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Microbes & Immunity Dietary emulsifiers affect the presence of AIEC

associated with higher carrageenan consumption. These findings suggest a
potential link between dietary emulsifiers, microbial dysbiosis, and AIEC-related CD
pathogenesis.

Keywords: Adherent-invasive Escherichia coli; Crohn’s disease; Dietary emulsifiers

1. Introduction inflammatory bowel disease (IBD), suggesting that early
exposure to an urbanized environment may contribute
Crohn’s disease (CD) is an intestinal inflammatory disorder to the development of IBD. Food additives in processed
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that predominantly affects the distal small intestine. foods, such as emulsifiers, have recently been shown to
The pathogenesis of CD involves a complex interplay induce chronic intestinal inflammation in rodents and may
between environmental factors, genetic variants, and potentially play a role in the development and exacerbation
abnormal gut microbiota, associated with a dysregulated of IBD in humans. Common food emulsifiers, such as
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immunological response. Studies have shown that polysorbate-80 and carboxymethylcellulose, promoted
1
patients with CD had a reduced abundance of beneficial gut inflammation in gnotobiotic mice colonized by
microbes such as Faecalibacterium, Roseburia, and AIEC. Another emulsifier, carrageenan, was associated
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Clostridium and an increased abundance of pathogenic with altered gut microbiome composition and increased
commensals, including Fusobacterium, Shigella, and expression of pro-inflammatory molecules in an in vitro
Escherichia, compared to healthy controls. In particular, cultivation system. 18
2,3
an increased abundance of adherent-invasive Escherichia
coli (AIEC) is commonly detected in the terminal ileum Importantly, despite experimental evidence linking
of patients with CD. AIEC has the ability to bind to the emulsifiers to AIEC pathogenicity, no human population
4
adhesion molecule receptor CEACAM6 on the membrane studies have examined this interaction. Our work addresses
of enterocytes through type 1 pili, and can invade and this gap by providing the first human evidence linking
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replicate in the intestinal epithelial cells. Moreover, the dietary carrageenan to AIEC prevalence in CD patients
CEACAM6 receptor has been shown to be overexpressed and uncovering diet-microbe-pathogen interactions in
in patients with CD, further facilitating AIEC adhesion CD pathogenesis. We further identify AIEC-associated
in the intestinal epithelial cells. Mechanistic studies have mucosal microbiota signatures, providing novel insights
6
revealed that AIEC can infect macrophages and lead to the into how urban environmental exposures and diet may
release of proinflammatory cytokines, including tumor interact with microbial factors in the pathogenesis of
necrosis factor-alpha and interleukin (IL)-1β. AIEC could CD. These findings offer translational insights into how
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also prevent the restoration of normal gut microbiota in urbanization and diet may synergistically promote AIEC-
dextran sodium sulfate-induced colitis mice models after driven CD.
fecal microbiota transplantation. Furthermore, AIEC
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is involved in the synthesis of propanediol dehydratase, 2. Materials and methods
which can increase the fermentation of propanediol and 2.1. Study population
trigger T cells-induced intestinal inflammation in mice The study population consisted of patients with CD residing
model. Altogether, these findings suggest that AIEC can in urban and rural areas of China and their corresponding
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potentially aggravate abnormal immune responses in CD controls. The rural cohort was recruited from the First
and contribute to chronic mucosal inflammation. Affiliated Hospital of Kunming Medical University in
CD incidence has substantially increased in newly Yunnan (population density <1000/km ) between August
2 19
industrialized countries over the past few decades in 2018 and January 2019. Patients with CD were diagnosed
parallel with rapid urbanization in these regions. Some of based on endoscopic, radiological, and histological
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the major culprits include early life exposure, consumption examinations. Healthy controls were subjects who underwent
of highly processed foods, and changes in hygiene and colonoscopies without gastrointestinal diseases in the same
socioeconomic status. 11-13 The interaction between the hospital. All subjects filled out questionnaires that measured
host and environment during urbanization may play a the social demographics and clinical characteristics, and
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role in initiating CD. A migrant study from Canada questionnaires that recorded the consumption of food
reported that immigration from developing countries at additives. The estimation of food additive intake in each
a younger age was associated with an increased risk of subject was described in the Supplementary Methods section

Volume 2 Issue 4 (2025) 68 doi: 10.36922/MI025230051