Table_1_A Probiotic Mixture Induces Anxiolytic- and Antidepressive-Like Effects in Fischer and Maternally Deprived Long Evans Rats.docx

A role of the gut microbiota in psychiatric disorders is supported by a growing body of literature. The effects of a probiotic mixture of four bacterial strains were studied in two models of anxiety and depression, naturally stress-sensitive Fischer rats and Long Evans rats subjected to maternal deprivation. Rats chronically received either the probiotic mixture (1.109 CFU/day) or the vehicle. Anxiety- and depressive-like behaviors were evaluated in several tests. Brain monoamine levels and gut RNA expression of tight junction proteins (Tjp) and inflammatory markers were quantified. The gut microbiota was analyzed in feces by 16S rRNA gene sequencing. Untargeted metabolite analysis reflecting primary metabolism was performed in the cecal content and in serum. Fischer rats treated with the probiotic mixture manifested a decrease in anxiety-like behaviors, in the immobility time in the forced swimming test, as well as in levels of dopamine and its major metabolites, and those of serotonin metabolites in the hippocampus and striatum. In maternally deprived Long Evans rats treated with the probiotic mixture, the number of entries into the central area in the open-field test was increased, reflecting an anxiolytic effect. The probiotic mixture increased Tjp1 and decreased Ifnγ mRNA levels in the ileum of maternally deprived rats. In both models, probiotic supplementation changed the proportions of several Operational Taxonomic Units (OTU) in the gut microbiota, and the levels of certain cecal and serum metabolites were correlated with behavioral changes. Chronic administration of the tested probiotic mixture can therefore beneficially affect anxiety- and depressive-like behaviors in rats, possibly owing to changes in the levels of certain metabolites, such as 21-deoxycortisol, and changes in brain monoamines.

众多文献资料支持了肠道菌群在精神疾病中的重要作用。本研究针对四种菌株组成的益生菌混合物在焦虑和抑郁两种模型中的影响进行了研究，包括对自然应激敏感的Fischer大鼠和经历母性剥夺的Long Evans大鼠。大鼠长期接受益生菌混合物（1.109 CFU/天）或溶剂。通过多项测试评估了焦虑和抑郁样行为。利用脑内单胺水平、肠道紧密连接蛋白（Tjp）和炎症标记物的RNA表达进行了量化分析。通过16S rRNA基因测序对粪便中的肠道菌群进行了分析。在盲肠内容物和血清中进行了非靶向代谢物分析，以反映初级代谢。接受益生菌混合物治疗的Fischer大鼠表现出焦虑样行为的减少，在强迫游泳测试中的不动时间缩短，以及多巴胺及其主要代谢物、海马体和纹状体中血清素代谢物的水平降低。在经历母性剥夺的Long Evans大鼠中，接受益生菌混合物治疗后，在旷场测试中进入中央区域的次数增加，这反映了抗焦虑效应。益生菌混合物在母性剥夺大鼠的回肠中增加了Tjp1的表达，并降低了Ifnγ mRNA水平。在两种模型中，益生菌补充剂改变了肠道菌群中几个操作分类单元（OTU）的比例，并且某些盲肠和血清代谢物的水平与行为改变相关。因此，长期给予测试的益生菌混合物可以有益地影响大鼠的焦虑和抑郁样行为，这可能是由于某些代谢物水平的变化，如21-脱氧皮质醇，以及脑内单胺的变化。