Gut-Brain-Microbiome Axis

Gut-Brain-Microbiome Axis

Gut-Brain-Microbiome Axis

How the communication between your gut, brain, and microbiome influences IBS

Irritable bowel syndrome (IBS) has been a bit of a medical mystery between trying to find better ways to diagnose a person with IBS, pinpointing what causes IBS in the first place, and finding the best treatment options. At first, the focus was on foods by trying to determine what dietary factors made symptoms better or worse. This gave rise to restrictive diets like gluten-free diets or the even stricter low-FODMAP diet. FODMAP stands for fermentable oligosaccharides, disaccharides, monosaccharides, and polyols; these are just short-chain carbohydrates and sugar alcohols that are difficult for the body to break down and absorb through the small intestine. When the small intestine has difficulty absorbing nutrients it triggers a reaction that causes more water to be drawn into the lumen and expand more than normal; this sends pain signals to the brain and creates the sensation of cramps, a symptom of IBS. Studies ultimately found that the low-FODMAP diet wasn’t really any more effective than the conventional IBS diets, but it did however, lead to major changes in the microbiome of the gut.1,3 Research found that low-FODMAP diets could throw the whole gut microbiome out of balance by killing off essential prebiotics. For this reason, even though it helped some patients with their symptoms, doctors realized that it could do more harm than good as a long-term solution for treating IBS. The same study also found that humans might actually need certain FODMAPs that promote the production of good bacteria our intestines need to function efficiently.1 When scientists realized how delicate the microbiome of the gut was, they began to look at the connection between changes of microbiome health and how it affects the brain.

Good microbiota is important to the gastrointestinal tract because they work with the epithelial cells that line our intestinal wall to strengthen our immunity, digest food, absorb essential nutrients, and have now been shown in mice to directly interact with the central nervous system.2,6 The two-way connection between the digestive tract and the brain has been well established. However, the idea that microbiota may have a direct link to brain function and development, and vice versa, could lead to medical breakthroughs on how to diagnose and treat many illnesses including IBS. The evidence from studies suggests that when the balance of the microbiome within the gut is thrown off, signals are sent to your brain, via the central nervous system, to tell it that something is wrong.2,6 The vagus nerve is an important part of the central nervous system that connects the brain to the visceral organs like the heart, lungs, and digestive tract. This cranial nerve plays a big role in digestion because it sends signals from the brain to control the subconscious muscle movement of the digestive system as well as visceral sensations from the digestive system to the brain.2 It has been shown in mouse studies that because of this bidirectional connection through the CNS, microbial imbalance can directly influence a variety of brain functions such as neurological development, cognitive ability, pain sensitivity, and even mental health.2,3 Since this pathway is bidirectional, it led scientists to believe that if microbial change in the gut can affect the brain, then changes in the brain should also affect the microbiome of the gut. They realized that if their theory was correct, this connection could lead to an explanation of what causes IBS and possible treatment options. 2

Researchers have taken this theory and linked possible causes of IBS to “perturbations of the gut microbiome”.2 These changes happen from many things, but when it comes to IBS researchers have narrowed their investigation down to excessive antibiotic use, previous gastrointestinal infections, and psychosocial trauma.2 When someone has a GI tract infection, they either let the body fight the infection naturally, or sometimes an antibiotic can be prescribed to help kill off the bad bacteria in the gut causing the infection. When an antibiotic is used, it can kill off groups of good bacteria that resemble the targeted bacteria causing an imbalance in the microbiome of the gut. Microbiologist William de Vos believes that in some cases those good bacteria don’t come back, and your microbiome gets locked into a perpetually disrupted state leading to gastrointestinal disorders like IBS.2 When certain gut microbes are wiped out it can also change the intestinal environment which can lead to long-term gut hypersensitivity, impaired digestion/excretion, and lowered stress response; which are all symptoms of IBS that are connected to the brain.2,3 Animal studies have revealed that mice who don’t have a specific microbiota showed an increase in cognitive irregularities that resemble symptoms of anxiety or depression in humans.2,3 This kind of connection between the microbiota and the brain could explain why gastrointestinal disorders, like IBS, usually go hand in hand with some sort of psychiatric issue.2

Early life trauma is a psychosocial trauma commonly expected to initiate the onset of mental illnesses like post-traumatic stress disorder or depression. There is now additional research that suggests there may be a link to gastrointestinal disorders as well.2 The theory is that since this axis is bidirectional, an early life trauma that alters the brain, structurally and functionally, could potentially affect the microbiome of the GI tract enough to induce IBS. Animal studies have shown that when a mouse experiences trauma, the region of their brain that responds to pain completely changes. This change in the brain then triggers the CNS to make changes to the microbiome of the gut. Consequently, these changes to their gut microbiome lowered production levels of dopamine, adrenaline, and serotonin.2 Serotonin is an important neurotransmitter that regulates mood, regulates digestive motor function, and conveys sensory signals from the GI tract to the vagus nerve. 2,5,6 Low levels of serotonin are commonly linked to depression, but it also leads to inflammation, visceral hypersensitivity, lowered gut motility, and lowered intestinal secretion; all of which are symptoms of IBS.6 Another study revealed that in healthy mice a specific subgroup of microbiota was found that stimulated the synthesis and secretion of serotonin from enterochromaffin cells in the epithelial wall.2,5,6 The evidence that these animal studies have provided highlight how versatile serotonin can be in future diagnoses and treatment for gastrointestinal disorders in humans.

Since research has continued to strengthen the connection of IBS to serotonin fluctuations, more doctors have started using “selective serotonin re-uptake inhibitors and tricyclic antidepressants” to effectively treat IBS symptoms.5 Another treatment option that has been proven to alleviate some patient’s IBS symptoms, is giving patients a big dose of healthy probiotics to help balance out their microbiome.2 As scientists learn more about the different groups of microbiota in the human digestive system through study of biomarkers, gene sequencing, and RNA sequencing, they can begin to determine how each of them influences digestive health and brain function.4 Once scientists have that information they can use it to easily diagnose what disorder they are dealing with by knowing what type of disorder certain microbiota in the gut are associated with. Then they can develop ways to add or take out specific microbiota in an individual’s microbiome to treat various disorders, including IBS and depression3,4 It’s exciting that there is so much research going into understanding the gut-brain-microbiome axis because if scientist can solve the mystery of how both directions work in humans, IBS could be just the beginning.

References

1. DeWeerdt, Sarah. Food for thought. Nature. 2016, Vol. 533, pp. S108-S09.

2. Eisenstein, Michael. Bacterial Broadband. Nature. 2016, Vol. 533, pp. S104-S106.

3. Ghosh, Dilip. Potential Role of Microbe-Gut-Brain Axis on Mood. Nutraceuticals World. 2018, p. 40.

4. Katsnelson, Alla. Filling in the missing pieces. Nature. 2016, Vol. 533, pp. S110-S111.

5. Morgan, Branwen. A healthy pipeline. Nature. 2016, Vol. 533, pp. S116-S117.

6. Hoffman, Benjamin U. and Lumpkin, Ellen A. A gut feeling. Science. 2018, Vol. 361, 6408, pp. 1203-1204.

Allergic Diseases

Over the past few decades the number of children that suffer from allergic diseases in western developing countries has increased dramatically. In fact, just between 1950-1995 the prevalence for allergic disease in children increased by 35%.1 In 1989 Dr. Davis Strachan came up with what is now known as the hygiene hypothesis, which suggested the increased allergic disease prevalence was consequently due to decreased contact with infectious microbes during early childhood. He explained how the bacteria that causes infections tend to strengthen the immune system by increasing the microbial diversity of the intestinal flora and triggering the production of regulatory T cells; these cells regulate the production of immunoglobin E (IgE) antibodies that release chemicals that cause allergic reactions.1,2 Atopic dermatitis is an IgE-associated allergic disease, common in children, that has previously been linked to population variations of commensal lactic acid-producing bacteria.1,2 Studies have shown that when Lactobacillus rhamnosus GG (LGG) was given as a probiotic to mothers from 36 weeks pregnant to when they stopped breast feeding, and then directly to the infant for 6-24 months, the risk of developing atopic dermatitis was decreased by about half.1,2 Evidence from these studies suggests that enhancing the intestinal microbiome by introducing specific probiotics at an early stage, can help prevent the onset of atopic dermatitis in high-risk children. The success of these studies has also produced viable evidence to support further investigation into finding different strains of probiotics that could possibly aid in the prevention of other atopic IgE-associated allergic diseases in the future. 

References

1.Biosci Microflora. 2011;30(4):119-28. doi: 10.12938/bifidus.30.119. Epub 2011 Nov 17

4.J Allergy Clin Immunol. 2008 Oct;122(4):788-794. doi: 10.1016/j.jaci.2008.07.011. Epub 2008 Aug 31

The microbiome of the gastrointestinal tract has been at the forefront of skin care research, but in the last few years the actual skin microbiome has become a focal point for research on inflammatory dermatological conditions like atopic dermatitis (AD).1,2 The human skin is home to about over million bacteria, fungi and virus per centimeter where species vary depending on a variety of factors including: location on the body, environment, sex, age, diet, and hygiene.1More and more people are becoming susceptible to dermatological conditions due to new lifestyle changes that can potentially alter the microbiome into a state of dysbiosis. Research has shown that introducing certain probiotics topically can treat different conditions by counteracting the imbalance of the microbiome, enhancing skin barrier functions, preventing biofilm formation, and encouraging the growth of beneficial bacteria on the skin.1,3 However, research has also shown that different strains of bacteria have different effects on the microbiome. For instance, Staphylococcus epidermidis promotes skin immune functions while Staphylococcus aureus does the opposite causing an imbalance in the microbiome and making the skin susceptible to pathogenesis.1,3 Understanding the different effects that certain microbiota have on the microbiome of the skin could lead to huge advancements in the skin care world. With every study, scientists get one step closer to cracking the code of how to hack the microbiome of the skin and personalize treatment options for a variety of skin conditions. Nevertheless, one biggest obstacles that they will have to consider is how diverse these microbiomes are from one person to the next.2

1. Cates T (2019) Enhancing the Skin Microbiome to Address Inflammatory Dermatologic Conditions. Townsend Letter:50-51.

2.Euromonitor International. 2019. The role of microbiome in the evolution of skincare [PowerPoint slides].

3.JCI Insight. 2018 May 3;3(9). pii: 120608. doi: 10.1172/jci.insight.120608..

Most people take oral probiotics to promote the health of their intestinal microbiome, but it’s now evident that topical probiotics can also benefit the microbiome of the biggest organ of all; the skin. In the past there have been studies that explain how taking oral probiotic supplements could benefit your skin from the inside out, but researchers are beginning to take a new perspective when it comes to probiotics from the outside in. The have begun investigating the possibilities of topically transplanting probiotics directly into the skin microbiome to treat different skin diseases. A study from Myles et.al., 2018 explained how large populations of Staphylococcus aureus (S.aureus) were found in areas affected by atopic dermatitis, and potentially worsening the symptoms. In hopes that they could combat the symptoms with a probiotic for the skin, they decided to try transplanting an “anti-S.aureus” bacteria, Roseomonas mucosa (R.mucosa), to a patient suffering from AD. They found that it was only when R. mucosa was transferred from a healthy volunteer to the affected area of an AD patient, that S.aureus populations decreased along with pruritis, inflammation, redness, and over all intensity of AD symptoms.2 The results of this study highlight how as researchers uncover how different probiotics affect the microbiome of the skin, they can figure out ways to utilize them in creating different treatments for a variety of skin disorders.

References

1.Cates T (2019) Enhancing the Skin Microbiome to Address Inflammatory Dermatologic Conditions. Townsend Letter:50-51.

2.JCI Insight. 2018 May 3;3(9). pii: 120608. doi: 10.1172/jci.insight.120608..