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Cited by 317Gut microbiota and healthCircadian rhythm and melatoninDietary Effects on Health

Gut Microbiota-Derived Short Chain Fatty Acids Induce Circadian Clock Entrainment in Mouse Peripheral Tissue

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Tahara, Yu, Yamazaki, Mayu, Sukigara, Haruna, Motohashi, Hiroaki, Sasaki, Hiroyuki, Miyakawa, Hiroki, Haraguchi, Atsushi, Ikeda, Yuko +2 more·2018·Scientific Reports
DOI 10.1038/s41598-018-19836-7PMC PMC5780501
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Abstract

Microbiota-derived short-chain fatty acids (SCFAs) and organic acids produced by the fermentation of non-digestible fibre can communicate from the microbiome to host tissues and modulate homeostasis in mammals. The microbiome has circadian rhythmicity and helps the host circadian clock function. We investigated the effect of SCFA or fibre-containing diets on circadian clock phase adjustment in mouse peripheral tissues (liver, kidney, and submandibular gland). Initially, caecal SCFA concentrations, particularly acetate and butyrate, induced significant day-night differences at high concentrations during the active period, which were correlated with lower caecal pH. By monitoring luciferase activity correlated with the clock gene Period2 in vivo, we found that oral administration of mixed SCFA (acetate, butyrate, and propionate) and an organic acid (lactate), or single administration of each SCFA or lactate for three days, caused phase changes in the peripheral clocks with stimulation timing dependency. However, this effect was not detected in cultured fibroblasts or cultured liver slices with SCFA applied to the culture medium, suggesting SCFA-induced indirect modulation of circadian clocks in vivo. Finally, cellobiose-containing diets facilitated SCFA production and refeeding-induced peripheral clock entrainment. SCFA oral gavage and prebiotic supplementation can facilitate peripheral clock adjustment, suggesting prebiotics as novel therapeutic candidates for misalignment.

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  • SCFAs have been implicated in GI function, blood-pressure regulation, circadian rhythm, and (neuro)immune function.

    “SCFAs have been implicated in a variety of host processes including GI function (Gill et al., 2018), blood-pressure regulation (Pluznick, 2017), circadian rhythm (Tahara et al., 2018), and (neuro)immune function (Erny et al., 2017)”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Tahara et al., 2018

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  1. [1]Bass J Takahashi JS Circadian integration of metabolism and energetics Science (New York, N.Y.) 2010 330 1349 1354 10.1126/science.1195027 PMC3756146 21127246 · DOI · Paper page
  2. [2]Tahara Y Shibata S Circadian rhythms of liver physiology and disease: experimental and clinical evidence. Nature reviews Gastroenterology & hepatology 2016 13 217 226 26907879
  3. [3]Albrecht U Timing to perfection: the biology of central and peripheral circadian clocks Neuron 2012 74 246 260 10.1016/j.neuron.2012.04.006 22542179 · DOI · Paper page
  4. [4]Albrecht U Molecular Mechanisms in Mood Regulation Involving the Circadian Clock Frontiers in neurology 2017 8 30 10.3389/fneur.2017.00030 28223962 PMC5293817 · DOI
  5. [5]McGinnis GR Young ME Circadian regulation of metabolic homeostasis: causes and consequences Nature and science of sleep 2016 8 163 180 27313482 PMC4890688
  6. [6]Kohsaka A High-fat diet disrupts behavioral and molecular circadian rhythms in mice Cell metabolism 2007 6 414 421 10.1016/j.cmet.2007.09.006 17983587 · DOI · Paper page
  7. [7]Tahara Y Shibata S Chronobiology and nutrition Neuroscience 2013 253 78 88 10.1016/j.neuroscience.2013.08.049 24007937 · DOI · Paper page
  8. [9]Li XM Cancer inhibition through circadian reprogramming of tumor transcriptome with meal timing Cancer research 2010 70 3351 3360 10.1158/0008-5472.CAN-09-4235 20395208 · DOI
  9. [10]Vuong HE Yano JM Fung TC Hsiao EY The Microbiome and Host Behavior Annual review of neuroscience 2017 28301775 PMC6661159
  10. [11]Fukuda S Ohno H Gut microbiome and metabolic diseases Seminars in immunopathology 2014 36 103 114 10.1007/s00281-013-0399-z 24196453 · DOI
  11. [14]Liang X Bushman FD FitzGerald GA Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clock Proceedings of the National Academy of Sciences of the United States of America 2015 112 10479 10484 10.1073/pnas.1501305112 26240359 PMC4547234 · DOI · Paper page
  12. [15]Murakami M Gut microbiota directs PPARgamma-driven reprogramming of the liver circadian clock by nutritional challenge EMBO reports 2016 17 1292 1303 10.15252/embr.201642463 27418314 PMC5007574 · DOI
  13. [16]Leone V Effects of diurnal variation of gut microbes and high-fat feeding on host circadian clock function and metabolism Cell host & microbe 2015 17 681 689 10.1016/j.chom.2015.03.006 25891358 PMC4433408 · DOI
  14. [17]Thaiss CA Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis Cell 2014 159 514 529 10.1016/j.cell.2014.09.048 25417104 · DOI · Paper page
  15. [18]Pluznick JL Gut microbiota in renal physiology: focus on short-chain fatty acids and their receptors Kidney Int 2016 90 1191 1198 10.1016/j.kint.2016.06.033 27575555 PMC5123942 · DOI
  16. [19]Kasubuchi M Hasegawa S Hiramatsu T Ichimura A Kimura I Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation Nutrients 2015 7 2839 2849 10.3390/nu7042839 25875123 PMC4425176 · DOI · Paper page
  17. [20]Canfora EE Jocken JW Blaak EE Short-chain fatty acids in control of body weight and insulin sensitivity Nat Rev Endocrinol 2015 11 577 591 10.1038/nrendo.2015.128 26260141 · DOI · Paper page
  18. [21]Tahara Y In vivo monitoring of peripheral circadian clocks in the mouse Current biology: CB 2012 22 1029 1034 10.1016/j.cub.2012.04.009 22578421 · DOI
  19. [22]Tahara Y Entrainment of the mouse circadian clock by sub-acute physical and psychological stress Scientific reports 2015 5 11417 10.1038/srep11417 26073568 PMC4466793 · DOI
  20. [23]Tahara Y Age-related circadian disorganization caused by sympathetic dysfunction in peripheral clock regulation Npj Aging And Mechanisms Of Disease 2017 3 16030 10.1038/npjamd.2016.30 28721279 PMC5515066 · DOI
  21. [24]Narishige S Effects of caffeine on circadian phase, amplitude and period evaluated in cells in vitro and peripheral organs in vivo in PER2::LUCIFERASE mice British journal of pharmacology 2014 171 5858 5869 10.1111/bph.12890 25160990 PMC4290722 · DOI
  22. [25]Okada T Microbiota-derived lactate accelerates colon epithelial cell turnover in starvation-refed mice Nature communications 2013 4 1654 10.1038/ncomms2668 23552069 · DOI
  23. [27]Thorburn AN Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites Nature communications 2015 6 7320 10.1038/ncomms8320 26102221 · DOI
  24. [28]Tahara Y Otsuka M Fuse Y Hirao A Shibata S Refeeding after fasting elicits insulin-dependent regulation of Per2 and Rev-erbalpha with shifts in the liver clock Journal of biological rhythms 2011 26 230 240 10.1177/0748730411405958 21628550 · DOI
  25. [29]Umeki M Oue K Mochizuki S Shirai Y Sakai K Effect of Lactobacillus rhamnosus KY-3 and cellobiose as synbiotics on lipid metabolism in rats Journal of nutritional science and vitaminology 2004 50 330 334 10.3177/jnsv.50.330 15754493 · DOI
  26. [30]Sanz ML Gibson GR Rastall RA Influence of disaccharide structure on prebiotic selectivity in vitro Journal of agricultural and food chemistry 2005 53 5192 5199 10.1021/jf050276w 15969496 · DOI
  27. [31]Sato M Murakami M Node K Matsumura R Akashi M The role of the endocrine system in feeding-induced tissue-specific circadian entrainment Cell reports 2014 8 393 401 10.1016/j.celrep.2014.06.015 25017062 · DOI
  28. [32]Furutani A Fish Oil Accelerates Diet-Induced Entrainment of the Mouse Peripheral Clock via GPR120 PloS one 2015 10 e0132472 10.1371/journal.pone.0132472 26161796 PMC4498928 · DOI
  29. [33]Tolhurst G Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2 Diabetes 2012 61 364 371 10.2337/db11-1019 22190648 PMC3266401 · DOI · Paper page
  30. [34]Psichas A The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents International journal of obesity (2005) 2015 39 424 429 10.1038/ijo.2014.153 25109781 PMC4356745 · DOI · Paper page
  31. [35]Kimura I Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41) Proceedings of the National Academy of Sciences of the United States of America 2011 108 8030 8035 10.1073/pnas.1016088108 21518883 PMC3093469 · DOI · Paper page
  32. [36]Terazono H Adrenergic regulation of clock gene expression in mouse liver Proceedings of the National Academy of Sciences of the United States of America 2003 100 6795 6800 10.1073/pnas.0936797100 12754374 PMC164526 · DOI
  33. [37]Kon N Activation of TGF-beta/activin signalling resets the circadian clock through rapid induction of Dec1 transcripts Nature cell biology 2008 10 1463 1469 10.1038/ncb1806 19029909 · DOI
  34. [40]Johansson AS Brask J Owe-Larsson B Hetta J Lundkvist GB Valproic acid phase shifts the rhythmic expression of Period2::Luciferase Journal of biological rhythms 2011 26 541 551 10.1177/0748730411419775 22215612 · DOI · Paper page
  35. [42]Miyazaki K Dietary heat-killed Lactobacillus brevis SBC8803 promotes voluntary wheel-running and affects sleep rhythms in mice Life sciences 2014 111 47 52 10.1016/j.lfs.2014.07.009 25058921 · DOI
  36. [43]Yoo SH PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues Proceedings of the National Academy of Sciences of the United States of America 2004 101 5339 5346 10.1073/pnas.0308709101 14963227 PMC397382 · DOI · Paper page
  37. [44]Refinetti R Lissen GC Halberg F Procedures for numerical analysis of circadian rhythms Biological rhythm research 2007 38 275 325 10.1080/09291010600903692 23710111 PMC3663600 · DOI
  38. [45]Tsukahara T Iwasaki Y Nakayama K Ushida K Stimulation of butyrate production in the large intestine of weaning piglets by dietary fructooligosaccharides and its influence on the histological variables of the large intestinal mucosa Journal of nutritional science and vitaminology 2003 49 414 421 10.3177/jnsv.49.414 14974732 · DOI

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Authors
Tahara, Y., Yamazaki, M., Sukigara, H., Motohashi, H., Sasaki, H., Miyakawa, H., Haraguchi, A., Ikeda, Y., Fukuda, S., & Shibata, S.
Affiliations
  • Waseda University (JP)
  • Keio University (JP)
Corresponding author
Shibata, Shigenobu
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2018-01-23
Volume
8
Issue
1
Pages
1395-1395
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-018-19836-7
PMC
PMC5780501
OpenAlex
W2801107067
Cited by
317
References
7
Citations by year
2026: 39 · 2025: 42 · 2024: 46 · 2023: 42 · 2022: 34 · 2021: 37 · 2020: 36 · 2019: 33 · 2018: 8
FWCI
10.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Japan Society for the Promotion of Science (15K18981, 17J10069, 26220201)
  • Japan Science and Technology Agency (JPMJPR1537)
  • Bio-oriented Technology Research Advancement Institution
  • Precursory Research for Embryonic Science and Technology (JPMJPR1537)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Health Sciences › Medicine › Physiology › Dietary Effects on Health
Keywords
gut microbiota, short-chain fatty acids, circadian entrainment, acetate, butyrate, propionate, lactate, caecal fermentation, prebiotics, cellobiose, Period2, peripheral clocks, refeeding, caecal pH, liver, kidney, submandibular gland, fibroblasts
MeSH terms
Gastrointestinal Microbiome, Animals, Bacteria, Fatty Acids, Volatile, Fermentation, Gene Expression Regulation, Kidney, Liver, Submandibular Gland, Mice, Circadian Rhythm Signaling Peptides and Proteins, Circadian Clocks

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