Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease.

Short-chain fatty acids (SCFAs) are gut microbial metabolites that promote the disease process in a rodent model of Parkinson disease (PD), but fecal levels of SCFAs in patients with PD are reduced. Simultaneous assessments of fecal and plasma SCFA levels, and their interrelationships with the PD disease process, are scarce. We aimed to compare fecal and plasma levels of different SCFA subtypes in patients with PD and healthy controls to delineate their interrelations and link to gut microbiota changes and clinical severity of PD. A cohort of 96 patients with PD and 85 controls were recruited from National Taiwan University Hospital. Fecal and plasma concentrations of SCFAs were measured using chromatography and mass spectrometry. Gut microbiota was analyzed using metagenomic shotgun sequencing. Body mass index and medical comorbidities were evaluated and dietary information was obtained using a food frequency questionnaire. To assess motor and cognitive impairment, we used the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the Mini-Mental Status Examination (MMSE). Compared with controls, patients with PD had lower fecal but higher plasma concentrations of acetate, propionate, and butyrate. After adjustment for age, sex, disease duration, and anti-PD medication dosage, MDS-UPDRS part III motor scores correlated with reduced fecal levels of acetate (ρ = -0.37, p = 0.012), propionate (ρ = -0.32, p = 0.036), and butyrate (ρ = -0.40, p = 0.004) and with increased plasma propionate concentrations (ρ = 0.26, p = 0.042) in patients with PD. MMSE scores negatively correlated with plasma levels of butyrate (ρ = -0.09, p = 0.027) and valerate (ρ = -0.032, p = 0.033) after adjustment for confounders. SCFAs-producing gut bacteria correlated positively with fecal levels of SCFAs in healthy controls but revealed no association in patients with PD. In the PD patient group, the abundance of proinflammatory microbes, such as Clostridiales bacterium NK3B98 and Ruminococcus sp AM07-15, significantly correlated with decreased fecal levels and increased plasma levels of SCFAs, especially propionic acid. Reductions in fecal SCFAs but increased plasma SCFAs were observed in patients with PD and corelated to specific gut microbiota changes and the clinical severity of PD. This study provides Class III evidence that gut metabolite SCFAs distinguish between patients with PD and controls and are associated with disease severity in patients with PD.

Chen SJ ，Chen CC ，Liao HY ，Lin YT ，Wu YW ，Liou JM ，Wu MS ，Kuo CH ，Lin CH ... -  《-》

Parkinson's Disease Is Associated with Impaired Gut-Blood Barrier for Short-Chain Fatty Acids.

Short-chain fatty acids (SCFAs) produced by gut microbiota are reduced in feces but paradoxically increased in plasma of patients with Parkinson's disease (PD), which may stem from intestinal wall leakage. Gut function should be taken into consideration when conducting microbial-metabolite research. The objective was to investigate synchronous changes of SCFAs in feces and plasma of patients with PD, taking constipation as a confounder to better disentangle the SCFA metabolism exclusively associated with PD. The concentrations of fecal and plasma SCFAs in 33 healthy control subjects and 95 patients with PD were measured using liquid and gas chromatography mass spectrometry, respectively. Patients with PD were divided into patients with PD without constipation (n = 35) and patients with PD with constipation (n = 60). Gut-blood barrier (GBB) permeability was assessed by plasma/fecal ratio of SCFA concentrations and fecal α1-antitrypsin concentration. Patients with PD displayed decreased concentrations of fecal acetic, propionic, and butyric acid and increased concentrations of plasma acetic and propionic acid. Fecal acetic, isobutyric, and isovaleric acid were lower and plasma acetic and propionic acid were higher in patients with PD with constipation than in patients with PD without constipation. Constipation aggravated GBB permeability in patients with PD. Combined fecal and plasma SCFAs could discriminate patients with PD from healthy control subjects. Fecal SCFAs, except propionic acid, were negatively correlated with disease severity, while plasma acetic, propionic, and valeric acid showed a positive correlation. Our study showed alterations of fecal and plasma SCFAs in patients with PD that were associated with an impaired GBB and might be aggravated by constipation. © 2022 International Parkinson and Movement Disorder Society.

Yang X ，Ai P ，He X ，Mo C ，Zhang Y ，Xu S ，Lai Y ，Qian Y ，Xiao Q ... -  《-》

Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson's disease.

Aho VTE ，Houser MC ，Pereira PAB ，Chang J ，Rudi K ，Paulin L ，Hertzberg V ，Auvinen P ，Tansey MG ，Scheperjans F ... -  《Molecular Neurodegeneration》

Serum short-chain fatty acids and its correlation with motor and non-motor symptoms in Parkinson's disease patients.

Parkinson's disease (PD) is associated with enteric nervous system dysfunction and gut microbiota dysbiosis. Short-chain fatty acids (SCFAs), derived from gut microbiota, are supposed to anticipate PD pathogenesis via the pathway of spinal cord and vagal nerve or the circulatory system. However, the serum concentration of SCFAs in PD patients is poorly known. This study aims to investigate the exact level of SCFAs in PD patients and its correlation with Parkinson's symptoms. 50 PD patients and 50 healthy controls were recruited, and their demographic and clinical characteristics were collected. The serum concentration of SCFAs was detected using a gas chromatography-mass spectrometer. SCFAs were compared between PD and control groups. The correlation between serum SCFAs and Parkinson's symptoms and the potential effects of medications on the serum SCFAs was analyzed. Serum propionic acid, butyric acid and caproic acid were lower, while heptanoic acid was higher in PD patients than in control subjects. However, only the serum level of propionic acid was correlated with Unified Parkinson's Disease Rating Scale (UPDRs) part III score (R = -0.365, P = 0.009), Mini-mental State Examination (MMSE) score (R = -0.416, P = 0.003), and Hamilton Depression Scale (HAMD) score (R = 0.306, P = 0.03). There was no correlation between other serum SCFAs and motor complications. The use of trihexyphenidyl or tizanidine increased the serum concentration of propionic acid. Serum SCFAs are altered in PD patients, and the decrease of serum propionic acid level is correlated with motor symptoms, cognitive ability and non-depressed state. Thus, the gut microbial-derived SCFAs potentially affect Parkinson's symptoms through the blood circulation. Propionic acid supplementation might ameliorate motor and non-motor symptoms of PD patients, although clinical trials are needed to test this hypothesis.

Wu G ，Jiang Z ，Pu Y ，Chen S ，Wang T ，Wang Y ，Xu X ，Wang S ，Jin M ，Yao Y ，Liu Y ，Ke S ，Liu S ... -  《-》

Idiopathic Rapid Eye Movement Sleep Behavior Disorder (iRBD) Shares Similar Fecal Short-Chain Fatty Acid Alterations with Multiple System Atrophy (MSA) and Parkinson's Disease (PD).

Idiopathic rapid eye movement sleep behavior disorder (iRBD) is considered as a prodromal stage of synucleinopathies. Fecal short-chain fatty acid (SCFA) changes in iRBD and the relationships with synucleinopathies have never been investigated. To investigate fecal SCFA changes among iRBD, multiple system atrophy (MSA), and Parkinson's disease (PD), and evaluate their relationships. Fecal SCFAs and gut microbiota were measured in 29 iRBD, 42 MSA, 40 PD, and 35 normal controls (NC) using gas chromatography-mass spectrometry and 16S rRNA gene sequencing. Compared with NC, fecal SCFA levels (propionic, acetic, and butyric acid) were lower in iRBD, MSA, and PD. Combinations of these SCFAs could differentiate NC from iRBD (AUC 0.809), MSA (AUC 0.794), and PD (AUC 0.701). Decreased fecal SCFAs were associated with the common reducing SCFA-producing gut microbiota in iRBD, MSA, and PD. iRBD shares similar fecal SCFA alterations with MSA and PD, and the combination of these SCFAs might be a potential synucleinopathies-related biomarker. © 2024 International Parkinson and Movement Disorder Society.

Du J ，Zhang P ，Tan Y ，Gao C ，Liu J ，Huang M ，Li H ，Shen X ，Huang P ，Chen S ... -  《-》