High-fat diet causes psychiatric disorders in mice by increasing Proteobacteria population

Area of Science:

• Neuroscience
• Microbiology
• Dietary Science

Background:

• High-fat diet (HFD) intake is linked to obesity, metabolic disorders, gut dysbiosis, and increased lipopolysaccharide (LPS).
• The connection between HFD-induced gut microbiota changes and psychiatric disorders remains under investigation.

Purpose of the Study:

• To investigate the role of gut microbiota in high-fat diet-induced psychiatric disorders in mice.
• To explore the mechanisms linking HFD, gut dysbiosis, and neurological effects.

Main Methods:

• Mice were fed a HFD for 9 weeks to induce obesity.
• Behavioral tests (Y-maze, novel object recognition, elevated plus maze) assessed memory and anxiety.
• Hippocampal and colonic tissues, blood, and fecal samples were analyzed for molecular and microbial changes.
• In vitro assays used cell lines (SH-SY5Y, BV-2) to test the effects of HFD-induced gut microbiota components.

Main Results:

• HFD induced obesity, memory impairment, and anxiety-like behaviors in mice.
• HFD suppressed hippocampal brain-derived neurotrophic factor (BDNF) expression and increased blood LPS and TNF-α.
• Gut microbiota alterations included an increased Proteobacteria population and elevated fecal LPS levels.
• HFD-induced gut microbiota components reduced BDNF and CREB phosphorylation in neuronal cells and activated microglia, effects mitigated by anti-LPS antibody.

Conclusions:

• Excessive HFD intake contributes to obesity and psychiatric disorders.
• Gut microbiota dysbiosis, characterized by increased Proteobacteria and LPS, plays a key role in HFD-induced psychiatric issues.
• Reduced hippocampal BDNF expression, driven by gut microbiota alterations, is a potential mechanism underlying these disorders.