New Study Links Gut Receptor to Sugar Preferences - EMJ

New Study Links Gut Receptor to Sugar Preferences

NOVEL research has uncovered how a gut receptor, free fatty acid receptor 4 (Ffar4), influences sugar consumption preferences. The research, conducted in China, suggests that targeting gut microbiota and related metabolites could offer new strategies to manage excessive sugar intake and associated metabolic disorders, such as Type 2 diabetes.

Excessive sugar consumption is a major contributor to obesity and diabetes worldwide. Researchers investigated how Ffar4 expression in the intestine affects sugar preference, using both human and animal models. Diabetic patients and diabetic mouse models demonstrated reduced Ffar4 expression, correlating with heightened sugar cravings.

Through genetic and behavioural experiments, researchers confirmed that intestinal Ffar4 plays a crucial role in distinguishing between natural sugars and artificial sweeteners. Mice with Ffar4 deficiencies showed an increased preference for natural sugars like sucrose, while those with Ffar4 overexpression displayed reduced sugar cravings.

The study also highlighted the role of gut microbiota in sugar preference regulation. Reduced levels of Bacteroides vulgatus, a key gut bacterium, were linked to Ffar4 deficiency. Restoring B. vulgatus through microbiota transplantation reduced sugar consumption in knockout mice, underscoring the gut microbiota’s role in dietary behaviour.

Notably, the metabolite pantothenate, produced by B. vulgatus, emerged as a critical factor. Pantothenate not only decreased sugar preference but also lowered fasting blood glucose levels in diabetic mice. This dual benefit makes it a promising candidate for diabetes therapy.

Pantothenate’s effects are mediated through gut hormone glucagon-like peptide 1 (GLP-1), which stimulates the liver-derived hormone FGF21. Together, GLP-1 and FGF21 form a feedback loop that regulates sugar consumption and glucose metabolism.

The study’s findings have illuminated the intricate relationship between gut health and dietary behaviour, offering new avenues for treating metabolic disorders. By targeting intestinal Ffar4, gut microbiota, and associated metabolites, researchers hope to develop interventions to curb sugar overconsumption and improve diabetes management.

This research provides a vital step toward understanding and tackling the global challenge of sugar-related metabolic diseases.

Reference

Zhang T et al. Free fatty acid receptor 4 modulates dietary sugar preference via the gut microbiota. Nat Microbiol. 2025;DOI:10.1038/s41564-024-01902-8.

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