Komagataella pastoris KM 71H 在母体分离小鼠模型中的抗抑郁作用由微生物群-肠-脑轴介导。

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research Pub Date : 2024-10-10 DOI:10.1016/j.bbr.2024.115287

Paloma T. Birmann , Airton Sinott , Giuliana P. Zugno , Rafael R. Rodrigues , Fabricio R. Conceição , Fernanda S.S. Sousa , Tiago Collares , Fabiana K. Seixas , Lucielli Savegnago

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引用次数: 0

摘要

背景：肠道微生物群在维持宿主健康方面发挥着重要作用，尤其是在童年时期，这是其建立的关键时期。早期的生活压力会导致肠道微生物群组成发生变化，从而增加成年后患重度抑郁症（MDD）的风险。补充益生菌可恢复肠道通透性和肠道微生物群落的健康，因此是治疗重度抑郁症的潜在研究目标。方法：因此，本研究旨在调查从 PND2 到 PND14 期间每天 3 小时母鼠分离（MS）对小鼠的影响。用 K. pastoris KM71H（8log UFC.g-1/每只动物，i.g.）或 PBS（500µl，i.g.）处理成年小鼠和母鼠 14 天。行为测试结束后，动物被安乐死，然后取出海马和肠子进行生化分析：结果：在行为测试中，K. pastoris KM71H 可减少成年小鼠在 TST 中的不动时间，并可增加 MS 诱导的成年小鼠和母亲在飞溅测试中的梳理活动。益生菌治疗恢复了海马血浆皮质酮水平和糖皮质激素受体的表达，以及肠道中硝酸盐/亚硝酸盐水平和超氧化物歧化酶活性，此外还降低了这两个结构中的活性物种水平。此外，它还使粪便 pH 值和粪便含水量正常化：因此，我们得出结论：K. pastoris KM71H 是一种治疗 MDD 的有前途的治疗策略。

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

Background

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.

Methods

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.

Results

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.

Conclusion

Thus, we conclude that K. pastoris KM71H is a promising therapeutic strategy for the treatment of MDD.

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来源期刊

Behavioural Brain Research 医学-行为科学

CiteScore

5.60

自引率

0.00%

发文量

383

审稿时长

61 days

期刊介绍： Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.