The Gut Microbiome in Human Health and Disease Functional Roles Dysbiosisand Emerging Interventions

Jamal Naini^*

Department of Microbiology, Tehran University of Medical Sciences, Tehran, Iran

*Corresponding Author:

Department of Microbiology, Tehran University of Medical Sciences, Tehran, Iran, E-mail: Naini_Jama5@ut.ir

Abstract

The gut microbiome is a complex and dynamic ecosystem composed of trillions of microorganismsincluding bacteria, viruses, fungi, and archaearesiding in the gastrointestinal tract. This microbial community contributes significantly to digestion, nutrient absorption, immune regulation, pathogen defense, and neurochemical signaling through the gutbrain axis. A balanced microbiome supports optimal physiological functioningwhile disturbancesreferred to as dysbiosisare associated with numerous disordersincluding obesity, inflammatory bowel disease (IBD)allergiesautoimmune conditionsneuropsychiatric disordersand colorectal cancer. Microbiome composition is shaped by various factors such as dietantibiotic exposurebirth modeagingstressand physical activity. Understanding these interactions provides opportunities for therapeutic interventions, including dietary modulationprobioticsprebioticsfecal microbiota transplantation (FMT)and emerging personalized microbiome-targeted strategies. This review summarizes the core functions of the gut microbiomeits role in disease pathogenesisand current evidence-based approaches to maintaining or restoring microbial balance.

Introduction

The human gastrointestinal tract harbors a dense microbial population estimated to contain over 10¹⁴ cells and a gene pool exceeding that of the human genome by at least 100- fold [1]. These microorganisms live in a mutually beneficial relationship with the host, influencing metabolic, immune, and neurological processes. Recent research emphasizes that disruptions in microbial diversity and stabilitycollectively termed dysbiosismay contribute to the onset and progression of numerous chronic conditions [2].Gut colonization begins at birth and evolves in response to diet, environmental exposure, antibiotic use, and lifestyle choices [3, 4]. A stable and diverse microbiome is generally associated with health, while imbalances can impair nutrient metabolism, compromise barrier integrity, and trigger abnormal immune responses [5]. This review discusses the biological functions of the gut microbiome, its association with major diseases, and emerging methods for restoring microbial equilibrium.

Biological Functions of the Gut Microbiome

Digestion and Nutrient Metabolism

Gut microbes metabolize dietary components that are otherwise indigestible by human enzymes. Fermentation of complex polysaccharides produces short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate, which provide energy to colonocytes, enhance intestinal barrier integrity, and regulate glucose and lipid metabolism [6].

Immune System Regulation

Microbiota-derived signals are essential for immune maturation. Commensal bacteria stimulate the development of regulatory T cells and promote immune tolerance, thereby preventing excessive inflammatory responses and reducing the risk of allergies and autoimmune disorders [7].

Defense Against Pathogens

Commensal organisms compete with harmful microbes for adhesion sites and nutrients. They also secrete antimicrobial compounds, such as bacteriocins and organic acids, which inhibit pathogen colonization [8].

Gut–Brain Axis Communication

The gut microbiome interacts bidirectionally with the central nervous system through neural (vagal), endocrine, and immune pathways. Microbial metabolites influence neurotransmitter production, stress hormone regulation, and inflammatory signaling, thereby affecting mood, cognition, and behavior [9].

Microbiome Composition in Health
A healthy gut microbiome is characterized by high diversity and resilience. Four dominant bacterial phyla are consistently found [Table 1]:

Phylum	Key Genera
Firmicutes	Lactobacillus, Clostridium
Bacteroidetes	Bacteroides, Prevotella
Actinobacteria	Bifidobacterium
Proteobacteria	Escherichia, Helicobacter

Table 1: Dominant microbial phyla and their primary functions

Diversity within and across these phyla ensures metabolic flexibility and a stronger defense against environmental challenges [6].

Gut Microbiome and Disease
Research suggests that obese individuals often have an increased Firmicutes-to-Bacteroidetes ratio, leading to enhanced caloric extraction and storage, low-grade systemic inflammation, and insulin resistance [10]. Patients with Crohn’s disease and ulcerative colitis exhibit reduced microbial diversity, diminished populations of anti- inflammatory species such as Faecalibacterium prausnitzii, and increased pro-inflammatory bacteria [5].

Mental Health Disorders

Altered microbial composition may influence neurotransmitter pathways, contributing to anxiety, depression, and autism spectrum disorders. Dysbiosis may increase intestinal permeability (“leaky gut”), leading to systemic inflammation and neuroinflammation [9].
Allergies and Autoimmune Conditions

Early-life factors such as cesarean delivery, lack of breastfeeding, and early antibiotic exposure can reduce microbial diversity, impair immune tolerance, and increase the risk of asthma, eczema, and type 1 diabetes [7].

Cancer

Certain bacteria, particularly Fusobacterium nucleatum, have been associated with colorectal cancer progression, possibly by promoting inflammation, DNA damage, and immune evasion
[10] [Figure 1].

Figure 1: Fusobacterium nucleatum in colorectal cancer progression

Strategies for Restoring and Supporting a Healthy Microbiome

Dietary Interventions
Consuming a diverse plant-based diet enriched in prebiotics (e.g., inulin, fructo-oligosaccharides) fosters beneficial bacterial growth [6]. Probiotics, including Lactobacillus and Bifidobacterium, may help restore balance [7]. Fermented foods such as yogurt, kefir, kimchi, and sauerkraut further enhance diversity.

Fecal Microbiota Transplantation (FMT)
FMT involves transferring processed stool from a healthy donor to a recipient’s gut. It is highly effective for treating recurrent Clostridioides difficile infections and is being studied for IBD, obesity, and neurological disorders [8].

Personalized Microbiome Therapies
Advancements in metagenomic sequencing and computational modeling are enabling individualized interventions, including targeted probiotics, precision dietary plans, and microbiome-modulating drugs [4].

Future Directions and Challenges

Although advancements in gut microbiome research have been significant, several challenges continue to limit its clinical translation. One of the primary concerns is the issue of causality versus correlation, as current evidence often fails to determine whether alterations in microbial communities are the cause of specific diseases or merely a consequence of those conditions [3]. Furthermore, the field lacks standardization, with no universally accepted criteria for what constitutes a “healthy” microbiome, making it difficult to establish reference ranges and therapeutic targets [1]. Regulatory issues also present barriers, particularly in the development and approval of probiotics and other microbiome-based interventions, which frequently vary in quality and lack standardized efficacy testing [7]. Lastly, ethical considerations remain, especially regarding donor screening, consent, and patient data privacy in procedures such as fecal microbiota transplantation (FMT) [8]. Addressing these challenges is essential for integrating microbiome science into safe, reliable, and evidence-based medical practice. Maintaining microbial diversity through healthy lifestyle choices remains a practical foundation for disease prevention and overall well-being.

Conclusion

The gut microbiome is a central determinant of human health, influencing metabolism, immunity, and neurological function. Dysbiosis has been linked to conditions ranging from obesity to colorectal cancer. While therapeutic interventions—including diet modification, probiotics, and FMT—show promise, more research is needed to translate microbiome science into standardized, evidence-based clinical practice. Maintaining microbial diversity through healthy lifestyle choices remains a practical foundation for disease prevention and overall well-being.

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