.
Studies have shown that smoking is significantly associated with CRC morbidity and mortality in humans, and smoking has also been observed to increase the risk of
CRC development in animal models.
However, the mechanism by which smoking promotes the development and progression of colorectal cancer is unclear
.

Increased
bacterial diversity was observed after smoking cessation in humans.
The report also suggests that changes in the microbiome and mucin structure are associated with
smoking.
In addition, gut microbes from CRC patients can promote colon tumorigenesis
in recipient mice.
However, whether changes in the gut microbiota represent a link between smoking and colorectal cancer remains elusive
.

Cigarette smoke increases the incidence of colorectal tumors in mice (Figure from Gut)

The study azomethane-treated C57BL/6 mice were exposed to cigarette smoke or clean air for 2 hours a day for 28 weeks
.
The study found a significant increase
in tumor incidence and cell proliferation in mice exposed to cigarette smoke compared to control mice that did not smoke.
Dysbiosis of the gut microbiome was observed in mice exposed to smoke, with significant differences in the abundance of bacterial species, including enrichment of Eggerthella lenta and depletion
of Parabacteroides distasonis and Lactobacillus spp.

Metabolomic analysis showed an increase in bile acid metabolites, particularly taurodeoxycholic acid (TDCA),
in the colons of mice exposed to smoke.
The study found that E.
lenta had the most positive association
with TDCA in mice exposed to smoke.
In addition, mice exposed to smoke exhibited enhanced oncogenic MAPK/ERK signaling (a downstream target of TDCA) and impaired
intestinal barrier function.
In addition, colon cells from germ-free mice transplanted with feces from smoke-exposed mice (GF-AOMS) increased
proliferation.
Similarly, GF-AOMS shows increased abundance of intestinal E.
coli and TDCA, and damage
to the intestinal barrier that activates the MAPK/ERK pathway and colonic epithelium.

In conclusion, the study found that intestinal dysbacteriosis caused by cigarette smoke has a pro-tumor effect
in colorectal cancer.
Intestinal dysbacteriosis caused by smoke alters intestinal metabolites and impairs intestinal barrier function, which may activate oncogenic MAPK/ERK signaling
in the colonic epithelium.

Reference Message:

https://gut.
bmj.
com/content/early/2022/04/05/gutjnl-2021-325021