May 30, 2024

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New Mechanism of Vitamin D Inhibiting Colorectal Cancer

New Mechanism of Vitamin D Inhibiting Colorectal Cancer



 

New Mechanism of Vitamin D Inhibiting Colorectal Cancer.

Colorectal cancer (CRC) is a common and fatal malignancy. Consumption of CRC-depleted bacteria as probiotics and/or their metabolites may create a gut microenvironment that does not allow CRC to develop. In particular, these preparations have a relatively high safety profile due to their natural origin.

 

On July 20th, the team led by Professor Yu at the Chinese University of Hong Kong published a research paper in “Cancer Cell” titled “Carnobacterium maltaromaticum boosts intestinal vitamin D production to suppress colorectal cancer in female mice.” The study found that maltaromaticum, a type of bacteria, colonizes the intestine in an estrogen-dependent manner and, together with other microorganisms, increases the production of vitamin D in the gut. This activation of the host’s VDR helps suppress colorectal cancer.

 

New Mechanism of Vitamin D Inhibiting Colorectal Cancer.https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00236-2#secsectitle0035

 

 

 


Research Background

 

A recent clinical study showed that Bifidobacteria and Lactobacilli reduced the levels of pro-inflammatory cytokines in postoperative patients with colorectal cancer.

 

Researchers found that two CRC-depleting bacteria, Streptococcus thermophilus and Lactobacillus galinarunus, prevented intestinal tumorigenesis in mice by secreting β-galactosidase and indole-3-lactic acid, respectively.

In addition, tumor suppressor metabolites secreted by probiotics can exert direct anticancer effects. To develop probiotics as a strategy for CRC prevention, it is crucial to identify other CRC-consuming bacteria.

 

Men have a higher risk of colorectal cancer than women. In this regard, sex-specific differences in gut microbiota may underlie observed sex differences in human disease.

However, how the sexually dimorphic gut microbiota influences the development of CRC remains poorly understood.

Notably, both the effects of sex hormones on the gut microbiota and sex-specific responses to the same microbiota have been reported.

Human studies have also reported greater variability in the gut microbiota in men, with sex-specific microbial interactions having a strong impact on chronic fatigue syndrome symptom presentation.

Thus, direct exposure of gut tissue to gut microbes requires consideration of sex-specific differences in gut microbiota when designing probiotic-based interventions.

 

 

 

 


Research progress

 

To investigate whether Clostridium maltosa could exert anti-CRC effects in a sex-specific manner, 200 μL of bacterial suspension containing 1 × 108 colony-forming units (CFU) of Clostridium maltosa (strain ATTC B270, unless otherwise specified) was orally administered daily ( germline mutant intestinal tumorigenesis model).

The same volume of brain heart infusion (BHI) or the same amount of E. coli (strain MG1655) was used as a control and administered to mice for 12 weeks under the same protocol as C. maltosa (Fig. 1A and 1D). We observed a visual reduction in tumor size under colonoscopy in C. maltosa-treated female but not male mice compared with BHI or E. coli administration (Fig. 1B and 1E).

 

After sacrifice, we observed a significant reduction in tumor number and tumor burden in the colon and small intestine only in female C. maltaromaticum-treated Apcmin/+ mice, but not in male mice (Fig. 1C and 1F) .

Researchers verified the sex-specificity of the anti-CRC effect of Clostridium maltosa in a carcinogen-induced CRC model, in which C57BL/6 female and male mice were injected weekly with the carcinogen pyrimidine methane (AOM; 10 mg/kg) for 6 weeks, followed by oral administration of Clostridium maltosa, E. coli, or BHI. We observed consistent female-specific tumor suppression by C. maltosa (Fig. 1G-1L). These findings suggest that C. maltosa can suppress intestinal tumorigenesis in a female-specific manner.

 

New Mechanism of Vitamin D Inhibiting Colorectal Cancer.
Clostridium maltosa prevents intestinal tumorigenesis in two mouse models of CRC in a sex-specific manner

 

 

 

 


Significance

 

In conclusion, our study found that C. maltica was specifically depleted in female colorectal cancer (CRC) patients.

Administration of Clostridium maltosa reduces intestinal tumor formation in two mouse CRC models in a female-specific manner. Estrogen increases the attachment and colonization of C. maltosa by increasing the colonic expression of SLC3A2, which binds to the DD-CPase of this bacterium.

Metabolomic and transcriptomic profiling reveals increased gut abundance of vitamin D-related metabolites and mucosal activation of vitamin D receptor (VDR) signaling in maltose-gavaged mice, with gut microbiome and VDR-dependent Way.

An in vitro fermentation system confirms metabolic cross-feeding of Clostridium maltosa with Faecalibacterium to convert 7-dehydrocholesterol produced by Clostridium maltosa into vitamin D to activate host VDR signaling.

In conclusion, Clostridium maltosa can be used as a probiotic-based preventive drug for the prevention of CRC in women. This study highlights the importance of sex-specific differences in the microbiota in the development of probiotic therapies.

 

 

 

 

 

 

References:

https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00236-2#secsectitle0035

New Mechanism of Vitamin D Inhibiting Colorectal Cancer.

(source:internet, reference only)


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