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<p>Messenger RNA (mRNA) vaccines represent a transformational advancement in the field of vaccinology, offering advantages that were demonstrated most clearly during the COVID-19 pandemic. Still, how individuals respond to these vaccines varies widely. In addition to age, genetics, and co-morbidity, one of the most significant factors shaping vaccine success is the gut microbiota. Through their ability to generate metabolites like short-chain fatty acids and microbial antigens, or interact with immune cells via receptors that affect antigen presentation and antibody production, gut microbes mediate the regulation of immune responses. Some bacterial groups, like <i>Bifidobacterium</i> and <i>Faecalibacterium prausnitzii</i>, seem to support a robust immune response, while other groups, such as <i>Bacteroides</i>, are likely associated with weaker responses. Nonetheless, the results are not always predictable, presumably due to variations in study designs, host characteristics, and analytic approaches. The evidence to date is mostly limited to observational data and animal studies, so the ability to make definitive recommendations for clinical practice remains limited. Nevertheless, it does suggest the promise of microbiome-directed interventions that may enhance vaccine function. This review brings together available mechanistic and clinical insights, highlights areas where knowledge is lacking, and discusses how future research could guide microbiome-based approaches to strengthen immunization outcomes.</p>

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Pharmacomicrobiomics of mRNA vaccines: gut microbiota-driven modulation of vaccine pharmacodynamics

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月21日

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  • Muhammad Shahid Mehmood,
  • Elsa Ahmed,
  • Amina Ahmed,
  • Noor un Nisa,
  • Javeria Taj,
  • Bushra Bibi,
  • Asma Azam,
  • Mohammad Jalal Nazari

摘要

Messenger RNA (mRNA) vaccines represent a transformational advancement in the field of vaccinology, offering advantages that were demonstrated most clearly during the COVID-19 pandemic. Still, how individuals respond to these vaccines varies widely. In addition to age, genetics, and co-morbidity, one of the most significant factors shaping vaccine success is the gut microbiota. Through their ability to generate metabolites like short-chain fatty acids and microbial antigens, or interact with immune cells via receptors that affect antigen presentation and antibody production, gut microbes mediate the regulation of immune responses. Some bacterial groups, like Bifidobacterium and Faecalibacterium prausnitzii, seem to support a robust immune response, while other groups, such as Bacteroides, are likely associated with weaker responses. Nonetheless, the results are not always predictable, presumably due to variations in study designs, host characteristics, and analytic approaches. The evidence to date is mostly limited to observational data and animal studies, so the ability to make definitive recommendations for clinical practice remains limited. Nevertheless, it does suggest the promise of microbiome-directed interventions that may enhance vaccine function. This review brings together available mechanistic and clinical insights, highlights areas where knowledge is lacking, and discusses how future research could guide microbiome-based approaches to strengthen immunization outcomes.