美国爱迪生家族基因组科学和系统生物学中心Jeffrey I. Gordon团队近期取得重要工作进展,他们研究发现了橘子纤维中的N-甲基羟色胺在无菌小鼠和人类中的微生物释放。该项研究成果2022年6月27日在线出版于《细胞》杂志上。
由非苛刻的食品加工方法产生的副产品流中的植物纤维代表了不同的、自然发生的和具有生理活性的生物分子的生物库。为了证明其表征的一种方法,对来自无菌小鼠的肠道内容物的质谱分析以及体外研究揭示了人类肠道微生物群成员(包括卵形细菌)从橘子纤维中释放出N-甲基羟色胺。在许可和非许可N-甲基羟色胺“采矿”条件下生长的卵形细菌(B. ovatus)菌株的功能基因组分析,发现了以果胶为靶标的多糖利用位点,其表达与该化合物的菌株特异性释放相关。
对无菌小鼠口服N-甲基羟色胺,减少了脂肪,改变了肝脏糖化作用,缩短了肠道转运时间,并改变了肝脏和结肠中调节昼夜节律的基因表达。在人类研究中,N-甲基羟色胺的剂量依赖性、橘子纤维特异性粪便积累与编码消化果胶聚糖的酶的微生物组基因水平呈正相关。识别这种类型的微生物“采矿”活动具有潜在的治疗意义。
附:英文原文
Title: Microbial liberation of N-methylserotonin from orange fiber in gnotobiotic mice and humans
Author: Nathan D. Han, Jiye Cheng, Omar Delannoy-Bruno, Daniel Webber, Nicolas Terrapon, Bernard Henrissat, Dmitry A. Rodionov, Aleksandr A. Arzamasov, Andrei L. Osterman, David K. Hayashi, Alexandra Meynier, Sophie Vinoy, Chandani Desai, Stacey Marion, Michael J. Barratt, Andrew C. Heath, Jeffrey I. Gordon
Issue&Volume: 2022-06-27
Abstract: Plant fibers in byproduct streams produced by non-harsh food processing methods represent biorepositories of diverse, naturally occurring, and physiologically active biomolecules. To demonstrate one approach for their characterization, mass spectrometry of intestinal contents from gnotobiotic mice, plus in vitro studies, revealed liberation of N-methylserotonin from orange fibers by human gut microbiota members including Bacteroides ovatus. Functional genomic analyses of B. ovatus strains grown under permissive and non-permissive N-methylserotonin “mining” conditions revealed polysaccharide utilization loci that target pectins whose expression correlate with strain-specific liberation of this compound. N-methylserotonin, orally administered to germ-free mice, reduced adiposity, altered liver glycogenesis, shortened gut transit time, and changed expression of genes that regulate circadian rhythm in the liver and colon. In human studies, dose-dependent, orange-fiber-specific fecal accumulation of N-methylserotonin positively correlated with levels of microbiome genes encoding enzymes that digest pectic glycans. Identifying this type of microbial mining activity has potential therapeutic implications.
DOI: 10.1016/j.cell.2022.06.004
Source: https://www.cell.com/cell/fulltext/S0092-8674(22)00709-7