scholarly journals Short-Chain Fatty Acids Manifest Stimulative and Protective Effects on Intestinal Barrier Function Through the Inhibition of NLRP3 Inflammasome and Autophagy

2018 ◽  
Vol 49 (1) ◽  
pp. 190-205 ◽  
Author(s):  
Yanhai Feng ◽  
Yu Wang ◽  
Pei Wang ◽  
Yalan Huang ◽  
Fengjun Wang
Keyword(s):  
Nlrp3 Inflammasome ◽  
Barrier Function ◽  
Trichostatin A ◽  
Hdac Inhibitors ◽  
Intestinal Barrier ◽  
Short Chain Fatty Acids ◽  
Paracellular Permeability ◽  
Intestinal Barrier Function ◽  
Protective Effects ◽  
Permeability Increase

Background/Aims: Short-chain fatty acids (SCFAs) are the major energy resources of intestinal epithelial cells. It has been reported that SCFAs can repair the dysfunction of intestinal barrier, however, the underlying mechanisms are still not fully understood. Here, we investigated the stimulative and protective effects of SCFAs on intestinal barrier function and the possible mechanisms. Methods: To investigate the effects of SCFAs on intestinal barrier function, the Caco-2 monolayers were exposed to acetate, propionate, butyrate respectively or simultaneously without or with lipopolysaccharide (LPS). Next, Caco-2 cells were treated with trichostatin A and etomoxir to identify whether SCFAs act as HDAC inhibitors or energy substances. To activate NLRP3 inflammasome and autophagy, Caco-2 cells were treated with LPS+ATP and rapamycin respectively without or with SCFAs. The transepithelial electrical resistance (TER) and paracellular permeability were respectively detected with a Millicell-ERS voltohmmeter and fluorescein isothiocyanate-labeled dextran. Immunoblotting and immunofluorescence were applied to analyze the expression and distribution of tight junction proteins, and the activation of NLRP3 inflammasome and autophagy. Results: Acetate (0.5mM), propionate(0.01mM) and butyrate (0.01mM) alone or in combination significantly increased TER, and stimulated the formation of tight junction. SCFAs also dramatically attenuated the LPS-induced TER reduction and paracellular permeability increase, accompanying significantly alleviated morphological disruption of ZO-1 and occludin. Meanwhile, the activation of NLRP3 inflammasome and autophagy induced by LPS were significantly inhibited by SCFAs. Trichostatin A imitated the inhibiting action of SCFAs on NLRP3 inflammasome, whereas etomoxir blocked the action of SCFAs on protecting intestinal barrier and inhibiting autophagy. In addition, the activation of autophagy and NLRP3 inflammasome by rapamycin and LPS+ATP resulted in TER reduction, paracellular permeability increase and morphological disruption of both ZO-1 and occludin, which was alleviated by SCFAs. Conclusion: It is suggested that SCFAs stimulate the formation of intestinal barrier, and protect the intestinal barrier from the disruption of LPS through inhibiting NLRP3 inflammasome and autophagy. In addition, SCFAs act as energy substances to protect intestinal barrier and inhibit autophagy, but act as HDAC inhibitors to suppress NLRP3 inflammasome. Furthermore, the mutual promoting action between NLRP3 inflammasome and autophagy would destroy intestinal barrier function, which could be alleviated by SCFAs.

scholarly journals Effects of Fermented Feed on the Growth Performance, Intestinal Function and Microbiota of Piglets Weaned at Different Age

2021 ◽  
Author(s):  
Shuai Liu ◽  
Yunxia Xiong ◽  
Jingping Chen ◽  
Hao Xiao ◽  
Qiwen Wu ◽  
...  
Keyword(s):  
Growth Performance ◽  
Barrier Function ◽  
Control Diet ◽  
Intestinal Barrier ◽  
Dietary Supplementation ◽  
Short Chain Fatty Acids ◽  
Intestinal Barrier Function ◽  
Intestinal Function ◽  
Feed Conversion ◽  
Fermented Feed

Abstract BACKGROUND: The beneficial function of fermented feed in livestock industry has been widely investigated. However, little is known about the effects of fermented feed on different weaned-day piglets. This study aimed to investigate the effects of fermented diet on the growth performance, intestinal function and microbiota of piglets weaned at age of 21 days and 28 days.RESULTS: The results found that weaning on d 21 significantly increased (P < 0.05) ADG, and ADFI (calculated based on wet weight and dry matter), while reduced (P < 0.05) F: G, the activities of trypsin and lipase of jejunum and villus height of ileum, compared with 28-d weaning. The protein levels of Occludin, Claudin-1, ZO-1 of ileum in the groups weaning on d 21 were less (P < 0.05) than the groups weaning on d 28. Moreover, dietary supplementation with fermented diet upregulated (P < 0.05) Occludin, Claudin-1, ZO-1 proteins of ileum, compared with the groups treated with control diet both weaning on d 21 and d 28. In addition, dietary supplementation with fermented diet decreased (P < 0.05) the relative abundance of Clostridia (class) and increased (P < 0.05) Bacteroidia (class) level of cecal microbiota, compared with the groups treated with control diet both weaning on d 21 and d 28. However, supplementation with fermented diet did not affect the concentrations of short-chain fatty acids in the cecum (P > 0.05).CONCLUSION: Therefore, our data suggest that feed digestibility is improved in piglets weaned at 21 days, but intestinal barrier function is weaker than in piglets weaned at 28 days. However, compared with feeding control diet, supplementation with fermented diet both improved feed conversion and intestinal barrier function of weaned piglets by modulating intestinal microbiota.

Effects of Synbiotics to Prevent Postoperative Infectious Complications in Highly Invasive Abdominal Surgery

2017 ◽  
Vol 71 (Suppl. 1) ◽  
pp. 23-30 ◽  
Author(s):  
Yukihiro Yokoyama ◽  
Takashi Asahara ◽  
Koji Nomoto ◽  
Masato Nagino
Keyword(s):  
Lactic Acid ◽  
Abdominal Surgery ◽  
Bacterial Translocation ◽  
Barrier Function ◽  
Intestinal Microflora ◽  
Surgical Stress ◽  
Controlled Trial ◽  
Intestinal Barrier ◽  
Short Chain Fatty Acids ◽  
Intestinal Barrier Function

Postoperative infectious complication (POIC) is one of the most common complications following highly invasive abdominal surgeries, such as hepatectomy, esophagectomy, and pancreatoduodenectomy. The surgical stress temporarily deteriorates the intestinal microenvironment, and the fecal concentrations of beneficial bacteria such as Bifidobacterium and Lactobacillus decrease following highly invasive abdominal surgery. In parallel with these changes, the concentrations of fecal short-chain fatty acids (SCFAs) such as acetic acid, propionic acid, and butyric acid also decrease after surgery. In contrast, the fecal concentration of lactic acid increases under this condition because of the deterioration of the metabolism from lactic acid to SCFAs by normal intestinal microflora. Decreased fecal concentration of SCFAs may lead to an impaired intestinal barrier function under stressful condition. Translocation of bacteria from the gut to lymphatic and bloodstream leads to bacteremia and subsequent POICs. The incidence of POICs in patients with unhealthy intestinal microflora before surgery may be more because their intestine is more susceptible to bacterial translocation induced by surgical stress. Therefore, improving the intestinal microenvironment and intestinal barrier function before surgery is crucial to prevent POICs following highly invasive abdominal surgeries. In this regard, the use preoperative synbiotics therapy may be one of the effective ways because it has been shown to improve intestinal microflora, increase fecal SCFAs, prevent bacterial translocation, and reduce the incidence of POICs in several randomized controlled trial in patients undergoing highly invasive abdominal surgeries.

Intestinal barrier failure during experimental necrotizing enterocolitis: protective effect of EGF treatment

2006 ◽  
Vol 291 (5) ◽  
pp. G938-G949 ◽  
Author(s):  
Jessica A. Clark ◽  
Sarah M. Doelle ◽  
Melissa D. Halpern ◽  
Tara A. Saunders ◽  
Hana Holubec ◽  
...  
Keyword(s):  
Cell Density ◽  
Necrotizing Enterocolitis ◽  
Goblet Cell ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Paracellular Permeability ◽  
Intestinal Barrier Function ◽  
Proximal Jejunum ◽  
Mucin Production ◽  
Goblet Cell Density

Necrotizing enterocolitis (NEC) is the most common intestinal disease of premature infants. Although increased mucosal permeability and altered epithelial structure have been associated with many intestinal disorders, the role of intestinal barrier function in NEC pathogenesis is currently unknown. We investigated the structural and functional changes of the intestinal barrier in a rat model of NEC. In addition, the effect of EGF treatment on intestinal barrier function was evaluated. Premature rats were divided into three groups: dam fed (DF), formula fed (NEC), or fed with formula supplemented with 500 ng/ml EGF (NEC + EGF); all groups were exposed to asphyxia/cold stress to develop NEC. Intestinal permeability, goblet cell density, mucin production, and composition of tight junction (TJ) proteins were evaluated in the terminal ileum, the site of NEC injury, and compared with the proximal jejunum, which was unaffected by NEC. Animals with NEC had significantly increased intestinal paracellular permeability compared with DF pups. Ileal goblet cell morphology, mucin production, and TJ composition were altered in animals with NEC. EGF treatment significantly decreased intestinal paracellular permeability, increased goblet cell density and mucin production, and normalized expression of two major TJ proteins, occludin and claudin-3, in the ileum. In conclusion, experimental NEC is associated with disruption of the intestinal barrier. EGF treatment maintains intestinal integrity at the site of injury by accelerating goblet cell maturation and mucin production and normalizing expression of TJ proteins, leading to improved intestinal barrier function.

scholarly journals Retinoic Acid, Leaky Gut, and Autoimmune Diseases

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 1016 ◽  
Author(s):  
Leila Abdelhamid ◽  
Xin Luo
Keyword(s):  
Retinoic Acid ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Protective Effects ◽  
Leaky Gut ◽  
Gut Colonization ◽  
Lactobacillus Spp

A leaky gut has been observed in a number of autoimmune diseases including type 1 diabetes, multiple sclerosis, inflammatory bowel disease, and systemic lupus erythematosus. Previous studies from our laboratory have shown that lupus mice also bear a leaky gut and that the intestinal barrier function can be enhanced by gut colonization of probiotics such as Lactobacillus spp. Retinoic acid (RA) can increase the relative abundance of Lactobacillus spp. in the gut. Interestingly, RA has also been shown to strengthen the barrier function of epithelial cells in vitro and in the absence of probiotic bacteria. These reports bring up an interesting question of whether RA exerts protective effects on the intestinal barrier directly or through regulating the microbiota colonization. In this review, we will discuss the roles of RA in immunomodulation, recent literature on the involvement of a leaky gut in different autoimmune diseases, and how RA shapes the outcomes of these diseases.

scholarly journals JAM-A associates with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and regulate epithelial barrier function

2013 ◽  
Vol 24 (18) ◽  
pp. 2849-2860 ◽  
Author(s):  
Ana C. Monteiro ◽  
Ronen Sumagin ◽  
Carl R. Rankin ◽  
Giovanna Leoni ◽  
Michael J. Mina ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Paracellular Permeability ◽  
Small Gtpase ◽  
Intestinal Barrier Function ◽  
Epithelial Permeability ◽  
Functional Link ◽  
Epithelial Barrier Function ◽  
And Control ◽  
Interfering Rna

Intestinal barrier function is regulated by epithelial tight junctions (TJs), structures that control paracellular permeability. Junctional adhesion molecule-A (JAM-A) is a TJ-associated protein that regulates barrier; however, mechanisms linking JAM-A to epithelial permeability are poorly understood. Here we report that JAM-A associates directly with ZO-2 and indirectly with afadin, and this complex, along with PDZ-GEF1, activates the small GTPase Rap2c. Supporting a functional link, small interfering RNA–mediated down-regulation of the foregoing regulatory proteins results in enhanced permeability similar to that observed after JAM-A loss. JAM-A–deficient mice and cultured epithelial cells demonstrate enhanced paracellular permeability to large molecules, revealing a potential role of JAM-A in controlling perijunctional actin cytoskeleton in addition to its previously reported role in regulating claudin proteins and small-molecule permeability. Further experiments suggest that JAM-A does not regulate actin turnover but modulates activity of RhoA and phosphorylation of nonmuscle myosin, both implicated in actomyosin contraction. These results suggest that JAM-A regulates epithelial permeability via association with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and control contraction of the apical cytoskeleton.

scholarly journals Oxyresveratrol protective effects against deoxynivalenol-induced intestinal barrier dysfunction and bacterial translocation on porcine intestinal epithelial IPEC-J2 cells

2018 ◽  
Vol 1 ◽  
Author(s):  
Murphy L.Y. Wan ◽  
Ka Ho Ling ◽  
Hani El-Nezami ◽  
Mingfu Wang
Keyword(s):  
Bacterial Translocation ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Mitogen Activated Protein Kinase ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Damage ◽  
Protective Effects ◽  
Barrier Dysfunction ◽  
Significant Difference

Deoxynivalenol (DON) is a major mycotoxin contaminant and is known to impair intestinal barrier function. Previous experiments in our laboratory have proven that polyphenols such as resveratrol (RES) may be effective in enhancing epithelial barrier function. Due to the structural similarity of oxyresveratrol (OXY) with RES, it was hypothesized that OXY could also protect against DON-induced intestinal damage. Accordingly, this study aimed to explore potential protective effects of OXY against DON-induced epithelial barrier dysfunction and bacterial translocation on IPEC-J2 cells, in comparison to resveratrol (RES).The results showed that OXY increased transepithelial electrical resistance (TEER) and reduced FD-4 diffusion, whereas DON reduced TEER and increased FD-4 diffusion in IPEC-J2 cells. On the other hand, OXY reduced FD-4 diffusion in DON-damaged cells but showed no significant difference in terms of TEER. Such protective effects coincided with the significantly reduced E. coli translocation in cells co-exposed to DON and OXY. Further mechanistic studies demonstrated that OXY protected against DON-induced barrier dysfunction by enhancing the expression of claudin-4 via mitogen-activated protein kinase(MAPK)-dependent pathways. Apparently, OXY worked through the same way as RES did, with results dovetailed nicely with anticipation. These results imply that OXY may share similar health benefits with RES by enhancing epithelial barrier functions and protecting against DON-induced intestinal damage.

scholarly journals Protective Effects of Let-7b on the Expression of Occludin by Targeting P38 MAPK in Preventing Intestinal Barrier Dysfunction

2018 ◽  
Vol 45 (1) ◽  
pp. 343-355 ◽  
Author(s):  
Zhihua Liu ◽  
Yinghai Tian ◽  
Yanqiong Jiang ◽  
Shihua Chen ◽  
Ting Liu ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Conditional Knockout ◽  
Intestinal Barrier Function ◽  
Control Group ◽  
Protective Effects ◽  
Barrier Dysfunction ◽  
Entire Study ◽  
Intestinal Barrier Dysfunction

Background/Aims: Let-7b was dramatically reduced after a dicer knockout of mice with intestinal barrier function injuries. This paper aims to investigate the molecular mechanism of let-7b by targeting p38 MAPK in preventing intestinal barrier dysfunction. Methods: A total of 186 patients were enrolled, with 93 in the control group and 93 in the PRO group. Only 158 patients completed the entire study, whereas the others either did not meet the inclusion criteria or refused to participate. To further verify the role of let-7b, intestinal epithelial conditional knockout (IKO) mice of mmu-let-7b model were established. Serum let-7b, zonulin, IL-6, and TNF-α concentrations were measured by ELISA or quantitative RT-PCR. Permeability assay was done by ussing chamber. The apoptotic cells were identified using an In Situ Cell Death Detection Kit. Protein was detected by western blot. Results: Probiotics can lower infection-related complications, as well as increase the serum and tissue let-7b levels. P38 MAPK was identified as the target of let-7b, as verified by NCM460 cells. P38 MAPK expression was increased, whereas tight-junction (TJ) proteins were significantly decreased in let-7b IKO mice (both P<0.05). Negative regulation of p38 MAPK molecular signaling pathways was involved in the protective effects of let-7b on intestinal barrier function. Conclusion: Let-7b was identified as a novel diagnosis biomarker or a potential treatment target for preventing intestinal barrier dysfunction.

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