多种奥米学揭示了与细菌体及其细胞外囊泡的炎症调节相关的菌株特异性神经活性代谢物生产
Basit Yousuf1, Walid Mottawea1,2, Galal Ali Esmail1
1NuGut Research Platform, School of Nutrition Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
Current research in microbial sciences
|March 3, 2025
概括
像Bacteroides这样的肠道细菌产生神经活性化合物,包括丰富的GABA. 虽然没有影响肠道屏障,但这种GABA显著影响免疫反应,突出其在宿主微生物相互作用中的作用.
科学领域:
- 微生物学和肠道微生物组研究
- 神经科学和新陈代谢学
- 宿主-微生物相互作用
背景情况:
- 细菌类物种是人类肠道微生物组的组成部分,影响宿主生理学.
- 这些细菌在肠道生态,新陈代谢和宿主微生物通信中发挥着重要作用.
- 了解它们产生的神经活性化合物对于肠道健康至关重要.
研究的目的:
- 为了研究细菌菌株特定的神经活性代谢物产生的细菌.
- 识别和量化关键的神经活性化合物及其前体.
- 阐明巴克泰罗伊德衍生GABA在调节肠道平衡和免疫反应中的作用.
主要方法:
- 多omics方法,包括基因组和非目标/目标代谢学.
- 基因编辑CRISPR/Cas12a,以创建一个Bacteroides finegoldii的淘汰突变 (ΔgadB).
- 在体外测定使用Caco-2/HT29-MTX共同培养和RAW264.7巨细胞.
主要成果:
- 基因组分析预测了产生GABA,酸,氨酸和氨酸代谢物的显著潜力.
- 代谢学研究发现了GABA,l-三,5-HTP,诺尔拉托尼,金酸,l-氨酸和北上腺素.
- GABA是最丰富的代谢物 (1-2 mM);细胞外囊泡 (EV) 也含有神经活性化合物.
- 一个B. B. B. B. 来自finegoldii的GABA对上皮质屏障完整性的影响有限,但显著调节了巨细胞的炎症反应.
结论:
- 细菌类物种以菌株和媒介特定的方式产生各种各样的神经活性代谢物.
- GABA是这些细菌产生的主要神经活性代谢物,在超级生物和EV中发现.
- 细菌体衍生GABA在调节宿主免疫反应,特别是炎症方面发挥着重要作用.
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