Background: To investigate the effect of creatine and coenzyme Q10 (CoQ10) combination therapy on mild cognitive impairment (MCI) in Parkinson's disease (PD; PD-MCI) and its influences on plasma phospholipid (PL) levels in PD-MCI. Methods: The demographic data of 75 PD-MCI patients who enrolled in this collaborative PD study were collected. These patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) III and the Montreal Cognitive Assessment (MoCA). These 75 PD-MCI patients were randomly treated with creatine monohydrate 5 g b.i.d. and CoQ10 100 mg t.i.d. orally or placebo. MoCA evaluation and PL level measurements were performed after 12 and 18 months of treatment. Results: After 12 and 18 months of treatment, the differences in the MoCA scores of the combination therapy and control groups were statistically significant (p < 0.05 at 12 months and p < 0.01 at 18 months), and the plasma PL levels of the combination therapy group were significantly lower than those of the control group (p < 0.01 at 12 months and p < 0.001 at 18 months). Conclusions: Combination therapy with creatine and CoQ10 could delay the decline of cognitive function in PD-MCI patients and could lower their plasma PL levels; therefore, this combination therapy may have a neuroprotective function.

Parkinson’s disease (PD) is mainly managed by pharmacological therapy (e.g., Benserazide and dopamine agonists). However, prolonged use of these drugs would gradually diminish their dopaminergic effect. Gut dysbiosis was observed in some patients with PD, suggesting close association between the gut microbiome and PD. Probiotics modulate the host’s gut microbiota beneficially. A 3-month randomized, double-blind, placebo-controlled clinical trial was conducted to investigate the beneficial effect of probiotic co-administration in patients with PD. Eighty-two PD patients were recruited and randomly divided into probiotic [n = 48; Bifidobacterium animalis subsp. lactis Probio-M8 (Probio-M8), Benserazide, dopamine agonists] and placebo (n = 34; placebo, Benserazide, dopamine agonists) groups. Finally, 45 and 29 patients from Probio-M8 and placebo groups provided complete fecal and serum samples for further omics analysis, respectively. The results showed that Probio-M8 co-administration conferred added benefits by improving sleep quality, alleviating anxiety, and gastrointestinal symptoms. Metagenomic analysis showed that, after the intervention, there were significantly more species-level genome bins (SGBs) of Bifidobacterium animalis, Ruminococcaceae, and Lachnospira, while less Lactobacillus fermentum and Klebsiella oxytoca in Probio-M8 group (P < 0.05). Interestingly, Lactobacillus fermentum correlated positively with the scores of UPDRS-III, HAMA, HAMD-17, and negatively with MMSE. Klebsiella oxytoca correlated negatively with feces hardness. Moreover, co-administering Probio-M8 increased SGBs involved in tryptophan degradation, gamma-aminobutyric acid, short-chain fatty acids, and secondary bile acid biosynthesis, as well as serum acetic acid and dopamine levels (P < 0.05). Taken together, Probio-M8 synergized with the conventional regimen and strengthened the clinical efficacy in managing PD, accompanied by modifications of the host’s gut microbiome, gut microbial metabolic potential, and serum metabolites.