Gin microbiota – the population of microbes living in our intestines – can be used to predict colon cancer and rectum, the second most common type of cancer in women and third in men t .
Research by an international team of scientists, including Brazil, has found a link between colon cancer and rectum and changes in gut microbiota patterns that do not depend on the dietary habits of the populations studied. The discovery prepares the way to develop unobtrusive tests that can predict the emergence of the disease.
The study is published on Monday, 1 April, in the journal Nature Medicine. His first author is Andrew Maltez Thomas, who has a PhD in bioinformatics from the University of São Paulo (USP), Brazil. Thomas was supported by the São Paulo Research Institute – FAPESP through a scholarship for a research internship at the University of Trento in Italy.
In one of the largest and most diverse surveys ever undertaken on the subject, the researchers combined metagenomics, bioinformatics and engineering learning (with the use of artificial intelligence) to correlate the event of colon cancer and the rectum with microbiota intestinal data. for 969 people in Canada, China, France, Germany, Japan and the United States.
He noted the findings of groups of microorganisms associated with colon cancer and rectum in each of the populations studied, and signatures in the microbial metabolism (patterns of micro-metabolites produced by micro- organisms). organisms) which can be used to predict the disease's events. The research had two other important outcomes. One is the discovery of colon cancer patients and the rectum of a particular species of bacteria that are commonly found in the mouth and the airways. The other is a correlation between colon cancer and the rectum and the presence of the gene for a microbial enzyme that degrades the pine, vitamin B essential nutrients.
The study found higher levels of the bacterial species Fusobacterium nucleatum in colon cancer patients and rectum than in healthy individuals. This bacterium usually lives in regions of the mouth, and the acidity of other parts of the gastrointestinal tract was thought to be fatal to it.
"More numbers of oral bacteria tend to travel to the bowel in colon cancer patients and the rectum. This migration can cause inflammation of the bowel, leading to the tumor," said Thomas. "However, we do not know the true reason for the migration, only that there is a link between the presence of these bacteria in the bowel and colon cancer and the rectum and that the loop merits further investigation."
The other discovery, which is the significant presence of the gene for the enzyme trimethylamine-lyase microbial gene in fecal samples of colon cancer patients and the rectum, reinforces the possibility of a carcinogenic link between a microbiota intestine. and fatty diet, identified by previous research. "When the enzyme splits a colony, which is abundant in a diet containing a large amount of red meat and other fatty foods, our acetaldehyde, a known carcinogen, is released," Thomas said.
In the study, the researchers used data on the composition and abundance of all bacteria found in 969 fecal samples. In order to develop a simple method of analysis that can be widely used by clinics and hospitals, the statistically significant bacteria were selected.
"Our results from 16 species of bacteria were similar to those of all analyzes using each species. This is an important step in the development of a simple diagnostic tool that omits the need to provide a sequence of microbiota whole again, "Thomas said.
Society is not a causal link
Research on the links between gut microfiche and human health has grown in the last ten years, but the new study is pioneering by conception as bacteria to develop disease.
"Markers are usually considered directly in connection with tumor cells. We use a different concept. Our analysis is based on changes in a relatively small set of bacteria in a spectrum of hundreds of bacteria living in The gut can show the presence of disease, "said Emmanuel Dias-Neto, a researcher at the Camargo Cancer Center International Research Center (CIPE) and co-author of the article.
DNA sequencing obtained from a gut microbiota enabled the researchers to identify the bacteria present in each fecal sample, to measure the size of each bacterium, and to identify variations in their genomes that may be related to results. different, as an increased risk of cancer colorectal.
It should be emphasized, however, that the study did not show that changes in gut microbiota cause colon cancer and rectum.
"We found a society, but that does not necessarily imply a causal link. The question is whether certain bacteria can cause cancer or cancer creating a different environment in the colorectal duct and therefore favors certain bacteria over others. solution, which would be fundamental for the research results described in the article to help develop therapies to treat colon cancer and rectum, "said João Carlos Setubal, Full Teacher in Department Biochemistry University of São Paulo, co-ordinator of the same Inter-University Graduates. Program in Bioinformatics, and also co-author of the article. Setubal and Dias-Neto supervised Thomas's PhD research.
According to the researchers, this may be the largest ever study of colon cancer and the rectum based on data from fecal samples and such diverse populations. The group analyzed data from five public studies and two further studies by researchers at the University of Trento.
With the data from these seven studies they were able to identify enzymes and bacteria, and work out how gut microbiota can predict the development of colon cancer and rectum. Data from two other studies was used with 200 samples to validate their findings.
The DNA sequencing of the samples, which required differentiation between microbiota DNA and human DNA, was a means of identifying and quantifying the species of microorganisms and their genes present in the samples, t "Thomas said. "We removed DNA from the fecal samples and put it in order. We then used computational methods to analyze the data. As a result, we were able to identify and quantify the species. and the gene numbers. "
Because the data came from different studies, the researchers used sophisticated statistical methods to analyze them as an ensemble.
"We used meta-analytic statistical methods and machine learning techniques to find out how predictable the results were," said Thomas.
The findings were validated by Nicola Segata, a computational biologist at the University of Trento and an overseas supervisor for the project, and was reinforced by another study conducted at the European Molecular Biology Laboratory (EMBL) in Germany on the links between gut microbiome and cancer. An article on the EMBL study is published in the same edition of Nature Medicine.
"In the preparation of the articles, we exchanged data and information with the other group in partnership that was extremely important to reinforce our findings. Although we used machine learning techniques and different statistical methods, we we reached the same conclusion that microbiofi the gut can predict the presence of colon cancer and rectum in different populations and studies, "Thomas said.