Fructose malabsorption induces dysbiosis and increases anxiety in male human and animal models.
Level 4 - case-series / case-control
Cross-sectional human observational study combined with an animal model
PubMed 41418890 · doi:10.1016/j.bbi.2025.106221
What was done
Researchers investigated the relationship between fructose malabsorption, gut microbiota, systemic inflammation, and anxiety in both humans and mice. In a cohort of healthy male human volunteers, fructose malabsorption was determined using a breath hydrogen test, daily fructose intake was recorded, gut microbiota was assessed by 16S rRNA sequencing, plasma inflammatory markers (LPS, IL-8, TNF-α) were quantified, and anxiety was measured via the State-Trait Anxiety Inventory (STAI). In a preclinical model, male GLUT5 knockout mice (lacking the intestinal fructose transporter) received a 5% fructose diet for four weeks, followed by behavioral testing for anxiety- and depressive-like behaviors, gut microbiota profiling, and analysis of microglia-associated gene expression.
What was found
In the human cohort, 60% of participants exhibited fructose malabsorption; these individuals displayed elevated plasma LPS, IL-8, and TNF-α levels, higher STAI anxiety scores, and distinct gut microbiota shifts. Average daily fructose intake was 30 g. The abstract reported no exact numerical values, standard deviations, or p-values for these comparisons. In the mouse model, GLUT5 knockout mice on a 5% fructose diet displayed increased anxiety- and depressive-like behaviors, substantial gut microbiota shifts, and altered expression of microglia-associated genes.
Why it matters
This work links intestinal fructose malabsorption to gut dysbiosis, low-grade peripheral inflammation, and neuroinflammation, suggesting a potential microbiome-mediated mechanism connecting diet and mood disorders.
Limits
The human component was cross-sectional and observational, preventing causal inferences. Sample sizes for both humans and mice were not reported in the abstract. Both human and animal experiments were restricted to males, limiting generalizability. No dietary intervention or treatment was tested in humans to determine if reducing fructose relieves anxiety.
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