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

• Published in: Scientific reports Vol. 8; no. 1; pp. 1395 - 12
• Main Authors: Tahara, Yu, Yamazaki, Mayu, Sukigara, Haruna, Motohashi, Hiroaki, Sasaki, Hiroyuki, Miyakawa, Hiroki, Haraguchi, Atsushi, Ikeda, Yuko, Fukuda, Shinji, Shibata, Shigenobu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23-01-2018; Nature Publishing Group
• Subjects: 14/5; 38; 631/326/2565/2134; 631/443/319/1557; 631/80/105; 64; 64/60; 82; Acetic acid; Animals; Bacteria - metabolism; Biological clocks; Cell culture; Cellobiose; Circadian Clocks; Circadian rhythm; Circadian Rhythm Signaling Peptides and Proteins - metabolism; Circadian rhythms; Clock gene; Diet; Dietary supplements; Entrainment; Fatty acids; Fatty Acids, Volatile - administration & dosage; Fatty Acids, Volatile - metabolism; Fatty Acids, Volatile - pharmacology; Fermentation; Fibroblasts; Gastrointestinal Microbiome; Gene Expression Regulation - drug effects; Homeostasis; Humanities and Social Sciences; Intestinal microflora; Kidney; Kidneys; Lactic acid; Liver; Mice; Microbiomes; Microbiota; multidisciplinary; Oral administration; Organic acids; Period 2 protein; pH effects; Prebiotics; Propionic acid; Science; Science (multidisciplinary); Submandibular Gland
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-19836-7

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.