Unraveling gut microbiota in Parkinson's disease and atypical parkinsonism

Michela Barichella1, Marco Severgnini2, Roberto Cilia1

  • 1Parkinson Institute, Azienda Socio Sanitaria Territoriale (ASST) Gaetano Pini-CTO, Milan, Italy.

Abstract

Insights

Gut microbiota alterations are linked to Parkinson's disease (PD) progression and clinical variability. Adjusting for confounders reveals specific bacterial changes, like lower Lachnospiraceae, associated with PD severity.

Area of Science:

  • Microbiome research
  • Neurodegenerative diseases
  • Gut-brain axis

Background:

  • Gut microbiota dysbiosis is implicated in Parkinson's disease (PD) pathogenesis.
  • Existing data on PD and gut microbiota are highly heterogeneous.
  • Environmental factors, including diet, may influence the gut microbiome in PD.

Purpose of the Study:

  • To investigate gut microbiota composition in idiopathic PD, progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and healthy controls (HC).
  • To identify microbial signatures associated with PD duration, disease severity, and specific clinical features.
  • To assess the impact of confounders on gut microbiota profiles in neurodegenerative diseases.

Main Methods:

  • 16S ribosomal RNA gene sequencing of fecal samples from 350 individuals.
  • Stratification of participants into idiopathic PD (including drug-naïve), PSP, MSA, and HC groups.
  • Statistical analysis accounting for confounders such as dietary habits and disease duration.

Main Results:

  • Unadjusted analyses showed numerous differences between PD and HC, but most were attenuated after confounder adjustment.
  • Lower abundance of Lachnospiraceae was the sole consistent difference in de novo PD compared to HC.
  • Decreased Lachnospiraceae and increased Lactobacillaceae/Christensenellaceae correlated with worse clinical outcomes (cognitive impairment, gait issues).
  • MSA and PSP showed some shared and distinct microbial alterations compared to PD and HC.

Conclusions:

  • Gut microbiota may modulate PD pathogenesis and contribute to clinical heterogeneity.
  • PD duration and confounders significantly influence gut microbiota findings.
  • Further prospective studies in de novo PD are crucial to understand dysbiosis's role in disease progression.

Related Concept Videos

Parkinson's Disease: Overview01:15

Parkinson's Disease: Overview

Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is to...
Dysbiosis of the Gut Microbiota01:18

Dysbiosis of the Gut Microbiota

The human gut microbiome includes a diverse array of microbial species, including beneficial commensals and opportunistic pathogens, which interact to support host health. These microbes contribute to essential functions such as nutrient metabolism, immune system modulation, and maintenance of intestinal barrier integrity. However, disruptions to this equilibrium—referred to as dysbiosis—can have widespread physiological consequences.Dysbiosis is often characterized by reduced microbial...
Gut-Brain Axis01:22

Gut-Brain Axis

The gut–brain axis is a bidirectional communication system that connects the gastrointestinal tract and the brain. This interaction is mediated through multiple pathways, including the vagus nerve, hormonal signals, immune responses, and chemical messengers produced by gut microbes.Microbial Contributions to Brain FunctionGut microbiota contributes significantly to brain function by producing neuroactive compounds. These include neuroactive compounds that influence neurotransmitters such as...
Microbiota Modulation by Antibiotics01:21

Microbiota Modulation by Antibiotics

Antibiotics have revolutionized modern medicine by saving countless lives from bacterial infections. However, their widespread use has inadvertently harmed the delicate balance of the human gut microbiota. The gut microbiota, a complex community of bacteria, archaea, viruses, and fungi, plays a vital role in regulating metabolism, immune responses, and maintaining intestinal health. Antibiotics, especially broad-spectrum types, disrupt this ecosystem by eradicating both harmful and beneficial...
Parkinson Disease l: Introduction01:24

Parkinson Disease l: Introduction

Parkinson’s disease is a chronic, progressive neurodegenerative disorder that primarily affects movement. It is characterized by motor symptoms such as resting tremors, muscle rigidity, bradykinesia (slowness of movement), and postural instability. Patients may notice hand tremors at rest, stiffness during movement, or a shuffling gait. In addition to motor features, non-motor symptoms include sleep disturbances, mood and behavioral changes, constipation, and cognitive impairment, all of which...
Parkinson Disease ll: Pathophysiology01:24

Parkinson Disease ll: Pathophysiology

Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...