A Brief Introduction to the Gut-Organ Axis

Did you know your gut can control how effective your heart is? It's true. Recent evidence suggests that bacterial compounds directly influence various organs, which may directly or indirectly regulate physiological and pathological processes. And it happens through the gut–organ axis.

The gut–organ axis is a term used to describe the communication between your gut and the heart, lungs, brain, and many other organs. It is the main player in the bidirectional cross-talk between the gut and the other organs of the body.

This blog talks about the gut–organ axis: what it is, how it works, and how it affects your body.

The Gut: A Central Organ that Maintains our Health

The human gut microbiota is a dynamic and complex population of microorganisms that are crucial for our survival and well-being. It is home to a diverse microbiota, including Firmicutes and Bacteroidetes (up to 75% of all gut flora). They are the key regulators of body homeostasis, including structural, metabolic, and protective benefits to the host.

The human gut microbiota shares a mutually beneficial relationship with its host and plays an important role in the evolutionary fitness of the host, through:

• Digestion
• Vitamin synthesis
• Safeguarding against pathogens
• Increasing fat storage efficiency
• Central nervous system (CNS) modulation
• Immune system development and maturation

Any alteration in the gut microbiota community structures not only triggers gut disorders but also influences other organs and human behaviour and causes associated diseases. This highlights that there is a link or a bi-or multidirectional communication axis between the gut and the other organs, thereby making the gut a vital organ.

The Gut-organ Axis: Establishing the Link Between the Organs

Our bodily functions are greatly influenced by the complex interactions between the gut microbiota and the immune system. This directly relates to other organs and results in the formation of an - 'axis’ between them. Such crosstalk takes place through an array of signalling pathways and direct chemical interactions between you and your microbes.

Within this axis, many vital compounds are produced, including short-chain fatty acids (SCFAs), choline, and bile acids, which are essential for our health. Further, the gut microbiota is influenced by dietary changes or environmental stresses that may influence health and decrease the diversity of the gut composition.

To summarise, the signals sent out by the microbes as well as their compounds which are secreted by the intestinal cells have a major impact on your bodily functions. Without further ado, let’s know more about the different links between the gut and other organs.

The Gut–Brain Axis (GBA)

The gastrointestinal (GI) tract and the brain share a bifacial communication (i.e. each of them has the ability to affect the function of other) that forms the basis of a ‘gut-brain axis’. Through this axis, the gut microbiota brain processes such as behaviour, appetite regulation, and serotonin (the happy hormone of our body) metabolism. Any alterations in gut microbiota have been linked to various neurological disorders like anxiety, multiple sclerosis, Parkinson’s disease (PD), autism spectrum disorders, and others.

Gut-brain axis links the intestinal functions with the cognitive and emotional centres of the brain. The gut-brain axis involves:

• Central nervous system (CNS) with the brain and spinal cord
• Autonomic nervous system (ANS) with its sympathetic and parasympathetic limbs
• Enteric nervous system (ENS) and the hypothalamic-pituitary-adrenal (HPA) axis

ENS regulates the physiology and the function of the GI tract, and bifacially communicates with CNS via vagal pathways, thereby forming the ‘gut-brain axis.’ The disruption in GBA governs changes in intestinal functions. And, any absence of microbial colonisation in the gut can alter the expression of neurotransmitters (like serotonin, melatonin etc).

Similarly, the brain influences various gut functions like the secretion of acids, mucus, gut motility and immune response. The malfunctioning of the cells in the gut-brain axis known as enteric glial cells (EGCs) can result in GI disorders such as inflammatory bowel disease (IBD) and neurodegenerative disorders like PD and infection-induced gut inflammation.

The Gut–Kidney Axis

Similar to the gut and the brain, the gut and the kidney also share a bidirectional relationship of synergy. Any interference between this bidirectional communication leads to various serious complications, such as chronic kidney disease, end-stage renal disease, and septic acute kidney injury (AKI).

Many uremic solutes and toxins are produced by the gut microbiota; these uremic toxins can circulate in the blood and are excreted by the kidney's tubular secretion. An imbalance in the colonic bacteria can cause epithelial barrier damage. An imbalance in the colonic bacteria can cause epithelial barrier damage. In addition, if they build up in the body, it increases the rate of the progression of kidney disease. Thus, their concentration in the blood can be used as a measure of the functional efficiency of the kidney.

The Gut–Liver Axis

The gut-liver axis is a bidirectional communication network between the gut and the liver. In this case, the liver produces beneficial substances that are absorbed by the intestine. The liver receives almost 70% of its blood supply from the intestine through a portal vein. Therefore, the liver is continuously exposed to the gut flora and its derived products.

The gut microbiota has a major impact on liver physiology since the microbial substances such as ammonia, acetaldehyde, and ethanol that enter the liver are metabolised by the liver cells. An altered intestinal barrier, either by inflammation and portal hypertension or variations in the gut microbiota, increases intestinal permeability that allows bacterial toxins to release excess inflammatory molecules in the liver that can damage the liver. Not an individual microbe, but microbial dysbiosis causes several liver-related diseases.

The Gut–Bone Axis

Besides being a specialised support framework of the body, the bones: protect vital organs, act as an environment for bone marrow (both for fat storage and blood formation); provide mineral reservoirs for calcium; and are the storehouse for growth factors.

A complex association between the gut and bone health via the ‘gut–bone axis’ has an impact on bone health. Exposure or restriction to environmental factors regulates growth retardation, bone mineralization, and body and gut microbial composition. The gut microbiota regulates bone growth via various potential mechanisms such as nutrition absorption, altering GI tract permeability, and immune system maturation.

For instance, the increased levels of Bifidobacterium longum and Lactobacillus reuteri in the gut result in increased bone mineral density via elevated levels of mineral absorption such as calcium, phosphate, and magnesium.

The gut microbiota has an important role in the synthesis of vitamins B and K, which are crucial for bone health regulation. Therefore, diet plays an important role in the functioning of the gut–bone axis. Experts believe that an appropriate carbohydrate-to-protein ratio in the diet is essential and any deviation leads to an imbalance in gut microbiota composition that may result in a malfunction of bone metabolic processes.

The Gut–Heart Axis

Most cardiovascular disease (CVD) risk factors can result in dysbiosis, which is associated with intestinal inflammation and reduced gut barrier integrity. This elevates the levels of microbial metabolites and gut bacteria-derived structural components in the circulation, which accelerates the development of CVD. This indicates the existence of a bi-directional communication network between the gut and the heart, that is, the ‘gut–heart axis’.

In the case of patients with heart failure, disturbances such as the constriction of blood vessels and reduced cardiac output can structurally and functionally impair the gut resulting in diminished intestinal blood flow and a thickened bowel wall. Furthermore, gut barrier dysfunction impairs nutrient absorption, leading to malnutrition. It also causes the toxins from the gut bacteria to bind with their receptors in the circulatory system, which results in structural tissue damage and impaired cardiac function.

The Gut–Skin Axis

Both the gut and skin are essential for maintaining the body’s internal balance, called homeostasis. The skin regeneration process is very important for the maintenance of its state of homeostasis, which is accomplished by the constant and efficient renewal of the epidermis (the outer layer of the skin). In the state of homeostasis, the skin can perform various essential functions, including temperature regulation, protection, and water retention.

The gut microbiota influences the skin microbiome by producing SCFAs, which have a significant role in deciding the prevalence of skin microbiome species that consequently affect the mechanism of an immune response. In the case of atopic dermatitis (AD), an inflammatory disease of the skin that is mainly governed by altered immune response and dysfunction of the skin barrier. This immune imbalance is caused by altered GM and their metabolites as a result of an inflamed microenvironment in response to the presence of specific microbiota.

A link between gut dysbiosis and alopecia areata ( an autoimmune disorder that usually results in unpredictable, patchy hair loss) has been proposed. Alopecia areata-related genes could affect gut colonisation with microorganisms that initiate an inflammatory pathway, causing abnormal growth of hair follicle cells and even hair loss.

Therefore, a functional interactive mechanism between the skin and the gut is strongly supported by evidence.

The Last Word

The complex role of the GI tract and associated microbiota, that is, the ‘gut–organ axis’, needs to be validated in maintaining the health of various organs. Optimising gut health certainly facilitates the smooth functioning of the gut-organ axis. Therefore, be mindful of your diet and lifestyle since they decide the fate of your gut composition.

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