Proof-of-principle demonstration of endogenous circadian system and circadian misalignment effects on human oral microbiota.
Proof-of-principle demonstration of endogenous circadian system and circadian misalignment effects on human oral microbiota.
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DOI：
10.1096/fj.202101153r
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发表时间：
2022-01
期刊：
影响因子：
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通讯作者：
Scheer FAJL
中科院分区：
文献类型：
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作者：
Chellappa SL;Engen PA;Naqib A;Qian J;Vujovic N;Rahman N;Green SJ;Garaulet M;Keshavarzian A;Scheer FAJL
昼夜节律失调-中枢生物钟与行为和环境周期（包括睡眠/清醒，禁食/进食，黑暗/光明）之间的失调-会导致不良的代谢影响。这些不良反应的潜在潜在机制包括口胃肠道微生物群的改变。然而，人类口腔微生物群是否具有内源性昼夜节律以及昼夜失调是否影响口腔微生物群群落组成仍然未知。健康年轻个体[27.3 ± 2.3岁（18-35岁），2名女性，体重指数范围：18-28 kg/m2]入选严格控制的14天实验室昼夜节律方案。这包括32小时恒定常规（CR）方案（昼夜节律基线评估）、在约3勒克斯下4个28小时“天”的强制性Despermancy（FD）方案以诱导昼夜节律失调，以及失调后40小时CR方案。在两种CR方案中，对每4小时收集的唾液样品进行微生物群评估。提取总DNA并使用高通量16 S核糖体RNA基因扩增子测序进行处理。特定口腔微生物群群体的相对丰度，即，5个优势门中的1个门和14个优势属中的3个属表现出明显的内源性昼夜节律性。重要的是，昼夜失调极大地改变了口腔微生物群景观，使得五个优势门中的四个和十四个优势属中的八个表现出显著的昼夜失调效应。此外，昼夜节律失调显著影响口腔微生物群的宏基因组功能含量（推断的基因含量分析），如与代谢控制和免疫相关的特定功能途径的变化所揭示的。总的来说，我们的概念验证研究为人类口腔微生物群昼夜节律提供了证据，并表明即使是相对短期的实验失调也可以显著改变微生物群结构和参与代谢和免疫的功能途径。这些发现与通常暴露于昼夜节律失调的个体（如夜班工人和频繁飞行者）具有翻译相关性。
Circadian misalignment—the misalignment between the central circadian clock and behavioral and environmental cycles (including sleep/wake, fasting/eating, dark/light)—results in adverse metabolic effects. Potential underlying mechanisms for these adverse effects include alterations in orogastrointestinal microbiota. However, it remains unknown whether human oral microbiota has endogenous circadian rhythmicity and whether circadian misalignment influences oral microbiota community composition. Healthy young individuals [27.3 ± 2.3 years (18–35 years), 2 women, body-mass index range: 18–28 kg/m2] were enrolled in a stringently controlled 14-day laboratory circadian protocol. This included a 32h constant routine (CR) protocol (circadian baseline assessment), a Forced Desynchrony (FD) protocol with four 28-h “days” under ~3 lux to induce circadian misalignment, and a post-misalignment 40h CR protocol. Microbiota assessments were performed on saliva samples collected every 4h throughout both CR protocols. Total DNA was extracted and processed using high-throughput 16S ribosomal RNA gene amplicon sequencing. The relative abundance of specific oral microbiota populations, i.e., one of the five dominant phyla, and three of the fourteen dominant genera, exhibited significant endogenous circadian rhythmicity. Importantly, circadian misalignment dramatically altered the oral microbiota landscape, such that four of five dominant phyla and eight of fourteen dominant genera exhibited significant circadian misalignment effects. Moreover, circadian misalignment significantly affected metagenome functional content of the oral microbiota (inferred gene content analysis), as revealed by changes in specific functional pathways associated with metabolic control and immunity. Collectively, our proof-of-concept study provides evidence for human oral microbiota circadian rhythmicity and show that even relatively short-term experimental misalignment can dramatically modify microbial population structure and functional pathways involved in metabolism and immunity. These findings have translational relevance to individuals typically exposed to circadian misalignment, as night shift workers and frequent flyers.