Gut microbes will be key to personalized medicine

Gut microbes will be key to personalized medicine

BarcelonaIt’s hard to believe that until about 20 years ago, little was known about the 40 trillion microorganisms that live within us and make up our microbiome. Viruses, fungi, yeasts, archaea and especially bacteria cover every surface of the body, from the mouth to the vagina, skin and eyes. Yet the vast majority of them are concentrated in the last section of the large intestine, the colon.

From there, these microorganisms, which are no less abundant than human cells themselves, function as a single organ and perform functions essential for our survival, such as digesting food and extracting energy from it, making vitamins and other essential molecules, eliminating toxins, as well as training. Our immune system.

Although the study of the microbiome is a preliminary activity, although in full ferment, studies conducted in the last two decades have been able to establish links between imbalances in the gut microbiota and the development and evolution of intestinal bacteria in practically all diseases: from cancer, diabetes and obesity to allergies, asthma and lupus, through neurological conditions, such as multiple sclerosis, Parkinson’s disease, depression or autism.

In addition, microorganisms are beginning to be discovered to influence the way we react to medical treatments and their potential effectiveness, such as with vaccines and immunotherapies, as well as many other medications.

“The gut microbiome will play a major role in personalized medicine in the future,” says Mireia Valles Colomer, head of the Microbiome Research Group at the Pompeu Fabra University (UPF). The biotech scientist continues: “Within a few years, we hope to be able to diagnose diseases early from the microbial composition and modify them through the use of probiotics or personalized fecal transplants to influence the risk of developing diseases, or to increase the effectiveness of drugs and treatments.”

Shake stool

Valles-Colomér is investigating how we acquire the bacteria that make up our gut microbiome. The core is known to be inherited from our mothers during vaginal birth, and we then add new species through breastfeeding, food and contact with our environment. The more diverse the bacteria in our colon, the more likely we are to be healthy. The opposite is true: having fewer species is associated with lower global well-being.

Several scientific studies have found that changes in the composition of these microorganisms early in life – such as birth by caesarean section, or frequent antibiotic use during the first years of life – increase the risk of developing autoimmune or metabolic diseases later on. In this regard, a small group of newborns born by caesarean section were given milk shakes and their mothers’ stools in an attempt to restore the natural process of transferring microbes between mothers and babies and thus reduce the risk of these babies getting sick.

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“At that time, they already saw that the composition of the microbiota of the babies was more similar to that of those born vaginally,” explains Valles-Colomér, who participated in continuing that study by carrying out a metagenomic analysis of the characteristics of the babies’ stool samples at 1 and 3 weeks, 6 and 12 months. “It was recovered effectively and the levels of pathogenic bacteria were lower, compared to babies born by caesarean section who did not take the milkshake,” highlights Valles-Colomér.

Although other studies that have followed children born in both directions during early childhood have concluded that after three years, the microbiota of one and the other remains almost the same, for this researcher, the first years of life “can be crucial developmental windows for training children’s immune systems.” He adds that these children, if left uninterrupted, remain “more susceptible to asthma, allergies and some autoimmune diseases.”

For Valles Colomer, their fecal transplantation of newborns through a mixture of breast milk and stool “opens the door to potential personalized treatments,” where the baby’s existing bacteria and missing bacteria will be analyzed to inoculate them — a “personal cocktail” that could reduce the risk of disease. “We’re not there yet, but we’re making progress,” he says.

she gave Years of driving in Catalonia

This week, the biotechnologist participated in an international conference on the human microbiome, the Barcelona Human Microbiome Debates., Organized by IrsiCaixa, it took place at the Cosmocaixa Science Museum in Barcelona. It is one of the reference scientific meetings in research in this field, and this year it reached its tenth edition.

“We were pioneers 10 years ago,” says Roger Paredes, principal investigator at IrsiCaixa, and head of the infectious diseases service at Germans Trias i Pujol Hospital in Badalona. Alma Mater “Then we started to feel that gut microbes were essential to human health, and that they would have important implications for the practice of medicine,” he recalls. At the time, “we were still a long way from there: a lot of basic research was needed to be able to use them as a diagnostic tool and implement therapeutic interventions. Now we are much closer,” Paredes says.

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“Understanding the human microbiome is fundamental to addressing global health challenges,” adds Francisco Guarner, a gastroenterologist at Vall d’Hebron Hospital and one of the first and most renowned researchers in this field at the hospital’s Research Institute (VHIR). He, along with Paredes, coordinated the organization of this international conference.

One of the challenges Garner highlights is understanding the role that bacteria in the colon play in the onset of disease. There are more and more studies linking imbalances, changes and depletion of the gut microbiota with diseases, especially immune diseases, such as multiple sclerosis, and inflammatory diseases, such as Covid, or cancer. Colon tumors are the most obvious case, but a link has also been shown in liver tumors, head and neck tumors and even pancreatic tumors.

Two years ago, CNIO researcher Nuria Malats demonstrated that pancreatic tumors can be diagnosed early based on a combination of bacteria. “It is a set of 27 microorganisms, mostly bacteria, which, when present in large quantities, predict the presence of a pancreatic tumor, opening the door to being able to operate and remove it,” he explains. “It is not clear that the microorganisms are the initiating factor, but they seem to promote the tumor and facilitate its progression,” he points out.

Influencing the effectiveness of medications

In addition to allowing early diagnosis of diseases, the intestinal microbiota influences our response to treatments, precisely because of this close relationship that it maintains with our defense system from birth. In this sense, the international Mistral project, funded by €10 million from EU Horizon 2020 funds and led by IrsiCaixa, is evaluating whether it is possible to predict the effectiveness of vaccines being developed against HIV as a function. From intestinal bacteria.

“We are looking to identify biomarkers, to understand the characteristics of the microbiome that allow us to predict who will respond better to vaccines,” explains Paredes, who adds that “the effectiveness of many drugs, such as cancer immunotherapies or vaccines, depends on the state of the immune system at any given moment, which we know is in constant interaction with microorganisms.” For Valles Colomer, it is clear that “in the future, the activity of many drugs will be linked to the composition of the microorganism and bacteria will be used as drugs, either to administer a specific drug or for the effects of the molecules they secrete.”

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Towards personalized medicine

Thus, in the future it will be possible to take a sample of a person’s stool, analyze their microbiome and assess their risk of developing a health problem; something very similar to current genetic analyses. This will open the door to being able to develop prevention strategies.

The next step will be to see if it is possible to restore or modify the gut microbiota to reverse the processes. There are already studies underway on obesity and type 2 diabetes using specific strains of bacteria or trying to alleviate symptoms of multiple sclerosis and rheumatoid arthritis and stop their progression from the colon. In addition, some researchers are working on designing personalized diets aimed at promoting the increase of beneficial bacteria to treat diseases or improve the effectiveness of treatment.

“Patience is required,” Paredes admits. “No microbiologist or immunologist doubts the fundamental role of microbes in human health, but transferring all the knowledge obtained to clinical experience is a challenge. There is still a long way to go, but we are getting closer,” concludes the doctor.

Treatment for bacterial vaginosis

Three out of 10 women of reproductive age suffer from bacterial vaginosis, a disease that has a negative impact on their quality of life as well as their sexual life. This is caused by a change in the vaginal microbiota, when some potentially pathogenic species grow excessively and displace the beneficial lactobacilli that help maintain a healthy vaginal ecosystem.

Today, despite the knowledge of its existence, there is no effective treatment, largely because it is understudied and underdiagnosed, “perhaps because of the gender bias that also pervades science,” notes Jacques Ravel, a researcher at the School of Medicine of the University of Maryland (USA), who participated in the Human Microbiome Conference held in Barcelona.

Ravel is coordinating a study with women in Africa and Boston to find an effective treatment for the disease. “What we have now is not effective: in most women, relapses occur after six months and it is the same antibiotic treatment that we have been using for more than 40 years. There has been no investment, no research, nothing to find an alternative,” he explains.

In his clinical trial, the researcher is trying to restore a healthy vaginal bacterial ecosystem using probiotics that he applies to the vagina in pill form along with an antibiotic.

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