title: Dietary resistant starch type 4-derived butyrate attenuates nuclear factor-kappa-B1 through modulation of histone H3 trimethylation at lysine 27.
abstract: Indigestible resistant starches (RS) are substrates for gut-microbial metabolism and have been shown to attenuate intestinal inflammation but the supporting evidence is inconsistent and lacks mechanistic explanation. We have recently reported dietary RS type 4 (RS4) induced improvements in immunometabolic functions in humans and a concomitant increase in butyrogenic gut-bacteria. Since inflammation is a key component in metabolic diseases, here we investigated the effects of RS4-derived butyrate on the epigenetic repression of pro-inflammatory genes in vivo and in vitro. RS4-fed mice, compared to the control-diet group, had higher cecal butyrate and increased tri-methylation of lysine 27 on histone 3 (H3K27me3) in the promoter of nuclear factor-kappa-B1 (NFκB1) in the colon tissue. The H3K27me3-enrichment inversely correlated with the concentration dependent down-regulation of NFκB1 in sodium butyrate treated human colon epithelial cells. Two additional inflammatory genes were attenuated by sodium butyrate, but were not linked with H3K27me3 changes. This exploratory study presents a new opportunity for studying underlying H3K27me3 and other methylation modifying mechanisms linked to RS4 biological activity.
authors.affiliation: Department of Health and Nutritional Sciences, Box 2203, South Dakota State University, Brookings, SD 57007, USA. Moul.Dey@sdstate.edu.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Health and Nutritional Sciences, Box 2203, South Dakota State University, Brookings, SD 57007, USA. Moul.Dey@sdstate.edu.
authors.forename: Bijaya
authors.initials: B
authors.lastname: Upadhyaya
authors.affiliation: Office of Regulatory Science, Center for Food Safety and Applied Nutrition, HFS-717, US Food and Drug Administration, College Park, MD 20740, USA.
authors.forename: Ali Reza
authors.initials: AR
authors.lastname: Fardin-Kia
authors.affiliation: Department of Health and Nutritional Sciences, Box 2203, South Dakota State University, Brookings, SD 57007, USA. Moul.Dey@sdstate.edu.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Juenemann
authors.affiliation: Department of Health and Nutritional Sciences, Box 2203, South Dakota State University, Brookings, SD 57007, USA. Moul.Dey@sdstate.edu.
authors.forename: Moul
authors.initials: M
authors.lastname: Dey
mesh_terms: D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D020148:Butyric Acid / Q000378:metabolism*; D002432:Cecum / Q000378:metabolism / Q000382:microbiology; D002460:Cell Line; D004040:Dietary Carbohydrates / Q000378:metabolism; D000069196:Gastrointestinal Microbiome; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008297:Male; D008745:Methylation; D051379:Mice; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013213:Starch / Q000378:metabolism*
chemical_list: D004040:Dietary Carbohydrates; D006657:Histones; D016328:NF-kappa B; D020148:Butyric Acid; D013213:Starch; D008239:Lysine