Medical Microbiology Specialist, Medical Genetics Specialist

"The human gut microbiota is a vital ecosystem that interacts bidirectionally with many systems in the body, playing a key role in everything from brain health to immune functions, and when its balance is disrupted, it can pave the way for the development of a wide range of diseases, including neurological, metabolic, immunological, and psychiatric disorders."

The Relationship Between Human Gut Microbiota and Health

Title:

| Definition of microbiota | Interactions Between Human Gut Microbiota and Physiological Systems | Diseases Associated with Human Gut Microbiota | Microbiota-Gut-Brain Axis | Neuroinflammation and Neurodegeneration in the Brain | Diseases Associated with Neuroinflammation | Diseases Associated with Neurodegeneration

Definition of microbiota

Microbiota is a term encompassing a vast diversity of trillions of microorganisms, including viruses, bacteria, fungi, parasites, and other microbes. These microorganisms exhibit various protective, metabolic, functional, and immune-related activities, significantly contributing to human health and disease pathogenesis (etiopathogenesis). The term "microbiome" is often used synonymously with microbiota. However, while microbiome is sometimes mistakenly used to refer to the genomes of microbiota organisms, the correct term for this concept is "metagenome," which specifically denotes the genomic structures of microbiota members and their analyses through advanced technological methods. The microbiota possesses a genomic content that is a hundred times greater than the human genome.

Although microbiota comprises more than just bacteria, the distribution of total microbial DNA reveals that bacteria (93%) constitute the most dominant group in terms of density and diversity, followed by viruses (5.8%) and fungi (0.1%). Consequently, when referring to microbiota, bacteria are predominantly considered, particularly those residing in the gastrointestinal tract and intestines, with anaerobic bacteria being of particular focus. The bacterial species forming the microbiota are classified into six major phyla: Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, Fusobacteria, and Verrucomicrobia.

The human gut microbiota maintains a homeostatic balance in terms of bacterial quantity and diversity, known as "eubiosis." Disruptions in this balance are referred to as "dysbiosis," which has been increasingly linked to various diseases through scientific studies and evidence. The preservation and maintenance of this balance are strongly associated with health, whereas dysbiosis plays a significant role in the etiology and pathogenesis of multiple diseases.

Interactions Between Human Gut Microbiota and Physiological Systems

It has been established that the human gut microbiota interacts bidirectionally with various physiological systems, forming axes such as the Gut-Brain Axis, Gut-Bone Axis, Gut-Heart Axis, Gut-Liver Axis, Microbiota-Genetic Axis, and Microbiota-Epigenetic Axis. These axes facilitate "cross-talk" and "bidirectional communication." The gut microbiota is often referred to as the "conductor" of the body's systems, highlighting its regulatory role. The interactions involve gut bacteria, their metabolic activities, and the normal or abnormal metabolic byproducts they produce, which exert multifaceted effects on different bodily functions. Conversely, these physiological systems also influence the composition and functionality of the gut microbiota. Ongoing scientific research is striving to decode the language of communication between the microbiome and various systems. The gut microbiota acts as a key element in cellular, intercellular, and systemic signaling processes, underscoring its role in both health and disease. The number of physiological systems and associated diseases linked to gut microbiota is expanding with continuous scientific discoveries.

Microbiota has been shown to influence both gene expression (gene expression regulation) and epigenetic modifications. Epigenetics refers to changes in gene function without altering the DNA sequence, resulting in different phenotypic expressions. Furthermore, alterations in gut microbiota composition have been found to affect human dietary habits and food preferences.

Diseases Associated with Human Gut Microbiota

Scientific research has provided strong evidence linking gut microbiota to the development of several diseases, including:

Neuropsychiatric disorders: Anxiety, depression, attention deficit hyperactivity disorder (ADHD).
Neurodevelopmental disorders: Autism spectrum disorder (ASD), schizophrenia.
Neurodegenerative diseases: Alzheimer’s disease (AD), dementia, Parkinson’s disease (PD), multiple sclerosis (MS).
Gastrointestinal diseases: Inflammatory bowel diseases (IBD), ulcerative colitis (UC), Crohn’s disease (CD), functional gastrointestinal disorders (e.g., irritable bowel syndrome (IBS)), non-alcoholic fatty liver disease (NAFLD).
Metabolic diseases: Obesity, metabolic syndrome, Type 1 and Type 2 diabetes (DM).
Addiction disorders: Food addiction, alcohol addiction, drug addiction (scientific evidence available).
Immune and autoimmune diseases: Asthma, allergies, fibromyalgia, scleroderma, systemic lupus erythematosus (SLE).
Respiratory and lung diseases: Chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF).
Genitourinary diseases: Urinary tract infections (UTI), polycystic ovary syndrome (PCOS), fertility/infertility.
Certain cancer types: Gastric cancer, colon cancer, pancreatic cancer, cervical cancer, prostate cancer, skin cancer.
Dermatological diseases: Psoriasis, atopic dermatitis, acne vulgaris, rosacea, alopecia areata, hidradenitis suppurativa.
Bone diseases: Osteoporosis, osteoarthritis, bone resorption.

Microbiota-Gut-Brain Axis

The gut microbiota and the brain interact bidirectionally through multiple pathways. Research has identified six key pathways involved in this interaction:

Metabolic pathway
Neuronal pathway
Neuroendocrine pathway
Immunological pathway
Barrier pathways (gut-blood barrier, blood-brain barrier)
Signal transmission molecules (neurotransmitter) pathway

A detailed discussion of the mechanisms underlying these pathways will be provided in a future study. For now, only their names are listed.

Neuroinflammation and Neurodegeneration in the Brain

Many neurological diseases are linked to two major pathological pathways: neuroinflammation and neurodegeneration. Microglial cells, which are a crucial component of the brain’s immune system, play a central role in both pathways.

Diseases Associated with Neuroinflammation

Neurodevelopmental disorders, including autism spectrum disorder (ASD) and schizophrenia, as well as attention deficit disorders (ADHD, ADD), anxiety, and depression, are closely linked to neuroinflammatory processes.

Diseases Associated with Neurodegeneration

Neurodegenerative disorders, including Alzheimer’s disease (AD), dementia, Parkinson’s disease, and multiple sclerosis, are strongly associated with neurodegenerative pathways.

Following the activation of these pathways, microglial cells undergo phenotypic changes and proliferate, playing a central role in disease pathogenesis.

Maintaining gut microbiota homeostasis is essential for preserving mental and neurological health.

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