Related Experiment Video
Updated: Aug 23, 2026
Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
Akkermansia muciniphila induces mitochondrial calcium overload and α -synuclein aggregation in an enteroendocrine
Dionísio Pedro Amorim Neto1,2, Beatriz Pelegrini Bosque1,2, João Vitor Pereira de Godoy1,2
1Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), 10000 Giuseppe Maximo Scolfaro St., 13083-100 Campinas, São Paulo, Brazil.
Abstract:
The gut microbiota influence neurodevelopment, modulate behavior, and contribute to neurodegenerative disorders. Several studies have consistently reported a greater abundance of Akkermansia muciniphila in Parkinson disease (PD) fecal samples. Therefore, we investigated whether A.muciniphila-conditioned medium (CM) could initiate α-synuclein (αSyn) misfolding in enteroendocrine cells (EEC) - a component of the gut epithelium featuring neuron-like properties. We found that A. muciniphila CM composition is influenced by the ability of the strain to degrade mucin. Our in vitro experiments showed that the protein-enriched fraction of mucin-free CM induces RyR-mediated Ca2+ release and increased mitochondrial Ca2+ uptake leading to ROS generation and αSyn aggregation. Oral administration of A. muciniphila cultivated in the absence of mucin to mice led to αSyn aggregation in cholecystokinin (CCK)-positive EECs but no motor deficits were observed. Noteworthy, buffering mitochondrial Ca2+ reverted the damaging effects observed. These molecular insights offer evidence that bacterial proteins can induce αSyn aggregation in EECs.
Insights
Certain gut bacteria, like Akkermansia muciniphila, may trigger alpha-synuclein misfolding in gut cells. This process, linked to Parkinson's disease, involves bacterial proteins and calcium signaling in enteroendocrine cells.
Area of Science:
- Microbiology
- Neuroscience
- Gastroenterology
Background:
- Gut microbiota plays a crucial role in neurodevelopment and neurodegenerative disorders.
- Elevated levels of Akkermansia muciniphila are frequently observed in Parkinson disease (PD) patients.
- Enteroendocrine cells (EECs) in the gut epithelium possess neuron-like properties and are implicated in gut-brain communication.
Purpose of the Study:
- To investigate if Akkermansia muciniphila-conditioned medium (CM) can induce alpha-synuclein (αSyn) misfolding in EECs.
- To explore the mechanisms underlying αSyn aggregation in EECs influenced by A. muciniphila.
- To assess the in vivo effects of A. muciniphila on αSyn aggregation in mice.
Main Methods:
- In vitro analysis of A. muciniphila CM composition and its effect on EECs.
- Assessment of calcium (Ca2+) release, mitochondrial Ca2+ uptake, and reactive oxygen species (ROS) generation.
- Oral administration of A. muciniphila to mice and subsequent analysis of αSyn aggregation in EECs.
- Evaluation of the impact of mitochondrial Ca2+ buffering on observed cellular effects.
Main Results:
- The composition of A. muciniphila CM varies based on the strain's mucin-degrading ability.
- Protein-enriched, mucin-free CM induced RyR-mediated Ca2+ release, mitochondrial Ca2+ uptake, ROS generation, and αSyn aggregation in vitro.
- Oral administration of mucin-deprived A. muciniphila led to αSyn aggregation in cholecystokinin (CCK)-positive EECs in mice.
- No motor deficits were observed in mice despite αSyn aggregation.
- Buffering mitochondrial Ca2+ effectively reversed the detrimental cellular effects.
Conclusions:
- Bacterial proteins from A. muciniphila can initiate αSyn aggregation within EECs.
- The process involves calcium signaling pathways and mitochondrial dysfunction.
- These findings provide molecular insights into the gut microbiota's potential contribution to neurodegenerative processes like Parkinson disease.
More Related Videos
06:07Author Spotlight: Establishing a New Fluorescence-Based Protocol for In Vivo Mitochondrial Morphology Analysis in Parkinson's Disease
Published on: June 23, 2023
06:41Quantitative Analysis of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Stabilization in a Neural Model of Alzheimer's Disease (AD)
Published on: January 10, 2025
