Impact of Kefir on the Gut-Brain Axis: Serotonin Metabolism and Signaling in Pediatric Rats

Abstract

Serotonin (5-hydroxytryptamine) is a key neurotransmitter involved in gastrointestinal and central nervous system functions. Given that approximately 90% of serotonin is synthesized in the gut, dietary interventions targeting the gut microbiota have emerged as promising strategies to modulate serotonin homeostasis. Kefir, a fermented milk beverage rich in probiotics and bioactive compounds, has been suggested to influence gut-brain axis signaling, yet its effects in the pediatric period remain insufficiently characterized. This study aimed to investigate the impact of kefir supplementation on serotonin biosynthesis, receptor expression, and metabolic pathways in a pediatric rat model, focusing on molecular markers across brain, jejunum, and serum tissues. Sixteen male Wistar rats (four weeks old) were divided into kefir and control groups. The kefir group received daily oral gavage of kefir (1 mL/100 g) for eight weeks, while controls received saline. Gene and protein expression levels of serotonergic markers (5-HT, TPH1, TPH2, SLC6A4, VMAT2, 5-HTR2B, 5-HTR3A, and 5-HTR4) were analyzed using quantitative PCR, ELISA, and Western blotting. Serotonin turnover was assessed via 5-HIAA levels. Kefir supplementation significantly increased 5-HT and TPH1 expression in both brain and jejunum tissues. In the brain, kefir elevated TPH2 and upregulated 5-HTR3A and 5-HTR2B, while reducing 5-HIAA levels, suggesting decreased serotonin degradation. In the jejunum, 5-HTR4 expression was markedly increased. Serum analyses revealed reduced TPH1/TPH2 expression but elevated 5-HTR4 levels, indicating systemic modulation of serotonergic signaling. Kefir exerts multifaceted effects on the serotonergic system in pediatric rats by enhancing serotonin biosynthesis, modulating receptor expression, and reducing serotonin turnover. These findings highlight kefir as a potential psychobiotic capable of influencing the gut-brain axis during early life, with implications for pediatric neurodevelopment and mental health. Further research, including clinical trials, is warranted to confirm its translational potential.