Abstract
High-Fat Diet-Induced Gut Microbiota Alterations Worsen Experimental Autoimmune Encephalomyelitis Severity
The Journal of immunology (1950), Vol.212(1_Supplement), pp.1364-1364_5388
05/01/2024
DOI: 10.4049/jimmunol.212.supp.1364.5388
Abstract
Abstract Multiple sclerosis (MS) is a complex neuroinflammatory disease caused by both genetic and environmental factors. Genetically, HLA class II alleles such as HLA-DR2 and –DR3 are strongly linked with MS. Among environmental factors, obesity and gut microbiota has emerged as an important risk factor in MS pathogenesis and severity. This study investigated the impact of High-Fat-Diet (HFD)-induced gut microbiota alterations on experimental autoimmune encephalomyelitis (EAE), utilizing HLA-DR3 (0301) and HLA-DR2(1501).DQ6(0602) transgenic (Tg) mice, crucial for investigating genetic-environment interactions. HFD induces obesity in HLA-DR3, HLA-DR2.DQ6 Tg, and C57BL/6 (B6) mice, exacerbated EAE severity and induced CNS inflammation, and demyelination. Fecal microbiota analysis revealed microbiome dysbiosis with a significant increase in hydrogen sulfide (H2S)-producing bacteria such as Desulfovibrio piger and Bilophila wadsworthia. Mono-colonization of D. piger and B. wadsworthia in gut microbiota-depleted B6 mice mirrored the heightened EAE severity observed in HFD-fed mice. Further, antibiotic depletion study in HFD-fed mice reduced EAE severity and fecal H2S levels, highlighting importance of H2S-producing gut bacteria in obesity-induced EAE modulation. This study identified a disease-promoting role of H2S-producing gut bacteria and underscored the possibility of targeting bacterial H2S as a potential therapeutic intervention to alleviate disease severity in obese MS patients.
Details
- Title: Subtitle
- High-Fat Diet-Induced Gut Microbiota Alterations Worsen Experimental Autoimmune Encephalomyelitis Severity
- Creators
- Shailesh Shahi - University of IowaAllison Rux - University of IowaSudeep Ghimire - University of IowaPeter Lehman - University of IowaDavid Meyerholz - University of IowaAshutosh Mangalam - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.212(1_Supplement), pp.1364-1364_5388
- DOI
- 10.4049/jimmunol.212.supp.1364.5388
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 05/01/2024
- Academic Unit
- Pathology; Iowa Neuroscience Institute
- Record Identifier
- 9984747819702771
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