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Son et al. Microbiome Res Rep. 2025;4:29 https://dx.doi.org/10.20517/mrr.2025.14 Page 11 of 19

[36]
SCFA-producing species, was found to be lower . These reductions in SCFA-producing bacteria may lead
to decreased SCFA levels and increased jejunal pH, creating favorable conditions for pathogenic bacteria.
Moreover, reduced SCFA availability - essential for enterocytes - can heighten susceptibility to
+
inflammation and disease. With respect to diarrhea, Gormley et al. reported that F18 E. coli challenge
increased the incidence of diarrhea alongside changes in the jejunal mucosa-associated microbiota .
[28]
Specifically, RA of Bradyrhizobium, Eubacterium, Romboutsia, Selenomonas, Terrisporobacter, and
Prevotella increased, while RA of Solobacterium, Bacillus, and Corynebacterium decreased. These microbiota
alterations may be directly linked to the incidence of diarrhea.

In this review, all data on jejunal mucosa-associated microbiota were obtained under consistent
experimental conditions by the same research group. Therefore, potential variability due to pig genetic
+
background, F18 E. coli strain, experimental setup, sampling procedure, or microbiome sequencing method
is minimized. Consistent changes in microbial composition at the phylum level were observed across
studies [36,37] , with similar patterns also found at the family [23,36,37] , genus [23,30,36] , and species levels [36,37] .
Nonetheless, some inconsistencies were noted, likely reflecting the microbiota’s sensitivity to factors such as
+
immune status and diet composition. For example, Bacteroidetes RA increased in response to F18 E. coli in
the study by Garavito-Duarte et al. , but decreased in the study by Duarte and Kim . Similar
[27]
[23]
inconsistencies were seen with Prevotellaceae [27,36] and Selenomonas [28,30,36] , which may stem from differences
in feed composition or individual pig variation. These findings highlight the complexity of the jejunal
mucosa-associated microbiota and underscore the need for further research to resolve these inconsistencies
regarding the impact of F18 E. coli challenge on intestinal microbiota.
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IMPACTS OF F18 E. coli CHALLENGE ON IMMUNITY AND OXIDATIVE STRESS IN THE
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JEJUNAL MUCOSA
Data on immune response and oxidative stress in the jejunal mucosa were collected from 10 studies
involving F18 E. coli challenges [9,19,23,27-31,36,37] . These data reflect host immune responses, including
+
+
inflammatory reactions, triggered by F18 E. coli infection. On average, these studies reported increases of
14.9%, 10.9%, 9.2%, and 19.7% in TNF-α, IL-8, immunoglobulin A (IgA), and immunoglobulin G (IgG)
levels, respectively, in the jejunal mucosa of pigs [Table 4]. The upregulation of immune responses is likely
[45]
due to the increased RA of Gram-negative bacteria [23,28,30] , which have LPS in their outer membranes . LPS
binds to a receptor complex (comprising TLR4, MD2, and CD14) on porcine epithelial cells [93,94] . This
complex activates the MyD88-dependent pathway, which in turn stimulates NF-κB activation . NF-κB
[55]
regulates the expression of pro-inflammatory genes and mediates the synthesis of TNF-α, IL-6, and IL-8 .
[55]
+
The F18 E. coli antigen is recognized by dendritic cells in Peyer’s patches and mesenteric lymph nodes,
where the antigen is presented to helper T cells [95,96] . These helper T cells subsequently activate naïve B cells,
+
inducing the secretion of IgA and IgG. Moreover, enterotoxins STa and LT secreted by F18 E. coli stimulate
the production of IL-6 and IL-8 via the cAMP-mediated pathway [97,98] . The STb enterotoxin indirectly
promotes the secretion of TNF-α, IL-6, and IL-8 by activating NF-κB through Ca influx .
2+
[99]
These immune responses act as defense mechanisms against F18 E. coli infection but also negatively impact
+
intestinal health. For instance, TNF-α and IL-8, secreted by immune cells, disrupt intestinal barrier function
by damaging tight junction proteins such as occludin and claudin [57-59] . TNF-α also induces apoptosis in both
intestinal epithelial cells and pathogens, contributing to reduced villus height (VH) and microbial
[19]
dysbiosis . Similarly, IL-8 promotes oxidative stress by generating reactive oxygen species (ROS), which
[59]
damage intestinal cells . Elevated levels of IgA and IgG have also been associated with dysbiosis and
intestinal barrier disruption [100,101] .