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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 |
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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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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 < 0.001) and hs-CRP (-0.36 (-1.57, -0.05) vs. 0.48 (-0.09-4.77), P-value < 0.001) and upregulated the fold change expression of CRY1 (2.22 ± 1.59 vs. 0.63 ± 0.49, P-value < 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 < 0.001) and QoL (IBDQ-9: 17.00 ± 11.36 vs. -3.50 ± 6.87, P-value < 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 < 0.001) and hs-CRP (-0.36 (-1.57, -0.05) vs. 0.48 (-0.09-4.77), P-value < 0.001) and upregulated the fold change expression of CRY1 (2.22 ± 1.59 vs. 0.63 ± 0.49, P-value < 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 < 0.001) and QoL (IBDQ-9: 17.00 ± 11.36 vs. -3.50 ± 6.87, P-value < 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 ; Masoumi, Seyed Jalil ; Mohammad-Kazem Hosseini Asl, Seyed ; Labbe, Aurélie ; Razeghian-Jahromi, Iman ; Fararouei, Mohammad ; Lankarani, Kamran Bagheri ; Dara, Mahintaj</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c317t-b665457d7fb9ab7ce013e3167717154d65b3945a2a113de81c6332e7e7a0d13a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Butyrate</topic><topic>Butyrates</topic><topic>Butyric Acid</topic><topic>C-Reactive Protein - genetics</topic><topic>C-Reactive Protein - metabolism</topic><topic>Care and treatment</topic><topic>Circadian Clocks - drug effects</topic><topic>Circadian Clocks - genetics</topic><topic>Circadian rhythms</topic><topic>Circadian-clock genes</topic><topic>Colitis, Ulcerative - drug therapy</topic><topic>Colitis, Ulcerative - genetics</topic><topic>Colitis, Ulcerative - metabolism</topic><topic>Dietary Supplements</topic><topic>Double-Blind Method</topic><topic>Fatty acids</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Inflammation - drug therapy</topic><topic>Inflammation - genetics</topic><topic>Leukocyte L1 Antigen Complex - genetics</topic><topic>Leukocyte L1 Antigen Complex - metabolism</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Quality of Life</topic><topic>Short-chain fatty acids</topic><topic>Sleep</topic><topic>Sleep disorders</topic><topic>Sleep Quality</topic><topic>Testing</topic><topic>Ulcerative colitis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><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><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Lipids in health and disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Firoozi, Donya</au><au>Masoumi, Seyed Jalil</au><au>Mohammad-Kazem Hosseini Asl, Seyed</au><au>Labbe, Aurélie</au><au>Razeghian-Jahromi, Iman</au><au>Fararouei, Mohammad</au><au>Lankarani, Kamran Bagheri</au><au>Dara, Mahintaj</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Lipids in health and disease</jtitle><addtitle>Lipids Health Dis</addtitle><date>2024-07-13</date><risdate>2024</risdate><volume>23</volume><issue>1</issue><spage>216</spage><epage>14</epage><pages>216-14</pages><artnum>216</artnum><issn>1476-511X</issn><eissn>1476-511X</eissn><abstract>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 < 0.001) and hs-CRP (-0.36 (-1.57, -0.05) vs. 0.48 (-0.09-4.77), P-value < 0.001) and upregulated the fold change expression of CRY1 (2.22 ± 1.59 vs. 0.63 ± 0.49, P-value < 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 < 0.001) and QoL (IBDQ-9: 17.00 ± 11.36 vs. -3.50 ± 6.87, P-value < 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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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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