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Published on: July 27, 2022
Biological pathways via which the anthocyanin malvidin alleviated the murine colitis induced by Citrobacter rodentium
Fang Liu1, Allen D Smith2, Thomas T Y Wang2
1College of Public Health, Zhengzhou University, Zhengzhou, China. yhy@zzu.edu.cn.
Insights
Blueberry anthocyanin malvidin 3-glucoside (MG) combats antibiotic-resistant E. coli infections by restoring gut health and enhancing beneficial bacteria. This natural compound offers a promising alternative to antibiotics for diarrheal diseases.
Area of Science:
- Gastroenterology
- Microbiology
- Nutraceuticals
Background:
- Enteropathogenic E. coli (EPEC) causes significant childhood diarrheal disease.
- Antibiotic-resistant E. coli strains necessitate new therapeutic strategies.
- Citrobacter rodentium serves as a model for EPEC infections in mice.
Purpose of the Study:
- To investigate the antimicrobial properties of malvidin 3-glucoside (MG), a blueberry anthocyanin.
- To explore MG's effects on C. rodentium infection using a multi-omics approach.
- To understand MG's impact on host-microbe interactions and gut health.
Main Methods:
- Multi-omics analysis in a mouse model of C. rodentium infection.
- Assessment of body weight, colonic histopathology, and gene expression.
- Microbiome analysis and metabolite profiling.
- Investigation of host-microbe interactions and endocannabinoid system modulation.
Main Results:
- MG supplementation reversed weight loss and improved colonic health in infected mice.
- MG modulated TNFα and TGFβ signaling pathways.
- MG partially restored gut microbiota balance, increasing Bifidobacterium animalis abundance.
- MG normalized oleoylethanolamine levels and altered host- and microbiota-derived metabolites.
Conclusions:
- Malvidin 3-glucoside exhibits significant antimicrobial and gut-protective effects against C. rodentium infection.
- MG acts through modulating host signaling, gut microbiota, and metabolite profiles.
- The findings highlight malvidin's potential as a natural therapeutic agent for gastrointestinal infections.
Abstract:
Enteropathogenic E. coli (EPEC) is a causal agent for diarrheal diseases and contributes to morbidity and mortality in children under the age of five years. The emergence and rapid spread of antibiotic resistant EPEC strains necessitate the search for novel alternatives to antibiotics. In this study, we used Citrobacter rodentium, a natural mouse pathogen that mimics many aspects of human EPEC infections, to investigate the antimicrobial properties of the blueberry anthocyanin malvidin 3-glucoside (MG) using a multi-omics approach. MG supplementation reversed the bodyweight loss induced by C. rodentium infection and improved colonic hyperplasia and histopathological scores. In the colon tissue, MG supplementation significantly increased the expression of Hace1, a key regulator of TNFα-driven signaling, and impacted multiple pathways, such as TGFβ signaling. MG partially restored C. rodentium-induced microbial dysbiosis and significantly enhanced the abundance of the probiotic Bifidobacterium animalis. Moreover, MG disrupted the interactions of E. coli with other gut microbes. MG significantly mediated several host- and microbiota-derived metabolites, such as cytosine, ureidopropionic acid, and glutaric acid. MG normalized the bioactive lipid oleoylethanolamine, a member of the endocannabinoid system, from the dysregulated level in infected mice, directly contributing to its overall beneficial effects. Our findings provided novel insights into molecular processes via which the flavonoid malvidin exerts its biological effects in the gastrointestinal tract.

