Definition of gut health

Gut health is physical and mental well-being without any gastrointestinal complaints requiring a doctor's consultation. Additionally, there are no indications of or risks of bowel disease, and no confirmed cases of bowel disease exist.¹ Gut health means the healthiness of both the upper and lower GI(Gastrointestinal) tract.

Five primary criteria have been defined that form the basis of a more positive and objective definition of gut health.¹³

Gut-related issues

Some of the crucial symptoms of gut health that people tend to seek the doctors for include functional dyspepsia, Irritable bowel syndrome(IBS), and consists of flatulence, bloating, regurgitation, heartburn, nausea, vomiting, constipation, diarrhoea, intolerance to food, incontinence, abdominal cramps, loss of appetite, weight loss, and blood in stools. These symptoms are not very harmful. It will not lead to death, but the quality of life is affected.

Symptoms which require thorough examination and should not be neglected are loss of appetite (anorexia), weight loss with no reason, difficulty in swallowing, vomiting continuously, severe pain in the abdomen, melena, and hematochezia. These symptoms are more important if they have a familial history of cancer and are 50 years old or older.¹

Gastrointestinal tract or digestive tract

It includes the mouth, oesophagus, stomach, small intestine, large intestine, and anus.¹⁴ 

The GI tract contains bacteria, known as gut flora or gut microbiome. These bacteria help with digestion. In addition, some parts of the nervous and circulatory systems also play an essential role in digestion.²

How does the mechanism of digestion occur?

Each part of the system aids in moving food and liquid throughout our GI tract. It helps break the food into smaller parts so that the body can absorb the nutrients needed. The large intestine absorbs water and waste products of digestion to form stool to be excreted.¹⁴

 Digested food - what happens to it?

• The small intestine absorbs the majority of food. It enters other parts of the body through our circulatory system. Our blood carries glucose, amino acids, glycerol, some vitamins, and salt to the liver. Our liver functions by storing, processing, and delivering nutrients to the body
• Finally, our body uses sugar, amino acids, fatty acids, and glycerol to build what we need for energy, growth, and cell repair²

Digestive process: how does my body control it?

Numerous data indicate that the function of the gut has many roles to play, not just the food and fluid absorption.

• The gut communes with bacteria, which help in digestion depending on their enzymatic activity
• It regulates the body's gut health and general health by maintaining major epithelial and immune functions
• It interacts with the brain regarding energy consumption and conditions affecting the mood through the Vagus nerve and hormones
• Recent research in germ-free mice has shown that the gut bacteria influence the behavioural development and neurochemical changes in the brain in accordance with the chemicals

Our hormones and nerves collaborate to control the digestive process. Signals within our GI tract flow back and forth from the GI tract to our brain.

Hormones

Cells lining the small intestine generate and release hormones that control the digestive system's functions. The small intestine tells our body to make digestive juices by sending signals to the brain when we are hungry and full. Our pancreas is also a vital organ that produces hormones for digestion.

Nervous system

1. Central nervous system: These nerves connect our brain and spinal cord to our digestive system and control it. For instance, saliva is produced from our salivary glands when we look at or smell food
2. Enteric nervous system: These are nerves located within our digestive tract, which regulate the movement of food and produce digestive juices. These nerves signal and control our gut muscles by contracting and relaxing, so that food pushes through our intestines

All in all, the gut and hormones are deeply interconnected; a healthy gut microbiome plays a crucial role in maintaining hormonal balance.

The gut microbiome: what it is and what it does

The gut microbiome is a highly diverse community that plays an important role in regulating metabolic balance. It comprises 100 trillion bacteria, which are mainly anaerobes. Bacteroides and Firmicutes are the dominant bacterial groups, while other microbes such as viruses, protozoa, archaea, and fungi are also present in smaller proportions. Proteobacteria, Actinomyces, Fusobacterium, and Verrucomicrobia are other less abundant bacterial types.⁴

The gut microbiome influences host hormone levels directly and also stimulates the release of gut hormones from enteroendocrine cells(EECs) via their metabolites and components.

For instance, Studies in mice have shown that lipopolysaccharides(LPS) from bacteria bind to toll-like receptor 4(TLR4) on L- L-cells, by promoting the secretion of glucagon-like peptide 1(GLP-1), a natural hormone in mice which plays a critical role in regulating blood sugar and appetite. It also triggers the release of cholecystokinin (CCK), a hormone which plays a critical role in digestion and appetite regulation.

Important functions of the gut microbiome

1. Barrier and structural functions

• It helps in the formation and maintenance of the intestinal barrier, continuously supporting microbial colonisation
• Stimulates intestinal epithelial cell regeneration
• Synthesises and nourishes the mucosa by generating short-chain fatty acids(SCFAs)

2. Immune system maturation and regulation

• Stimulates the innate immune system in early life by promoting the development of intestinal-related lymphoid tissue
• Activates acquired immunity by triggering local and systemic immune responses
• Maintains immune stimulation to defend against pathogens

3. Nutrient and metabolic functions

• It engages in producing and metabolising nutrients, hormones, and vitamins
• Assists in drug and toxin metabolism and elimination

4. Protective and competitive function

• Involves protective competition in the gut
• Produces nutrients required for pathogen survival
• Produces cytokines that stop pathogen growth.
• Role in digestion and immune system support

Overview of gut-brain and gut-hormone communication

There has been a lot of research to understand the mechanism of gut microbiome and brain in in past 15 years.⁴

Finally, the core importance was how the gut microbiome impacts the brain through

1. The nervous system
2. The hormone system(neuroendocrine system)
3. The immune system

The direct mechanism between the gut microbiome and the brain is still unknown. In general, the gut microbiome affects the brain not only through the nervous system, even the endocrine, immune, and metabolic systems participate in its effects. This communication, which is associated with them, is known as the gut-brain axis.⁵

This interaction within them is referred to as the gut microbiota-gut-brain axis. The belief is that we can understand the information in depth and protect the brain.

Neuroanatomical pathways 

There are two pathways through which the gut communicates with the brain.

The first pathway is communication between the gut and brain, which is done by the autonomic nervous system and then the vagus nerve in the spinal cord.

The second pathway is interaction via bilateral communication between the ENS (enteric nervous system) in the gut and the ANS (autonomic nervous system) and the VN (vagus nerve) in the spinal cord.

The Neuroendocrine hypothalamic pituitary adrenal axis

The gut microbiota plays a crucial role in the development of the neuroendocrine system. A lack of gut microbiomes leads to an altered immune response to pathogens in the gut.⁴ The gut microbiota is essential in early life for proper HPA axis development and adequate stress response.

Stress also affects gut microbiota. Research conducted with rats demonstrates that early-life stress and separation from the mother have long-term effects on both the HPA axis and microbiota. A constant amount of stress decreases Bacteroides in the cecum and increases Clostridium. Stress also increases blood levels of Interleukin-6 (a pro-inflammatory cytokine) and Monocyte chemotactic protein-1(MCP-1).

Gut immune system

The improvement of the gut's immune system is dependent on gut microbiota. For example, the segmented filamentous bacterium in the gut restores the complete immune function of B and T lymphocytes in the gut. Bacteria communicate through Toll-like receptors (TLRs), which are also found in neuron cells. 

There are ten types of TLRs, known as pattern recognition receptors. This implies that the neurons can also respond to bacteria and viruses, and not just immune cells.

Intestinal epithelial cells move microbial components or their metabolites into the inner body, enabling the nervous system to communicate with these substances.

The balance of the gut microbiome influences how the body regulates inflammation. This inflammatory regulation, in turn, controls emotions and behaviour.

The role of gut microbes in neurotransmitter production

Gut bacteria synthesise important substances like Gamma-aminobutyric acid (GABA), butyric acid, serotonin(5-HT), dopamine, and short-chain fatty acids( SCFAs). These substances can be exchanged with the microbial cells in the intestine, which produces an enormous amount of serotonin that affects the brain.

Bacterial enzymes create neurotoxic byproducts such as D-lactic acid and ammonia. Hence, many essential neurotransmitters in our body are produced by gut microbes, which play an important role in the body and brain.

Intestinal mucosal barrier and blood-brain barrier (barrier system)

Rodent studies proved that stress weakens the intestinal mucosal barrier, allowing lipopolysaccharides and cytokine-like substances to enter the bloodstream. This enhances TLR4 and other TLRs to make inflammatory cytokines. These inflammatory factors affect the blood-brain barrier permeability, allowing them to directly affect the brain.

The evidence from both animals and humans strongly supports that gut microbiota is essential for brain development and function.

Production of hormones in the gut

GI hormones modulate mucosal growth and influence the pathogenesis of gut mucosal atrophy, neoplasm, and cancers. Gastrin, CCK, Secretin, Somatostatin, Ghrelin, bombesin, and gastrin-releasing peptide(GRP) are some hormones that regulate the gut mucosal growth.⁹

Gut microbiome and the endocrine system

The gut microbiota is an endocrine organ with glands that synthesise humoral factors. The microbiota produces many hormones released into the blood at distant sites of different organs.

The gut microbiota adjusts glucocorticoid synthesis in the HPA axis. It influences the brain by controlling the accessibility of serotonin precursor tryptophan. Gut microbiota synthesise metabolites from choline, which impact the cardiovascular system.¹⁰

Gut microbiome and autoimmune disease

There has been irregular gut microbiota in several autoimmune diseases like Type I diabetes, Inflammatory bowel disease, Asthma, and Rheumatoid arthritis.

In type I diabetes patients, the immune cells destroy the pancreatic beta cells because they have to be on lifelong insulin. The cause of this is unclear, and the primary focus now has been on immune and genetic factors. Researchers are now focusing on and investigating the gut microbiome. It could be a potential contributor to type 1 diabetes development.

Link to sex hormones (testosterone, estrogen)

Sex hormones, both androgens and estrogens, affect the gut microbiota composition.⁸

Also, gut microbiome and its metabolites are connected in the development of sex hormone-related diseases and impact the levels of sex hormones.

Continuous research is ongoing on the gut microbiome in sex hormone-associated diseases.

The role of the gut barrier and inflammation

The composition of the gut microbiota affects intestinal barriers. Dysbiosis can lead to enhanced intestinal permeability, which is referred to as leaky gut.¹²

Increased intestinal permeability allows microbial toxins and products to enter the bloodstream, triggering systemic inflammation. This impacts our health, leading to metabolic disorders, cardiovascular diseases, and other autoimmune conditions.

There are therapeutic remedies suggested that balance the gut microbiota. Through dietary interventions, probiotics, and prebiotics, we could restore our intestinal barrier. However, more research is required to establish these approaches.

Gut-related hormonal imbalances^11,16

Ways to support gut health for better hormonal balance

• Consume more fibre
• Our diet should include phytoestrogens
• Intake of probiotic and prebiotic-rich food 
• Decrease exposure to environmental toxins
• Try various meditation techniques to stimulate the vagus nerve
• Manage stress
• Avoiding unnecessary antibiotics
• Sleep and regular exercise
  

Summary

All in all, gut health is critical. It helps us to maintain both physical and mental well-being. It constitutes the health of both the upper and lower GI tracts. We should be aware of the gut-related symptoms and take appropriate diet and measures to maintain the gut microbiome, which is very essential in maintaining many hormones directly and indirectly. 

In addition, we have seen that the gut-brain axis has different communication pathways between the gut and the brain. We have also seen that any abnormality in gut microbiota is linked to many hormonal dysfunctions, affecting the immune system, the cardiovascular system, the enteric nervous system, metabolic disorders, and sex hormone disorders. Irregular gut microbiota is also linked to many autoimmune diseases. Therefore, we have to take adequate steps to support gut health by taking necessary probiotics, prebiotics, and also by following a holistic approach. There is still ongoing research regarding gut health and its various associations with our body's health.