We are half human, half bacteria: what can the microbes that inhabit our body do for us?

We are not alone.

Never quite.

Although they cannot be seen with the naked eye and do not make noise, one is always accompanied by thousands and thousands of bacteria, viruses, fungi and yeasts, archaea and protozoa.

An immense living world of microbes populates, in reasonable harmony, the skin, the vagina, the mouth, the lungs and, especially, the intestine, to help the human being with functions as basic as protecting themselves against external pathogens or metabolizing certain foods.

It is the human microbiome, a complex ecosystem of microbes that functions like another organ within the body.

Some of its essential tasks are already known, but the scientific community is still trying to fully decipher its critical role in health and disease: there are changes in this microworld related to infectious diseases, autoimmune diseases, and even

An individual is, in the words of microbiologist Ignacio López-Goñi, “half human, half bacteria”.

It's a bit of both because there are as many human cells in the body as there are microbes of this type.

“We have about 23,000 human genes, but our microbes as a whole can house about three million genes.

Some already consider this microbiome our second genome.

We are superorganisms in which 1% of our genome is inherited from our parents and 99% from our microbes”, he summarizes in his book

(Almuzara, 2018).

More information

The evolution of humans is in your bacteria

Of all those tiny microorganisms that roam freely throughout the body, bacteria are the most common guild of what has been called the microbiota or microbiome —some experts use both terms as synonyms, although they have a differential nuance: the first is refers to the community of microbes and, the second, to their genes.

"It is estimated that more than 10,000 different bacterial species inhabit our healthy body, of which less than 1% can be potential pathogens," says López-Goñi in his book.

The greatest bacterial diversity is found in the mouth and in the intestinal tract.

The scientific community has conspired to unravel what this amalgam of microbes that cohabits in humans does and how it is organized.

And although they have found out something, there is still a lot to know, says Jordi Guardiola, head of the Digestive System service at the Hospital de Bellvitge in Barcelona and one of the heads of the Unit for the Study of the Microbiome at his center: "The main thing that What we know is that we know very little: the microbiome is extremely complex.”

For José Manuel Fernández-Real, a scientist at the Josep Trueta Biomedical Research Institute of Girona, the microbiota is like the black box of an airplane, "a continuous record of daily activity", from eating to the level of stress or the state of cheer up.

"It is a brutal volume of information that we have to unravel", admits the expert,

Each microbiome is unique.

No two are the same.

And they constantly change with age, habits, diet or drug use.

There are about 150 dominant bacterial species, says Francisco Guarner, a gastroenterologist and member of the scientific committee of the International Human Microbiome Consortium.

“In a study it was shown that there were only 18 species that were in all the participants, but in some it was at the level of 1 and, in others, at the level of 10,000.

We could not define the essential nucleus of bacteria.

They were not random mixtures, but living ecosystems.

And it changes a lot: it is not static, but it is stable, there is always a balance, a balance between bacteria”.

The intestinal microbiota, being the largest, most varied and with the most key organic functions, is the most studied area.

Their role, Guarner points out, is essential: “We have an organ, which is the colon, prepared to receive bacteria and we want them to be there to help us digest food.

In the colon there is a bag, the cecum, where what we could not absorb with the pancreas is deposited.

Plant cells, for example, are digested by bacteria in the cecum.

Stimulate the immune system

The intestinal microbiota is also "a great filter of the external environment", Fernández-Real intervenes: "It is a marker of the diet we follow, a transformer of many substances —like a liver before the liver—, and it is also a species immune system that protects us from foreign elements.

In fact, Guardiola adds, another of its functions is to stimulate the immune system: “Microbes interact with each other and with us.

There is a constant conversation.

In the first years of life, it is essential to have a microbiome to develop the immune system normally."

The microbiome is influenced by diet, medications, smoking, physical exercise, diseases.

The use of antibiotics in early childhood, for example, may be a risk factor that alters this microbial balance.

“The price we have to pay in order not to die from infections is that immune-mediated diseases can appear.

Most of the genetic variants detected as risk factors for these diseases are genes that encode aspects related to the microbiota”, says Guardiola.

Being born by caesarean section, without being impregnated with the mother's vaginal microbiome, increases the risk of asthma or allergies, and breastfeeding also influences the composition of the child's microbiota and is key to the creation of her immune system.

The scientific community has focused on finding out exactly what the role of the microbiome is when someone is healthy or sick.

Can an alteration of the microbiome cause diseases or do diseases modulate the microbial ecosystem?

Probably both.

Researchers from half the world are beginning to define how these microorganisms mediate various pathologies, but it is not an easy task to limit their influence.

"Surely, the microbiota is one more factor that we did not count on, but not necessarily the decisive factor," Guarner settles.

What they know for sure, explains this gastroenterologist, is that, to a greater or lesser extent, these microbes influence "colon and breast cancer, depression, allergies, obesity, type 2 diabetes and ulcerative colitis."

“The common factor that appears in almost all diseases is the loss of diversity and this is possibly also related to diets rich in protein and fat and few vegetables.

The microbiota that we had in the colon to digest those vegetables is lost and disappears”, Guarner ponders.

In mouse models, there are studies that also suggest that the intestinal microbiota can influence neurophysiology, behavior, and even the wound healing process.

It was also found that it can affect cognition and anxiety.

Other research, also in animal models, suggested that gut microbes are potentially relevant to neurodegenerative diseases, such as Parkinson's, and found that "there is a significant difference in the component of gut microbes in children with and without spectrum disorders." autistic".

Periodontal diseases, which are spread by a disruption of the oral microbiota, also raise the risk of cardiovascular disease by up to 25%.

In cancer, it has been described that the alteration of the microbiota can trigger inflammation and an immune response that are related to the onset of tumors.

Guardiola explains, on the other hand, that they are also studying whether a certain microbiota can predispose to a tumor or not.

For now, she adds, "a very clear relationship has been found between the microbiome and the possibility of responding to immunotherapy": "The microbiota of patients who respond to immunotherapy is different from that of those who do not respond.

If you pass this to experimental animals and you put feces from responding patients to the non-responding mice, they eventually respond too.

The microbiota has the capacity to influence these treatments and can be used as a prognostic factor or as a treatment:

stool transplant

An ailment closely linked to the microbiota is infection by

, a very resistant bacterium that, in debilitated people, can cause mild colitis (diarrhea) or severe, with a toxic megacolon that can lead to death.

This disease is clearly related to an alteration of the microbiota to the point that donor fecal microbiota transplantation is the indicated treatment for patients who do not respond to conventional therapies.

“In 20% of patients, the infection recurs.

Then, the possibility of recurrence again already amounts to 40%, ”says Guardiola, who does about twenty transplants of this type a year in his hospital.

The study of the microbiota has followed different paths, from describing it to understanding its function or learning to modulate it as a therapeutic tool.

In this last field, stool transplantation, which repopulates the patient's intestine with the fecal microbiota of a healthy donor, has been one of the most promising strategies.

However, for now, it has only succeeded in

.

For irritable bowel, Guarner notes, it didn't fare so well.

“In a disease there is a defect of some species and an overabundance of others.

When you take the feces from a donor, you transplant there some good bacteria and some bad ones and, perhaps, the good ones do not fit well in that inflamed intestine and the bad ones do and the inflammation increases.

That has happened in ulcerative colitis, where some transplants went well and others did not.

The problem is that you introduce a world with many unknown bacteria and the particular situation of each patient can make some not fit well.

Guardiola, who has set up a stool bank at his hospital, agrees that while fecal transplantation is "a necessity" to treat

, "for other aspects it has not gone as well as predicted," such as in inflammatory bowel disease.

But research continues, also with cocktails of bacteria "designed in the laboratory and perfectly characterized so that there are no surprises" with unknown potential microbes, Guarner points out.

The American regulatory agency (FDA) approved in November the first prepackaged fecal microbiota biodrug for

Scientists are also experimenting with bacteria modified in the laboratory to modulate the microbiota and probiotics and prebiotics continue to be tested, although the efficacy of the latter two remains scarce and highly controversial.

"As an idea, probiotics are attractive, but in clinical practice we rarely achieve almost nothing," concludes Guardiola.

Fernández-Real agrees: “Talking about probiotics that try to change health is difficult.

It's like trying to move an aircraft carrier with a bunch of flies."

Mediterranean diet

The investigation continues.

But at the therapeutic level, the experts consulted advocate starting with what is known to be positive: the Mediterranean diet.

"The people who follow it have the closest thing we know to a healthy microbiome," defends Fernández-Real.

Guarner agrees: "We must recover the functionality of the microbiota, return to ancestral diets, eat lentils, peppers and aubergines."

About the ins and outs of the microbiome, they admit, there is a world to discover.

For example, the role of viruses in this intricate ecosystem, Guarner points out: “The virome is the most unknown.

35,000 viruses have been found in the intestine: 98% are viruses that affect bacteria, not human cells, and 75% of them we don't know what they do”.

Because they don't know, they don't know or even know exactly what "the definition of a healthy microbiome" is, laments Fernández-Real.

And neither where does the influence of the microbiome reach.

“The difficult thing is to say when it does not influence.

What can be said for sure that is happening is that we have entered a path, during the last 70 years, in which the microbiota has atrophied a lot.

By changing nutritional patterns and the use of antibiotics, it has become atrophic," says Guarner.

There is much to do.

As for "better understanding of the mechanisms by which the microbiota and the immune system speak to each other", Guardiola agrees.

For Guarner, "the key will be to detect critical deviations for the gut microbiome and find methods to correct them."

Fernández-Real, for his part, proposes a twist: "Not to insist on changing the bacteria [of the microbiota], but their function because they will continue with us."

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