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Probiotic modulation of energy metabolism ameliorates experimental autoimmune encephalomyelitis via Nrf2-associated
1Health Services Vocational School of Higher Education, Pamukkale University, 20070, Denizli, Turkey.
Abstract:
Alterations in the gut microbiome not only impact immune processes associated with the pathogenesis of multiple sclerosis (MS) but also affect the regulation of metabolic pathways. In MS and experimental autoimmune encephalomyelitis (EAE) models, probiotics are thought to contribute not only to immunomodulatory effects but also to the reprogramming of energy metabolism. In light of these findings, this study assessed the efficacy of the probiotic Lactobacillus acidophilus LA-5 (LA-5) in disorders of pentose phosphate pathway (PPP) energy metabolism during disease processes. LA-5 supplementation markedly improved disease severity in the EAE model, as reflected by reduced clinical scores and increased expression and activity of key pentose phosphate pathway enzymes, including glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6-PGD). The treatment also restored diminished transaldolase (TALDO) expression and normalized the NADPH levels in the brain tissue. Moreover, LA-5 reactivated the Nrf2 pathway, which was suppressed under EAE conditions, indicating increased antioxidant capacity. In conclusion, the present findings establish a direct connection between PPP dysfunction and MS pathology, indicating the therapeutic potential of metabolic modulation. This study provides new insights that could inform future strategies for the treatment of MS.
Insights
Probiotic Lactobacillus acidophilus LA-5 improved multiple sclerosis (MS) symptoms in EAE models by restoring pentose phosphate pathway (PPP) energy metabolism and boosting antioxidant capacity.
Area of Science:
- Neuroimmunology
- Metabolic pathways
- Gut microbiome
Background:
- Gut microbiome alterations impact immune responses and metabolic pathways in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE).
- Probiotics may offer immunomodulatory effects and reprogram energy metabolism in MS and EAE models.
Purpose of the Study:
- To assess the efficacy of Lactobacillus acidophilus LA-5 (LA-5) in addressing pentose phosphate pathway (PPP) energy metabolism disorders during MS-related disease processes.
- To investigate the impact of LA-5 on immune and metabolic parameters in an EAE model.
Main Methods:
- Supplementation with Lactobacillus acidophilus LA-5 (LA-5) in an experimental autoimmune encephalomyelitis (EAE) model.
- Assessment of clinical scores, expression and activity of key pentose phosphate pathway (PPP) enzymes (G6PDH, 6-PGD, TALDO), NADPH levels, and Nrf2 pathway activation in brain tissue.
Main Results:
- LA-5 supplementation significantly reduced EAE disease severity and clinical scores.
- Increased expression and activity of PPP enzymes (G6PDH, 6-PGD) and restored transaldolase (TALDO) expression were observed.
- LA-5 normalized brain NADPH levels, reactivated the suppressed Nrf2 pathway, and enhanced antioxidant capacity.
Conclusions:
- A direct link exists between pentose phosphate pathway (PPP) dysfunction and multiple sclerosis (MS) pathology.
- Metabolic modulation, specifically using probiotics like LA-5, shows therapeutic potential for MS treatment.
- Findings offer new insights for developing future MS treatment strategies targeting metabolic pathways.
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