The effects of microbiota abundance on symptom severity in Parkinson’s disease: A systematic review

Abstract

IntroductionParkinson’s disease (PD) is neurodegenerative disease with a multifactorial etiopathogenesis with accumulating evidence identifying microbiota as a potential factor in the earliest, prodromal phases of the disease. Previous research has already shown a significant difference between gut microbiota composition in PD patients as opposed to healthy controls, with a growing number of studies correlating gut microbiota changes with the clinical presentation of the disease in later stages, through various motor and non-motor symptoms. Our aim in this systematic review is to compose and assess current knowledge in the field and determine if the findings could influence future clinical practice as well as therapy in PD.MethodsWe have conducted a systematic review according to PRISMA guidelines through MEDLINE and Embase databases, with studies being selected for inclusion via a set inclusion and exclusion criteria.Results20 studies were included in this systematic review according to the selected inclusion and exclusion criteria. The search yielded 18 case control studies, 1 case study, and 1 prospective case study with no controls. The total number of PD patients encompassed in the studies cited in this review is 1,511.ConclusionThe link between gut microbiota and neurodegeneration is a complex one and it depends on various factors. The relative abundance of various microbiota taxa in the gut has been consistently shown to have a correlation with motor and non-motor symptom severity. The answer could lie in the products of gut microbiota metabolism which have also been linked to PD. Further research is thus warranted in the field, with a focus on the metabolic function of gut microbiota in relation to motor and non-motor symptoms.

The effects of lactulose on constipation in patients with Parkinson's disease: An exploratory pilot study

“…Evidence of alterations in gut microbiota provided by multiple case-control studies conducted using diverse populations suggest that bowel dysfunction in PD may occur alongside dysbiosis [ 9 ]. However, whether the previously reported changes in gut microbiota play a causal role in the development of gut pathology in PD or whether they are a consequence of altered gut function remain unclear.…”

Buty and the beast: the complex role of butyrate in Parkinson’s disease

“…Composition of the intestinal bacteria in individuals with PD has been assessed in several studies ( Hasegawa et al, 2015 ; Keshavarzian et al, 2015 ; Scheperjans et al, 2015 ; Unger et al, 2016 ; Bedarf et al, 2017 ; Hill-Burns et al, 2017 ; Hopfner et al, 2017 ; Li et al, 2017 ; 2019 ; Li et al, 2022 Z. ; Mertsalmi et al, 2017 ; Minato et al, 2017 ; Petrov et al, 2017 ; Heintz-Buschart et al, 2018 ; Lin et al, 2018 ; 2019 ; Qian et al, 2018 ; Aho et al, 2019 ; Barichella et al, 2019 ; Pietrucci et al, 2019 ; Weis et al, 2019 ; Baldini et al, 2020 ; Cosma-Grigorov et al, 2020 ; Ren et al, 2020 ; Wallen et al, 2020 ; 2022 ; Zhang et al, 2020 ; Murros et al, 2021 ; Rosario et al, 2021 ; Takahashi et al, 2022 ; Nuzum et al, 2023 ) (see ( Nuzum et al, 2020 ; Plassais et al, 2021 ; Romano et al, 2021 ; Papić et al, 2022 ) for review and metanalyses). Reporting of changes in the α-diversity of the PD microbiome is mixed.…”

“…More consensus is reached regarding changes in β-diversity however, with studies consistently finding differences between PD and control groups regardless of differences in methodology, geographical location, and having accounted for potential confounding factors such as age and medication use ( Nuzum et al, 2020 ; Romano et al, 2021 ; Papić et al, 2022 ). Specifically, a reduction of bacterial taxa typically associated with anti-inflammatory and neuroprotective effects was found, such as bacterial strains belonging to the Lachnospiraceae family ( Barichella et al, 2019 ; Pietrucci et al, 2019 ; Vascellari et al, 2020 ; Romano et al, 2021 ; Papić et al, 2022 ). Additionally, bacteria that are typically associated as being beneficial (e.g., Lactobacillus and Bifidobacterium ) were, perhaps counterintuitively, found to be more abundant in the PD microbiome ( Hasegawa et al, 2015 ; Hill-Burns et al, 2017 ; Minato et al, 2017 ; Barichella et al, 2019 ; Nuzum et al, 2020 ; Romano et al, 2021 ; Papić et al, 2022 ; Takahashi et al, 2022 ) and in some studies were found to correlate with disease severity ( Minato et al, 2017 ; Barichella et al, 2019 ; Baldini et al, 2020 ).…”

“…Specifically, a reduction of bacterial taxa typically associated with anti-inflammatory and neuroprotective effects was found, such as bacterial strains belonging to the Lachnospiraceae family ( Barichella et al, 2019 ; Pietrucci et al, 2019 ; Vascellari et al, 2020 ; Romano et al, 2021 ; Papić et al, 2022 ). Additionally, bacteria that are typically associated as being beneficial (e.g., Lactobacillus and Bifidobacterium ) were, perhaps counterintuitively, found to be more abundant in the PD microbiome ( Hasegawa et al, 2015 ; Hill-Burns et al, 2017 ; Minato et al, 2017 ; Barichella et al, 2019 ; Nuzum et al, 2020 ; Romano et al, 2021 ; Papić et al, 2022 ; Takahashi et al, 2022 ) and in some studies were found to correlate with disease severity ( Minato et al, 2017 ; Barichella et al, 2019 ; Baldini et al, 2020 ). This is partially attributed to these bacteria’s ability to survive in a proinflammatory environment ( Romano et al, 2021 ) and their ability to outcompete other genera ( Wallen et al, 2022 ).…”

“…Dysfunction of the gastrointestinal (GI) system is often related with a change in microbiota composition. In addition, several studies also have found correlations between disease severity and an altered microbiota ( Barichella et al, 2019 ; Romano et al, 2021 ; Boertien et al, 2022 ; Nuzum et al, 2023 ) (reviewed ( Boertien et al, 2019 ; Bullich et al, 2019 ; Nuzum et al, 2020 ; Papić et al, 2022 )).…”