Probiotic-Fermented Camel Milk Attenuates Neurodegenerative Symptoms via SOX5/miR-218 Axis Orchestration in Mouse Models

Abstract

Multiple sclerosis is an autoimmune-mediated myelin damage disorder in the central nervous system that is widespread among neurological patients. It has been demonstrated that several genetic and epigenetic factors control autoimmune encephalomyelitis (EAE), a murine model of MS, through CD4+ T-cell population quantity. Alterations in the gut microbiota influence neuroprotectiveness via unexplored mechanisms. In this study, the ameliorative effect of Bacillus amyloliquefaciens fermented in camel milk (BEY) on an autoimmune-mediated neurodegenerative model using myelin oligodendrocyte glycoprotein/complete fraud adjuvant/pertussis toxin (MCP)-immunized C57BL6j mice is investigated. Anti-inflammatory activity was confirmed in the in vitro cell model, and inflammatory cytokines interleukins IL17 (from EAE 311 to BEY 227 pg/mL), IL6 (from EAE 103 to BEY 65 pg/mL), IFNγ (from EAE 423 to BEY 243 pg/mL) and TGFβ (from EAE 74 to BEY 133 pg/mL) were significantly reduced in BEY-treated mice. The epigenetic factor miR-218-5P was identified and confirmed its mRNA target SOX-5 using in silico tools and expression techniques, suggesting SOX5/miR-218-5p could serve as an exclusive diagnostic marker for MS. Furthermore, BEY improved the short-chain fatty acids, in particular butyrate (from 0.57 to 0.85 µM) and caproic (from 0.64 to 1.33 µM) acids, in the MCP mouse group. BEY treatment significantly regulated the expression of inflammatory transcripts in EAE mice and upregulated neuroprotective markers such as neurexin (from 0.65- to 1.22-fold) (p < 0.05), vascular endothelial adhesion molecules (from 0.41- to 0.76-fold) and myelin-binding protein (from 0.46- to 0.89-fold) (p < 0.03). These findings suggest that BEY could be a promising clinical approach for the curative treatment of neurodegenerative diseases and could promote the use of probiotic food as medicine.

Attenuation of Immunogenicity in MOG-Induced Oligodendrocytes by the Probiotic Bacterium Lactococcus Sp. PO3

“…Disturbance of the gut-brain axis, a bidirectional relationship between the microbiota in the digestive tract and the brain, has been linked to neuroinflammatory response and neurological disorders [29,30]. Cow milk offers a suitable nutritional medium for many microorganisms, including probiotics, due to its high content of essential molecules including carbohydrates, proteins, lipids, vitamins, and minerals.…”

“…It has been reported that Hsp65-producing Lactococcus lactis inhibits experimental autoimmune encephalomyelitis by preventing cell migration into the spinal cord [35]. Furthermore, other probiotic species such as Bacillus amyloliquifaciens-supplemented camel milk suppress the neuroinflammation of autoimmune encephalomyelitis by regulating inflammatory markers [29], as well as by regulating SOX5/miR-218 axis orchestration in mouse models [30]. STAT-3 diminished apoptosis and polarized the OLs in LPS-induced immunogenicity, which resulted in defective regulation of MBP and GFAP in OLs.…”

“…The neurological disorder known as multiple sclerosis was also treated with probiotics [25]. Several ailments such as diabetes [26], inflammatory bowel disease [27,28], and neuronal inflammatory disorder [29,30] were improved by the immunomodulatory mechanisms of specific probiotic organisms.…”