Sodium propionate and sodium butyrate effects on histone deacetylase (HDAC) activity, histone acetylation, and inflammatory gene expression in bovine mammary epithelial cells1

Silva, Lorrayny G; Ferguson, Bradley S.; Ávila, André Sanches de; Faciola, A.P.

doi:10.1093/jas/sky373

Cited by 55 publications

(71 citation statements)

References 30 publications

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“…This could result in more SCFA production in the faeces. Both butyrate and propionate have been proposed to increase histone deacetylase inhibition [16], which is a known mechanism of cellular radiosensitisation [17,18]. In this study, we demonstrated that these phenotypes exist in bladder cancer cells (Fig.…”

Section: Discussionsupporting

confidence: 55%

Association of Bacteroides acidifaciens relative abundance with high-fibre diet-associated radiosensitisation

et al. 2020

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Background: Patients with pelvic malignancies often receive radiosensitising chemotherapy with radiotherapy to improve survival; however, this is at the expense of increased normal tissue toxicity, particularly in elderly patients. Here, we explore if an alternative, low-cost, and non-toxic approach can achieve radiosensitisation in mice transplanted with human bladder cancer cells. Other investigators have shown slower growth of transplanted tumours in mice fed high-fibre diets. We hypothesised that mice fed a high-fibre diet would have improved tumour control following ionising radiation (IR) and that this would be mediated through the gut microbiota. Results: We investigated the effects of four different diets (low-fibre, soluble high-fibre, insoluble high-fibre, and mixed soluble/insoluble high-fibre diets) on tumour growth in immunodeficient mice implanted with human bladder cancer flank xenografts and treated with ionising radiation, simultaneously investigating the composition of their gut microbiomes by 16S rRNA sequencing. A significantly higher relative abundance of Bacteroides acidifaciens was seen in the gut (faecal) microbiome of the soluble high-fibre group, and the soluble high-fibre diet resulted in delayed tumour growth after irradiation compared to the other groups. Within the soluble high-fibre group, responders to irradiation had significantly higher abundance of B. acidifaciens than non-responders. When all mice fed with different diets were pooled, an association was found between the survival time of mice and relative abundance of B. acidifaciens. The gut microbiome in responders was predicted to be enriched for carbohydrate metabolism pathways, and in vitro experiments on the transplanted human bladder cancer cell line suggested a role for microbial-generated short-chain fatty acids and/or other metabolites in the enhanced radiosensitivity of the tumour cells. Conclusions: Soluble high-fibre diets sensitised tumour xenografts to irradiation, and this phenotype was associated with modification of the microbiome and positively correlated with B. acidifaciens abundance. Our findings might be exploitable for improving radiotherapy response in human patients.

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Section: Discussionsupporting

confidence: 55%

Association of Bacteroides acidifaciens relative abundance with high-fibre diet-associated radiosensitisation

et al. 2020

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“…Interestingly, this defensin also induced the production of nitric oxide (NO) and the secretion of the endogenous antimicrobial peptide DEFB1 by bMECs (7). In addition, the induction of epigenetic modifications has been reported in bMECs, such as H3 acetylation (8). Besides, recently Kweh et al (9) have reported that β-defensin expression in bMECs is likely influenced by DNA methylation and histone acetylation.…”

Section: Introductionmentioning

confidence: 92%

Plant Defensin γ-Thionin Induces MAPKs and Activates Histone Deacetylases in Bovine Mammary Epithelial Cells Infected With Staphylococcus aureus

et al. 2020

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Defensins are an important group of host defense peptides. They have immunomodulatory properties, which have been mainly described for mammal defensins, but similar effects for plant defensins remain unknown. Previously, we showed that the defensin γ-thionin (Capsicum chinense) reduces Staphylococcus aureus internalization into bovine mammary epithelial cells (bMECs) while inducing Toll-like receptor 2 (TLR2), modulating the inflammatory response. Here, we analyze the effect of γ-thionin on the TLR2 pathway in bMECs infected with S. aureus and determine if it modulates epigenetic marks. Pre-treated bMECs with γ-thionin (100 ng/ml) reduced the basal activation of p38 and ERK1/2 (∼3-fold), but JNK was increased (∼1.5-fold). Also, infected bMECs induced p38, but this effect was reversed by γ-thionin, whereas ERK1/2 was reduced by infection but stimulated by γ-thionin. Likewise, γ-thionin reduced the activation of Akt kinase ∼50%. Furthermore, γ-thionin induced the activation of transcriptional factors of inflammatory response, highlighting EGR, E2F-1, AP-1, and MEF, which were turned off by bacteria. Also, γ-thionin induced the activation of histone deacetylases (HDACs, ∼4-fold) at 24 h in infected bMECs and reduced LSD1 demethylase (HDMs, ∼30%) activity. Altogether, these results demonstrated the first time that a plant defensin interferes with inflammatory signaling pathways in mammalian cells.

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“…36,37 Furthermore, the therapeutic use of butyrate to modulate gene expression has been employed for various diseases, including cancer [38][39][40][41] and inflammatory disease. [42][43][44][45] Notably, It was recently shown in mouse mast cells that butyrate suppressed FcεRIdependent cytokine release, likely via inhibition of HDAC activity, without affecting β-Hexosaminidase. 46 Here, we investigated the effects of SCFAs in a clinically relevant ex vivo model of mast cell-mediated pathology.…”

Section: G R a P H I C A L Abstractmentioning

confidence: 99%

Butyrate inhibits human mast cell activation via epigenetic regulation of FcεRI‐mediated signaling

Folkerts

Redegeld

Folkerts

et al. 2020

Allergy

117

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Background: Short-chain fatty acids (SCFAs) are fermented dietary components that regulate immune responses, promote colonic health, and suppress mast cell-mediated diseases. However, the effects of SCFAs on human mast cell function, including the underlying mechanisms, remain unclear. Here, we investigated the effects of the SCFAs (acetate, propionate, and butyrate) on mast cell-mediated pathology and human mast cell activation, including the molecular mechanisms involved. Method: Precision-cut lung slices (PCLS) of allergen-exposed guinea pigs were used to assess the effects of butyrate on allergic airway contraction. Human and mouse mast cells were co-cultured with SCFAs and assessed for degranulation after IgE-or non-IgE-mediated stimulation. The underlying mechanisms involved were investigated using knockout mice, small molecule inhibitors/agonists, and genomics assays. Results: Butyrate treatment inhibited allergen-induced histamine release and airway contraction in guinea pig PCLS. Propionate and butyrate, but not acetate, inhibited IgE-and non-IgE-mediated human or mouse mast cell degranulation in a concentration-dependent manner. Notably, these effects were independent of the stimulation of SCFA receptors GPR41, GPR43, or PPAR, but instead were associated with inhibition of histone deacetylases. Transcriptome analyses revealed butyrate-induced downregulation of the tyrosine kinases BTK, SYK, and LAT, critical transducers of FcεRI-mediated signals that are essential for mast cell activation. Epigenome analyses indicated that butyrate redistributed global histone acetylation in human mast cells, including significantly decreased acetylation at the BTK, SYK, and LAT promoter regions. Conclusion: Known health benefits of SCFAs in allergic disease can, at least in part, be explained by epigenetic suppression of human mast cell activation. | 1967 FOLKERTS ET aL.

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Sodium propionate and sodium butyrate effects on histone deacetylase (HDAC) activity, histone acetylation, and inflammatory gene expression in bovine mammary epithelial cells1

Cited by 55 publications

References 30 publications

Association of Bacteroides acidifaciens relative abundance with high-fibre diet-associated radiosensitisation

Association of Bacteroides acidifaciens relative abundance with high-fibre diet-associated radiosensitisation

Plant Defensin γ-Thionin Induces MAPKs and Activates Histone Deacetylases in Bovine Mammary Epithelial Cells Infected With Staphylococcus aureus

Butyrate inhibits human mast cell activation via epigenetic regulation of FcεRI‐mediated signaling

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