CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
·
2018
·Vol. 47
·期 4
·1617-1629
·
IF 5.5
Feng Wenqian,Wu Yancheng,Chen Guangxin,Fu Shoupeng,Li Bai,Huang Bingxu,Wang Dali,Wang Wei,Liu Juxiong
Background/Aims: Butyric acid plays an important role in maintaining intestinal health. Butyric acid has received special attention as a short-chain fatty acid, but its role in protecting the intestinal barrier is poorly characterized. Butyric acid not only provides energy for epithelial cells but also acts as a histone deacetylase inhibitor; it is also a natural ligand for G protein-coupled receptor 109A (GPR109A). A GPR109A analog was expressed in Sus scrofa and mediated the anti-inflammatory effects of beta-hydroxybutyric acid. This study investigated the effects of butyrate on growth performance, diarrhea symptoms, and tight junction protein levels in 21-day-old weaned piglets. We also studied the mechanism by which butyric acid regulates intestinal permeability. Methods: Twenty-four piglets that had been weaned at an age of 21 days were divided randomly into 2 equal groups: basal diet group and sodium butyrate + basal diet group. Diarrhea rate, growth performance during 3 weeks of feeding on these diets were observed, the lactulose-mannitol ratio in urine were detected by High Performance Liquid Chromatography, the expression levels of tight junction proteins in the intestinal tract and related signaling molecules, such as GPR109A and Akt, in the colon were examined by quantitative real-time PCR or western blot analyses on day 21. Caco-2 cells were used as a colon cell model and cultured with or without sodium butyrate to assess the expression of tight junction proteins and the activation of related signaling molecules. GPR109A-short hairpin RNA (shRNA) and specific antagonists of Akt and ERK1/2 were used as signaling pathway inhibitors to elucidate the mechanism by which butyric acid regulates the expression of tight junction proteins and the colonic epithelial barrier. Results: The sodium butyrate diet alleviated diarrhea symptoms and decreased intestinal permeability without affecting the growth of early weaned piglets. The expression levels of the tight junction proteins Claudin-3, Occludin, and zonula occludens 1 were up-regulated by sodium butyrate in the colon and Caco-2 cells. GPR109A knockdown using shRNA or blockade of the Akt signaling pathway in Caco-2 cells suppressed sodium butyrate-induced Claudin-3 expression. Conclusions: Sodium butyrate acts on the Akt signaling pathway to facilitate Claudin-3 expression in the colon in a GPR109A-dependent manner
研究领域:
动物营养学
·
胃肠病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2022
·Vol. 66
·期 23
·2200300
·
IF 6.575
Zhaodi Zhang,Jiahong Li,Ming Zhang,Binbin Li,XiaoHua Pan,Xiaoliang Dong,Li-Long Pan,Jia Sun
Scope Dietary fibers can alter gut microbiota and microbial metabolite profiles. SCFAs are produced by bacterial fermentation of fiber, mediating immune homeostasis through G-protein-coupled receptors (GPCRs). GPR109a, a receptor for niacin and butyrate, expressed by immune cells and non-immune cells, is a key factor regulating immune responses. However, the role and underlying mechanisms of GPR109a in type 1 diabetes (T1D) remain unclear. Methods and results Experimental T1D was induced by streptozotocin in GPR109a-deficient ( Gpr109a −/− ) and wild type mice. The study found that Gpr109a −/− mice were more susceptible to T1D with dysregulated immune responses, along with increased M1 macrophage polarization (from 10.55% to 21.48%). Further, an adoptive transfer experiment demonstrated that GPR109a-deficient macrophages promoted the homing of intestine-derived type 1 cytotoxic T cells to pancreas (from 18.91% to 24.24%), thus disturbing the pancreatic immune homeostasis in non-obese diabetic mice. Mechanistically, GPR109a deficiency promoted M1 macrophage polarization associated with the activation of suppressor of cytokine signaling 3-signal transducer and activator of transcription 1 signaling pathway. Conclusion The findings reveal that macrophage GPR109a deficiency accelerates the development of T1D. Activation of GPR109a on macrophage by dietary components may provide a new strategy for preventing or treating T1D.
研究领域:
免疫学
·
内分泌学
·
代谢学
·
胃肠病学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-17
·
IF 10.6
Li Nannan,Niu Lili,Liu Yao,Wang Yang,Su Xiaomin,Xu Ce,Sun Zanya,Guo Huishu,Gong Jingru,Shen Shun
Background Colorectal cancer (CRC) incidence is increasing in recent years due to intestinal flora imbalance, making oral probiotics a hotspot for research. However, numerous studies related to intestinal flora regulation ignore its internal mechanisms without in-depth research.Results Here, we developed a probiotic microgel delivery system (L.r@(SA-CS)2) through the layer-by-layer encapsulation technology of alginate (SA) and chitosan (CS) to improve gut microbiota dysbiosis and enhance anti-tumor therapeutic effect. Short chain fatty acids (SCFAs) produced by L.r have direct anti-tumor effects. Additionally, it reduces harmful bacteria such as Proteobacteria and Fusobacteriota, and through bacteria mutualophy increases beneficial bacteria such as Bacteroidota and Firmicutes which produce butyric acid. By binding to the G protein-coupled receptor 109A (GPR109A) on the surface of colonic epithelial cells, butyric acid can induce apoptosis in abnormal cells. Due to the low expression of GPR109A in colon cancer cells, MK-6892 (MK) can be used to stimulate GPR109A. With increased production of butyrate, activated GPR109A is able to bind more butyrate, which further promotes apoptosis of cancer cells and triggers an antitumor response.Conclusion It appears that the oral administration of L.r@(SA-CS)2 microgels may provide a treatment option for CRC by modifying the gut microbiota.
研究领域:
肿瘤学
·
微生物学
·
药学
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）