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2025 ; 13
(1
): 213
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Host miRNAs regulate Escherichia coli O157 mucosal colonization through
host-mucosa-attached microbiota interactions in calves
#MMPMID41131553
Pan Z
; Chen Y
; Zhou M
; McAllister TA
; McNeilly TN
; Guan LL
Microbiome
2025[Oct]; 13
(1
): 213
PMID41131553
show ga
INTRODUCTION: Host responses to pathogen colonization are central to
understanding host homeostasis dynamics. Here, we used Shiga toxin
(Stx)-producing Escherichia coli (STEC) O157 as an example to illustrate how
pathogen colonization alters host-microbiome interactions and stimulates host
responses. The STEC O157 is a critical foodborne pathogen, and cattle are the
major asymptotic carrier with rectal anal junction (RAJ) being the major
colonization site, leading to the transmission of this organism through the
production chain. Therefore, this study leverages the multi-omics to evaluate
host mechanisms to STEC O157 and to illustrate how mucosa-attached microbiome
together with host miRNAs respond to the colonization of STEC O157. RESULTS: The
calf model was orally challenged with E. coli O157 with and without Stx2a during
the 30-day trial. Mucosa-attached microbiome analysis revealed that mucosal E.
coli O157 colonization limited niche occupancy of mucosa-attached microbiota
regardless of the presence or absence of Stx2a. The production of Stx2a did not
induce proper local host mRNA responses but miRNA profiles were more responsive
to this virulent factor during high fecal shedding. The shift of toll-like
receptor (TLR) expressions together with Stx2a production possibly underlined
varied miRNAome-mucosa-attached microbiota interactions. For instance, during the
high fecal shedding, the increased expression of TLR2 promoted bta-miR-181b
mediated host functionality, a response that was possibly blocked by Stx2a.
Decreased fecal O157 shedding promoted activation of TLR4-stimulated host
responses, which were coregulated by multiple miRNAs (i.e. bta-miR-146a and-184)
and mucosa-attached microbes. CONCLUSION: Host mechanisms regulating STEC O157
colonization are complex interplay among mucosa-attached microbiota and host
miRNAs where virulence factors could modulate such crosstalk and cause
differential host responses, highlighting the importance of
host-microbiome-pathogen virulence factor interactions for pathogen colonization
process. Video Abstract.