Probiotics - The Gut-Brain Axis

Many of us tend to underestimate the power of our gastrointestinal tracts (GIT). As far as it concerns us in the most basic sense, our stomach digests the food we eat, and then we poop it out; sounds like a pretty effective and concise system. But the world inside the GIT is actually an entire ecosystem, carrying on in constant activity. The bacterial colonies within this system interact with the food we send down, create a habitat, and take up space along the intestinal lining; sending signals, communicating with us! There are literally trillions of living microorganisms inside of you, with the power of suggestion over you. Are you experiencing constant sugar cravings? Feel anxious or have a low mood? Do you tend to have abdominal cramping and/or bowel urgency when you’re anxious or stressed? These experiences are all guided by the enteric-gut-brain axis.

The gut-brain axis essentially is the connection between the enteric nervous system and the central nervous system, including all communications between the GIT and the brain. Gut microbiota plays a critical role in the function of this axis as well as many other processes, from inflammatory control and immune responses to gut barrier integrity and permeability.^[1] The term “gut microbiota” is used to describe the multitude of species and colonies of bacteria and yeast in the GIT. The composition of the gut microbiota is influenced by diet, stress, and environmental factors, and it influences the production of metabolites that help to maintain host homeostasis.^[2] The gut microbiota is very much influenced by our diet, as the bacteria feed on the nutritional contents in our intestines. This drives the fermentation of carbohydrates and releases short-chain fatty acids for energy production for other, more specialized bacteria.^[3] The balance of bacterial strains is crucial to our health; many health concerns have been linked to gut dysbiosis, whereby an imbalance in the strains or a lack of bacteria in the gut can influence intestinal-wall integrity and transit time.^[4] For example, small-intestine bacterial overgrowth (SIBO) describes a condition where the GIT is inhabited by a multitude of pathogenic bacteria and relatively little commensal bacteria. SIBO has been shown to impair intestinal transit time, causing constipation, but also can accelerate transit time, causing diarrhea.^[4] This dysbiosis is a reflection of diet, sleep quality, and stress in the body.^[4] In addition to influencing changes in intestinal permeability and motility, this bacterial flora also plays a key role in mucosal immune function, and in the production of GABA and serotonin as signaling molecules to the nervous system.^[1] Serotonin functions as a major signaling molecule in the enteric nervous system, functioning and overlapping with the central nervous system.^[1] Tryptophan, a precursor to serotonin, is found in seeds, soybeans, meat, and fish. From our diet, tryptophan is absorbed in the gut and crosses the blood-brain barrier, where it is transformed into serotonin.^[1] Interestingly, the majority of serotonin in our bodies is actually located in the gut, synthesized by enterochromaffin (EC) cells.^[1] This production of serotonin is used to modulate the functioning of the GIT via secretion, peristalsis, vasodilation, and the perception of pain and nausea.^[1] Not only do the EC cells synthesize serotonin, but the gut microbiota also has the ability to produce serotonin from tryptophan and use it as a signal within the gut-brain axis to modify host behaviour.^[1] Drawing on the gut-brain axis, serotonin influences the brain and our mood, but it also regulates the development of structures in the intestinal lining. Microvilli are microscopic protrusions that increase the surface area of the intestinal lining. This extra surface area is utilized for nutrient absorption, and its development is induced by 5‑HTP, the precursor to serotonin.^[5] These connections demonstrate how bacterial gut flora can influence intestinal health as well as nutrient absorption, and contribute to signaling within the enteric and central nervous systems.

Initiation and Maintenance of a Healthy Gut Microbiota

The colonization of the GIT by microbiota is initially determined at birth by the mode of delivery. Vaginally delivered babies have a microbiota dominated by Lactobacillus species originating from the mother’s vaginal and fecal microbiota.^[1] By comparison, babies that have been born via caesarean section have a microbiota influenced predominantly by the mother’s skin microflora. This flora is typically composed of Staphylococcus, Corynebacterium, and Propionibacterium species, with a larger susceptibility to C. difficile.^[6] These babies have also been shown to have very low amounts of Bifidobacteria species; however, breast-feeding can provide an abundance of Bifidobacteria species.^[1] This bacterial flora will become more diversified as the infant is later weaned onto solid foods.As mentioned above, diet plays a key role in the maintenance of beneficial gut bacteria. After all, these bacteria are feeding on the compounds and nutrients that are found in our GIT. Fibre plays an especially important role, and its absence can lead to bacterial migration. If their preferred food source isn’t available, the microbiota will look to feed on other compounds such as amino acids, releasing potentially harmful substances during metabolism.^[3] These substances may contribute to inflammation and “leaky gut,” issues with intestinal permeability and a loss of integrity in the tight junctions between intestinal cells. This process may influence the development of IBD or colon cancer, in addition to food sensitivities and/or allergies.^[3]

Antibiotics and Gut Health

As adults, our microbiota is heavily influenced by our dietary choices, and can be easily disturbed by the use of antibiotics.^[1] It’s becoming more common—though not regular practice—for medical doctors to advise patients to take a probiotic during or after a course of antibiotics. Taking a probiotic a few hours apart from an antibiotic dose can help to correct the wipe-out effect of antibiotics on gut microflora. However, repeated antibiotic use without the repopulation of healthy gut bacteria can lead to permanent alterations in the gut.^[1] More specifically, antibiotic use in children reduces the colonization of Bifidobacterium and Lactobacillus strains. These species of bacteria help to shift the immune system altering the immunological homeostasis between Th1 and Th2 responses.^[1] Early and frequent antibiotic use has been associated with allergies and irritable bowel disease (IBD).^[1] In children and adolescents, brain development is dependent on serotonergic neurotransmission and is required for the function of structures in the brain such as the amygdala, the hippocampus, and the frontal cortex. Serotonin signaling may then influence sleep, sexual behaviour, and mood, strengthening the requirement for a healthy gut microflora.^[1]

Benefits of Probiotics on the Gut-Brain Axis

The interconnectedness of the brain and the gut cannot be understated. Intestinal dysbiosis, an altered gut microbiota with few beneficial bacterial colonies relative to pathogenic species, has been linked to anxiety and depression.^[1] By using probiotics as an intervention, some studies are showing benefit to psychological distress and depression.^[7] Probiotics, by definition, are live microorganisms that are administered in high-enough doses to provide beneficial health outcomes to the host.^[8] Their use for gastrointestinal disorders has been widely studied, but research into their role in benefiting the nervous system has greatly increased over the past decade.^[8] Several human studies have even shown that multistrain probiotics can improve the symptoms of anxiety and depression, as well as cognition.^[4][8] The adult stress response via the hypothalamic-pituitary axis (HPA) has also been linked to gut microbiota. Abnormal stress responses have been observed in adults with gut dysbiosis, which can be reversed with proper colonization and restoration of the gut microbiota.^[4] Multistrain probiotics have been shown to decrease cortisol and/or adrenocorticotropic hormone (ACTH). Human studies are ongoing; some of which are investigating the involvement of gut microbiota in areas such as autism, Parkinson’s, and chronic pain.^[4] Strains most notable for their ability to improve anxiety, depression, and stress responses, in addition to gastrointestinal relief, include B. longum, B. breve, B. infantis, L. helveticus, L. rhamnosus, L. plantarum, and L. casei, with doses ranging from 10 million to 40 billion colony-forming units (CFU) per day.^[8]

The colonization of the GIT by bacterial species influences several areas of our overall health including digestion, mood, and behaviour. The ability of our intestinal cells and gut microflora to modulate serotonin synthesis plays a key role in signaling between the enteric and central nervous systems. Irritable bowel syndrome, although presenting as a dysfunctional digestive disorder, is greatly affected by stress and anxiety, the symptoms of which could be traced back to the composition of the gut microflora. Human studies continue to investigate the role of probiotics in mental health and stress responses, and may very well be an indicated intervention in gastrointestinal disorders linked to anxiety and stress. Repopulating the gut after antibiotic use is critical to overall health, including the development of structures within the brain in children and adolescents.