Fructose malabsorption induces dysbiosis and increases anxiety in male human and animal models.

Fiche publication

Date publication

décembre 2025

Journal

Brain, behavior, and immunity

Auteurs

Membres identifiés du Cancéropôle Est :
Dr PAIS DE BARROS Jean-Paul

Tous les auteurs :
Coursan A, Polve D, Leroi AM, Monnoye M, Roussin L, Benatar C, Tavolacci MP, Muraine MQ, Maccarone M, Guérin O, Houivet E, Guérin C, Brunel V, Bellenger J, de Barros JP, Gourcerol G, Naudon L, Layé S, Madore C, Fioramonti X, Melchior C, Douard V

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/41418890

Résumé

Excessive fructose intake is a growing public health concern, yet many individuals have a limited capacity to absorb typical dietary levels, leading to chronic fructose malabsorption and intestinal spillover. In animal models, this spillover disrupts the gut microbiota, but its impact in humans remains unexplored. We hypothesized that fructose malabsorption-induced dysbiosis contributes to peripheral inflammation, which, together with neuroinflammation, plays a role in mood disorders. This study investigates the link between fructose malabsorption, gut microbiota, and mood disorders in a human cohort, and explores their association with neuroinflammation in a GLUT5 knockout mouse model of fructose-malabsorption. In a human cohort of male healthy volunteers, fructose malabsorption was assessed using a breath hydrogen test, while plasma lipopolysaccharide (LPS), IL8 and TNFα levels and anxiety traits (measured using the State-Trait Anxiety Inventory, STAI) were analyzed. Gut microbiota composition was characterized through 16S rRNA sequencing, and dietary fructose intake was recorded. In the preclinical study, Glut5-KO male mice, which lack intestinal fructose transport, were fed a 5% fructose diet for four weeks. Behavioral assays assessed anxiety- and depressive-like behaviors, while gut microbiota composition and microglia-associated gene expression were analyzed. Sixty % of volunteers exhibited fructose malabsorption, along with elevated plasma LPS, IL8 and TNFα levels, increased anxiety traits on the STAI, and distinct gut microbiota alterations, partially linked to fructose intake patterns. The average daily fructose intake was 30 g per individual, with significant variability in dietary sources. In the preclinical model, Glut5-KO mice on a 5% fructose diet displayed increased anxiety- and depressive-like behaviors, pronounced gut microbiota shifts, and altered expression of microglia-associated genes. These findings highlight the complex interplay between dietary fructose, gut microbiota, low grade inflammation and neuroinflammation in shaping mental health. Chronic fructose malabsorption may contribute to mood disorders through gut dysbiosis and microglia-dependent neuroinflammation, warranting further investigation into dietary interventions.