Gut microbiota: how it could directly prevent colorectal cancer

Microbiota intestinale: come previene il tumore del colon

New research, published in the journal Nature Communications, shows how our diet affects bacteria in our gut, which, in turn, can alter the behavior of our genes and the risk of cancer. The good bacteria in our gut offer a protective barrier against harmful viruses, but they can also influence the behavior of our genes. The link between intestinal bacteria and the risk of colorectal cancer has received increasing attention in recent years. Last year, the NCI estimated more than 135,000 new cases of this cancer, with over 50,000 people dying from the disease. According to the National Cancer Institute (NCI), colorectal cancer is the fourth most common type of cancer, after breast, lung and prostate. About a year ago, there has been reported a study showing how different diets alter the bacteria in our gut which, in turn, affects the risk of developing colorectal cancer. Now, new research deepens our understanding of the connection between intestinal bacteria and the risk of developing colorectal cancer and various infections. The new study, led by dr. Patrick Varga-Weisz, of the Babraham Institute of Cambridge, England, shows how intestinal bacteria can influence genes, which therefore influence the risk of disease. Dr. Varga-Weisz and the team conducted experiments with mice and cultures of human cells, focusing on the role of molecules called short-chain fatty acids (SCFA) in disease prevention.

SCFAs are produced by intestinal bacteria during the digestion of fruits, vegetables and generally plant fibers. They can be used as a source of energy from our intestine lining cells, influencing their genes. Researchers used antibiotics to reduce intestinal bacteria in mice, analyzed their fecal samples and cells from their intestinal epithelium, i.e. the mucosa. A link between cellular metabolism, SCFAs, and transcriptional regulation is particularly relevant in the intestine where microorganisms break down complex carbohydrates to SCFAs such as acetate, propionate, and butyrate. SCFAs are an important component of normal gut physiology by providing a major energy source for the colon epithelial cells. They also affect cellular functions and modulate immune responses, in part by affecting gene expression and the epigenome Dr. Varga-Weisz and his team added SCFAs to human colon cancer cells and found that crotonylations increased, which are protein modifications that can activate or deactivate genes. These crotonylations were produced by inhibiting a protein called HDAC2. Previous studies have shown that a high number of HDAC2 proteins can increase the risk of colorectal cancer. Furthermore, bacteria-free mice showed a high number of HDAC2 proteins. Fruits and vegetables are essential for producing SCFA and these acids help regulate crotonylations.

So the results, the researchers explain, suggest that the regulation of crotonylation in the genome of intestinal cells can prevent cancer, and that a healthy diet of fruit and vegetables is essential for this prevention. A surprising finding of our work is that depletion of the microbiota of mice with antibiotics not only led to a drop in luminal and serum SCFAs, but also an increased expression of HDAC2 in colon. A reduction in histone crotonylation is consistent with both changes. A loss of SCFAs upon microbiota depletion may lead to stabilization or increased expression of HDAC2. In this context, it is interesting to note that a previous study has shown that the stability of HDAC2 is selectively reduced by the HDAC inhibitor valproic acid (a branched SCFA). Dr. Rachel Fellows explains: “SCFAs are a key energy source for cells in the gut, but we have also shown that they influence the genome’s crotonilation. Crotonilation is found in many cells but is particularly common in the gut. Our study reveals why this is the case by identifying a new role for HDAC2, which in turn is implicated in cancer and offers a new interesting drug target to be studied further. There is no need to remember how our gut is the home of countless bacteria, which produce certain vitamins, or that aid in the digestion of foods, elimination of harmful bacteria and educate our immune system to tolerance, a fundamental part of these processes”.

  • a cura del Dr. Gianfrancesco Cormaci, Medico specialista in Biochimica Clinica.

Bibliografia

Fellows R., Varga-Weisz P. et al. Nat Commun. 2018 Jan 9; 9(1):105.

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Han M et al. Protein Pept Lett. 2017 May 10; 24(5):388-396. 

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O’Keefe SJ. Nat Rev Gastroenterol Hepatol. 2016; 13(12):691-706.

Informazioni su Dott. Gianfrancesco Cormaci 1120 Articoli
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry specialty in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Detentore di un brevetto sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento immunologicamente neutralizzata (owner of a patent concerning the production of bakery gluten-free products, starting from regular wheat flour). - Autore di un libro riguardante la salute e l'alimentazione, con approfondimenti su come questa condizioni tutti i sistemi corporei. - Autore di articoli su informazione medica, salute e benessere sui siti web salutesicilia.com e medicomunicare.it

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