Gut Microbiota: 8 Important Roles in Preventing Disease

Key Points

1. The large intestine harbors over 70% of the body’s microorganisms, with a vast array of over 1,000 bacterial species and 1014 bacterial cells.
2. Next-generation sequencing (NGS) of microbial DNA has revolutionized our understanding of human microbiota, showcasing the integral role of gut microbiota (GM) in human health.
3. GM plays a vital role in our nutrition, metabolism, and immune response, contributing to essential processes such as vitamin and neurotransmitter synthesis.
4. The “estrogen-gut microbiome axis” highlights the significant relationship between GM, estrogen levels, and bone health.
5. While GM produces beneficial molecules, it can also produce harmful metabolites like lipopolysaccharide (LPS), which has been linked to chronic diseases.
6. Our GM begins to form at birth, influenced by factors like diet, sleep, and exercises, and changes over time, often reducing in diversity and stability with age.
7. Lifestyle choices such as diet, sleep, and exercise significantly shape GM, impacting its composition and function, and subsequently our health.
8. Dysbiosis of GM can lead to various diseases, and its composition is profoundly connected to our immune system, affecting immune cell formation and potentially leading to systemic inflammation and pain.

World of Gut Microbiota (GM)

The large intestine is a bustling metropolis, home to over 70% of the body’s microorganisms ¹.

The term gut microbiota (GM) encompasses the various microorganisms—commensal, symbiotic, and pathogenic—occupying our intestines.

This diverse collection has evolved alongside humans, influencing our health and well-being through complex interactions ².

In the vast world of the human gut, over 1,000 bacterial species and 1014 bacterial cells exist ³.

Yet, the true diversity of anaerobic bacteria remains elusive, often escaping traditional culture techniques.

Thankfully, modern science has gifted us with high-throughput “next-generation sequencing” (NGS) of microbial DNA, revolutionizing our ability to unravel the mysteries of human microbiota.

This innovative technology has thrust GM into the spotlight, highlighting its integral role in human health.

When in harmony, GM is our ally, playing a vital role in nutrition, metabolism, and immune response while safeguarding against pathogenic invasion.

Conversely, a disrupted GM can be our foe, potentially leading to inflammation, pain, and various diseases.

Embracing and understanding this microscopic universe is essential for unlocking the secrets to optimal health.

The Marvelous Role of Gut Microbiota in Our Health

GM: A Silent Powerhouse of Nutrients and Metabolites

The human gut isn’t just responsible for digestion.

It’s an active site where numerous beneficial processes occur, thanks to the presence of GM.

This intricate microbial community helps ferment dietary fibers, producing essential components like bile acids which aid in calcium absorption.

GM also plays a role in synthesizing vitamins B and K, along with important amino acids, short-chain fatty acids (SCFA), and even neurotransmitters ⁴.

Some even regard GM as an endocrine organ due to its profound impact on distant organs ⁵.

GM’s Interplay with Estrogen and Bone Health

GM has a subtle influence on our bone health.

It’s involved in processes like calcium absorption and vitamin K production, which are essential for bone strength⁶.

Interestingly, GM impacts estrogen levels, a crucial hormone for bone health.

A diverse GM ensures optimal estrogen levels.

However, disruptions in GM can lead to decreased estrogen, potentially increasing the risk for conditions like postmenopausal osteoporosis ⁷.

This intricate relationship between GM and estrogen is often termed the “estrogen-gut microbiome axis“.

Neurotransmitters, SCFA, and Pain Management

B vitamins, particularly B12, are recognized for their pain-relieving properties ⁸.

Moreover, SCFA, produced in the colon by GM, is vital for controlling intestinal inflammation and regulating various metabolic processes, such as bone metabolism, appetite, and even sleep⁹.

Neurotransmitters like dopamine and serotonin, which play roles in mood regulation, pain, and inflammation, have close ties with GM.

Remarkably, a significant portion of these neurotransmitters is produced in the gut ¹⁰.

Furthermore, other neurotransmitters like noradrenaline and GABA have important functions in pain processing¹¹.

A Double-Edged Sword: The Good and Bad of GM

While GM contributes many beneficial molecules to our system, it can also produce harmful ones.

Lipopolysaccharide (LPS), a metabolite from certain bacteria, promotes inflammation.

Elevated LPS levels have been observed in several chronic diseases, including obesity, osteoporosis, and various spine-related disorders ¹².

Thus, GM can have both protective and detrimental effects on structures like bones, ligaments, and muscles, and may be linked with spinal degenerative diseases (SDD) and pain associated with them ¹³.

Dysbiosis of GM

Initial Acquisition and Diversity of Gut Microbiota (GM)

Our gut microbiota (GM) is a complex and dynamic ecosystem that begins to form at birth, primarily influenced by our mothers ¹⁴.

In a state of optimal health, our GM boasts a rich and diverse composition, exhibiting stability and resilience against various disturbances ¹⁵.

However, it’s important to note that our GM composition is not static; it evolves and changes as we age, and can be affected by environmental and lifestyle factors such as diet, sleep, and exercise¹⁶.

The Aging Gut: How GM Changes with Time

As we grow older, our GM composition undergoes significant changes.

Older adults typically have a GM characterized by reduced diversity and stability, decreased ability to degrade glycoconjugates, and enrichment of certain bacteria types that can be harmful¹⁷.

Interestingly, reduced diversity in GM has been correlated with the “frailty index,” which is an indicator of biological age and a predictor of life expectancy¹⁸.

Additionally, aging affects the gut’s physical structure and its protective functions, which can lead to systemic inflammation often seen in older adults¹⁹.

A notable aspect of aging is cellular senescence, which results in an accumulation of senescent cells (SCs) in tissues and organs.

These SCs can secrete inflammatory cytokines, contributing to chronic inflammation and increasing the risk of diseases and mortality in older adults ^{20 21}.

Research has shown that neutralizing oxidative and inflammatory stress can potentially delay the accumulation of SCs²².

Furthermore, senolytics, which are compounds that target SCs, have shown promising results in clinical trials²³.

GM plays a crucial role in our aging process, as various metabolites of GM have strong anti-inflammatory and antioxidant properties that can be beneficial in preventing age-related inflammatory and tumorigenic environments ²⁴.

However, an imbalance in GM, known as dysbiosis, can lead to chronic inflammation and may promote cellular senescence, affecting the development and prognosis of senescence-associated diseases (SDD).

Lifestyle and GM: The Impact of Diet, Sleep, and Exercise

In a nutshell, our lifestyle choices, specifically diet, sleep, and exercise, play a crucial role in shaping our gut microbiota (GM), affecting both its composition and function²⁵.

First off, our diet can significantly influence GM, with nutrients impacting the microenvironment of GM, consequently altering its composition, metabolism, and immune response ²⁶.

Next, sleep, or lack thereof, has a profound impact on our GM.

Inadequate sleep can lead to a less diverse GM, which is linked to chronic inflammation-related diseases ²⁷.

Sleep disruptions also contribute to hormonal and metabolic disturbances, increasing the risk of diabetes and obesity²⁸.

Lastly, exercise is a key player in maintaining a healthy GM.

Studies have shown that physical activity can bring about positive changes in GM’s composition and metabolic functions, providing numerous health benefits ²⁹.

Regular exercise can enhance GM’s stability, thereby benefiting older adults, particularly those who are overweight³⁰.

Causes and Effects of GM Dysbiosis: From Lifestyle to Disease

Your gut microbiota (GM) is like a unique fingerprint, significantly shaped by factors like age, diet, smoking, alcohol consumption, disease, antibiotics, and pathogens ³¹.

When these factors tip the balance, they can lead to dysbiosis, a state where harmful changes in your GM occur, potentially leading to inflammation and disease ³².

A prime example of this is the “leaky gut syndrome,” where the protective barrier of your intestine becomes compromised, allowing harmful substances to enter your bloodstream and trigger a systemic inflammatory and abnormal immune response ³³.

This disruption can have far-reaching impacts beyond your gut. In ophthalmology, GM dysbiosis has been linked to chronic low-grade inflammation and exacerbated pathological angiogenesis, a process that plays a crucial role in various eye diseases³⁴.

But the impacts don’t stop there.

Dysbiosis can also pave the way for a slew of other diseases, from metabolic diseases like diabetes to cardiovascular diseases, neurodegenerative conditions, and even cancer ^{35 36}.

Moreover, the connection between GM and your immune system is profound.

Research suggests that the metabolites from your gut bacteria can affect immune cells in your bone marrow,

which in turn, can have implications for immune cell formation in your spinal bone marrow and potentially lead to systemic inflammation and back pain ³⁷.

Exploring the Sterility of Spinal Structures

Thanks to advancements like 16S rRNA sequencing and shotgun metagenomics, we now know that bacteria reside in places once thought sterile, including the reproductive tract, sperm, fetus, breast, and eye ³⁸.

This discovery has reshaped our understanding of microbiomes and their presence outside traditional joint environments.

During the neovascularization phase of osteoarthritis (OA), bacteria, and bacterial products may infiltrate cartilage and subchondral bone, which are typically less vascularized ³⁹.

Evidence of microbiomes has been found in knee and hip OA (Dunn et al., 2020), as well as in degenerated intervertebral discs (IVDs)⁴⁰.

Dysbiosis, or the imbalance of gut microbiota (GM), can lead to impaired intestinal barrier function and a weakened immune system.

This may allow GM to migrate from the gut to the bloodstream, potentially settling directly in joints or using immune cells like leukocytes and macrophages as “Trojan horses” to infiltrate joints and IVDs ⁴¹.

These migrations can contribute to deformity changes in subchondral bone marrow and cartilage or discs ⁴².

The chronic inflammation and adverse immune effects from GM dysbiosis and transient bacteremia may also increase the risk of postoperative infections for spinal degenerative diseases (SDD) ⁴³.

Discussion

In the intricate tapestry of human health, the gut microbiota (GM) stands out as a central character.

These findings underscore the indispensable role that GM plays in various aspects of human physiology, from nutrient synthesis and metabolism to immune system regulation.

The vast population of microorganisms residing in our gut, including over 1,000 bacterial species, serves as a testament to the complexity and intricacy of this microscopic universe.

The interplay between GM and other bodily processes, such as bone health and neurotransmitter production, is fascinating.

The “estrogen-gut microbiome axis” and the production of essential nutrients like vitamins B and K highlight the symbiotic relationship between humans and their gut microbiota.

It is as if we have our own internal pharmacy, meticulously synthesizing compounds that are crucial for our well-being.

However, this relationship is a double-edged sword.

The production of harmful metabolites like lipopolysaccharide (LPS) can tip the balance from beneficial to detrimental, potentially leading to a range of diseases.

This duality of GM as both a protector and potential harm inducer necessitates a nuanced approach to understanding and manipulating it for health benefits.

Conclusion

Embracing the world of gut microbiota is like opening a Pandora’s box – albeit one that holds the keys to unlocking optimal health.

The complexity of this microscopic universe is mind-boggling, but our exploration has only scratched the surface.

High-throughput sequencing technologies have opened new vistas, but we must tread carefully, ensuring that our interventions are based on solid scientific understanding.

The gut microbiota is not just a silent witness to our lives; it is an active participant, intricately woven into the fabric of our being.

As we move forward, it is crucial to adopt a holistic approach that considers the myriad ways in which GM influences our health.

This understanding will be pivotal in developing interventions that harness the power of GM to prevent and treat diseases, ultimately unlocking the full potential of this microscopic world within us.