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Effects of short-chain fatty acid-butyrate supplementation on expression of circadian-clock genes, sleep quality, and inflammation in patients with active ulcerative colitis: a double-blind randomized controlled trial

The regulation of the circadian clock genes, which coordinate the activity of the immune system, is disturbed in inflammatory bowel disease (IBD). Emerging evidence suggests that butyrate, a short-chain fatty acid produced by the gut microbiota is involved in the regulation of inflammatory responses...

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Published in:Lipids in health and disease 2024-07, Vol.23 (1), p.216-14, Article 216
Main Authors: Firoozi, Donya, Masoumi, Seyed Jalil, Mohammad-Kazem Hosseini Asl, Seyed, Labbe, Aurélie, Razeghian-Jahromi, Iman, Fararouei, Mohammad, Lankarani, Kamran Bagheri, Dara, Mahintaj
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container_title Lipids in health and disease
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creator Firoozi, Donya
Masoumi, Seyed Jalil
Mohammad-Kazem Hosseini Asl, Seyed
Labbe, Aurélie
Razeghian-Jahromi, Iman
Fararouei, Mohammad
Lankarani, Kamran Bagheri
Dara, Mahintaj
description The regulation of the circadian clock genes, which coordinate the activity of the immune system, is disturbed in inflammatory bowel disease (IBD). Emerging evidence suggests that butyrate, a short-chain fatty acid produced by the gut microbiota is involved in the regulation of inflammatory responses as well as circadian-clock genes. This study was conducted to investigate the effects of sodium-butyrate supplementation on the expression of circadian-clock genes, inflammation, sleep and life quality in active ulcerative colitis (UC) patients. In the current randomized placebo-controlled trial, 36 active UC patients were randomly divided to receive sodium-butyrate (600 mg/kg) or placebo for 12-weeks. In this study the expression of circadian clock genes (CRY1, CRY2, PER1, PER2, BMAl1 and CLOCK) were assessed by real time polymerase chain reaction (qPCR) in whole blood. Gene expression changes were presented as fold changes in expression (2^-ΔΔCT) relative to the baseline. The faecal calprotectin and serum level of high-sensitivity C-reactive protein (hs-CRP) were assessed by enzyme-linked immunosorbent assay method (ELIZA). Moreover, the sleep quality and IBD quality of life (QoL) were assessed by Pittsburgh sleep quality index (PSQI) and inflammatory bowel disease questionnaire-9 (IBDQ-9) respectively before and after the intervention. The results showed that sodium-butyrate supplementation in comparison with placebo significantly decreased the level of calprotectin (-133.82 ± 155.62 vs. 51.58 ± 95.57, P-value 
doi_str_mv 10.1186/s12944-024-02203-z
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Emerging evidence suggests that butyrate, a short-chain fatty acid produced by the gut microbiota is involved in the regulation of inflammatory responses as well as circadian-clock genes. This study was conducted to investigate the effects of sodium-butyrate supplementation on the expression of circadian-clock genes, inflammation, sleep and life quality in active ulcerative colitis (UC) patients. In the current randomized placebo-controlled trial, 36 active UC patients were randomly divided to receive sodium-butyrate (600 mg/kg) or placebo for 12-weeks. In this study the expression of circadian clock genes (CRY1, CRY2, PER1, PER2, BMAl1 and CLOCK) were assessed by real time polymerase chain reaction (qPCR) in whole blood. Gene expression changes were presented as fold changes in expression (2^-ΔΔCT) relative to the baseline. The faecal calprotectin and serum level of high-sensitivity C-reactive protein (hs-CRP) were assessed by enzyme-linked immunosorbent assay method (ELIZA). Moreover, the sleep quality and IBD quality of life (QoL) were assessed by Pittsburgh sleep quality index (PSQI) and inflammatory bowel disease questionnaire-9 (IBDQ-9) respectively before and after the intervention. The results showed that sodium-butyrate supplementation in comparison with placebo significantly decreased the level of calprotectin (-133.82 ± 155.62 vs. 51.58 ± 95.57, P-value &lt; 0.001) and hs-CRP (-0.36 (-1.57, -0.05) vs. 0.48 (-0.09-4.77), P-value &lt; 0.001) and upregulated the fold change expression of CRY1 (2.22 ± 1.59 vs. 0.63 ± 0.49, P-value &lt; 0.001), CRY2 (2.15 ± 1.26 vs. 0.93 ± 0.80, P-value = 0.001), PER1 (1.86 ± 1.77 vs. 0.65 ± 0.48, P-value = 0.005), BMAL1 (1.85 ± 0.97 vs. 0.86 ± 0.63, P-value = 0.003). Also, sodium-butyrate caused an improvement in the sleep quality (PSQI score: -2.94 ± 3.50 vs. 1.16 ± 3.61, P-value &lt; 0.001) and QoL (IBDQ-9: 17.00 ± 11.36 vs. -3.50 ± 6.87, P-value &lt; 0.001). Butyrate may be an effective adjunct treatment for active UC patients by reducing biomarkers of inflammation, upregulation of circadian-clock genes and improving sleep quality and QoL.</description><identifier>ISSN: 1476-511X</identifier><identifier>EISSN: 1476-511X</identifier><identifier>DOI: 10.1186/s12944-024-02203-z</identifier><identifier>PMID: 39003477</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Adult ; Butyrate ; Butyrates ; Butyric Acid ; C-Reactive Protein - genetics ; C-Reactive Protein - metabolism ; Care and treatment ; Circadian Clocks - drug effects ; Circadian Clocks - genetics ; Circadian rhythms ; Circadian-clock genes ; Colitis, Ulcerative - drug therapy ; Colitis, Ulcerative - genetics ; Colitis, Ulcerative - metabolism ; Dietary Supplements ; Double-Blind Method ; Fatty acids ; Female ; Gene expression ; Gene Expression Regulation - drug effects ; Genetic aspects ; Health aspects ; Humans ; Inflammation ; Inflammation - drug therapy ; Inflammation - genetics ; Leukocyte L1 Antigen Complex - genetics ; Leukocyte L1 Antigen Complex - metabolism ; Male ; Middle Aged ; Quality of Life ; Short-chain fatty acids ; Sleep ; Sleep disorders ; Sleep Quality ; Testing ; Ulcerative colitis</subject><ispartof>Lipids in health and disease, 2024-07, Vol.23 (1), p.216-14, Article 216</ispartof><rights>2024. The Author(s).</rights><rights>COPYRIGHT 2024 BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c317t-b665457d7fb9ab7ce013e3167717154d65b3945a2a113de81c6332e7e7a0d13a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925,37013</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39003477$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Firoozi, Donya</creatorcontrib><creatorcontrib>Masoumi, Seyed Jalil</creatorcontrib><creatorcontrib>Mohammad-Kazem Hosseini Asl, Seyed</creatorcontrib><creatorcontrib>Labbe, Aurélie</creatorcontrib><creatorcontrib>Razeghian-Jahromi, Iman</creatorcontrib><creatorcontrib>Fararouei, Mohammad</creatorcontrib><creatorcontrib>Lankarani, Kamran Bagheri</creatorcontrib><creatorcontrib>Dara, Mahintaj</creatorcontrib><title>Effects of short-chain fatty acid-butyrate supplementation on expression of circadian-clock genes, sleep quality, and inflammation in patients with active ulcerative colitis: a double-blind randomized controlled trial</title><title>Lipids in health and disease</title><addtitle>Lipids Health Dis</addtitle><description>The regulation of the circadian clock genes, which coordinate the activity of the immune system, is disturbed in inflammatory bowel disease (IBD). Emerging evidence suggests that butyrate, a short-chain fatty acid produced by the gut microbiota is involved in the regulation of inflammatory responses as well as circadian-clock genes. This study was conducted to investigate the effects of sodium-butyrate supplementation on the expression of circadian-clock genes, inflammation, sleep and life quality in active ulcerative colitis (UC) patients. In the current randomized placebo-controlled trial, 36 active UC patients were randomly divided to receive sodium-butyrate (600 mg/kg) or placebo for 12-weeks. In this study the expression of circadian clock genes (CRY1, CRY2, PER1, PER2, BMAl1 and CLOCK) were assessed by real time polymerase chain reaction (qPCR) in whole blood. Gene expression changes were presented as fold changes in expression (2^-ΔΔCT) relative to the baseline. The faecal calprotectin and serum level of high-sensitivity C-reactive protein (hs-CRP) were assessed by enzyme-linked immunosorbent assay method (ELIZA). Moreover, the sleep quality and IBD quality of life (QoL) were assessed by Pittsburgh sleep quality index (PSQI) and inflammatory bowel disease questionnaire-9 (IBDQ-9) respectively before and after the intervention. The results showed that sodium-butyrate supplementation in comparison with placebo significantly decreased the level of calprotectin (-133.82 ± 155.62 vs. 51.58 ± 95.57, P-value &lt; 0.001) and hs-CRP (-0.36 (-1.57, -0.05) vs. 0.48 (-0.09-4.77), P-value &lt; 0.001) and upregulated the fold change expression of CRY1 (2.22 ± 1.59 vs. 0.63 ± 0.49, P-value &lt; 0.001), CRY2 (2.15 ± 1.26 vs. 0.93 ± 0.80, P-value = 0.001), PER1 (1.86 ± 1.77 vs. 0.65 ± 0.48, P-value = 0.005), BMAL1 (1.85 ± 0.97 vs. 0.86 ± 0.63, P-value = 0.003). Also, sodium-butyrate caused an improvement in the sleep quality (PSQI score: -2.94 ± 3.50 vs. 1.16 ± 3.61, P-value &lt; 0.001) and QoL (IBDQ-9: 17.00 ± 11.36 vs. -3.50 ± 6.87, P-value &lt; 0.001). Butyrate may be an effective adjunct treatment for active UC patients by reducing biomarkers of inflammation, upregulation of circadian-clock genes and improving sleep quality and QoL.</description><subject>Adult</subject><subject>Butyrate</subject><subject>Butyrates</subject><subject>Butyric Acid</subject><subject>C-Reactive Protein - genetics</subject><subject>C-Reactive Protein - metabolism</subject><subject>Care and treatment</subject><subject>Circadian Clocks - drug effects</subject><subject>Circadian Clocks - genetics</subject><subject>Circadian rhythms</subject><subject>Circadian-clock genes</subject><subject>Colitis, Ulcerative - drug therapy</subject><subject>Colitis, Ulcerative - genetics</subject><subject>Colitis, Ulcerative - metabolism</subject><subject>Dietary Supplements</subject><subject>Double-Blind Method</subject><subject>Fatty acids</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation - genetics</subject><subject>Leukocyte L1 Antigen Complex - genetics</subject><subject>Leukocyte L1 Antigen Complex - metabolism</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Quality of Life</subject><subject>Short-chain fatty acids</subject><subject>Sleep</subject><subject>Sleep disorders</subject><subject>Sleep Quality</subject><subject>Testing</subject><subject>Ulcerative colitis</subject><issn>1476-511X</issn><issn>1476-511X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNptUsFu1DAQjRCIlsIPcECWuHBoih0ncZZbVRWoVIkLSNysiT3ZujhxajvA7p_yN8zulgokZFsej957Y49fUbwU_EyIrn2bRLWq65JXu1VxWW4fFceiVm3ZCPH18V_xUfEspVvOK67a9mlxJFecy1qp4-LX5TCgyYmFgaWbEHNpbsBNbICcNwyMs2W_5E2EjCwt8-xxxClDdmFiNPHnHDGl_WlgxkUD1sFUGh_MN7bGCdMpSx5xZncLeJc3pwwmy9w0eBjHgw6Vmyki3cR-uHxDZbP7jmzxBqnwLjSBuC69Y8BsWHqPZe8d6UQSC6PboiXIlGPwnsIcHfjnxZMBfMIX9_tJ8eX95eeLj-X1pw9XF-fXpZFC5bJv26ZulFVDv4JeGeRCohStUkKJprZt08tV3UAFQkiLnTCtlBUqVMCtkCBPiquDrg1wq-foRogbHcDpfSLEtYaYnfGoeWul6TvkhiRVJ6iesKbrpKga2dEPnhRvDlpzDHcLpqxHlwx6DxOGJWnJ1WrVtKpSBH19gK6BlKmfIUcwO7g-77ioFKdBqLP_oGhYHB11DAdH-X8I1YFgYkgp4vDwIsH1znX64DpNrtN71-ktkV7dX3vpR7QPlD82k78B14LWjw</recordid><startdate>20240713</startdate><enddate>20240713</enddate><creator>Firoozi, Donya</creator><creator>Masoumi, Seyed Jalil</creator><creator>Mohammad-Kazem Hosseini Asl, Seyed</creator><creator>Labbe, Aurélie</creator><creator>Razeghian-Jahromi, Iman</creator><creator>Fararouei, Mohammad</creator><creator>Lankarani, Kamran Bagheri</creator><creator>Dara, Mahintaj</creator><general>BioMed Central Ltd</general><general>BMC</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>DOA</scope></search><sort><creationdate>20240713</creationdate><title>Effects of short-chain fatty acid-butyrate supplementation on expression of circadian-clock genes, sleep quality, and inflammation in patients with active ulcerative colitis: a double-blind randomized controlled trial</title><author>Firoozi, Donya ; 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Emerging evidence suggests that butyrate, a short-chain fatty acid produced by the gut microbiota is involved in the regulation of inflammatory responses as well as circadian-clock genes. This study was conducted to investigate the effects of sodium-butyrate supplementation on the expression of circadian-clock genes, inflammation, sleep and life quality in active ulcerative colitis (UC) patients. In the current randomized placebo-controlled trial, 36 active UC patients were randomly divided to receive sodium-butyrate (600 mg/kg) or placebo for 12-weeks. In this study the expression of circadian clock genes (CRY1, CRY2, PER1, PER2, BMAl1 and CLOCK) were assessed by real time polymerase chain reaction (qPCR) in whole blood. Gene expression changes were presented as fold changes in expression (2^-ΔΔCT) relative to the baseline. The faecal calprotectin and serum level of high-sensitivity C-reactive protein (hs-CRP) were assessed by enzyme-linked immunosorbent assay method (ELIZA). Moreover, the sleep quality and IBD quality of life (QoL) were assessed by Pittsburgh sleep quality index (PSQI) and inflammatory bowel disease questionnaire-9 (IBDQ-9) respectively before and after the intervention. The results showed that sodium-butyrate supplementation in comparison with placebo significantly decreased the level of calprotectin (-133.82 ± 155.62 vs. 51.58 ± 95.57, P-value &lt; 0.001) and hs-CRP (-0.36 (-1.57, -0.05) vs. 0.48 (-0.09-4.77), P-value &lt; 0.001) and upregulated the fold change expression of CRY1 (2.22 ± 1.59 vs. 0.63 ± 0.49, P-value &lt; 0.001), CRY2 (2.15 ± 1.26 vs. 0.93 ± 0.80, P-value = 0.001), PER1 (1.86 ± 1.77 vs. 0.65 ± 0.48, P-value = 0.005), BMAL1 (1.85 ± 0.97 vs. 0.86 ± 0.63, P-value = 0.003). Also, sodium-butyrate caused an improvement in the sleep quality (PSQI score: -2.94 ± 3.50 vs. 1.16 ± 3.61, P-value &lt; 0.001) and QoL (IBDQ-9: 17.00 ± 11.36 vs. -3.50 ± 6.87, P-value &lt; 0.001). Butyrate may be an effective adjunct treatment for active UC patients by reducing biomarkers of inflammation, upregulation of circadian-clock genes and improving sleep quality and QoL.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>39003477</pmid><doi>10.1186/s12944-024-02203-z</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1476-511X
ispartof Lipids in health and disease, 2024-07, Vol.23 (1), p.216-14, Article 216
issn 1476-511X
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source Publicly Available Content Database; PubMed Central
subjects Adult
Butyrate
Butyrates
Butyric Acid
C-Reactive Protein - genetics
C-Reactive Protein - metabolism
Care and treatment
Circadian Clocks - drug effects
Circadian Clocks - genetics
Circadian rhythms
Circadian-clock genes
Colitis, Ulcerative - drug therapy
Colitis, Ulcerative - genetics
Colitis, Ulcerative - metabolism
Dietary Supplements
Double-Blind Method
Fatty acids
Female
Gene expression
Gene Expression Regulation - drug effects
Genetic aspects
Health aspects
Humans
Inflammation
Inflammation - drug therapy
Inflammation - genetics
Leukocyte L1 Antigen Complex - genetics
Leukocyte L1 Antigen Complex - metabolism
Male
Middle Aged
Quality of Life
Short-chain fatty acids
Sleep
Sleep disorders
Sleep Quality
Testing
Ulcerative colitis
title Effects of short-chain fatty acid-butyrate supplementation on expression of circadian-clock genes, sleep quality, and inflammation in patients with active ulcerative colitis: a double-blind randomized controlled trial
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