Review on: Targeting the Gut Microbiome in Disease

Abstract

The gut microbiome is a complex and dynamic community of microorganisms essential for maintaining host health. Advances in sequencing technologies have revealed significant changes in microbial composition across disease states. Dysbiosis has been linked to obesity, diabetes, inflammatory bowel disease, neurological disorders, cardiovascular conditions, and cancer. These imbalances contribute to disease progression through immune disruption, metabolic dysfunction, compromised gut barrier integrity, and systemic inflammation. Current research emphasizes the microbiome’s role in disease mechanisms and its potential as both a biomarker and therapeutic target, opening pathways for precision medicine and innovative treatments.

Introduction

The human microbiome is a vast community of microorganisms—including bacteria, archaea, viruses, and fungi—outnumbering human cells and possessing a gene pool far larger than the human genome. The gut microbiome, concentrated in the gastrointestinal tract, plays a crucial role in digestion, metabolism, immune regulation, and protection against pathogens. Dysbiosis, or microbial imbalance, is linked to obesity, type 2 diabetes, cardiovascular diseases, cancer, and neurological disorders.

Factors Influencing the Gut Microbiome:
Diet, medications, age, lifestyle, and genetics shape microbial diversity and function. Fiber-rich diets support beneficial microbes, while high-fat, high-sugar diets, antibiotics, and stress can disrupt balance. Early life factors, like mode of birth and breastfeeding, critically influence microbiome development.

Techniques to Study Microbiomes:
Modern research employs 16S rRNA sequencing, metagenomics, metatranscriptomics, metabolomics, culturomics, gnotobiotic models, and computational modeling to explore microbial diversity, function, and host interactions.

Functions and Importance:
Healthy microbiomes aid nutrient metabolism (producing SCFAs), regulate the immune system, and maintain gut barrier integrity. Dysbiosis contributes to chronic inflammation, metabolic dysfunction, autoimmune diseases, and neurological disorders.

History:
Microbiome research dates to van Leeuwenhoek’s 17th-century observations. Probiotic theory was advanced by Metchnikoff in the 19th century. Techniques like anaerobic culturing and 16S rRNA sequencing revealed microbial diversity, culminating in the Human Microbiome Project (2007–2015) and multi-omics approaches that clarified host–microbe interactions.

Gut Microbiome and Metabolic Disorders:

• Obesity: Linked to reduced microbial diversity, altered Firmicutes/Bacteroidetes ratios, impaired gut barrier, chronic inflammation, and enhanced energy harvest.

• Type 2 Diabetes: Dysbiosis promotes insulin resistance, endotoxemia, disrupted SCFA and bile acid metabolism, and elevated branched-chain amino acids.

Therapies targeting microbiota include probiotics, prebiotics, synbiotics, postbiotics, fecal microbiota transplantation (FMT), engineered consortia, and dietary modulation.

Gut Microbiome and Cancer:
Certain microbes influence cancer risk and therapy response. Strategies include probiotics, prebiotics, FMT, and microbiome restoration post-therapy. Specific cancers (colorectal, gastric, esophageal, breast) show microbial shifts affecting immunity, inflammation, and therapy outcomes.

Gut Microbiome and Neurological Disorders:
The microbiota-gut-brain axis links gut microbes to brain function and behavior. Dysbiosis contributes to Alzheimer’s, Parkinson’s, depression, and anxiety. Dietary fiber and microbial metabolites can modulate cognitive function and mental health.

Therapeutic Applications:

• Probiotics, prebiotics, synbiotics, postbiotics: Support beneficial microbes, gut barrier, immune regulation, and SCFA production.

• FMT and precision targeting (bacteriophage/CRISPR): Restore microbial balance and eliminate harmful strains.

• Disease applications: Include gastrointestinal, metabolic, hepatic, dermatologic, gynecologic, oral, neurobehavioral disorders, and oncology/immunotherapy, highlighting microbiome modulation as a precision medicine tool.

Conclusion

The gut microbiome plays a pivotal role in both health and disease. In a healthy state, diverse microbial communities maintain intestinal barrier integrity, regulate immunity, synthesize vitamins, and produce metabolites such as short chain fatty acids that support metabolic balance and neurological function. This symbiosis fosters resilience against pathogens and contributes to overall well being. Conversely, in a disease state, microbial imbalance or dysbiosis can disrupt these protective mechanisms, leading to inflammation, impaired metabolism, and increased susceptibility to conditions such as irritable bowel syndrome, inflammatory bowel disease, obesity, diabetes, and even neuropsychiatric disorders. Therapeutic strategies—including probiotics, prebiotics, fecal microbiota transplantation, and engineered microbial consortia—seek to restore microbial equilibrium and functional outputs. The future of microbiome research lies in precision medicine, tailoring interventions to individual microbial signatures. Thus, the gut microbiome represents both a guardian of health and a therapeutic frontier in managing human disease.

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Copyright

Copyright © 2025 Satwika Devi Pudi, Lepakshi Sri Soundarya Putta, Fouziya Begum Sheik, Raja Rajeswari Darmireddy, Yajna Sri Donga, Lakshmi Sree Badugu, Y. B. Manjulatha, V. Bhaskara Raju. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.