The bugs in my gut make me happy!

A symbiont is an organism that lives in tight connection with, on or inside another organism (the host) and exploits some of its host services (usually shelter or food) in exchange of others (usually food). Corals and microalgae zooxhantellae live in such a mutual advantage cooperation: the microalgae produce oxygen for the coral polyps and the coral protect the algae inside its soft transparent tissues. Gut microbiota are similarly hosted inside our intestine and produce amino acids, vitamins and some fats ftom indigested food. In exchange we protect them inside our body, but well isolated inside the gut lumen.

Gut and the brain. Gut microbes are at the center of the relationship between our diet, our metabolism, systemic inflammation, and also behaviour and mood, making these factors all connected. Scientific curiosity in modified behaviour and psychological problems as related to microbes in the gut is growing widely. Why so much interest in mood? In the Western developed nations, up to one third of all visits to doctors involve patients with emotional disorders, especially anxiety and/or depressive condition. The 1990 World Health Organisation report indicated that 5 of the 10 leading causes of disability were psychiatric conditions. This is one of the reasons that motivate scientists and research founders in finding solutions for a good mood. Gut bacteria are a central part of this search for “happiness”.

There is in fact a link between the gut and the brain and the health of one affects the other. For example, most of the patients who consult with a doctor for gastrointestinal problems show an associated psychological disorder. Further, in conditions in which depression is one of the symptoms–like in irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia, rheumatoid arthritis, alcohol dependency, insulin resistance and obesity, there is also intestinal permeability and associated problems. Gut condition affects the brain. But how are the two connected at this high level?

That an emotional condition can affect the gut has already been accepted and known for a long time. The gastrointestinal tract (from the mouth to the anus) is sensitive to emotions: anger, anxiety, sadness, happiness can all trigger symptoms in the gut. The feeling of nausea or intestinal disorders before an exam or a text or in the dentist waiting room are known to us all. The gastro-intestinal system has a complex assemblage of nervous cells (the enteric nevous system) that controls its functioning. However, such communication brain-gut goes two-ways. The gut also talks to the brain (and this was well known- since the brain needs to know the coindition of the gut) but sometimes via the microbes inside it. And this is part of a newly researched story....

As a first explanation of this newly explored communication microbes-brain, we can look at what happens in our first days of life. A normal gut biota can affect brain development and behaviour. The microbes composing our complex ecosystem of gut bacteria, viruses and fungi play a central function in the development of our brain when we are new-born (and maybe earlier through our mother intestinal environment). Moreover, in this stage of early development the brain is not the only organ affected. The baby organism is rapidly populated with many forms of microbes and this contributes to the development of many tissues, organs and systems like the gut, the arteries and the immune system and possibly many others. While the good guys (the favourable bacteria that start to inhabit our gut) have positive effect on the development of such organs, an infection with the wrong bacteria can cause a neurological disorder. In fact, in this very delicate period of our first stage of life we are prone to become affected by disorders like autism and schizophrenia that are associated with microbial pathogen (the bad guys) infections.

Even before teh few days of life, the actual act of birth can make a difference in the mood of teh future adult. In experiments done on mice, a caesarean section would produce adult mice that are significantly more anxious and have more symptoms of depression compared to mice that passed through the vaginal canal and got 'infected' by the mohter's microbes. This natural birth in humans is considered indespensable to give the baby a good set of microbes to well train the immune system. However, the fucntion of these bugs coudl go well beyond a strong immune function.

How does the connection between gut bacteria and ‘happiness vs. stress’ continue in our life?

Via: 1. Hormones and neurotransmitters, 2. direct nervous connection between the gut and the brain via the vagus nerve and 3. effects caused by bacteria products.

1. Hormonal-neurotransmitter action: It was shown that some gut bacteria can influence the production of tryptophan, others of GABA or other neurotransmitters (communicating molecules similar to hormones but released by neurons). Tryptophan is the precursor of serotonin, a key hormone affecting different organs as well as behaviour: this is the hormone of happiness, good sleep, appetite and relaxation. GABA is a relaxing neurotransmitter, another hormone–type molecule produced by the nervous system. As a consequence, a specific composition of our gut microbes could influence our happiness, mental status and behaviour by affecting the production of specific hormones or neurotransmitters. As a side factor, microbiota of the gut also control production of neurotransmitters that modulate food intake and energy balance (which control our body shape!).

2. Gut microbiota can send signals via the vagal nerve to the brain and vice versa. This bidirectional communication between brain and gut microbiota is essential to maintain homeostasis, or equilibrium, and to send messages to and from the gut. The vagal nerve transport system is hitchiked upon by bacteria. There is more in the transport than just the gut signals to the brain.

3. What is key in keeping a good balance in our behaviour (no mood changes please, and especially no depression!) is the maintenance of the integrity of the gut wall. If this layer of internal skin separating the gut lumen from the blood and other tissues is disrupted, the gut becomes leaky (“leaky gut” condition) and bacteria, fungi, parasites and their toxins, along with undigested protein, fat and waste pass into the blood circulation with bad consequences for our body and brain.

Among the molecules that pass into the blood, a type of LPS (lipopolysaccharide) has been studied with attention. This is a compound that is part of the bacterial wall (in some of our gut bacteria). Such LPS is related to mood and behaviour changes. There are at least five mechanisms that explain how a product of bacteria can have such big impact on our brain and mental wellbeing.

1. An increased level of this compound can increase neuronal activity in the amygdala, the

area in the brain that processes fear and alert.

2. High LPS can also increase the activity of an enzyme that breaks down tryptophan, the necessary precursor of serotonin (the hormone of happiness); a high level of this breaking-down enzyme is associated with lower serotonin and appearance of depression and anxiety.

3. LPS can also cause brain changes by making the blood-brain-barrier more permeable to substances in the blood and letting potential molecules (toxins, pathogens) reach the brain tissue. By the way, high levels of this LPS are also associated with markers of cardiovascular disease and diabetes, like abdominal obesity, higher insulin, triglycerides, total cholesterol and others.

4. Some bacteria can lead to changes in the expression of genes that govern intestinal permeability, nutrient absorption, blood vessel growth, the metabolism of environmental toxins – all of these events could influence behaviour.

5. Moreover LPS causes a state of general inflammation and oxidative stress when circulating in the blood, similar to what happens in the presence of environmental toxins. Such inflammation reaches the brain and can compromise nervous function. Several mental health disorders are associated with inflammation in the body. Alzheimer’s disease is now recognized as an effect of inflammation inside the brain. (Inflammation is a normal reaction of the body to danger and infection. However, when protracted over long periods, it becomes harmful).

Thus it is VERY important to keep the gut barrier in good conditions so that such products do not leech into the blood and reach the brain to make us depressed… or prone to dementia later in life. What threatens the gut integrity? Use of antibiotics, excessive use of alcohol and caffeine and contaminated food are all causes of gut lining inflammation and possible loss of permeability. And also, smoke, overuse of medications, chemicals in processed food (dyes, preservatives, peroxidised fats), non-steroidal anti-inflammatory drugs, like aspirin, advil, nurofen, ibuprofen, indomethacin, prescription corticosteroids, high refined carbohydrate diet (e.g. candy bars, cookies, cake, soft drinks, white bread), prescription hormones like the birth control pill.

Beside these factors that we inhale or ingest, stress, especially psychological stress, increases the gut permeability by slowing small intestinal transit time, thus encouraging overgrowth of some bacteria which compromise the intestinal barrier. Exhaustive exercise (also a source of inflammation) has also been shown to increase the permeability of the intestinal barrier

Symptoms of a “leaky gut”:

  • fatigue and bloating due to bad absorption of nutrients and foods

  • food allergies due to large food particles crossing the gut barrier and reaching the blood circulation

  • nutrient deficiencies

  • chemical sensitivity due to overburden of the liver for high detoxification process caused by presence of toxins in the blood

So we see a direct chain event:

- un-managed stress leads’ to

- gut permeability, which leads ’ to

- translocation (passage) of toxins into the blood ’creating

- systemic inflammation and ’

- reaching the brain and affecting our mood.

Further, increased permeability of the gut barrier lets go through other substances like food antigens (e.g. gliadin found in gluten) and environmental toxins (e.g. polychlorinated biphenyls etc.), exposure to which is a further risk factor for depressive symptoms.

Low acidity (hypochloridria) in the stomach can make it worse; when the stomach produces low levels of acid, there is less efficient digestion and overgrowth of bacteria in the small intestine (small intestinal bacterial overgrowth, or SIBO), which further damages the intestinal barrier and compromises proper absorption of proteins, fats, carbohydrates, B vitamins, and other micronutrients indispensable for the body and the brain, leading to disease. Gastric acid-blocking medications can provoke this condition, which has been associated with anxiety and depression, Irritable Bowel Syndrome, Chronic Fatigue Syndrome, Fibromyalgia and obesity. Eradication of SIBO with antibiotic improves emotional symptoms and restores the normal intestinal barrier.

These findings are a proof that scientists at the end of the 19th and beginning of 20th century had seen things right although could not prove them. Food and bacteria in it, as well as a proper intestinal function and transit, have an effect on brain health and psychological conditions. However, for serious conditions of depression, a simple change of diet or supplementation of probiotics can only be of assistance as addition to a normal therapy. But...let’s try not to get to that stage by keeping a healthy life style and eating healthy food. More about this in the third chapter of this gut biota story.

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