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Linking active rectal mucosa–attached microbiota to host immunity reveals its role in host–pathogenic STEC O157 interactions

Published: 2024

Authors:

  • Zhe Pan

  • Yanhong Chen

  • Mi Zhou

  • Tim A McAllister

  • Tom N Mcneilly

  • Le Luo Guan

Abstract:

The rectal–anal junction (RAJ) is the major colonization site of Shiga toxin–producing Escherichia coli (STEC) O157 in beef cattle, leading to transmission of this foodborne pathogen from farms to food chains. To date, there is limited understanding regarding whether the mucosa-attached microbiome has a profound impact on host–STEC interactions. In this study, the active RAJ mucosa–attached microbiota and its potential role in host immunity–STEC commensal interactions were investigated using RAJ mucosal biopsies collected from calves orally challenged with two STEC O157 strains with or without functional stx2a (stx2a+ or stx2a−). The results revealed that shifts of microbial diversity, topology, and assembly patterns were subjected to stx2a production post-challenge and Paeniclostridium and Gallibacterium were the keystone taxa for both microbial interactions and assembly. Additional mucosal transcriptome profiling showed stx2a−dependent host immune responses (i.e. B- and T-cell signaling and antigen processing and presentation) post-challenge. Further integrated analysis revealed that mucosa–attached beneficial microbes (i.e. Provotella, Faecalibacterium, and Dorea) interacted with host immune genes pre-challenge to maintain host homeostasis; however, opportunistic pathogenic microbes (i.e. Paeniclostridium) could interact with host immune genes after the STEC O157 colonization and interactions were stx2a−dependent. Furthermore, predicted bacterial functions involved in pathogen (O157 and Paeniclostridium) colonization and metabolism were related to host immunity. These findings suggest that during pathogen colonization, host–microbe interactions could shift from beneficial to opportunistic pathogenic bacteria driven and be dependent on the production of particular virulence factors, highlighting the potential regulatory role of mucosa–attached microbiota in affecting pathogen–commensal host interactions in calves with STEC O157 infection.

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