Disrupting the Gut-Brain Axis: How Artificial Sweeteners Rewire Microbiota and Reward Pathways

Area of Science:

• Microbiology
• Neuroscience
• Metabolic Health

Background:

• Artificial sweeteners (non-caloric sweeteners, NCSs) are common sugar substitutes for weight management.
• Emerging evidence indicates NCSs impact host physiology, including gut microbiota and feeding-related neural circuits.
• This review focuses on how NCSs disrupt the gut-brain axis (GBA), emphasizing microbial and neural reward mechanisms.

Purpose of the Study:

• To synthesize current knowledge on NCSs' disruption of the gut-brain axis.
• To highlight microbiota-mediated effects and alterations in neural reward processing.
• To identify research priorities for mitigating NCSs' health impacts.

Main Methods:

• Literature review synthesizing current scientific knowledge.
• Focus on microbiota-mediated effects on the gut-brain axis.
• Analysis of neural reward processing alterations due to NCS consumption.

Main Results:

• NCSs induce gut dysbiosis, reducing beneficial bacteria (e.g., Akkermansia muciniphila) and short-chain fatty acid production.
• Impaired gut barrier integrity and systemic inflammation result from NCS-induced dysbiosis.
• NCSs alter hedonic circuits by providing sweetness without calories, weakening reward signaling and impacting neuropeptides.
• Microbial disruption exacerbates neural reward instability, contributing to maladaptive eating behaviors.
• NCSs foster metabolic dysregulation and increase overeating vulnerability.

Conclusions:

• NCSs disrupt the gut-brain axis through both microbial and neural pathways.
• These disruptions can lead to maladaptive food seeking, metabolic issues, and increased overeating.
• Microbiome-targeted interventions are a key research priority to counteract NCS health effects.