GUT MICROBIOTA
The gut microbiota is the collection of microorganisms (bacteria, viruses, fungi and protozoa) that populates the gastrointestinal tract. Its composition differs from individual to individual but there can be similarities between people who live together due to sharing eating habits and the environment in which they live.
The microbiota establishes a mutual relationship with the host body, mainly through two species, Firmicutes and Bacteroidetes, which alone represent approximately 70% of the microbial presence in the intestine.
Due to its complexity and the functional role it plays in the body, the gut is considered an organ in itself and the microbiota performs specific activities that are fundamental to the host’s health. To give you an idea of the importance of bacteria in the gut, just think that the overall weight of the gut microbiota is estimated to be around 1.5kg.
Another element that makes us understand the importance of the intestinal microbiota is the genetic heritage of our gut bacteria.
It is composed of over 3 million genes (microbiome). Therefore, the idea that the gut microbiota is a “super-organ” is not far off the mark. The number of bacteria in the microbiota is six times higher than the total amount of cells in the entire body. This world inside us has various functions that are beneficial to the body, such as:
This ecosystem is kept in balance by a perfect quantitative and qualitative composition (eubiosis) and its interaction with the gastrointestinal tract.
If this balance is altered by changes to the quantitative and qualitative composition of the microbial population, the mechanisms linked to it are altered (dysbiosis).
Many diseases are related to dysbiosis, such as diabetes, obesity, asthma, inflammatory bowel diseases and probably some neurodegenerative diseases and psychiatric illnesses.
Every individual seems to have such a unique gut microbiota that can be considered similar to a fingerprint.
There are three main groups of gut microbiota, depending on the bacterial strains that are most prevalent in each individual. These groups are called enterotypes and perform vital functions for the entire ecosystem, ensuring its survival.
Enterotypes are divided into three types:
Type 1: Bacteroides
Type 2: Prevotella
Type 3: Ruminococcus
Genetic, dietary and environmental conditions determine the prevalence of one type over another. Although a microbiota can have a prevalence of these enterotypes, the species present in lower numbers are also very important. When an individual is healthy, its gut ecosystem is balanced with a low number of species, which can all perform specific functions to benefit the host.
A typical example is lactobacillus and bifidobacteria. Their importance to the host’s health has been noted for years, although their quantitative presence is certainly secondary.
Therefore, it is the overall microbial population that determines an individual’s health and affects how the microbiota “organ” works.
The conditions to the future development of the gut flora are determined at birth.
For example, childbirth is a fundamental moment that affects a child’s life in its first months and in his growth. During childbirth, the baby encounters the mother’s bacterial species for the first time and the microorganisms will be different with a vaginal birth than with a caesarean section. During a natural birth, the baby comes into contact with the bacterial species present in the vagina, such as lactobacillus and Prevotella; while with a caesarean, the baby will be exposed to the bacteria present on the skin, such as Staphylococcus, Corynebacterium and Propionibacterium.
The different bacterial pattern acquired by the newborn will shape its life, making it less susceptible to some inflammatory diseases because certain bacterial species, like bifidobacteria, promote the proper development of the immune system.
Another important factor is breastfeeding. Breast milk is rich in oligosaccharides, which are powerful prebiotics that stimulate the growth of bifidobacteria and lactobacillus.
CHANGES IN THE MICROBIOTA
Over the years, the microbiota has changed as the human diet has. Variations in our diets encouraged the formation of a gut microbiota that can create a pro-inflammatory microbial pattern with a subsequent predisposition to some chronic illnesses.
To live, gut microorganisms use food sources that we take in through our diet and in doing so, they metabolise the food in a process of symbiosis with the host.
The bacteria aid digestion, breaking down and fermenting some foods that would not otherwise be digestible by humans, creating secondary metabolites that can be beneficial for our health.
Microorganisms can have a metabolism that is not very selective, i.e. they can feed off numerous food sources, or one that is extremely selective, i.e. they mainly feed off one food. If that one nutritional substance that they need to survive is not present in the environment, they will die off and no longer exist in the gut. If there is a lack of bacterial strains that metabolise certain substances, it is possible to accumulate harmful metabolites when there is an excess of these substances and it is not always possible to regain gut colonisation of the bacteria that are missing, regardless of the cause. The intake of certain medications can affect the survival of bacteria in the gut. In fact, the indiscriminate use of antibiotics, which took place over the last few decades, has certainly had a strong impact on the composition and health of the microbiota.
DYSBIOSIS: IMBALANCE OF THE GUT MICROBIOTA
Dysbiosis is a condition characterised by a general alteration in the gut microbiota, where the balance between the different species of microorganisms populating the gut changes. This can be caused by various factors.
Dietary changes can affect the composition of the gut microbiota. Depending on the nutritional substances that we make available, specific bacterial strains will proliferate or die off.
Other factors that can affect the balance of bacterial flora are: lifestyle (sedentary or active), the seasonality, the immune system, autoimmune diseases or bowel diseases (e.g. steatorrhoea), intestinal infections, stress and anxiety.
The consumption of medications also profoundly affects the composition of the gut microbiota. In particular, the oral intake of antibiotics leads to imbalances because their bactericidal action extends to helpful bacteria in the gut.
Dysbiosis can cause bloating, poor digestion, constipation or diarrhoea. It also increases the risk of contracting illnesses, such as inflammatory bowel diseases (e.g. Crohn’s disease and irritable bowel syndrome), infections and accumulations of non-metabolised substances that, in excess, can be harmful and cause other diseases, such as secondary hyperoxaluria.
THE GUT MICROBIOTA IN CYSTIC FIBROSIS
People with cystic fibrosis, like everyone else, have gut flora mostly inherited from their mother at birth. However, because of the lung infection these patients have, they often undergo cycles of antibiotics from a young age. Additionally, they have altered gut function linked to the disease (e.g. steatorrhoea). These alterations combined with drug therapy can hinder the colonisation of some good bacteria, typical of the ideal gut flora. So dysbiosis can have negative consequences on the person’s health.
CYSTIC FIBROSIS AND HYPEROXALURIA
Some studies indicate that in patients with cystic fibrosis, there is a higher incidence of hyperoxaluria than in the general population.
Hyperoxaluria is a condition characterised by the increased excretion of oxalates in the urine, which can lead to the formation of kidney stones over time.
Oxalates are derived from oxalic acid, which is quite a strong acid with a strong pro-inflammatory action on the intestinal walls. As it easily binds to metallic ions like calcium, oxalic acid forms oxalate crystals that irritate the gut and kidneys. Oxalate crystals are painful and can be found in various parts of the body like the kidneys, the cardiac muscle and the musculoskeletal system. Kidney stones can result from hyperoxaluria and are generally formed by calcium oxalate.
Oxalic acid is an end product of the metabolism of ascorbic acid and glyoxylic acid. The majority of oxalic acid (80–90%) is of endogenous origin but part of it is also exogenous, which comes from our diet. Most of the oxalate is excreted through the urine, while a small part of it is eliminated through the gut. Deficiencies in the metabolism of oxalic acid cause more oxalates to pass into the kidneys and increase the risk of hyperoxaluria and the formation of kidney stones.
In the short term, the reduced metabolism of oxalic acid causes inflammation of the gut but in the long term, it can cause inflammation of the kidneys, hyperoxaluria and stones. In fact, oxalic acid that is eliminated through the kidneys tends to precipitate. When in excess, it can lead to calcium oxalate deposits and kidney stones.
The gut microbiota plays an important role in the excretion of some of the body’s oxalates.
However, humans have no enzymes that can break down oxalates. This task is generally carried out by the gut microbiome.
Oxalobacter formigenes is a bacteria in the human gastrointestinal tract that has the capacity to produce an enzyme (oxalyl-CoA decarboxylase) that can break down oxalic acid. Therefore, Oxalobacter formigenes helps humans to eliminate the majority of excess oxalates from the body.
So, what is Oxalobacter formigenes?
It is an anaerobic bacterium present in the intestines of vertebrates. This bacterium has a symbiotic relationship with the host (the human being) because it regulates the absorption of oxalic acid by the gut and consequently its concentration in the plasma. Oxalobacter formigenes uses oxalates from the diet as food for its survival, lowering their concentration in the intestinal lumen and therefore in the blood. Infants acquire this bacterium at between 9 and 12 months of age and, in general, it has colonised in almost all children by the age of 6 to 8 years.
Clinical studies have highlighted that in patients with cystic fibrosis, there is a reduced presence of Oxalobacter formigenes in the gut. It was found that the use of oral antibiotics compromises the bacterium’s capacity to colonise patients’ guts.
Other studies have shown that Oxalobacter formigenes cannot be reintroduced through probiotics as it is a bacterium that is not stable in formulation synthesis. Consequently, once an individual’s gut has no Oxalobacter formigenes left, it is no longer possible to colonise that gut.
However, Oxalobacter formigenes is not the only bacterium that can break down oxalates. It can be replaced by introducing other bacterial strains that have the same capacity.
Some lactobacillus and bifidobacteria have been identified that have a good capacity to break down oxalates and can be reintroduced to the gut orally. These bacterial strains have also shown a certain degree of anti-inflammatory potential, which could be of further benefit to the patient.
SUPPLEMENTATION OF LACTIC ACID BACTERIA
It is possible to mitigate the problems related to dysbiosis in cystic fibrosis and the risk of hyperoxaluria through the regular intake of lactic acid bacteria.
Bear in mind that following cycles of oral antibiotics, it is always advisable to take lactic acid bacteria; therefore, all patients with cystic fibrosis that must undergo cycles of oral antibiotic treatment are recommended to take special lactic acid bacteria formulations.
In particular, the use of products with bacterial strains selected for their capacity to break down oxalic acid and produce anti-inflammatory interleukins can be particularly helpful in these patients, to prevent the risk of hyperoxaluria and simultaneously reduce intestinal inflammation.
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