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Microbial liberation of N-methylserotonin from orange fiber in gnotobiotic mice and humans
Cell ( IF 64.5 ) Pub Date : 2022-06-27 , DOI: 10.1016/j.cell.2022.06.004
Nathan D Han 1 , Jiye Cheng 1 , Omar Delannoy-Bruno 1 , Daniel Webber 2 , Nicolas Terrapon 3 , Bernard Henrissat 4 , Dmitry A Rodionov 5 , Aleksandr A Arzamasov 5 , Andrei L Osterman 5 , David K Hayashi 6 , Alexandra Meynier 6 , Sophie Vinoy 6 , Chandani Desai 1 , Stacey Marion 7 , Michael J Barratt 2 , Andrew C Heath 7 , Jeffrey I Gordon 1
Affiliation  

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.



中文翻译:

限生小鼠和人类从橙色纤维中微生物释放 N-甲基血清素

非苛刻食品加工方法产生的副产品流中的植物纤维代表了多种、天然存在的、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,对限生小鼠肠道内容物进行质谱分析,加上体外研究,揭示了包括卵形拟杆菌在内的人类肠道微生物群成员从橙色纤维中释放 N-甲基血清。对在允许和非允许的N-甲基血清素“挖掘”条件下生长的卵形芽胞杆菌菌株的功能基因组分析揭示了靶向果胶的多糖利用位点,其表达与该化合物的菌株特异性释放相关。给无菌小鼠口服 N-甲基血清素,可以减少肥胖,改变肝糖生成,缩短肠道转运时间,并改变调节肝脏和结肠昼夜节律的基因表达在人类研究中,剂量依赖性、橙色纤维特异性的N-甲基血清素粪便积累与编码消化果胶聚糖的酶的微生物组基因的水平呈正相关。识别这种类型的微生物采矿活动具有潜在的治疗意义。

更新日期:2022-06-27
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