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Updated: Jan 8, 2026
Author Spotlight: Creating a Versatile Experimental Autoimmune Encephalomyelitis Model Relevant for Both Male and Female Mice
Published on: October 13, 2023
Multi-omics identification of a microbial metabolite driving OXPHOS-mediated epithelial damage in experimental
Eunike Tiffany1, Panida Sittipo2, Chanyoung Lee1
1Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-Bio Science, Soonchunhyang University, Cheonan 31151, Korea.
Abstract:
Bowel syndrome is a prevalent and debilitating symptom in patients with multiple sclerosis (MS), substantially impairing their quality of life. However, the underlying mechanisms of MS development remain poorly understood. In this study, we demonstrated that intestinal epithelial cells (IECs) and the mucosal barrier were disrupted during experimental autoimmune encephalomyelitis (EAE) induction, driven by the inhibition of mitochondrial oxidative phosphorylation (OXPHOS). Proteomic analysis confirmed alterations in OXPHOS complexes, with a pronounced decrease in the expression of cytochrome c oxidase and ATP synthase subunits in small intestinal epithelial cells (sIECs). We identified a gut microbiota-derived metabolite that induces IEC dysfunction by downregulating OXPHOS protein complexes. Specifically, metabolomic analysis revealed an enrichment of phenyllactic acid (PLA), a phenolic acid typically produced by Lactobacillus murinus, in the cecal contents of EAE mice. Our findings indicate that PLA actively downregulates OXPHOS complexes and restrains maximal mitochondrial respiration. Using a multi-omics approach, this study elucidated a potential mechanism by which gut microbiota dysbiosis observed in EAE mice compromises IEC integrity and disrupts the mucosal barrier. [BMB Reports 2026; 59(2): 151-160].
Insights
Multiple sclerosis (MS) bowel issues stem from gut bacteria disrupting intestinal cells. Phenyllactic acid (PLA) from gut microbes inhibits mitochondrial function, compromising the gut barrier in MS.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Bowel dysfunction significantly impacts multiple sclerosis (MS) patients' quality of life.
- The precise mechanisms driving MS pathogenesis, particularly gut involvement, require further elucidation.
Purpose of the Study:
- To investigate the link between gut microbiota, intestinal barrier integrity, and MS development.
- To identify specific microbial metabolites contributing to intestinal dysfunction in MS models.
Main Methods:
- Induction of experimental autoimmune encephalomyelitis (EAE) in mice to model MS.
- Proteomic and metabolomic analyses of small intestinal epithelial cells (sIECs) and cecal contents.
- Multi-omics approach to analyze gut microbiota and host interactions.
Main Results:
- EAE induction led to disrupted intestinal epithelial cells (IECs) and mucosal barrier integrity.
- Mitochondrial oxidative phosphorylation (OXPHOS) was inhibited in sIECs, with decreased expression of key complexes.
- Phenyllactic acid (PLA), a metabolite from Lactobacillus murinus, was enriched and found to downregulate OXPHOS and impair mitochondrial respiration.
Conclusions:
- Gut microbiota dysbiosis contributes to IEC dysfunction and mucosal barrier compromise in EAE.
- Phenyllactic acid (PLA) emerges as a key microbial metabolite negatively impacting mitochondrial function in the gut.
- This study reveals a potential mechanism linking gut health, microbial metabolites, and MS pathogenesis.
