Probiotics in Combination with C16 Peptide and Angiopoietin-1 Synergistically Ameliorate Multiple Sclerosis in Mice

Multiple sclerosis (MS) is a debilitating autoimmune disease of the central nervous system (CNS), characterized by demyelination, axonal loss, and neuronal injury. At present, effective treatment options remain limited. Prior research demonstrated the protective effects of a compound that consists of C16 peptide and angiopoietin-1 (C16-Ang-1) in experimental autoimmune encephalomyelitis (EAE), a validated animal model of MS. This study aims to investigate the potential synergistic effects of probiotics with C16+Ang-1, and elucidate its underlying mechanisms in mice.

C57/BL6 mice were randomly assigned to control, vehicle, probiotics, and C16+Ang-1+probiotics groups. Histological examinations, behavioral tests, and 16S rRNA gene sequencing of fecal samples, were conducted to determine the levels of CNS inflammation, demyelination and axonal loss, neuronal survival, and functional recovery.

Compared to the probiotics group, the C16+Ang-1+probiotics group exhibited significant synergistic effects. Specifically, the combined treatment with C16+Ang-1+probiotics had significantly greater effects than probiotics alone in reducing inflammatory severity in the CNS and colon, improving the microenvironment, protecting the gut-blood barrier, and preserving blood-brain barrier integrity. These effects collectively led to the greater amelioration of functional disability in the mouse model of MS. Further mechanistic studies suggested that these effects involved the modulation of the brain-gut axis, and maintenance of gut microbiota homeostasis.

These findings demonstrate that the combination of probiotics and C16-Ang-1 acts synergistically to ameliorate MS in mice, resulting in a greater effect. Therefore, this combination therapy warrants further investigation to explore its potential clinical benefits, ultimately improving the care for patients with MS.