Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines

Area of Science:

• Biochemistry
• Microbiology
• Neuroscience

Background:

• Propionic acid (PPA) is a short-chain fatty acid produced by the gut microbiome.
• PPA is involved in metabolism and found in food, with roles in both health and disease.
• Mitochondrial dysfunction is linked to disorders like propionic acidemia and autism spectrum disorders (ASDs).

Purpose of the Study:

• To investigate the dual health and disease effects of PPA on mitochondrial function.
• To examine PPA's impact on mitochondrial function in ASD and control cell lines.
• To assess the influence of reactive oxygen species (ROS) on PPA's effects.

Main Methods:

• Incubation of lymphoblastoid cell lines (LCLs) from ASD patients and controls with PPA.
• Varying PPA concentrations and exposure durations.
• Assessing mitochondrial function with and without induced ROS.

Main Results:

• PPA optimally enhanced mitochondrial function in ASD LCLs at specific concentrations and durations.
• Increased ROS negated PPA's beneficial effects in ASD LCLs, causing greater detriment.
• Effects of PPA on mitochondrial function were amplified in ASD LCLs.

Conclusions:

• Gut microbiome metabolites like PPA can beneficially or detrimentally affect mitochondrial function.
• Concentration, duration, and redox state modulate PPA's impact on mitochondria.
• These findings have implications for understanding and potentially treating ASD and other diseases linked to PPA and the microbiome.