The Intestinal Microbiota: Impacts of Antibiotics Therapy, Colonization Resistance, and Diseases Original paper

What was reviewed?

This paper reviewed how the intestinal microbiota mediates colonization resistance, how antibiotic therapy disrupts this protective function, and how these changes contribute to infectious and non-infectious diseases. The authors synthesized molecular, microbial, immunological, and clinical evidence to explain how trillions of resident microbes normally maintain intestinal homeostasis and suppress pathogen expansion. The review emphasized that colonization resistance is not a single mechanism but an emergent property of microbial diversity, metabolic output, and immune crosstalk. Antibiotic exposure was positioned as a central destabilizing force that alters microbial composition, reduces beneficial taxa, enriches antibiotic resistance genes, and creates ecological niches that favor opportunistic and multidrug-resistant organisms. The paper integrated microbiome science with clinical observations from hospital settings, immunocompromised populations, and antibiotic-treated patients, framing dysbiosis as a mechanistic driver of disease rather than a secondary association.

Who was reviewed?

The review drew on evidence from human clinical populations, including healthy adults, infants, hospitalized patients, immunocompromised individuals, transplant recipients, and patients receiving chemotherapy or prolonged antibiotic therapy. These human data were complemented by findings from animal models such as germ-free mice, antibiotic-treated mice, and gnotobiotic systems that enabled causal evaluation of microbiota–pathogen interactions. The authors also reviewed studies involving pediatric populations to highlight the long-term developmental consequences of early-life antibiotic exposure. This broad scope allowed comparison between controlled mechanistic insights and real-world clinical outcomes.

What were the most important findings?

The review demonstrated that effective colonization resistance depends on both direct microbial antagonism and indirect immune-mediated mechanisms. Major microbial associations linked to protection included members of the phyla Firmicutes, Bacteroidetes, and Actinobacteria, particularly butyrate-producing Clostridia, Bifidobacterium species, Lactobacillus species, and commensal Escherichia coli strains such as E. coli Nissle 1917. These organisms restricted pathogen growth through bacteriocin and microcin production, nutrient competition, iron sequestration, and secretion of short-chain fatty acids that directly inhibited pathogens such as Clostridioides difficile, Salmonella enterica, vancomycin-resistant Enterococcus, and pathogenic E. coli. Secondary bile acid production by Clostridia emerged as a critical metabolic barrier against spore germination and vegetative growth of C. difficile. The review further highlighted immune reinforcement mechanisms, including microbiota-driven induction of antimicrobial peptides such as defensins and Reg3 lectins, stimulation of IgA secretion, and regulation of cytokines such as IL-10, IL-17, and IL-22 that maintain epithelial integrity and pathogen clearance. Antibiotic therapy consistently disrupted these mechanisms, reduced microbial diversity, increased pathobiont abundance, and promoted expansion of antibiotic-resistant organisms.

What are the greatest implications of this review?

The key clinical implication is that many infectious complications arise from microbiome disruption rather than unavoidable pathogen exposure. The findings strongly support antibiotic stewardship, microbiome-preserving therapies, and microbiota restoration strategies such as targeted probiotics or fecal microbiota transplantation in selected patients. For clinicians, the review reinforces that maintaining colonization resistance is central to preventing infection, limiting antimicrobial resistance, and improving outcomes in vulnerable populations.