Pomegranate peel extract ameliorates the severity of experimental autoimmune encephalomyelitis via modulation of gut
Xin-Yu Lu1,2, Bing Han1, Xin Deng1
1National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, Shaanxi Normal University , Xi'an, Shaanxi, China.
Abstract:
Multiple sclerosis (MS) is a CNS autoimmune disease characterized by demyelination and inflammatory infiltration with a high disability rate. Increasing evidence has demonstrated the importance of gut microbiota as an environmental risk factor in MS and its animal model experimental autoimmune encephalomyelitis (EAE). Diet is the main determinant of gut microbiota composition and function, which greatly affects the shaping of microbial structure. Pomegranate peel, a waste product in the production of juice, is rich in health-promoting compounds. However, its individual constituents, immunoregulatory activities, and action associated with bacterial diversity in the gut microbiota are largely unknown. Here, the main nutrient ingredients of pomegranate peel extract (PPE) were identified as phenols, flavonoids, amino acids, carbohydrates, fatty acids, lipids, nucleotides, organic acids, alcohols, and vitamins via metabolomics evaluation. We found, for the first time, oral PPE (100 mg/kg/day) not only effectively relieves EAE, inhibits CNS inflammatory factor infiltration and myelin loss, but also reshapes gut microbiota. Furthermore, recipient EAE mice with fecal transplantation from the PPE-treated donor delayed the disease development significantly. 16S rRNA gene sequencing revealed the increased gut microbiota richness in PPE-treated group. Among them, Lactobacillaceae enriched significantly, while Alcaligenaceae and Acidaminococcacea decreased remarkably. In conclusion, our data demonstrated that gut microbiota mediated the beneficial effects of oral PPE on EAE, and provided new ideas for developing the prebiotic value of pomegranate peel for the treatment of autoimmune diseases.
Insights
Pomegranate peel extract (PPE) effectively treats experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis model, by modulating gut microbiota. Fecal transplants from treated mice also delayed disease, highlighting microbiota
Area of Science:
- Immunology
- Microbiology
- Nutritional Science
Background:
- Multiple sclerosis (MS) is a CNS autoimmune disease linked to gut microbiota.
- Diet significantly influences gut microbiota composition and immune responses.
- Pomegranate peel, a rich source of bioactive compounds, has unexplored immunomodulatory potential.
Purpose of the Study:
- To investigate the effects of pomegranate peel extract (PPE) on experimental autoimmune encephalomyelitis (EAE).
- To determine if PPE modulates gut microbiota composition and function.
- To explore the role of gut microbiota in mediating PPE's therapeutic effects in EAE.
Main Methods:
- Metabolomics analysis to identify PPE constituents.
- Oral administration of PPE (100 mg/kg/day) to EAE mice.
- Assessment of clinical EAE scores, CNS inflammation, and myelin integrity.
- 16S rRNA gene sequencing for gut microbiota analysis.
- Fecal microbiota transplantation (FMT) from PPE-treated donors to recipient EAE mice.
Main Results:
- PPE administration significantly alleviated EAE symptoms and reduced CNS inflammation and demyelination.
- PPE treatment altered gut microbiota composition, increasing overall richness.
- Specific bacterial families like Lactobacillaceae were enriched, while Alcaligenaceae and Acidaminococcacea decreased post-PPE treatment.
- FMT from PPE-treated donors conferred protection against EAE development in recipient mice.
Conclusions:
- Oral PPE exerts beneficial effects on EAE, likely mediated by gut microbiota modulation.
- PPE reshapes the gut microbial community, promoting a potentially protective profile.
- Pomegranate peel holds potential as a prebiotic for managing autoimmune diseases like MS.
