MICROBIOTA.
WHAT IT IS AND WHY IT IS SO IMPORTANT

The human microbiome has become the crucial moderator in the interactions between food and our body.
It is increasingly recognized that the microbiome can change our minds and our state of health, or activate a wide range of diseases, such as cancer, cardio-metabolic diseases, allergies, obesity and inflammatory diseases including intestinal diseases.
More recent studies also demonstrate the existence of a two-way communication pathway linking the gut and microbiota to the brain, suggesting that these microbes may play a role in neurological disorders.
The causes of diseases are often only partially understood.
Environmental factors can adversely alter the gut ecosystem and lead to dysbiosis that is associated with increased susceptibility to infections and noncommunicable diseases.
Nutrients, metabolites, and microbes are increasingly seen as key players, even as the full mechanisms of the disease remain unclear.

In this article we will refer to four aspects in relation to the Microbiota:

1. What is it
2. Why it’s so important
3. Where it comes from and how we incorporate it
4. Why scientists are betting on it
5. Microbiota and immunity
6. The future of the microbiota
7. The use of Probiotics

1.WHAT IS THE MICROBIOTA

The definition that we can extract from the Spanish Society of Biochemistry and Molecular Biology (SEBBM) says that the microbiota “is the set of microorganisms present in the human body and that it is mainly composed of bacteria, viruses and fungi”.

Let’s be honest, for ordinary mortals, when we talk about microorganisms, the first thing that comes to mind is the word disease.
And no wonder.
Until some time ago and with the microbial theory of disease proposed by Louis Pasteur, it was thought in a simplistic way that all microorganisms present in humans could cause diseases – this would later light the flame of antibiotics in the twentieth century.
But it wasn’t until relatively recently that it was discovered that these life forms were an indispensable and incredibly important part of our bodies.
What’s more, each human being has a microbiota as characteristic and exclusive as their fingerprint.

It is known that most of the microbiota of human populations is composed of 5 phyla, Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria and Verrucomicrobia, with Bacteroidetes and Firmicutes accounting for around 90% of the total bacterial species

2. WHY IS IT IMPORTANT?

These colonies are so important to humans because they are involved in numerous metabolic, physiological, and immunological functions that the body cannot perform on its own.
They synthesize vitamins B and K, essential amino acids, short-chain fatty acids.
For example, phyllokinones (vitamin K1) are absorbed from leafy green foods primarily and through bile salts.
But menaquinones (vitamin K2) are absorbed by the interaction of the microbiota in the colon.
Another case is represented by some bacteria that are responsible for the digestion of complex sugars, such as dietary fiber.

Trophic functions helping to maintain the structures and functions of the intestinal epithelium.

Defence functions, i.e. competitive exclusion of pathogens (adhesion and nutrients), maturation of the immune system and stimulation of the production of mucus and antimicrobial peptides.

There are different receptacles within the human body where the microbiota is located.

These include the skin, mouth, and intestine.
Today we will talk about the last two, since it is in those places where they have the greatest influence on health.

To give us an idea of the complexity of microorganisms present, we can say that in the mouth alone there are more than 700 different species of bacteria.
And with functions that range from the assimilation of nutrients to more complex issues.
Some bacteria, such as those expressing nitrate-reductase, catalyze the conversion of dietary nitrates into nitrites.
Thus, nitrites are converted into nitric oxide, which is a powerful vasodilator, in addition to the fact that it has antimicrobial activity and, as if that were not enough, plays a crucial role in maintaining cardiovascular health.

https://www.sciencedirect.com/science/article/pii/S0025775317304414?via%3Dihub

It is not the purpose of this article to delve into the amount of microorganisms present in our intestine, but until recently it was said that 1 to 2 kg of our body weightwould be represented by the intestinal microbiota.
We would be talking about 10¹⁴, and taking into account that our total cell count would be approximately 10¹³, it was said that bacteria and other microorganisms exceeded the total number of human cells by ten orders of magnitude.
These amounts of microbiota today are closer to 200 grams and that is why the figures are still under discussion. (https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.10…)

3. WHERE DOES IT COME FROM?

Continuing with our order of topics, the origin of these microorganisms is also still discussed to date without reaching a general consensus.
One of the most accepted scientific theories is that we receive them through the birth canal during birth.
This could partly explain the bacterial colony deficiencies found in children born by cesarean section.

There is also some controversy when thinking about whether the intestine of the fetus already has some bacterial colonies of its own in the maternal uterus or if the microorganisms that appear gradually during its development are the product of the transfer of these colonies from the mother to the child through the placenta.

On the other hand, during breastfeeding, breast milk would play a primary role as it would be the vial through which the mother would pass part of her colonies to the newborn.
The bacterial load in breast milk is called the “human milk bacteriome.”
This was thought to be due to the fact that children fed with formula milk presented various digestive and/or pathological alterations that were not found in those who were breastfeeding.

https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0268-4

4. WHY ARE SCIENTISTS BETTING ON IT?

Before all the organic functions they represent in our body were known, the microbiota was an “accumulation of germs necessary” for survival.
And it was also in this way that the degree of affectation produced by the indiscriminate use of antibiotics, which can cause dysbiosis, began to be studied.
Currently, the symbiotic relationships that some bacteria, fungi, viruses, prions and yeasts have with respect to the development and resolution of many diseases are being discovered.
Without going into detail, there are studies that relate the dysregulation of the microbiota with the etiopathogenesis of autism spectrum syndrome, schizophrenia, bipolar disorder, among other neurological diseases. https://www.wjgnet.com/1007-9327/full/v22/i1/361.htm

This topic is of such importance that there are already some studies that reveal the crucial role that some microorganisms would play with respect to inflammation and oxidative stress in age-related cardiovascular diseases. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232723/

The composition of bacterial diversity seems to change between lean and obese, increasing the number of Firmicutes to the detriment of Bacteroidetes.
There is an association of obesity and metabolic disorders related to different profiles of the gut microbiome, including metagenomics studies.
But the studies do not seem to find enough consistency in the results, most likely because it may be influenced by several factors, including different methodologies and growing knowledge of data management.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933040/

5.MICROBIOTA AND IMMUNITY

A notable feature of the gut immune system is its ability to establish immune tolerance to an enormous and changing wealth of harmless microorganisms, while preserving immune responses against pathogenic infection or commensal intrusion into the sterile body environment.

In a healthy state, the host’s immune response to the gut microbiota is strictly compartmentalized on the mucosal surface.

A single layer of epithelium separates the intestinal lumen from the underlying tissues.
Many mechanisms are used to achieve compartmentalization of the microbiota.
A dense layer of mucus separates the intestinal epithelium from the resident microbes.
The mucosal barrier is organized around the hyperglycosylated mucin MUC2.
However, MUC2 not only offers protection through static shielding, but also limits the immunogenicity of intestinal antigens by imprinting enteric dendritic cells (DCs) into an anti-inflammatory state.
Tight junctions are a critical structure for restricting transepithelial patency.
Microbial signals, for example, through the indole metabolite, promote the strengthening of the epithelial barrier.
In addition, secretory IgA antibodies and antimicrobial peptides (AMPs) maintain mucosal barrier function.

The microbiota and innate immunity are involved in extensive two-way communication.

One of the oldest phylogenetically systems of innate immunity is represented by antimicrobial peptides (AMPs).
Most intestinal MPAs are produced by Paneth cells, which represent specialized secretory cells from the mucosa of the small intestine.

Recent research also uncovers mechanisms that govern mutualism between the microbiome and the adaptive immune system. One example involves B cells, crucial mediators of intestinal homeostasis by producing a wide variety of secretory IgA antibodies that respond to commensals.

Under the influence of certain environmental factors and the genetic susceptibility of the host, aberrant interactions between the microbiome and the host’s immune system contribute to the development of various immune-mediated disorders.

In inflammatory bowel disease, e.g., antibiotic use or dietary changes, in the presence of genetic susceptibility (e.g.
E.g., NOD2 mutation), can lead to alterations of the configuration of the gut microbiome, including decreased richness and alteration of taxonomic and metabolite composition.
These microbiome alterations are strongly associated with aberrant mucosal immune responses, including upregulated Th17, Th1, and Th2-type responses, negative regulatory T cells, and dysregulated humoral immunity.
This can ultimately result in chronic, clinically manifest intestinal inflammation and tissue injury.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264227/

6.THE FUTURE OF THE MICROBIOTA

The key to progress in the future will be to use and exploit additional and emerging disciplines, such as metagenomics, to complement patient information and take our understanding of diseases and the interrelationship and effects of nutritional molecules to the next level.

Examples of this type of evidence can be found in Eugenomic.com.

The EU has already funded 216 projects under the Seventh Framework Programme and Horizon 2020 programmes to promote metagenomics and advance our knowledge of microbes.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009232/

https://pubmed.ncbi.nlm.nih.gov/28042926/

7.
EL USO DE LOS PROBIÓTICOS

Probiotics are non-pathogenic live microbes that play a central role in host health benefits when administered in sufficient amounts.

Regardless of this definition, dead probiotics and their metabolic secretions have the same or more response in different biological activities compared to live probiotics.
The main characteristics of probiotics are acid resistance, bile tolerance, adhesion of mucous cells or epithelia, antimicrobial resistance, hydrolase potential of bile salts, immunostimulation, antagonistic activity against pathogens, antimutagenic and anticancer activities.

Colorectal cancer (CRC) remains one of the most common and deadly cancers.
It is well known that changes in the gut microbiota or dysbiosis can have an essential impact on the initiation and promotion of chronic inflammatory pathways and also have different profound genetic and epigenetic alterations leading to dysplasia, clonal expansion and malignant transformation.

Probiotic bacteria have antitumor activity with various mechanisms, such as nonspecific physiological and immunological mechanisms.
A https://pubmed.ncbi.nlm.nih.gov/30912128/ review evaluates the effects of microbiota and probiotics in clinical trials, in vitro studies, and in animal models that have explored how probiotics act against cancer development and also discuss potential immunomodulatory mechanisms.
Several mechanisms of alteration of the intestinal microflora; inactivation of carcinogenic compounds; competition with putrefying and pathogenic microbiota; improvement of the host’s immune response; antiproliferative effects by regulating apoptosis and cell differentiation; fermentation of undigested food; tyrosine kinase inhibition; it reduces enteropathogenic complications before and after colon cancer surgery and improves diarrhea and has been able to create the integrity of the intestinal mucosa and have stimulatory effects on the systemic immune system and prevent CRC metastasis.

Looking to the future, we will surely continue to read that what we saw some time ago as a pathogen, today is an ally and tomorrow could become part of the cure or treatment for some diseases such as obesity, Alzheimer’s, arthritis or inflammatory bowel diseases.

We especially like Active flora for its diversity of bacteria, it contains a multispecies probiotic mixture of broad spectrum for the maintenance of adult intestinal health.

In the future, new strategies for disease management can be designed by manipulating the gut microbiota.
The common practice now available is the use of probiotics to rehabilitate the gut ecosystem.
Microbiota-based therapies, such as faecal transplantation, for the treatment of recurrent antibiotic-resistant Clostridium difficile infection are now in clinical trials and are reported to be highly successful.
In the next decade, we will likely see even more exciting approaches, for example, the use of advanced microbiota engineering technologies to create “smart” or “smart” bacteria for use in diagnosis, prevention, prediction, and treatment of inflammatory diseases and possibly some gastrointestinal cancers.
Microbiota-based therapeutics together with personalized medicine may be the most precise and optimal strategy for the future treatment of some difficult-to-control diseases.