The antidepressant effect of Komagataella pastoris KM 71 H in maternal separation mice model mediated by the microbiota-gut-brain axis

• Published in: Behavioural brain research 2025-01, Vol.476, p.115287, Article 115287
• Main Authors: Birmann, Paloma T., Sinott, Airton, Zugno, Giuliana P., Rodrigues, Rafael R., Conceição, Fabricio R., Sousa, Fernanda S.S., Collares, Tiago, Seixas, Fabiana K., Savegnago, Lucielli
• Format: Article
• Language: English
• Subjects: Depression; Microbiota-gut-brain axis; Probiotic; Stress; Yeast
• ISSN: 0166-4328; 1872-7549; 1872-7549
• DOI: 10.1016/j.bbr.2024.115287

The intestinal microbiota plays a fundamental role in maintaining host health, especially during childhood, a critical period for its establishment. Early life stress can lead to shifts in gut microbiota composition, thus increasing the risk of major depressive disorder (MDD) in adulthood. The supplementation with probiotics restores intestinal permeability and the health of gut microbial communities, therefore being potential study targets for the treatment of MDD. In this sense, the yeast Komagataella pastoris was reported as a promising probiotic with antidepressant effect. Hence, the present study aims to investigate this effect in mice submitted to maternal separation (MS) 3 h per day from PND2 to PND14. Adult mice and mothers were treated with K. pastoris KM71H (8 log UFC.g−1/per animal, i.g.) or PBS (500 µl, i.g.) for 14 days. After behavioral tests, the animals were euthanized, followed by hippocampi and intestines removal for biochemical analysis. On behavioral tests, K. pastoris KM71H treatment reduced the immobility time in TST of adult mice and increased the grooming activity in splash test of adult mice and mothers induced by MS. The probiotic treatment restored plasma corticosterone levels and glucocorticoid receptor expression in hippocampi, alongside nitrate/nitrite levels and superoxide dismutase activity in intestine, in addition to reducing reactive species levels in both structures. Moreover, it also normalized the fecal pH and water content of feces. Thus, we conclude that K. pastoris KM71H is a promising therapeutic strategy for the treatment of MDD. •Probiotic supplementation shows promise in restoring gut health and potentially mitigating MDD symptoms.•K. pastoris KM71H treatment reduced depressive-like behaviors and increased grooming activity in mice.•K. pastoris KM71H treatment restored plasma corticosterone levels.•K. pastoris KM71H treatment restored glucocorticoid receptor expression in the hippocampus of mice•K. pastoris KM71H treatment improved antioxidant activity and reduced reactive species levels in the intestine of mice•K. pastoris KM71H treatment normalized fecal pH and water content, suggesting comprehensive therapeutic potential for MDD.