Oxidative stress plays a key role in the degeneration of dopaminergic neurons in Parkinson’s disease (PD), which may be aggravated by concomitant PD-associated gut dysbiosis. Probiotics and prebiotics are therapeutically relevant to these conditions due to their antioxidant, anti-inflammatory, and gut microbiome modulation properties. However, the mechanisms by which probiotic/prebiotic supplementation affects antioxidant capacity and the gut microbiome in PD remains poorly characterized. In this study, we assessed the effects of a Lactobacillus salivarius AP-32 probiotic, a prebiotic (dried AP-32 culture medium supernatant), and a probiotic/prebiotic cocktail in rats with unilateral 6-hydroxydopamine (6-OHDA)-induced PD. The neuroprotective effects and levels of oxidative stress were evaluated after eight weeks of daily supplementation. Fecal microbiota composition was analyzed by fecal 16S rRNA gene sequencing. The supplements were associated with direct increases in host antioxidant enzyme activities and short-chain fatty acid production, protected dopaminergic neurons, and improved motor functions. The supplements also altered the fecal microbiota composition, and some specifically enriched commensal taxa correlated positively with superoxide dismutase, glutathione peroxidase, and catalase activity, indicating supplementation also promotes antioxidant activity via an indirect pathway. Therefore, L. salivarius AP-32 supplementation enhanced the activity of host antioxidant enzymes via direct and indirect modes of action in rats with 6-OHDA-induced PD.

Inflammation significantly influences the degeneration of dopaminergic neurons in Parkinson's disease (PD), which is potentially intensified by associated gut dysbiosis. The therapeutic potential of probiotics, due to their antioxidant, anti-inflammatory, and gut microbiota modulatory properties, is explored herein as a means to improve gut health and influence the gut–brain–microbiota axis in the context of PD. In this study, we investigated the role and possible mechanism of Bifidobacterium animalis subsp. lactis MH-022 (B. lactis MH-022) supplementation in a 6-hydroxydopamine (6-OHDA)-induced rat model of PD. Findings demonstrated that B. lactis MH-022 supplementation markedly ameliorated motor deficits, preserved dopaminergic neurons, enhanced the antioxidant capacity, and mitigated inflammation through restoring mitochondrial function. Furthermore, B. lactis MH-022 supplementation significantly altered the gut microbiota composition, augmenting the production of short-chain fatty acids and promoting the proliferation of beneficial bacterial taxa, thereby reinforcing their anti-inflammatory properties. Correlation analyses established strong associations between specific bacterial taxa and improvements in motor function, antioxidant levels, and reductions in inflammation markers. These insights emphasize the therapeutic potential of B. lactis MH-022 in modulating diverse aspects of PD, particularly highlighting its role in reducing inflammation, restoring mitochondrial function, enhancing antioxidant capacity, and reshaping the gut microbiota. This multifaceted approach underscores the probiotic's potential in reducing neuroinflammation and protecting dopaminergic neurons, thus offering a promising avenue for PD treatment.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra, resulting in motor symptoms such as bradykinesia, tremor, rigidity, and postural instability, as well as a wide variety of non-motor manifestations. Branched-chain amino acids (BCAAs)—leucine, isoleucine, and valine—are essential nutrients involved in neurotransmitter synthesis, energy metabolism, and cellular signaling. Emerging evidence suggests that BCAA metabolism is intricately linked to the pathophysiology of PD. Dysregulation of BCAA levels has been associated with energy metabolism, mitochondrial dysfunction, oxidative stress, neuroinflammation, and altered neurotransmission. Furthermore, the branched-chain ketoacid dehydrogenase kinase (BCKDK), a key regulator of BCAA catabolism, has been implicated in PD through its role in modulating neuronal energetics and redox homeostasis. In this review, we synthesize current molecular, genetic, microbiome, and clinical evidence on BCAA dysregulation in PD to provide an integrative perspective on the BCAA–PD axis and highlight directions for future translational research. We explored the dualistic role of BCAAs as both potential neuroprotective agents and metabolic stressors, and critically examined the therapeutic prospects and limitations of BCAA supplementation and BCKDK targeting.

Ascophyllum nodosum and Fucus vesiculosus both contain unique polyphenols called phlorotannins. Phlorotannins reportedly possess various pharmacological activities. A previous study reported that the activity of phlorotannin is strongly correlated with the normalization of metabolic function, and phlorotannins are extremely promising nutrients for use in the treatment of metabolic syndrome. To date, no study has explored the antihyperlipidemic effects of phlorotannins from A. nodosum and F. vesiculosus in animal models. Therefore, in the present study, we investigated the effects of phlorotannins using a rat model of high-energy diet (HED)-induced hyperlipidemia. The results showed that the rats that were fed an HED and treated with phlorotannin-rich extract from A. nodosum and F. vesiculosus had significantly lower serum fasting blood sugar (FBS), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triacylglyceride (TG) and free fatty acids (FFAs) levels and hepatic TG level and had higher serum insulin, high-density lipoprotein cholesterol (HDL-C) levels and lipase activity in their fat tissues than in the case with the rats that were fed the HED alone. A histopathological analysis revealed that phlorotannin-rich extract could significantly reduce the size of adipocytes around the epididymis. In addition, the rats treated with phlorotannin-rich extract had significantly lowered interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels and increased superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities than did those in the HED group. These results suggested that the phlorotannin-rich extract stimulated lipid metabolism and may have promoted lipase activity in rats with HED-induced hyperlipidemia. Our results indicated that A. nodosum and F. vesiculosus, marine algae typically used as health foods, have strong antihyperlipidemic effects and may, therefore, be useful for preventing atherosclerosis. These algae may be incorporated into antihyperlipidemia pharmaceuticals and functional foods.

Oxidative stress and gut dysbiosis have been known to precede Parkinson’s disease (PD). An antioxidant-rich product, mangosteen pericarp (MP), has the ability to counterbalance excessive free radicals and the imbalanced gut microbiota composition, suggesting the MP’s capacity to delay PD progression. In this study, we explored the effects of two doses of MP extract in a unilateral 6-hydroxydopamine (6-OHDA)-induced PD rat model. We revealed that the 8-week supplementation of a low dose (LMP) and a high dose of the MP extract (HMP) improved motor function, as observed in decreased contralateral rotation, improved time spent on rod, and higher dopamine binding transporter (DAT) in the substantia nigra pars compacta (SNc). The MP extract, especially the HMP, also increased antioxidant-related gene expressions, restored muscle mitochondrial function, and remodeled fecal microbiota composition, which were followed by reduced reactive oxygen species levels in brain and inflammation in plasma. Importantly, bacterial genera Sutterella, Rothia, and Aggregatibacter, which were negatively correlated with antioxidant gene expressions, decreased in the HMP group. It is imperative to note that in addition to directly acting as an antioxidant to reduce excessive free radicals, MP extract might also increase antioxidant state by rebuilding gut microbiota, thereby enhanced anti-inflammatory capacity and restored mitochondrial function to attenuate motor deficit in 6-OHDA-induced PD-like condition. All in all, MP extract is a potential candidate for auxiliary therapy for PD.