Butyrate inhibits IL-1β-induced inflammatory gene expression by suppression of NF-κB activity in pancreatic beta cells

Pedersen, Signe Schultz; Prause, Michala; Williams, Kristine; Barrès, Romain; Billestrup, Nils

doi:10.1016/j.jbc.2022.102312

Cited by 30 publications

(17 citation statements)

References 90 publications

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“…Butyrate decreased IL-1b-increased H3K27ac in proximity to several genes associated with inflammatory processes and increased IL-1b-reduced H3K27ac near genes involved in hormone secretion. These changes in H3K27ac levels correspond well to our previous findings that butyrate prevents IL-1b-induced impairment of insulin secretion and inhibits the expression of proinflammatory genes such as the NF-jB target genes Cxcl1 and Nos2 [8,22,23]. In our previous study, we showed that butyrate reduced inflammatory gene expression by inhibition of NF-jB signaling.…”

Section: Discussionsupporting

confidence: 90%

“…In our previous study, we showed that butyrate reduced inflammatory gene expression by inhibition of NF-jB signaling. Both butyrate and the pan-HDAC inhibitor SAHA reduced IL-1b-induced Nos2 promoter activity in INS-1E cells [23]. This supports that HDAC inhibition might be a mechanism by which butyrate protects against inflammation and that some of effects we observe in whole islets, at least partially, occur in beta cells.…”

Section: Discussionsupporting

confidence: 81%

“…In addition to counteracting IL‐1β‐induced inflammation [23], butyrate significantly increased the acetylation of H3K27 at promoters of genes such as Ins2 , Kcnj11 , Snap25 , Stxbp2 , Esyt3 , Syt3 , Syt7 , Syt12 and subunits of voltage‐gated calcium channels ( Cacna1a , Cacna1g , Cacna1h and Cacna1i ). These genes are involved in regulating Ca 2+ influx, insulin granule docking, priming and exocytosis.…”

Section: Discussionmentioning

confidence: 99%

“…Butyrate has been shown to have beneficial effects on glucose homeostasis by increasing insulin sensitivity and energy expenditure, improving the intestinal barrier function, and reducing inflammation [21]. Recently, we showed that butyrate also targets beta cells and prevents cytokineinduced beta cell dysfunction and inhibits inflammatory NF-jB signaling [22,23]. However, the underlying mechanisms remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Butyrate functions as a histone deacetylase inhibitor to protect pancreatic beta cells from IL‐1β‐induced dysfunction

Pedersen,

Ingerslev,

Olsen

et al. 2023

The FEBS Journal

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Butyrate, a gut microbial metabolite, has beneficial effects on glucose homeostasis and has become an attractive drug candidate for type 2 diabetes (T2D). Recently, we showed that butyrate protects pancreatic beta cells against cytokine‐induced dysfunction. In this study, we explored the underlying mechanisms of butyrate action. Pancreatic mouse islets were exposed to a non‐cytotoxic concentration of interleukin‐1β (IL‐1β) for 10 days to mimic low‐grade inflammation in T2D. Similar to the effect of butyrate, an isoform‐selective histone deacetylase 3 (HDAC3) inhibitor normalized IL‐1β‐reduced glucose‐stimulated insulin secretion and insulin content. In contrast, free fatty acid receptor 2 and 3 (FFAR2/3) agonists failed to normalize IL‐1β‐induced beta cell dysfunction. Furthermore, butyrate inhibited HDAC activity and increased the acetylation of histone H3 and H4 by 3‐ and 10‐fold, respectively. Genome‐wide analysis of histone H3 lysine 27 acetylation (H3K27ac) revealed that butyrate mainly increased H3K27ac at promoter regions (74%), while H3K27ac peaks regulated by IL‐1β were more equally distributed at promoters (38%), introns (23%) and intergenic regions (23%). Gene ontology analysis showed that butyrate increased IL‐1β‐reduced H3K27ac levels near several genes related to hormone secretion and reduced IL‐1β‐increased H3K27ac levels near genes associated with inflammatory responses. Butyrate alone increased H3K27ac near many genes related to MAPK signaling, hormone secretion, and differentiation, and decreased H3K27ac at genes involved in cell replication. Together, these results suggest that butyrate prevents IL‐1β‐induced pancreatic islet dysfunction by inhibition of HDACs resulting in changes in H3K27ac levels at genes relevant for beta cell function and inflammatory responses.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Butyrate functions as a histone deacetylase inhibitor to protect pancreatic beta cells from IL‐1β‐induced dysfunction

Pedersen,

Ingerslev,

Olsen

et al. 2023

The FEBS Journal

Self Cite

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“…Similarly, we observed an up-regulation expression of intestinal IL-8, IL-1b, TNF-a and IL-12 and the down-regulation of intestinal IL-10 in SBM-fed fish, which was in accordance with previous observations (Wang et al, 2017a;Li et al, 2020;Zhao et al, 2021b). Intestinal TGF-b1 is involved in the inactivation of the NF-kB signaling pathway, playing a role in the regulation of the inflammatory response and controlling the expression of genes encoding pro-inflammatory cytokines (Inan et al, 2000;Pedersen et al, 2022). Butyrate and SB are shown to function as an energy source for intestinal epithelial cells to exhibit anti-inflammatory as well as immune modulatory effects on mammals (Nancey et al, 2002;Weber and Kerr, 2006;Meijer et al, 2010;Ali et al, 2022).…”

Section: Expression Of Intestinal Inflammatory Factor Genesmentioning

confidence: 99%

Dietary sodium butyrate administration alleviates high soybean meal-induced growth retardation and enteritis of orange-spotted groupers (Epinephelus coioides)

Qin²,

Song³

et al. 2022

Front. Mar. Sci.

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An 8-week feeding trial was conducted to investigate whether dietary sodium butyrate (SB) administration alleviates growth reduction and enteritis of orange-spotted grouper (Epinephelus coioides) caused by high soybean meal (SBM) feeding. The control diet (FM diet) was formulated to contain 48% protein and 11% fat. Soybean meal was used to replace 60% FM protein in FM diet to prepare a high SBM diet (HSBM diet). Sodium butyrate (SB) at 0.1%, 0.2%, and 0.3% were added to HSBM diets to prepare three diets. Triplicate groups of 30 groupers (initial weight: 33.0 ± 0.3 g) were fed one of the diets twice daily, to apparent satiety. HSBM diets had lowered growth rate and feed efficiency vs FM diets (P <0.05). Growth rate and feed efficiency were improved by dietary SB administration and were in a dose-dependent manner (P <0.05). A similar pattern to the growth rate was observed for plasma LDL-C and gut digestive activity of lipase, trypsin, and protease, but the opposite trend was observed for intestinal contents of D-lactic acid and endotoxin, in response to dietary SB inclusion levels (P >0.05). The muscular thickness in the middle and distal intestines in SB-treated diets were higher than that in HSBM diets (P <0.05). The mRNA levels of intestinal pro-inflammatory cytokines IL-8, IL-1β, IL-12 and TNF-α had a decreasing trend, and the mRNA level of intestinal anti-inflammatory cytokine TGF-β1 had the opposite trend, with increasing SB inclusion levels (P < 0.05). The above results indicate that dietary SB intervention could enhance growth and feed utilization of groupers with SBM-induced enteritis by promoting intestinal digestive enzyme activities, reducing mucosa permeability, maintaining the integrity of intestinal morphology and attenuating the intestinal inflammatory response.

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The role of the gut microbiome in modulating immunotherapy efficacy in colorectal cancer

Zuo,

Huang,

Zou

2024

IUBMB Life

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This systematic literature review and meta‐analysis provide an overview of the critical role of gut microbiota in modulating the efficacy of immunotherapy for colorectal cancer. Gut microbes influence host immune responses through multiple mechanisms including modulation of immune cell activity, metabolite action, and immune tolerance. The ability of specific gut microbes to improve the efficacy of immune checkpoint inhibitors has been linked to their ability to improve gut barrier function, modulate immune cell activity, and produce key immunomodulatory metabolites such as short‐chain fatty acids. In addition, the composition and diversity of the gut microbiota are strongly associated with the efficacy of immunotherapies, demonstrating the potential to improve therapeutic response by modifying the gut microbiota. This paper also discusses the prospect of manipulating the gut microbiota through strategies such as fecal microbial transplantation, probiotic supplementation, and dietary modifications to optimize the efficacy of immunotherapy.

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Butyrate inhibits IL-1β-induced inflammatory gene expression by suppression of NF-κB activity in pancreatic beta cells

Cited by 30 publications

References 90 publications

Butyrate functions as a histone deacetylase inhibitor to protect pancreatic beta cells from IL‐1β‐induced dysfunction

Butyrate functions as a histone deacetylase inhibitor to protect pancreatic beta cells from IL‐1β‐induced dysfunction

Dietary sodium butyrate administration alleviates high soybean meal-induced growth retardation and enteritis of orange-spotted groupers (Epinephelus coioides)

The role of the gut microbiome in modulating immunotherapy efficacy in colorectal cancer

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