Metabolic Alterations of Short-Chain Organic Acids in the Elderly Link Antibiotic Exposure with the Risk for Depression.

Background: Our previous study showed that antibiotic exposure was linked to depressive symptomatology in community-dwelling older adults in China. Our current study aims to explore the underlying mechanisms by assessing the intermediated effects of circulating short-chain organic acids (SCOAs) on this association.

Methods: Depressive symptoms were screened by the 30-item Geriatric Depression Scale (GDS-30). Urinary concentrations of antibiotics and serum SCOAs were measured using a liquid chromatography-mass spectrometry method.

Results: Increased exposure to sulfadiazine, azithromycin, tetracyclines, or veterinary antibiotics (VAs) was positively associated with GDS-30 scores. Tetracycline reduced levels of caproic acid, iso-butyric acid, and iso-caproic acid (iso-CA), with iso-CA concentration inversely correlating with GDS-30 scores, while β-hydroxybutyric acids showed a positive correlation. The mediating effect of serum iso-CA on the association between depression and ofloxacin, with a mediating effect of 25.3%, and the association between depression and tetracycline, with a mediating effect of 46.3%, were both statistically significant, indicating partial mediation.

Conclusions: Antibiotics may affect the levels of SCOAs in older adults and could potentially contribute to depressive symptoms by influencing alterations in serum iso-CA levels.