Simple Summary
Infectious diseases remain a major threat to global health. While antibiotics are essential, they often fail to eliminate pathogens fully and can lead to drug resistance and side effects. This review examines how the gut microbiome—the community of bacteria, viruses, and fungi residing in our digestive system—protects against infections. Evidence based on animal studies, we explain how these microbes fight harmful pathogens by producing antimicrobial substances, competing for nutrients, strengthening the gut barrier, and boosting the body’s immune response—even influencing distant organs like the lungs through the “gut–lung axis”. Understanding these mechanisms paves the way for novel strategies to bolster the body’s natural defenses by targeting modulation of the gut microbiota. This knowledge may help reduce reliance on antibiotics, improve patient outcomes, and offer more sustainable strategies to combat infectious diseases in the future.
Abstract
Infectious diseases present persistent and complex challenges to global public health, with conventional antibiotic therapies increasingly limited by antimicrobial resistance, microbiota disruption, and adverse effects. There is a critical need to explore complementary strategies that augment host defense mechanisms without exacerbating these limitations. Accumulating evidence underscores the integral role of the gut microbiota—a diverse microbial ecosystem within the gastrointestinal tract—in regulating systemic immunity and pathogen susceptibility. This review synthesizes recent advances from animal models to delineate the multi-faceted mechanisms by which commensal microbes and their metabolites confer protection against enteric and respiratory infections. Key processes include competitive exclusion for nutrients and ecological niches, production of antimicrobial compounds, reinforcement of intestinal barrier integrity, and orchestration of local and systemic immunity via gut–lung axes. We further discuss the potential of microbiota-targeted interventions to enhance treatment efficacy and patient outcomes. By integrating mechanistic insights with translational applications, this review aims to inform the rational design of next-generation anti-infective strategies grounded in microbial ecology and host immunobiology.