The Edison Family Center for Genome Sciences and Systems Biology, St. Louis, MO 63110, USA; Center for Gut Microbiome and Nutrition Research, St. Louis, MO 63110, USA.
The Edison Family Center for Genome Sciences and Systems Biology, St. Louis, MO 63110, USA; Center for Gut Microbiome and Nutrition Research, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cell. 2022 Jul 7;185(14):2495-2509.e11. doi: 10.1016/j.cell.2022.06.004. Epub 2022 Jun 27.
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.
非剧烈食品加工方法产生的副产物流中的植物纤维代表了各种天然存在的、具有生理活性的生物分子的生物库。为了展示一种对其进行表征的方法，对无菌小鼠肠道内容物的质谱分析以及体外研究表明，包括卵形拟杆菌在内的人类肠道微生物群成员可以从橙纤维中释放 N-甲基血清素。在允许和不允许 N-甲基血清素“开采”的条件下生长的卵形拟杆菌菌株的功能基因组分析显示，靶向果胶的多糖利用基因座，其表达与该化合物的菌株特异性释放相关。N-甲基血清素经口给予无菌小鼠，可降低肥胖，改变肝脏糖生成，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，与微生物组基因编码消化果胶聚糖的酶的水平呈正相关的、与橙纤维特异性相关的 N-甲基血清素粪便积累与剂量呈依赖性。鉴定这种类型的微生物矿化活性具有潜在的治疗意义。
