The "microbiota" is defined as a complex population of microorganisms that resides on every surface of the body exposed to the outside world (skin, respiratory, intestinal, urogenital, mucous membranes).
In the intestine, which alone counts more than 70% of all the microbes of the human body, these organisms reach an enormous density (the intestinal microbiota is now assimilated to a real organ, weighing about 1.5 kg, which includes millions of bacteria of about 2,000 different species).
Microbes have always been present in the human intestine and the intestinal microbiota has developed together with the host organism where it has performed and continues to perform two important functions:
• the digestion of food macromolecules which improves the digestive efficiency of the host and, at the same, time guarantees a supply of useful nutrients also for the microbes themselves
• the maturation of the Immune System; the microbiota is essential for the induction, formation and functions, in the host organism, of the immune system which, in turn, has largely developed as a tool capable of regulating and maintaining an adequate and effective symbiotic relationship between the host individual and its highly heterogeneous and constantly evolving bacteria.
In healthy subjects, the distribution of the intestinal microbiota is extremely differentiated, with a notably higher prevalence of protective bacterial types than potentially harmful ones. This composition, called Eubiosis, ensures the efficient and advantageous implementation of the activities that take place in the intestine.
Intestinal eubiosis therefore results from the right balance of presence and growth between the various microorganisms and it is the indispensable condition for maintaining an intestinal environment suitable for guaranteeing a correct redistribution of the bacterial species constituting, as a whole, the intestinal microbiota.
The loss of this diversification and, therefore, the disruption of the balance in the intestinal microbial ecosystem, combined with the appearance of imbalances between the proportions of the bacterial strains or with the opportunistic invasion of the host tissue by the resident bacteria due to an alteration of the barrier protective mucosa ordinarily underlying the microbiota, can have serious health consequences.
Our intestinal microbiota and our microbiome are closely linked to our state of health or disease and, together with genetics and the environment, they certainly represent a discriminating point in preparing us for the onset of some particular diseases rather than that of others.
The gut microbiota is closely related to our metabolic balance as well as the development and functioning of our immune system, as studies on germ-free animals have clearly demonstrated.
It is also closely connected with the intestinal and systemic endocrine systems, and indirectly with the central nervous system, via the enteric nervous system, within what is commonly called the gut-brain axis.
The microbiota does not represent an inheritance dependent on our species or our genes, but rather an environmental inheritance, mainly due to the type of environment we were exposed to in the first 3-4 years of our life. This also implies that we can act throughout life with the aim of improving our microbiota.
There are conditions that have a decisive impact on the composition and function of the intestinal microbiota. The first in importance and for the daily life with which it is implemented is certainly our diet, which can cause positive or negative changes in the microbiota.
Another condition, often overlooked, is our lifestyle. Smoking and alcohol, for example, can negatively alter the microbiota, while regular physical activity appears to be able to improve it significantly.
Aging is certainly a condition that negatively impacts various parameters of the intestinal microbiota.
Finally, there are many different pathologies, and consequent therapies, which can alter our intestinal microbiota, sometimes irreversibly. The most illuminating example concerns transmissible pathologies of bacterial origin, found at an early age.
The antibiotic therapies that are often necessary can, in the first 3 years of life, irreversibly modify the evolutionary trajectory of the intestinal microbiota leading, in adulthood, to a microbiota that is substantially different from the one that would have developed in the absence of broad-spectrum antibiotic therapies.
Differently, antibiotic therapy in adults only reversibly modifies the gut microbiota, which returns exactly to the starting point some time after the end of therapy.
The microbiota well represents the complex relationships that exist between our health and the environment in which we are born and where we spend the first years of our lives. A compromised environment, due to excessive sterilization or pollution, certainly has a strong impact on the structure of our microbiota in adulthood and, consequently, also on our state of health and well-being. Although fecal microbiota transplantation has opened new frontiers in the prevention and treatment of many pathologies, it is indisputably true that this community of microorganisms represents a central node in the functioning of all our organs and systems, and at the same time shows a fundamental point of interaction between us and the environment in which we spend our lives.
When there is an alteration of the microbiota, an intestinal dysfunction is generated which we notice immediately. The intestine does not work as it should, digestion becomes difficult, abdominal swelling forms.
Intestinal bacteria protect the intestine from pathogens by producing a mucus barrier. When this mucus fails, because the "good" microbiota decreases its effectiveness, the other bacteria attack the mucosa causing it to become inflamed, creating the disturbances mentioned above. Dysbiosis is an overgrowth of bad bacteria, which have nothing to do with the microbiota, which causes irritation of the intestine with consequent digestive disorders. Disturbances, which can contribute to generating problems of indirect food intolerance which arise, therefore, not because there is an intolerance to any specific food, but because the intestinal villi, becoming inflamed, no longer absorb well all the substances we ingest, therefore many of these - and not only one - can create annoyances.
To intervene on this type of intolerance it is therefore necessary to intervene on the inflammation. Where Dysbiosis does occur, it is usually associated with a wide range of disorders such as:
- diarrhea
- irritable bowel syndrome (IBS)
- inflammatory bowel disease (IBD)
- colorectal cancer
- some liver diseases
- Allergic pathologies
- diet-related diseases such as obesity, type 2 diabetes or celiac disease.
It is also known that dysbiosis can also be the consequence of the action, single or combined, of different factors such as:
- incorrect feeding
- environmental toxins
- drug abuse
- intestinal infections
- intense and prolonged stressful conditions
- long-lasting dysfunctional and inflammatory processes.
To allow the return to intestinal eubiosis, especially in the presence of diarrhea, intestinal disinfectants are generally used, which are practically not absorbed by the body and which have the task of eliminating the intestinal pathogens responsible for dysbiosis in a non-specific way. Probiotics are used in association with disinfectants or in monotherapy if the dysbiosis is not serious. For years it was believed that probiotics were a panacea suitable for everyone and therefore numerous formulations have proliferated, both parapharmaceutical and food (yogurt and other foods enriched with lactic ferments).
It is good to know the new findings on probiotics and the lights and shadows that such data cast on this product category. Since the second half of the 19th century, with Metchnikoff's studies on the possibility of using lactic acid bacteria to slow down the process of autointoxication and infection by intestinal microbes, probiotics have been suggested as a tool to modulate the intestinal microbiota while conferring health benefits.
Their economic value was recognized soon after, and their global market is estimated to reach $69.3 billion by 2023.
Nowadays, probiotics represent one of the most commonly consumed food supplements worldwide, being present in yogurts, cheeses, ice creams, snacks and nutritional bars, breakfast cereals, infant formulas and more recently also added to products cosmetics. The administration of probiotics is a more than feasible approach in clinical practice, compared, for example, to diet, despite its recognized role as a fundamental determinant of the structure and function of the intestinal microbiota, able to support homeostasis or vice versa to contribute to susceptibility to disease, due to the sometimes modest effects of nutritional interventions and the difficulty of enforcing and monitoring patient compliance.
The pillar of the commercial offer is represented by the species Lactobacillus and Bifidobacterium, together with E. coli Nissle 1917, Streptococcus thermophilus and Saccharomyces boulardii, all with a long history of use, having the status "Generally Recognized as Safe" (GRAS) in the United States United States or in the process of being granted the status of “Qualified Presumption of Safety” by the European Food Safety Authority (EFSA).
Coming from the intestine or from traditional fermented foods, they have been selected, in large part, for their technological properties, i.e. the ability to survive processing and to retain vitality during the shelf-life of the product. According to the Consensus meeting of the International Scientific Association for Probiotics and Prebiotics in October 2013 the framework "probiotics" must include microbial species that, in well-controlled studies, have been shown to confer health benefits. With specific regard to the intestinal microbiota, probiotics can impact resident communities through at least three different mechanisms:
• trophic interactions (i.e. stimulating growth through the supply of metabolites such as lactate, acetate or propionate, growth factors such as vitamins or exopolysaccharides, or other substrates)
• a direct alteration of fitness, through a decrease in pH, niche competition, or bacteriocin production, or indirectly through the host
• through changes in the intestinal environment (i.e. by stimulating mucin production, increasing secretory IgA levels, and inducing secretion of defensins, which represent the first line of defense of the intestinal epithelium against microbial invasion)
Although these effects may be relevant in the context of dysbiosis, i.e. when there is a bloom of potential opportunistic pathogens and/or a depletion of health-associated taxa (mainly SCFA producers, sensitive to oxidative stress), there is no convincing evidence of consistent effects on the intestinal microbiota of healthy subjects, by probiotics, or on a eubiotic and resilient microbial ecosystem. Among the main (although sometimes only suggested) indications and prophylactic and therapeutic claims of probiotics, we can certainly mention gastrointestinal diseases, including the prevention or treatment of acute diarrhea associated with antibiotics and associated with Clostridium difficile, and the improvement of IBD and IBS.
Recent reviews have also cautiously suggested a beneficial role of probiotics in preterm infants, especially in terms of prevention of necrotizing enterocolitis and reduction of risk of late-onset sepsis.
However, conflicting data have been reported in the context of many other disorders, including, for example, respiratory infections and metabolic syndrome. This confusing situation may arise from the heterogeneity of probiotic agents, from the dosage, duration and method of administration, but also from other issues related to study design and communication of results (not always transparent, easy to evaluate and rigorous), to the population (e.g. demographic characteristics) and environmental variables (e.g. habitual diet).
In this regard, the awareness that one size does not fit all is rapidly gaining ground. It is now a fact that distinct underlying characteristics of the host (e.g. age and underlying medical condition) and its microbiota (taxa represented and functions performed), including variable environmental exposures (mainly diet), can actually lead to different results even with the same probiotic preparation.
As recently discussed, this could for example be due to the fact that the individual configuration of the gut microbiota can be permissive or resistant even to the transient colonization of probiotics. Furthermore, it has been shown that probiotics may even disrupt rather than aid in the gut microbiota recovery process after antibiotic treatment.
It is therefore now clear not only that their validity is not to be considered absolute, but also that, if not tailor-made, probiotic-based interventions may not be completely risk-free. Future directions will be the adoption of a mechanism-based approach, in which probiotic strategies are designed ad hoc, taking into account a series of "precision" aspects related to the host and its microbiota, i.e. with careful consideration of the subject to be treated and the medical objective to be achieved.
Finally, it should be remembered that some of the most used probiotics fail to maintain the necessary vitality for the entire declared shelf life and that in any case it is not always so automatic for all probiotics to pass unscathed from the gauntlet represented by the pH of the stomach and the salts gallstones.