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<p>Emerging viral threats, including COVID-19, influenza, and hepatitis B, underscore the urgent need for innovative antiviral strategies. Traditional antiviral drugs and vaccines are often limited by viral mutations, drug resistance, and inter-individual variability. The human microbiota has emerged as an active regulator of viral pathogenesis, influencing host susceptibility, immune responses, and therapeutic outcomes. This review comprehensively explores microbiota–virus interactions, including direct viral modulation by commensal bacteria and bacteriophages, metabolic reprogramming of host cells, and immunomodulation by microbial metabolites such as short-chain fatty acids (SCFAs) through the GPR43–NLRP3–MAVS axis. The gut–lung–immune axis and systemic consequences of virus-induced dysbiosis, including “leaky gut” and amplified cytokine responses (TNF-α, IL-6), are highlighted. Translational applications discussed include probiotics, prebiotics, postbiotics, fecal microbiota transplantation (FMT), and next-generation engineered microbial consortia. Evidence from clinical FMT trials in chronic hepatitis B, liver cirrhosis, and COVID-19 recovery, along with FDA-approved oral microbiota therapies, suggests therapeutic promise. The integration of AI-guided multi-omics approaches enables patient stratification and personalized interventions while addressing safety, strain specificity, and regulatory challenges. This review integrates mechanistic insights and clinical evidence to guide the development of next-generation microbiota-based precision antiviral therapies with improved efficacy and durability.</p>

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Decoding Microbiota–Immune Interplay in Viral Pathogenesis: Toward Next-Generation Antiviral Therapies

  • 期刊论文

  • 发表日期：

    2026年3月28日

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  • Ameen S. S. Alwashmi,
  • Najeeb Ullah Khan,
  • Ahsanullah Unar

摘要

Emerging viral threats, including COVID-19, influenza, and hepatitis B, underscore the urgent need for innovative antiviral strategies. Traditional antiviral drugs and vaccines are often limited by viral mutations, drug resistance, and inter-individual variability. The human microbiota has emerged as an active regulator of viral pathogenesis, influencing host susceptibility, immune responses, and therapeutic outcomes. This review comprehensively explores microbiota–virus interactions, including direct viral modulation by commensal bacteria and bacteriophages, metabolic reprogramming of host cells, and immunomodulation by microbial metabolites such as short-chain fatty acids (SCFAs) through the GPR43–NLRP3–MAVS axis. The gut–lung–immune axis and systemic consequences of virus-induced dysbiosis, including “leaky gut” and amplified cytokine responses (TNF-α, IL-6), are highlighted. Translational applications discussed include probiotics, prebiotics, postbiotics, fecal microbiota transplantation (FMT), and next-generation engineered microbial consortia. Evidence from clinical FMT trials in chronic hepatitis B, liver cirrhosis, and COVID-19 recovery, along with FDA-approved oral microbiota therapies, suggests therapeutic promise. The integration of AI-guided multi-omics approaches enables patient stratification and personalized interventions while addressing safety, strain specificity, and regulatory challenges. This review integrates mechanistic insights and clinical evidence to guide the development of next-generation microbiota-based precision antiviral therapies with improved efficacy and durability.