June 16, 2024

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How does spinach affect the gut microbiota and prevent colon cancer?

How does spinach affect the gut microbiota and prevent colon cancer?


How does spinach affect the gut microbiota and prevent colon cancer?

According to the latest global cancer burden data released by the International Agency for Research on Cancer (IARC) of the World Health Organization in 2020.


Colorectal cancer is expected to add 1.93 million people in 2020, second only to breast and lung cancer. The number of deaths from colorectal cancer is second only to lung cancer, ranking second in the number of deaths from cancer.


The vast majority of colon cancers (85%-90%) are sporadic, which means they are not caused by genetic variation.

Carcinogens in the diet and environment can change the way genes are expressed in the gastrointestinal tract, leading to colon polyps and possibly cancer.

This is why the American Cancer Society recommends starting colorectal cancer screening at the age of 45.


Intestinal flora is closely related to human health. For example, studies on sterile colon cancer models have shown that compared with corresponding animals under conventional feeding conditions, intestinal inflammation and tumor prognosis have been improved.

Fecal microbiota transplantation has been successfully used to treat recurrent Clostridium difficile infections and has clinical benefits for patients with inflammatory bowel disease, functional gastrointestinal disease and obesity.



Previous studies have shown that eating green vegetables and fiber can reduce the risk of colon cancer by half. However, little is known about how these dietary intakes affect the interactions between the gut microbiota, host transcriptomics, and the pathogenesis of colon cancer.



Recently, a research team from the Health Science Center of Texas A&M University in the United States published a research paper titled Dietary spinach reshapes the gut microbiome in an Apc-mutant genetic background: mechanistic insights from integrated multi-omics in the Gut Microbes journal.



The study found that in the rat colon polyp model through multi-omics techniques, the consumption of spinach has a significant anti-cancer effect. Metagenomic prediction involves the metabolism of linoleic acid and butyric acid, the tricarboxylic acid cycle, and cancer pathways. This is supported by transcriptomics and metabolomics analysis, laying the foundation for the future development of methods to prevent colon cancer.



How does spinach affect the gut microbiota and prevent colon cancer?



The research team used a genetic disease model called familial adenomatous polyposis, Pirc, which is a genetic disease that causes multiple noncancerous growths (polyps) in the colon in young people. Most people with this disease must have their colon removed surgically and receive toxic NSAID treatment to prevent tumors from forming in the colon and small intestine.



After feeding freeze-dried spinach to Pirc rats for 26 weeks, the research team observed significant anti-cancer activity in the colon and small intestine.

In fact, tumor suppression occurred as early as the 8th week of feeding spinach, and the tumor was significantly suppressed after the 16th week. Immunohistochemistry and WB experiments showed that the overexpression of β-catenin protein in tumors was not affected by spinach.

Therefore, despite the genetic background of Apc mutations, the research team is still exploring anti-cancer mechanisms other than down-regulation of β-catenin protein.



How does spinach affect the gut microbiota and prevent colon cancer? How does spinach affect the gut microbiota and prevent colon cancer?



Next, the research team used multiple omics methods to discover the connections between different systems in the body.

They first analyzed the gut microbiota of wild-type and Pirc rats fed with normal diet or spinach by metagenomic sequencing, and found that there was no community difference between wild-type and Pirc.

Feeding spinach significantly increases the abundance of beneficial microorganisms such as verrucobacterium, and reduces the abundance of harmful microorganisms such as proteobacteria and microbacteria.

This shows that diet plays a more dominant role in shaping the inter-individual variation of the host-related microbiota than genetic background.



Subsequently, they used the metabolome to analyze the community. The data showed that spinach intake significantly reduced linoleic acid and ether lipid metabolism, the tricarboxylic acid cycle pathway was down-regulated, while membrane transporter, cell motility, signal transduction, transcription, carbohydrate metabolism, and kinase pathways were significantly up-regulated.



Finally, they used RNA-seq to identify five pathways that are significantly altered in Pirc’s colon. Three of these pathways are further altered in colorectal tumors, namely, inflammation, TNFα signaling through NFκB, and myogenesis. They verified that Cxcl6, Serpine1 and Il-1b, Hspb8, Tpm2, and Fhl1 were down-regulated in Pirc, while MYH11 and Myl9 were up-regulated in Pirc.



After feeding spinach, they observed a reversal of Pirc’s up- or down-regulated pathway relative to normal tissues. miRNA-seq showed that 115 differentially expressed miRNAs were associated with tumor formation, among which miR-215, miR-143 and mir-145 were significantly down-regulated in Pirc colon tumors. After feeding spinach, they also observed that the up- and down-regulation trend of some miRNAs was reversed.



Combining the three kinds of omics data, the research team observed that butyrate metabolism and calcium signal transduction are significantly negatively correlated, peptidase is positively correlated with cancer pathways; Labeospiraceae and Slc30a10, Bacteroides, Rumenococcus and Plcd1 And Rumenococcus is positively correlated with serine protease inhibitors; Rumenococcus is negatively correlated with Tcf7l1.


How does spinach affect the gut microbiota and prevent colon cancer?



In conclusion, this work proves that spinach has a significant anti-cancer effect in the Apc mutant colon polyp rat model, and confirms the significant remodeling of the intestinal microbiome of rats fed spinach, as well as the host transcriptomics and metabolome. Changes have laid the foundation for the development of methods to prevent colon cancer in the future.




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