Gut Microbiome's Role in Antibiotic Resistance: A Review of Mechanisms and Therapeutic Strategies

Antimicrobial resistance (AMR) represents a severe global health crisis, compromising the efficacy of essential antibiotics. The human gut harbors a complex microbial ecosystem, the gut microbiota, crucial for normal physiological processes. However, this ecosystem is highly susceptible to antibiotic-mediated disruption, leading to dysbiosis and undermining host protection against pathogens and metabolic dysfunction. Crucially, the gut microbiome also acts as a vast reservoir for antimicrobial resistance genes, collectively known as the resistome, which can readily transfer between bacteria. Understanding this dynamic is vital for developing effective strategies against AMR.

This comprehensive review synthesized current literature on the human gut microbiota's composition, function, and its pivotal role in antibiotic-driven antimicrobial resistance (AMR). The authors systematically examined the mechanisms of antibiotic-induced gut dysbiosis and evaluated the profound impact of various host factors, including age, genetics, diet, and immune status, on microbiome dynamics and AMR development. They also assessed emerging methodologies for resistome characterization, such as PCR, next-generation sequencing, functional metagenomics, and advanced artificial intelligence-driven tools. Finally, the review discussed a range of innovative microbiome-targeted therapeutic strategies aimed at combating AMR and restoring gut microbial homeostasis.

The review firmly establishes the gut microbiota as a complex, metabolically interdependent ecosystem vital for host physiology, yet highly vulnerable to antibiotic-induced disruption. It functions as a significant reservoir for antimicrobial resistance genes (the resistome), which can be mobilized and transferred between commensal and pathogenic bacteria via horizontal gene transfer mechanisms like conjugation, transformation, and transduction. Host factors such as age, genetics, diet, and immune status are identified as critical modulators influencing both microbiome dynamics and the trajectory of AMR development. The review highlights that advanced characterization methods, including functional metagenomics and AI-driven tools, are indispensable for comprehensively understanding the resistome's complexity and dynamics. These tools provide unprecedented insights into the genetic landscape of resistance.

Ultimately, the review concludes that microbiome-targeted therapeutic strategies, including faecal microbiota transplantation (FMT), phage therapy, CRISPR-based therapies, and antimicrobial peptides, offer promising avenues for combating AMR and restoring gut microbial homeostasis. Maintaining and re-establishing the integrity of the gut microbiome is presented as a fundamental component of global antimicrobial stewardship strategies.