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INTESTINAL DISORDERS
Hippocrates from ancient times had assumed that “death is hidden in the gut”. Hippocrates’ theories form the basis for the Dysvivosis Hypothesis today.
Intestinal Dysbiosis refers to the qualitative and quantitative changes that occur in the composition of the intestinal microbiome, its local distribution and its metabolic activity. It has been the subject of intensive research over the last 20 years, and there are many questions still to be answered. However, it is clear that disturbances in the normal gut microflora play a role in the development of many chronic diseases.
Before describing dysbiosis and its effects, it is necessary to consider the gut microbiome and its role.
THE MICROBIOME
Microbiome is a complex ecosystem consisting of 100 trillion microorganisms of which 90% is found in the gut (500-1000 different species) and the remaining 10% in the skin, respiratory and urogenital tract. The gut microbiome does not have the same DNA as our body – in fact it consists of 10 million microbial genes – about 400 times more genes than human genes.
WHAT IS THE GUT MICROBIOME AND WHERE IS IT FOUND?
About 2/3 of the gut microbiome (the “microbiotic core”) is the same in all people. The remaining 1/3 changes between people, but also in the same person at different times.
The gut microbiome is classified into 3 heterotypes based on studies of different populations. Heterotypes are determined by the predominance of a particular bacterial genus:
- Bacteroides, digesting carbohydrates
- Prevotella, digesting proteins
- Ruminococcus, which digests mucin and metabolizes sugars
Depending on the balance of the three enterotypes in our body, our ability to digest different foods changes. The ability of different peoples to consume local foods that seem exotic to us is due to and reflects their different gut microbiome. The diversity of microbes and bacteria in the gut, and the balance between them, are characteristics of a healthy microbiome.
The microbiome refers to the beneficial microbes in our gut that live there symbiotically. That is, the gastrointestinal tract provides food and suitable conditions for their growth, while they facilitate digestion, vitamin synthesis, inhibition of pathogen growth, immune regulation, and hormone production.
Not the entire intestinal tract is hospitable to the microbiome though. The stomach, because of the acidity of its secretions (low pH), is not conducive to the presence of bacteria and so their numbers there are small. The same is true in the duodenum due to the secretions of pancreatic and bile enzymes. The numbers (expressed as ‘CFU’) and variety of bacteria increase in the small intestine and peak in the large intestine, particularly in the rectum (the last part).
HOW DOES THE MICROBIOME EVOLVE?
From birth to around 5 years of age, the gut microbiome is constantly changing. It then stabilises for the rest of adult life until the age of 65, when there is a decrease in the diversity of the microbiome.
Until birth, the gastrointestinal system of a fetus is sterile. Immediately after birth it begins to colonise. Even the mode of delivery has an initial effect on its episiotomy: with normal delivery the microbiota composition of the newborn has a composition similar to that of the vagina, whereas with caesarean delivery it has a composition similar to that of the skin. Breastfeeding and the general environment (e.g. place of birth) also have long-term effects on the composition of the microbiome: the precursor bacteria of the infant microbiome can alter the expression of epithelial cell genes, creating conditions more favourable to them and possibly more hostile to other bacteria to which the infant has not been exposed. More generally, the immune system is affected in the long term by these early years as it learns to distinguish between symbiotic and pathogenic species. The diversity of the microbiome increases dramatically with the introduction of solid foods, and begins to resemble the microbiome of an adult.
Diet is a critical factor in shaping the gut microbiome, which changes population in a way that maximises the energy it can get from food that reaches it from the small intestine, and has not already been absorbed by our body. For example, when we consume mostly complex carbohydrates over a long period of time, the appropriate bacteria that digest these carbohydrates will proliferate rapidly, while others will decline. Western diets, high in fat and sugars, favour the microbes that metabolize such foods.
Our gut microbiome only needs a few days to adapt (to some extent) to changes in our diet. However, it seems that the microbiome has a kind of “memory” which makes it difficult to recover from chronic bad eating habits. This is why long-term good nutrition is important for a healthy microbiome and health.
WHAT DOES THE GUT MICROBIOME DO?
The main functions of the microbiome for the host (our body) are four
- defense (immune system support)
- the regulation of Central and Enteric Nervous System (CNS/ENS) communication
- the support of digestion
- the regulation of metabolism
Regulation of metabolism by the microbiome is still at an early stage of study. However studies in mice have shown that eg, if a sterile gut (ie a mouse with a non-existent microbiome) is colonized by the microbiome of an obese mouse, then it becomes obese and/or diabetic. Such experiments show that the microbiome can affect the energy we extract from food and store it as fat, by 5-10%. It has been shown that the number of Bacteroides in the large intestine of obese individuals is reduced, and that restriction of carbohydrates and fats in the diet is associated with an increase in the number of Bacteroides and with weight loss.
The role of the microbiome in the functioning of the Central (CNS) and Enteric Nervous System (ENS) is bidirectional. The CNS causes changes in intestinal permeability, gastrointestinal motility and secretory activity, which in turn modify the composition of the gut microbiota. Conversely, the gut microbiome directly influences the process of synaptogenesis and the production of neurotransmitters (e.g., serotonin), while products of the gut microbes (short-chain fatty acids, “SCFA”) may enter the function of specific brain regions. These changes have a significant effect on brain function and can lead to pathologies. Digestive support from the microbiome occurs in many ways – however the key mechanism is that our gut bacteria metabolize foods that our bodies cannot absorb in the small intestine. These foods are called “prebiotics” as they nourish the microbiome. Bacteria ferment prebiotics into short chain fatty acids “SCFA” (acetate, propionate and butyrate) and gases (so prebiotics can carry aeration). SCFAs are valuable substances. On the one hand, they strengthen the intestinal mucosa and prevent pathogenic bacteria from escaping from the intestine. On the other hand, acetic and propionic acid reduce insulin secretion and inhibit hunger. Butyric acid inhibits cell growth and helps repair damaged cells. Failure to oxidize butyrate in colon cells in genetically predisposed individuals has been shown to lead to the development of ulcerative colitis and colon cancer. Butyrate oxidation may also contribute to increased colonic uptake of glucose, sodium, magnesium, and iron and increased mucus and lipid synthesis. Finally, the intestinal microbiome has multiple beneficial effects on our body:
- It produces enzymes to digest food and absorb trace elements such as iron
- Contains vitamins (K, B9, B12)
- It produces SCFA, the main source of energy for colon cells and some beneficial bacteria
- It converts bile acids for the proper digestion of proteins and lipids
- It produces antimicrobial and antifungal substances and regulates immune function
- Strengthens the intestinal barrier
- Regulates the pH of the intestine
- It enhances the metabolism of various carcinogenic substances
DYSBIOSIS
What is dysbiosis?
Not all of the hundreds of species of organisms that make up the intestinal flora are beneficial. There are many microorganisms that either directly harm us, or provide no benefit, or are only harmless when their population is low relative to the beneficial microbiome, e.g., coliforms (E.coli, etc.), yeasts /fungi, parasites and Bacteroides.
Dysbiosis refers to adverse changes in the composition and functioning of the intestinal microbiome that overcome the resistance and resilience of the ecosystem. Changes in the composition of the microbiome that cause dysbiosis can be the overgrowth of the pathogen population, the reduced diversity of the microbiome, or the loss of the population of beneficial bacteria. Thus, direct damage is caused to the organism or the beneficial functions of the beneficial bacteria are prevented.
How is it caused?
There are several factors that can disturb the balance of organisms in the gut and cause dysbiosis:
- The use of antibiotics
- The use of contraceptives
- The use of immunosuppressants (eg, steroids) and other hormones
- High consumption of sugar, protein and alcohol
- Stress, chronic fatigue and depression
- Medical conditions, such as irritable bowel syndrome, food allergies
Antibiotics, in addition to the pathogenic microbes for which they are intended, also destroy beneficial elements of the microbiome, and this can lead to dysbiosis. For example, eradication of H. Pylori with short-term antibiotic use has been shown to result in massive disruption of the gut and oral microbial flora lasting from 6 months to 4 years.
Stress and chronic fatigue affect the microbiome in several ways. They can reduce gastric acid secretion, alter gut motility and the production of some compounds in the small intestine, resulting in a reduction in the Lactobacillus population, even for a week after a short period of emotional stress. The decrease in the number of Lactobacillus enhances the possibility of colonization of the intestine by exogenous microorganisms. In addition, stress may be responsible for reduced mucus production, which prevents pathogenic bacteria from adhering to the intestinal walls.
Poor nutrition is a very important factor in dysbiosis. Foods containing sulfate compounds (such as food preservatives, packaged fruit juices, dried fruit, white bread, eggs, cow’s milk, and cheese) help over-grow some hydrogen sulfide-producing bacteria. Furthermore, since these bacteria compete with beneficial bacteria for nutrients, their overgrowth undermines the nutrition of friendly bacteria.
Overconsumption of protein also increases harmful gut bacteria. When the amount is such that the small intestine cannot fully digest it, the excess protein reaches the large intestine where it is broken down by the microbiome producing ammonia, phenols and other toxic compounds. These are particularly harmful as they are linked to the development of neoplasms, cancers and encephalopathy.
A diet rich in simple refined sugars shortens intestinal transit time, which can cause prolonged exposure of the colonic epithelium to toxic end products such as acetic acid and alcohol. In addition, refined sugars, by increasing bile production, indirectly mediate an overgrowth of opportunistic bacterial species that utilize bile acids in their metabolism.
What effects does it have on our health?
Dysbiosis has multiple negative effects that can be distressing and escalate over time. Changes in the composition of the intestinal microflora and its metabolic activity are considered important predisposing factors for the development of diseases such as irritable bowel syndrome (IBS), inflammatory bowel diseases (IBD), rheumatoid arthritis, ankylosing spondylitis, allergies, obesity and diabetes.
Early signs of gut microbiome disorders include:
- Stomach and bowel upset, accompanied by gas, bloating, constipation or diarrhea. Especially diarrhea after administration of antibiotics is a common phenomenon, affecting up to 25% of patients. It is more likely to occur with amoxicillin and erythromycin
- Increased need for sweets. The imbalance in the microbiome as a result of overconsumption of sugars causes further cravings for them, and a vicious cycle.
- Unexpected weight changes that do not come from dietary changes. These may be indicative of disturbances in insulin levels and the ability to store fat, or an increase in the bacterial population in the small intestine
- Sleep disorders. Serotonin produced in the gut regulates sleep quality among other things, and related disturbances may indicate problems in the microbiome
- Autoimmune diseases and skin irritations. These may be due to the production of certain proteins or disturbances in the function of the immune system, which is regulated by the gut microbiome