MAINTENANCE – The Small Intestinal Bacterial Overgrowth (SIBO), or bacterial overgrowth of the small intestine, is one of the very many pathologies of Covid-19. It is linked to dysfunction of the renin-angiotensin system which can be induced by infection with the Sars-CoV-2 virus or appear following anti-Covid-19 vaccination. Jean-Marc Sabatier, research director at the CNRS and doctor in cell biology and microbiology in Marseillereturns for FranceEvening on the pathophysiological aspects of SIBO to explain its biological mechanisms. We specify that Jean-Marc Sabatier speaks here on his behalf.
Estelle Fougères – In your first scientific study on Sars-CoV-2 published in April 2020 and entitled SARS-CoV-2 & Covid-19 : key-roles of the renin-angiotensin system / Vitamin D impacting drug and vaccine developments, you and your colleagues describe the complete mode of action of Sars-CoV-2 on the renin-angiotensin system (RAS), this complex and ubiquitous system found in the various organs and tissues of the human body. You have understood that the real responsible for the manifestations of Covid-19 is precisely a dysfunctional ARS, and not directly the virus. This allowed you to anticipate certain pathologies such as coagulopathies and thromboses (which are normally “opposed” because one corresponds to a coagulation deficiency, unlike the second which corresponds to hyper-coagulation), atherosclerosis, reproductive organ damage, dermatitis, lipid metabolism damage, eye disorders (retinopathy, glaucoma), neurological disorders, type 2 diabetes (glucose intolerance), and other autoimmune diseases as well as cancers. Since then, you have continued research and discovered other pathologies of Covid-19. What are they ?
Jean-Marc Sabatier – The SIBO (Small Intestinal Bacterial Overgrowth or bacterial overgrowth of the small intestine) is a pathology of Covid-19. SIBO is thought to be linked to dysfunction of the renin-angiotensin system (RAS) which can be induced by infection with the SARS-CoV-2 virus, or by the vaccine Spike protein (Spike protein from anti-Covid-19 vaccines).
As a reminder, the RAS is a ubiquitous physiological and hormonal system in the human body. It controls renal, pulmonary and cardiovascular autonomic functions, as well as innate immunity and the various microbiota (microbial flora), including the intestinal microbiota. RAS dysfunction is responsible for Covid-19 diseases.
The intestinal microbiota is made up of approximately 10,000 billion micro-organisms (bacteria, fungi and yeasts) living in specific communities delimited along the walls of the intestines, and normally acts in perfect symbiosis with our body. About 160 bacterial species have been identified there. This microbiota plays a central role in digestion, cellular metabolism and immunity (the intestinal microbiota actively participates in the proper functioning of our immune system).
SIBO (whose origin is still mysterious) is, in my opinion, an intestinal dysbiosis induced by the dysfunction of the RAS. Dysbiosis, which is an imbalance of the intestinal microbiota, results in a disruption of the intestinal flora which can lead to a decrease in the number of “good” bacteria or an increase in the number of “bad” bacteria or both.
We thus find in SIBO and dysfunctional RAS common associated disorders, such as irritable bowel syndrome (disorder of the digestive tract resulting in abdominal pain, diarrhea or constipation, and bloating), fibromyalgia (syndrome associated with diffuse chronic joint and muscle pain, intense fatigue, and sleep disorders), myalgic encephalomyelitis (chronic fatigue syndrome), gastroparesis (impairment of the digestive function resulting in the slowing of stomach emptying via the vagus nerve which does not properly regulate gastric muscle activity), diabetic neuropathy (peripheral or autonomic, due to hyperglycemia which damages or disrupts the functioning of the nerves ensuring the connection between the brain, the spinal cord and the various organs : there is orthostatic hypotension causing discomfort and falls, postural tachycardia syndrome (or POTS which is t transient increase in heart rate when changing position, accompanied by intense and persistent fatigue and intolerance to physical exertion), disorders of urinary function and erection, insensitivity to pain or contact or heat, “electrical” pain without apparent cause, a feeling of “cooking”, tachycardia, frequent involvement of the lower limbs and difficulty in movement, etc.), immune deficiency, maldigestion and/or malabsorption, and other pathologies. These are disorders frequently observed in people suffering from severe Covid-19, and/or post-Covid-19 sequelae known as long covid, including long post-vaccination covid.
Estelle Fougères – What are the biological mechanisms of an imbalance of the intestinal microbiota?
Jean-Marc Sabatier – Under normal conditions, there are low numbers of aerobic (Gram+) bacteria in the small intestine and very high numbers of anaerobic (Gram-) bacteria in the colon of an individual. Aerobic bacteria in the small intestine are beneficial because they help digest food and absorb nutrients (they also allow the production of vitamins K, B8, B9 and B12, as well as short-chain fatty acids , while regulating the absorption of calcium, magnesium and fatty acids). These bacteria promote mobility – in the intestinal tract – of ingested food. The bacterial balance in the small intestine is maintained thanks to the ileo-colic valve (which opposes reflux from the large intestine to the ileum, preventing retrograde migration of bacteria), gastric acids (killing micro-organisms, including pathogenic bacteria) produced by stomach cells, and the presence of immunoglobulin A from the intestinal tract.
SIBO results from the migration of bacteria from the colon to the small intestine where they will multiply excessively (hence an overgrowth of bacteria from the colon into the small intestine). While the function of the small intestine is the absorption of food, the function of the colon is the subsequent fermentation of the indigestible food residues or waste products. Thus, during SIBO, an early and abnormal fermentation of food is initiated directly in the small intestine by the anaerobic bacteria of the colon, causing more or less severe digestive disorders, associated with various potentially very disabling pathologies.
During SIBO, the dysregulation of the intestinal microbiota is induced by the dysfunction of the RAS (via the overactivation of its “deleterious” AT1R receptor) which controls the various microbiota. The repercussions on the body of the person suffering from SIBO can be multiple, with: (1) damage to the metabolism of proteins, lipids, fibers and carbohydrates of the host (linked to the abnormal degradation and/or assimilation of food/ nutrients), (2) deficiencies or deficiencies in essential vitamins (eg vitamins B/folates and K) and minerals (eg calcium, magnesium), and other compounds (via the action of specific enzymes of bacteria/micro-organisms) , (3) a change in the characteristics of the intestinal mucosa (ie enterocytes, protective mucus, vascularization, peristalsis/digestive motricity) affecting the barrier effect against pathogens, (4) a functional impairment of the immune system (anexic animals – devoid of intestinal microbiota – have a strongly impaired immunity which can be restored experimentally after inoculation with a normal microbiota), (5) a decrease in protection against pathogenic microorganisms nes (intestinal bacteria are able to secrete molecules with anti-microbial properties directed against other micro-organisms). At the same time, it has been shown that an imbalance of the intestinal microbiota can be associated with weight loss or gain, as well as with inflammatory bowel diseases, irritable bowel syndrome (or functional colopathy), allergies, cancers, diabetes (types 1 and 2), and neurological disorders (the nerve fibers of our enteric nervous system connect the intestinal wall to the central nervous system, hence the name “second brain” given to the intestine ).
For neurological damage, intestinal dysbiosis is observed in patients suffering from depression or anxiety, Alzheimer’s or Parkinson’s neurodegenerative disease, schizophrenia, and other autistic or bipolar disorders. All of these pathologies are associated with dysfunction of the RAS (and overactivation of the AT1R receptor).
Thus, SIBO – a Covid-19 pathology not described to date – includes many symptoms and diseases of Covid-19 and covid long more or less severe and disabling (these disorders also depend on a dysregulation of the ARS). It is notable that the factors responsible for SIBO can be related to anatomical problems (diverticulosis of the small intestine, intestinal stenosis/restriction, etc.) or functional (intestinal motility disorders, hypochlorhydria). They include – alongside the pathologies already mentioned – depression, asthma, fatigue, joint or abdominal pain, dermatitis (rash, eczema, acne, rosacea), malnutrition, vomiting, gastroesophageal reflux, nausea, bloating/flatulence, diarrhea or constipation . SIBO may be relieved or treated with RAS inhibitors (such as vitamin D, melatonin, sartans, quercetin, thymoquinone, and others), as well as oral broad-spectrum antibiotic treatments (eg Ciprofloxacin, Amoxicillin/ clavulanic acid or Augmentin, Rifaximin, Metronidazole). It is possible to make a diagnosis of SIBO with a breath test based on glucose, with a measurement of the release of hydrogen (and methane) resulting from the fermentation of glucose by bacteria. A confirmatory test can be performed by taking a sample of intestinal fluid. A diet limiting fermentable carbohydrates (little digested by the small intestine) is then recommended.
Estelle Fougères – In the early 2000s, people spoke of the digestive system as being the second brain. We now know that this system is rich in neuronal transmissions and that it produces, for example, serotonin, which plays a role in mood regulation. Indeed, the discoveries of recent years have revealed that the intestinal flora is not only responsible for digestion and that it has a determining role in mental health. Doctors today are highly specialized. However, it seems that what you described above would sometimes require collaboration between scientists or doctors from various disciplines and specialties in order to treat certain disorders, particularly psychological ones. For example, when a person has a depressive syndrome, shouldn’t there be collaboration between a neurologist or a psychiatrist and a gastroenterologist?
Jean-Marc Sabatier – Indeed, the human body functions thanks to organs and tissues interacting with each other, in one way or another. The brain and the intestine “communicate” in a very close and permanent way. The connection between the central nervous system and the digestive tract is said to be “bidirectional”, in particular via the parasympathetic and sympathetic pathways of the autonomic nervous system. While the parasympathetic nerves work by promoting the motility and secretory activity of the intestine, the sympathetic nerves oppose it, thus slowing down or blocking motility and secretory activity. A balance between these nervous systems allows the proper functioning of the human body.
An interaction between specialists from different scientific or medical disciplines is desirable for the good of the patient. Aren’t SARS-CoV-2, Covid-19 and ARS at the interface of various disciplines such as virology, immunology, pharmacology, endocrinology and physiology?