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Human Infant Fecal Microbiota Differentially Influences the Mucosal Immune Pathways Upon Influenza Infection in a Humanized Gnotobiotic Pig Model. | LitMetric

AI Article Synopsis

  • This study explored how different gut microbiota from rural and urban infants affect immune responses in the respiratory tract of gnotobiotic piglets infected with H1N1 influenza virus.
  • Piglets with urban infant fecal microbiota showed higher viral loads in the upper respiratory tract, while both groups had similar virus-specific antibody responses, indicating a complex interaction between gut bacteria and immune response.
  • The research highlighted distinct immune regulation patterns and changes in gut microbiota following influenza infection in piglets, suggesting that different microbiota can influence respiratory health and may help in developing new therapies.

Article Abstract

In this study, we evaluated the impact of human gut microbiota on the immune pathways in the respiratory tract using a gnotobiotic (Gn) piglet model. We humanized piglets with rural and urban infant fecal microbiota (RIFM and UIFM, respectively) and then infected them with a H1N1 swine influenza virus. We analyzed the microbial diversity and structure of the intestinal and respiratory tracts of the piglets before and after the influenza virus infection and measured the viral load and immune responses. We found that the viral load in the upper respiratory tract of UIFM transplanted piglets was higher than their rural cohorts (RIFM), while virus-specific antibody responses were comparable. The relative cytokine gene expression in the tracheobronchial (respiratory tract) and mesenteric (gastrointestinal) lymph nodes, lungs, blood, and spleen of RIFM and UIFM piglets revealed a trend in reciprocal regulation of proinflammatory, innate, and adaptive immune-associated cytokines as well as the frequency of T-helper/memory cells, cytotoxic T cells, and myeloid immune cell subsets. We also observed different phylum-level shifts of the fecal microbiota in response to influenza virus infection between the two piglet groups, suggesting the potential impact of the gut microbiota on the immune responses to influenza virus infection and lung microbiota. In conclusion, Gn piglets humanized with diverse infant fecal microbiota had differential immune regulation, with UIFM favoring the activation of proinflammatory immune mediators following an influenza virus infection compared to their rural RIFM cohorts. Furthermore, Gn piglets can be a useful model in investigating the impact of diverse human microbiota of the gastrointestinal tract, probably also the respiratory tract, on respiratory health and testing specific probiotic- or prebiotic-based therapeutics.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11247059PMC
http://dx.doi.org/10.1007/s00284-024-03785-8DOI Listing

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