Altered gut microbiota in Parkinson's disease patients/healthy spouses and its association with clinical features

Abstract

Increasing evidence shows that gut microbiota dysbiosis may play important roles in the occurrence and progression of Parkinson's disease (PD), but the findings are inconsistent. Besides, the effect of family environment on gut microbiota dysbiosis remains unclear. Methods: We characterized the gut microbial compositions of 63 PD patients, 63 healthy spouses (HS) and 74 healthy people (HP) using 16S rRNA sequencing. Clinical phenotypes and microbial composition were analyzed comprehensively. Results: There were markedly different microbial compositions among PD, HS and HP samples by alpha/beta diversity. We also found differential microbial compositions among Hoehn & Yahr stage/disease duration. Eight inflammation-associated microbial genera shared a continuously increase trend with increased Hoehn & Yahr stage and disease duration, indicating characteristic bacteria associated with deterioration in PD. Additionally, seven bacterial markers were identified for accurately differentiating PD patients from the controls (area under the curve [AUC]: 0.856). Conclusions: Our study shows altered gut microbiota in PD patients. Importantly, inflammation-associated microbial genera may play roles in PD progression. Differential microbial compositions in HS and HP samples demonstrate that the gut microbiota are also affected by family environment. Disease-associated metagenomics studies should consider the family environmental factor. Our research provides an important reference and improves the understanding of gut microbiota in PD patients.

New Avenues for Parkinson’s Disease Therapeutics: Disease-Modifying Strategies Based on the Gut Microbiota

“…They identified 16 case-control studies concerning original gut microbiome data, and they agreed in the pathological imbalance between the microbial community in PD patients compared with HC. Additional studies [ 111 , 113 , 114 , 115 , 116 , 117 , 118 , 119 ] have been published since then and we have summarized all findings in Table 1 . At the phylum level, the increase of Proteobacteria, Actinobacteria , and Verrucomicrobia was reported in 4, 5, and 6 studies, respectively ( Table 1 ).…”

Association of Parkinson’s Disease With Microbes and Microbiological Therapy

“…Increased in PD Lactobacillaceae (Holmqvist et al, 2014;Keshavarzian et al, 2015;Mao et al, 2016;Manfredsson et al, 2018;Lin et al, 2018;Haikal et al, 2019) (6/17) Lactobacillus (Flavin et al, 2017;Hopfner et al, 2017;Lin et al, 2018;Haikal et al, 2019) (4/17) Enterobacteriaceae (Keshavarzian et al, 2015;Mao et al, 2016;Manfredsson et al, 2018;Haikal et al, 2019) 4/17Verrucomicrobiaceae (Jangula and Murphy, 2013;Holmqvist et al, 2014;Keshavarzian et al, 2015;Jiang et al, 2017;Hopfner et al, 2017;Lin et al, 2018;Aho et al, 2019;Zhang et al, 2020) 8/17Akkermansia (Jangula and Murphy, 2013;Keshavarzian et al, 2015;Jiang et al, 2017;Hopfner et al, 2017;Lin et al, 2018;Barichella et al, 2019;Aho et al, 2019;Zhang et al, 2020) 8/17Enterococcaceae (Holmqvist et al, 2014;Hopfner et al, 2017) (2/17) Bacteroidaceae (Jiang et al, 2017;Qian et al, 2018) 2/17Bacteroides (Jiang et al, 2017) (1/17) Rikenellaceae (Li et al, 2017;Haikal et al, 2019) 2/17Streptococcaceae…”

“…Streptococcus 1/17Clostridiaceae (Jiang et al, 2017) 1/17ClostridiumIV (Petrov et al, 2017) (1/17) ClostridiumXVIII (Petrov et al, 2017) (1/17) Lachnospiraceae (Jiang et al, 2017;Petrov et al, 2017) (2/17) Bifidobacteriaceae (Jangula and Murphy, 2013;Scheperjans et al, 2015;Keshavarzian et al, 2015;Lin et al, 2018) 4/17Bifidobacterium (Jangula and Murphy, 2013;Flavin et al, 2017;Lin et al, 2018) (3/17) Ruminococcaceae 57 (1/17) Decreased in PD Prevotellaceae (Holmqvist et al, 2014;Mao et al, 2016;Flavin et al, 2017;Li et al, 2017;Lin et al, 2018;Aho et al, 2019;Zhang et al, 2020) 7/17Prevotella (Holmqvist et al, 2014;Flavin et al, 2017;Hopfner et al, 2017;Li et al, 2017;Lin et al, 2018;Zhang et al, 2020) 6/17Lachnospiraceae (Jangula and Murphy, 2013;Scheperjans et al, 2015;Keshavarzian et al, 2015;Li et al, 2017;Manfredsson et al, 2018;Qian et al, 2018;Lin et al, 2018) 7/17Roseburia (Jangula and Murphy, 2013;Keshavarzian et al, 2015;Li et al, 2017;Lin et al, 2018)…”

“…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 ).…”

Gut Microbiota Interaction with the Central Nervous System throughout Life

“…However, the current evidence in humans remains inconsistent, with reports of both replication and contradictory findings across studies, mainly attributed to methodological differences and patients’ heterogeneity (discussed in more detail [ 227 ]). For example, some studies have shown changes in alpha diversity (e.g., either increased or decreased), whereas others do not find differences in this parameter [ 227 , 228 ]. Similarly, the effects of some antiparkinsonian drugs on gut microbiota have also been questioned [ 228 , 229 , 230 ], thus puzzling the role of gut dysbiosis in human PD pathology and making difficult a straight forward translation from animal model results to the clinic.…”