Disrupted diurnal oscillation of gut-derived Short chain fatty acids in shift workers drinking alcohol: Possible mechanism for loss of resiliency of intestinal barrier in disrupted circadian host.
Disrupted diurnal oscillation of gut-derived Short chain fatty acids in shift workers drinking alcohol: Possible mechanism for loss of resiliency of intestinal barrier in disrupted circadian host.
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DOI：
10.1016/j.trsl.2020.04.004
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发表时间：
2020-07
期刊：
影响因子：
--
通讯作者：
Keshavarzian A
中科院分区：
文献类型：
--
作者：
Swanson GR;Siskin J;Gorenz A;Shaikh M;Raeisi S;Fogg L;Forsyth C;Keshavarzian A
微生物衍生的短链脂肪酸（SCFAs）是由不可消化纤维发酵产生的，是肠道屏障稳态的关键组成部分。由于微生物组具有昼夜波动，我们假设人类体内的scfa具有昼夜节律，其节律性将受到宿主中心昼夜节律失调（夜班工作）的影响，这将使肠道屏障更容易受到酒精的破坏。为了验证这一假设，我们研究了三组受试者：有酒精使用障碍但没有肝脏疾病（AD）的患者、健康的白班工人（DW）和夜班工人（NW）。所有受试者在基线时进行研究，然后在每天适量饮酒（0.5 g/kg） 7天后对DW和NW受试者进行研究。余弦分析显示，DW患者肠道源性血浆SCFAs表现出明显的昼夜振荡；然而，AD和NW受试者的SCFA丧失了24小时节律性。SCFA降低与结肠通透性增加相关。根据手腕活动记录和尿液褪黑素，慢性和中度饮酒一周都会导致昼夜节律紊乱。我们的研究表明：(1)肠道来源的血浆SCFAs在人体中具有受宿主中央时钟影响的昼夜节律；(2)适度酒精抑制与结肠通透性增加相关的scfa；(3)低创性尿6-SM与血浆褪黑素相关，静息活动活动图与血浆褪黑素相关。未来的研究需要检验昼夜节律失调在肠道来源的SCFAs中所起的作用，作为肠道屏障对酒精等有害物质丧失弹性的可能机制。
Microbiota derived short chain fatty acids (SCFAs) are produced by fermentation of non-digestible fiber, and are a key component in intestinal barrier homeostasis. Since the microbiome has diurnal fluctuations, we hypothesized that SCFAs in humans have a diurnal rhythm and their rhythmicity would be impacted by the host central circadian misalignment (night shift work) which would make intestinal barrier more susceptible to disruption by alcohol. To test this hypothesis, we studied three groups of subjects: patients with alcohol use disorder, but no liver disease (AD), healthy day workers (DW), and night workers (NW). All subjects were studied at baseline and then in DW and NW subjects after moderate daily alcohol (0.5 g/kg) for seven days. Gut derived plasma SCFAs showed a significant circadian oscillation by cosinor analysis in DW; however, SCFA in the AD and NW subjects lost 24 hour rhythmicity. Decrease in SCFA correlated with increased colonic permeability. Both chronic and moderate alcohol consumption for one week caused circadian disruption based on wrist actigraphy and urinary melatonin. Our study shows that: (1) gut derived plasma SCFAs have a diurnal rhythm in humans that is impacted by the central clock of the host; (2) moderate alcohol suppresses SCFAs which was associated with increased colonic permeability; and (3) less invasive urinary 6-SM correlated and rest-activity actigraphy correlated with plasma melatonin. Future studies are needed to examine the role circadian misalignment on gut derived SCFAs as possible mechanism for loss of intestinal barrier resiliency to injurious agents like alcohol.
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DOI：
10.1098/rsif.2017.0885
发表时间：
2018-03
期刊：
Journal of the Royal Society, Interface
影响因子：
--
作者：
Huang Q;Cohen D;Komarzynski S;Li XM;Innominato P;Lévi F;Finkenstädt B
通讯作者：
Finkenstädt B
DOI：
10.1096/fj.201600353r
发表时间：
2016-11
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Hand LE;Hopwood TW;Dickson SH;Walker AL;Loudon AS;Ray DW;Bechtold DA;Gibbs JE
通讯作者：
Gibbs JE
影响因子：
3.5
作者：
Alterman, Toni;Luckhaupt, Sara E.;Calvert, Geoffrey M.
通讯作者：
Calvert, Geoffrey M.
影响因子：
4.8
作者：
Chakradeo, Prachi S.;Keshavarzian, Ali;Swanson, Garth R.
通讯作者：
Swanson, Garth R.
影响因子：
4.1
作者：
Cresci GA;Glueck B;McMullen MR;Xin W;Allende D;Nagy LE
通讯作者：
Nagy LE