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.