Policosanol Alleviates Chronic Stress-Induced Growth Impairment via Gut Microbiota-Metabolite Interactions: Insights from 16S rRNA Sequencing and LC-MS Metabolomics

ABSTRACT:

Background/Objectives: Policosanol, a bioactive compound derived from rice bran wax, has demonstrated potential for alleviatingshown potential in combating stress, yet its underlying mechanisms remain elusive. This study aimed to elucidate its role in mitigating chronic stress-induced growth impairment and to explore its interactions with the gut microbiota and metabolomics.

Methods: Male rats were subjected to a 4-week chronic restraint stress protocol with or without policosanol supplementation (2 mg/kg/day). Systemic responses were evaluated through by measuring growth parameters (including weight gain, gain and muscle mass), serum biomarkers (cortisol, cortisol and catecholamines [CA]), 16S rRNA sequencing (for cecal microbiotamicrobiota analysis), and LC-MS metabolomics (for cecal metabolites). metabolite profiling).

Results: Stress led to induced a significant reduction in weight gain (−11.0%, 0.01<P < 0.05) and a marked elevation in of serum cortisol (+86.2%) and CAcatecholamines (+88.3%, 0.01<both P < 0.05). Policosanol treatment restored weight gain to 85.5% of the control level (P<levels (P < 0.05) and reduced cortisol and catecholamines catecholamine levels by 29.5% and 26.8%, respectively (P<both P < 0.05). Stress-induced alterations in gut microbiota included a 4.1-fold increase in p_Verrucomicrobiota and a 3.8-fold rise increase in g_Akkermansia, along with metabolite changes in metabolites such as a 4.2-fold upregulation of elevation in Proscillaridin and a 65% decrease in Phenylacetylglutamine (PAGln) (P<both P < 0.05). Policosanol supplementation normalized the gut microbiota (p_Verrucomicrobiota↓composition (p_Verrucomicrobiota decreased by 36%, P<P < 0.05) and restored metabolite levels (Phenylacetylglutamine↑PAGln increased by 80%, P<P < 0.01). Negative correlations were observed between g_Akkermansia abundance and weight gain (P < 0.01), while PAGlnPhenylacetylglutamine positively correlated with growth (P<P < 0.05) and negatively correlated with GSH-Px (P < 0.001), cortisol (P < 0.001), and catecholamine (P<CA (P < 0.001). The Moreover, the g_Bacteroides–PAGlnPhenylacetylglutamine axis exhibited a strong interaction (P < 0.001).

Conclusions: Policosanol mitigates stress-induced growth deficits impairment by modulating gut microbiota (e.g., suppressing reducing p_Verrucomicrobiota and g_AkkermansiaAkkermansia abundances) and restoring metabolites metabolite levels (e.g., enhancing increasing PAGlnPhenylacetylglutamine). Our multiThe coregulation of the gut microbiota and metabolome was highlighted by a strong correlation between g_Bacteroides and Phenylacetylglutamine (PAGln), suggesting a potential functional interaction that may contribute to the anti-stress effects of policosanol. These findings provide valuable insights for developing microbiota-targeted therapies in for stress-related disorders.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS13189 | MetaboLights | 2025-10-21

REPOSITORIES: MetaboLights