Probiotic Supplementation Facilitates Recovery of 6-OHDA-Induced Motor Deficit via Improving Mitochondrial Function and Energy Metabolism

Abstract

Parkinson’s disease (PD) is a neurodegenerative disease associated with progressive impairment of motor and non-motor functions in aging people. Overwhelming evidence indicate that mitochondrial dysfunction is a central factor in PD pathophysiology, which impairs energy metabolism. While, several other studies have shown probiotic supplementations to improve host energy metabolism, alleviate the disease progression, prevent gut microbiota dysbiosis and alter commensal bacterial metabolites. But, whether probiotic and/or prebiotic supplementation can affect energy metabolism and cause the impediment of PD progression remains poorly characterized. Therefore, we investigated 8-weeks supplementation effects of probiotic [Lactobacillus salivarius subsp. salicinius AP-32 (AP-32)], residual medium (RM) obtained from the AP-32 culture medium, and combination of AP-32 and RM (A-RM) on unilateral 6-hydroxydopamine (6-OHDA)-induced PD rats. We found that AP-32, RM and A-RM supplementation induced neuroprotective effects on dopaminergic neurons along with improved motor functions in PD rats. These effects were accompanied by significant increases in mitochondrial activities in the brain and muscle, antioxidative enzymes level in serum, and altered SCFAs profile in fecal samples. Importantly, the AP-32 supplement restored muscle mass along with improved motor function in PD rats, and produced the best results among the supplements. Our results demonstrate that probiotic AP-32 and A-RM supplementations can recover energy metabolism via increasing SCFAs producing and mitochondria function. This restoring of mitochondrial function in the brain and muscles with improved energy metabolism might additionally be potentiated by ROS suppression by the elevated generation of antioxidants, and which finally leads to facilitated recovery of 6-OHDA-induced motor deficit. Taken together, this work demonstrates that probiotic AP-32 supplementation could be a potential candidate for alternate treatment strategy to avert PD progression.

Probiotic Enhancement of Antioxidant Capacity and Alterations of Gut Microbiota Composition in 6-Hydroxydopamin-Induced Parkinson’s Disease Rats

“…Moreover, probiotics can generate antioxidant metabolites, such as glutathione [ 45 ], folate [ 47 ], and butyrate [ 46 ]. In this study, our probiotic/prebiotic treatments directly increased the activity of host antioxidant enzymes, in accordance with previous studies [ 38 , 48 , 49 ]. Furthermore, Romo-Araiza et al [ 49 ] reported that probiotic, prebiotic, and synbiotic supplementation could suppress the levels of the pro-inflammatory cytokines IL-1β and TNF-α.…”

“…Improved host antioxidant activity and reduced oxidative stress may also play roles in the suppression of TNF-α observed in this study. Additionally, the antioxidant and anti-inflammatory effects conferred by the probiotic and its residual medium may further prevent deleterious changes in mitochondrial function, as we described previously [ 38 ]. Overall, our results indicated that the probiotic, its medium residue, and the cocktail prevented the vicious cycle of mitochondrial dysfunction, oxidative stress, and inflammation in the rat model of PD, and these supplements eventually improved motor function and restored dopaminergic neurons.…”

“…salicinius AP-32 culture broth. MR contains numerous nutrients, including macronutrients, amino acids, and SCFAs [ 38 ]. Synbiotic 1XMR (Bioflag Biotech Co., Ltd.) is a combination of the probiotic AP-32 and potential prebiotic MR. All supplements were dissolved in distilled water (1 mg/mL) before oral gavage.…”

“…Unilateral 6-OHDA lesions were induced by stereotaxic surgery using a modified version of a protocol from a previous study [ 38 ]. Briefly, 20–40 mg/kg BW of tiletamine with zolazepam (Zoletil ® , Virbac, New Zealand Ltd., Hamilton, New Zealand) and 5 to 10 mg/kg BW of xylazine (Rompun ® , Bayer Health Care, Leverkusen, Germany) were used to anesthetize the rats before surgery.…”

“…A stereotaxic apparatus for rats (David Kopf Instruments, Tujunga, CA, USA) was used to restrain the rats. A 1-mm burr hole was created, using a micro motor handpiece (Saeshin Production Co., Ltd., Daegu, Korea), on the coordinates of the right medial forebrain bundle [ 38 ]. Freshly prepared 3 μg/μL 6-OHDA solution (6-OHDA in 0.9% NaCl containing 0.02% ascorbic acid ( w / v ); Sigma-Aldrich, Darmstadt, Germany) was injected with a 10-μL Hamilton syringe using an infusion pump at 0.2 μL/min.…”