Reply to: ‘Comment on “Microbiota Composition and Metabolism Are Associated With Gut Function in Parkinson’s Disease”’

Abstract

I would like to comment on the recently published article titled "Microbiota Composition and Metabolism Are Associated With Gut Function in Parkinson's Disease" in Movement Disorders. Cirstea et al 1 analyzed the correlation between intestinal symptoms, intestinal flora, and serum metabolomics in patients with Parkinson's disease (PD) based on large samples and came up with novel findings. The researchers evaluated 300 participants in detail, including daily dietary intake and intestinal complications. However, I have some concerns. First, it was declared in the Results section that p-cresol (HMDB0001858) and phenylacetylglutamine (HMDB0006344) were both significantly positively correlated with constipation severity among patients (Fig. 3E). Nevertheless, the result of phenylacetylglutamine cannot be found in Figure 3E, and there are 2 plots of different correlations between p-cresol and constipation severity among patients with PD. Second, as shown in the Discussion section, nearly half of controls (43 of 103) were spouses of the PD patients. In other words, within the cohort composed of pairs of couples, the diet-driven heterogeneity in gut microbiota between the patient and the control might be negligible because couples share more of their gut microbiota than individuals from different households. 2 However, an individual's dietary pattern might be a confounding factor for analysis of gut microbiota for the rest of the 147 patients and the other healthy controls. Notably, several studies 2-4 assessing the relationship between gut microbiota and PD included merely couples-based populations to reduce the interfering effect of different dietary patterns. Therefore, we hope that the authors will make a further subgroup analysis to validate their findings in different patient cohorts. To sum up, the present study is interesting and inspiring research in which more detailed information should be analyzed and available to readers so as to be more helpful in a deep understanding of intestinal symptoms, intestinal flora, and serum metabolomics in PD patients.

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

“…In stool, we documented lower levels of SCFAs and higher levels of calprotectin in PD patients. This is consistent with other reports of SCFA and SCFA-producing bacteria reductions 3, 12, 13, 19, 22, 31 as well as increased stool calprotectin 24, 25 in PD. While SCFAs and calprotectin are beginning to emerge as some of the most reliable indicators of a dysregulated and inflammatory gut environment in PD, our results suggest that these associations may be sexually dimorphic.…”

“…11 In a study contrasting fecal SCFA levels in PD patients and control subjects, decreased concentrations of SCFAs, particularly butyric acid, in PD patients were linked to microbiota alterations, 12 and several bacterial taxa reportedly reduced in PD are SCFA producers. 2, 3, 13…”

Association of Parkinson’s Disease With Microbes and Microbiological Therapy

“…Current studies have also shown that SCFAs can cause dyskinesia and lead to α -SYN responsive microglia in the brain ( Sampson et al., 2016 ). Evidence from Cirstea’s clinical study also suggests that PD patients have fewer bacterial clusters associated with SCFAs ( Cirstea et al., 2020 ). Currently, the specific role of intestinal bacteria and α -SYN in the etiology of PD is not clear, but the exploration and understanding of the inflammatory process caused by intestinal flora may provide relevant clues for clinical treatment and the pathogenesis of PD.…”

“…At present, there are 17 studies on the comparison between PD patients and healthy people ( Keshavarzian et al., 2015 ; Scheperjans et al., 2015 ; Bedarf et al., 2017 ; Hill-Burns et al., 2017 ; Hopfner et al., 2017 ; Li et al., 2017 ; Petrov et al., 2017 ; Heintz-Buschart et al., 2018 ; Lin et al., 2018 ; Qian et al., 2018 ; Aho et al., 2019 ; Barichella et al., 2019 ; Pietrucci et al., 2019 ; Cirstea et al., 2020 ; Cosma-Grigorov et al., 2020 ; Qian et al., 2020 ; Zhang et al., 2020 ), including five studies from China ( Li et al., 2017 ; Lin et al., 2018 ; Qian et al., 2018 ; Qian et al., 2020 ; Zhang et al., 2020 ), three from Germany ( Bedarf et al., 2017 ; Hopfner et al., 2017 ; Cosma-Grigorov et al., 2020 ), two from Italy ( Barichella et al., 2019 ; Pietrucci et al., 2019 ), two from Finland ( Scheperjans et al., 2015 ; Aho et al., 2019 ), two from the United States ( Keshavarzian et al., 2015 ; Hill-Burns et al., 2017 ), one from Luxembourg ( Heintz-Buschart et al., 2018 ), one from Russia ( Petrov et al., 2017 ), and one from Canada ( Cirstea et al., 2020 ). A total of 13 studies reported the diversity of intestinal microflora, and the diversity index (α and β diversity) was primarily used to describe the overall characteristics of microbial community composition ( Table 2 ) ( Cosma-Grigorov et al., 2020 ).…”

MIND diet associated with later onset of Parkinson’s disease

“…225 participants diagnosed with PD within the last 12 years and 156 control participants were recruited through the Pacific Parkinson’s Research Centre (PPRC) at the University of British Columbia (UBC), Canada, using inclusion/exclusion criteria described previously 11 . Incomplete dietary surveys (n=93) were not included in the analysis, as well as PD participants with no recorded age of onset (n=2), leaving a total of 167 and 119 PD and control participants, respectively.…”