Probiotics and undernourishment impact on brain 5-Hydroxytryptamine system and neurotrophin BDNF in rats: Risk of depression and anxiety?

Undernourishment can significantly affect the serotonergic system, potentially increasing the risk of neuropsychiatric disorders such as depression and anxiety. Probiotic therapy has emerged as a potential modulator of the serotonergic system and brain-derived neurotrophic factor (BDNF). Our hypothesis posits that probiotic treatment positively influences the serotonergic system and BDNF levels in the prefrontal cortex (PFC) and hippocampus (HIP), mitigating the effects of malnutrition.

We conducted an experiment using 38 adult isogenic rats, divided into four groups: nourished control (n = 9), undernourished control (n = 9), nourished probiotic (n = 10), and undernourished probiotic (n = 10). The animals experienced undernourishment for 10 days, followed by probiotic supplementation while continuing food restriction for an additional 15 days. On the 25th day of the experiment, we euthanized the animals, microdissected their brains, and extracted samples from the HIP and PFC. We performed immunoblotting analysis to assess the expression levels of the following proteins: BDNF, tryptophan hydroxylase 2 enzyme, and 5-HT1A and 5-HT2C serotonergic receptors.

Our findings revealed the following effects of probiotic administration: tryptophan hydroxylase 2 expression increased in the PFC of nourished rats (P = 0.033) and in the HIP of undernourished rats (P = 0.013); improved 5-HT2C expression was observed in the PFC under both nutritional conditions (P < 0.01). The proBDNF levels were elevated in the HIP of undernourished rats (P = 0.001).

Probiotic administration effectively modulated the gut-microbiota-brain axis by enhancing serotonergic system proteins in the prefrontal cortex and hippocampus of both nourished and undernourished rats.