Dr David Glass – MBChB, FCOG (SA) Over the last few weeks we have been exploring the role of our gut microbiome on various functions within the body. This is a rapidly expanding field of research and discovery.
We have already discussed the role of the microbiome in producing small chain fatty acids (SCFAs) such as acetate, propionate and butyrate, and the role they have in both the integrity of the gut wall, as well as promoting general immunity within the body.
This week we are going to discuss the role that our microbiome has in modulating the function of our brains. Imagine bacteria telling our brains how to work! This may seem a bit complicated, but we will do our best to simplify a very complex physiology. The implications of this research are profound.
A couple weeks ago we mentioned that there are some 100 million nerves connecting our brain through our spinal cord to the muscles of our body, but there are 500 million nerves connecting our gut to our brain. Now that is quite a thought. In fact some people refer to the gut and its colony of micro-organisms as the second brain. Just a short detour. Some of the effects of these SCFAs include the modulation of secretion of insulin by the pancreas, as well as production of ghrelin, which is involved in the development of obesity by stimulating hunger and fat deposition.
We also know that SCFAs can reduce auto-immune conditions through the control of excess permeability of the gut wall (the so-called leaky gut syndrome). A leaky gut allows large proteins capable of stimulating the immune system passage into the blood stream, as well other toxins which can have effects on multiple organs.
It has long been known that the brain has a strong impact upon the gut through the vagus nerve. We know that gut motility (the action of muscles which propel foods down the intestine) can be influenced by our mood, and stress levels; we know too that mental stress can affect the production of digestive enzymes and acids. The blood flow to the gut is also modified by our brain function, as does the role of pain and anxiety on the normal functioning of the gut. Remember how you tend to get diarrhoea before an examination, or lose your appetite when in pain. One of the ways in which a healthy microbiome affects brain function is through suppression of chronic inflammation related to dysbiosis (imbalance in our microbiome). This chronic inflammation can increase the chances of cancers, high blood pressure, diabetes, heart disease as well as degenerative brain conditions such as dementia, Parkinson’s and depression.
But studies are now showing that these SCFAs also have a profound effect on brain function. For one thing they affect the integrity of not only the gut/blood barrier but also the integrity of the blood/brain barrier. An increased permeability of this latter barrier allows unwanted and toxic metabolites and chemicals to penetrate the brain and cause damage to the delicate neurons. This is one of the mechanisms proposed for the development of Alzheimer’s disease. SCFAs also influence the function of glial and microglial cells, which are the maintenance crew of the brain, ridding the brain of a build up of waste products and toxins and sculpting the inter-neural connections. They eliminate excess or unnecessary synaptic connections, and refine or develop new circuits and connections in the nervous system. One of the manifestations of a deficit of SCFAs is the complaint of brain-fog, mental fatigue, poor memory and retention that many people suffer from who are not eating a healthy diet. This results in an impoverished microbiome.
Another more serious concern from the study of a deficient gut microbiome, particularly in infants – impacted by the method of birth and lack of exposure to a healthy maternal microbiome, or the effect of antibiotic “wholesale slaughter” of much of the natural microbiome, is the effect on early neurodevelopment and the development of brain disorders later in life.
Note this statement from the article we refer to for most of the information in this week’s blog: “Growing evidence has shown that alterations in maternal microbiome during pregnancy such as use of antibiotics or probiotics, variations in diet, immune activation, and exposure to stress can modulate the microbiome, neurodevelopment, and behaviour of offspring in both rodents and humans.
Furthermore, delivery mode and early life occurrences such as feeding changes, infection, and antibiotics treatment have a huge effect on the gut microbiota composition with a long-term impact on brain and behaviour. In fact there is some evidence that disorders in behaviour – such as communications deficits, repetitive behaviours, and sensitivity to environmental changes as found with autism spectrum disorder(ASD) are associated with microbiome disorders.
For instance the occurrence and severity of the disease seems to be affected by the relative preponderance of propionate-producing bacteria and versus butyrate-producing bacteria. It is possible to experimentally introduce high levels of propionate in the brain of rodents and reproduce many of the signs and symptoms of ASD. Giving higher levels of butyrate reduce those symptoms. However there is still much work that has to be done to confirm this hypothesis. What about other neuronal disorders? Depression is a serious and common disease and has been associated with generalised inflammation. We know that a healthy gut microbiome suppresses chronic inflammation . High levels of butyrate have an antidepressant-like effect. We know that the progression of Alzheimer’s disease can be slowed by having a healthy microbiome, and dysbiosis (disturbed balance in the microbiome) is associated with disease progression. A similar experience has been found with Parkinson’s disease. Correcting the dysbiosis can improve the motor impairment and dopamine deficiency. Multiple sclerosis has also been shown to benefit from a microbiome where butyrate and acetate producing micro-organisms predominate. Already mentioned earlier is the role of SCFAs in the prevention and modulation of both obesity and insulin resistance, with its consequence – type 2 diabetes.
Much of the research on the interaction between microbiota and the brain and other […]