Neurobiotechnology Research Group, Postgraduate Program in Biotechnology, Technologic Development Center, Federal University of Pelotas, Pelotas, RS, Brazil.
Applied Immunology Laboratory, Postgraduate Program in Biotechnology, Technological Development Center, Federal University of Pelotas, Pelotas, RS, Brazil.
Behav Brain Res. 2025 Jan 5;476:115287. doi: 10.1016/j.bbr.2024.115287. Epub 2024 Oct 10.
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/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.
肠道微生物群在维持宿主健康方面起着至关重要的作用，尤其是在儿童时期，这是其建立的关键时期。早期生活压力会导致肠道微生物群落组成的变化，从而增加成年后患重度抑郁症（MDD）的风险。益生菌的补充可以恢复肠道通透性和肠道微生物群落的健康，因此是治疗 MDD 的潜在研究目标。在这方面，酵母 Komagataella pastoris 被报道为一种具有抗抑郁作用的有前途的益生菌。
因此，本研究旨在调查在 PND2 至 PND14 期间每天接受 3 小时母婴分离（MS）的小鼠中这种效应。成年小鼠和母亲用 K. pastoris KM71H（8log UFC.g/动物，ig）或 PBS（500µl，ig）治疗 14 天。行为测试后，处死动物，然后取出海马体和肠道进行生化分析。
在行为测试中，K. pastoris KM71H 治疗减少了 MS 诱导的成年小鼠 TST 中的不动时间，并增加了成年小鼠和母亲在飞溅测试中的修饰活动。益生菌治疗恢复了海马体中的血浆皮质酮水平和糖皮质激素受体表达，以及肠道中的硝酸盐/亚硝酸盐水平和超氧化物歧化酶活性，同时降低了这两种结构中的活性氧水平。此外，它还使粪便的 pH 值和含水量正常化。
因此，我们得出结论，K. pastoris KM71H 是治疗 MDD 的一种有前途的治疗策略。
