Propionic Acid Targets the TLR4/NF-κB Signaling Pathway and Inhibits LPS-Induced Intestinal Barrier Dysfunction: In Vitro and In Vivo Studies

Yang, Randong; Hu, Xiaoxiao; Xie, Xianzheng; Chen, Haiqiong; Fang, Huang-Yi; Zhu, Lihong; Li, Zhongrong

doi:10.3389/fphar.2020.573475

Cited by 17 publications

(9 citation statements)

References 37 publications

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“…An increment in propionic acid levels, whose production in our study was strongly stimulated in the presence of IDW, has been previously reported after the intake of grape/wine polyphenols and the adherence to the Mediterranean diet [ 50 , 51 , 53 ]. Furthermore, a recent study has reported that this acid promoted cell migration, inhibited activation of NLRP3 inflammasome, and maintained intestinal barrier function in LPS-induced IEC-6 cells [ 54 ]. Besides, some species belonging to the Akkermansia genus, such as Akkermansia municiphila , considered acetate and propionate producing bacteria [ 55 ], have been reported to enhance the expression of TJ proteins in Caco-2 cells [ 56 ].…”

Section: Resultsmentioning

confidence: 99%

Effects of Wine and Its Microbial-Derived Metabolites on Intestinal Permeability Using Simulated Gastrointestinal Digestion/Colonic Fermentation and Caco-2 Intestinal Cell Models

et al. 2021

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This paper explores the effects of wine polyphenols on intestinal permeability in in vitro conditions. A red wine (2500 mg/L of gallic acid equivalents) was sequentially subjected to gastrointestinal and colonic digestion in the Dynamic Gastrointestinal Simulator (simgi®) to obtain two simulated fluids: intestinal-digested wine (IDW) and colonic-digested wine (CDW). The two fluids were incubated with Caco-2 cell monolayers grown in Transwell® inserts, and paracellular permeability was measured as transport of FITC-dextran. Non-significant decreases (p > 0.05) in paracellular permeability were found, which was attributed to the relatively low phenolic concentration in the solutions tested (15.6 and 7.8 mg of gallic acid equivalents/L for IDW and CDW, respectively) as quercetin (200 µM) and one of its microbial-derived phenolic metabolites, 3,4-dihydroxyphenylacetic acid (200 µM), led to significant decreases (p < 0.05). The expression of tight junction (TJ) proteins (i.e., ZO-1 and occludin) in Caco-2 cells after incubation with IDW and CDW was also determined. A slight increase in mRNA levels for occludin for both IDW and CDW fluids, albeit without statistical significance (p > 0.05), was observed. Analysis of the microbiome and microbial activity during wine colonic fermentation revealed relevant changes in the relative abundance of some families/genera (i.e., reduction in Bacteroides and an increase in Veillonella, Escherichia/Shigella and Akkermansia) as well as in the microbial production of SCFA (i.e., a significant increase in propionic acid in the presence of IDW), all of which might affect paracellular permeability. Both direct and indirect (microbiota-mediated) mechanisms might be involved in the protective effects of (wine) polyphenols on intestinal barrier integrity. Overall, this paper reinforces (wine) polyphenols as a promising dietary strategy to improve gut functionality, although further studies are needed to evaluate the effect on the intestinal barrier under different conditions.

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Section: Resultsmentioning

confidence: 99%

Effects of Wine and Its Microbial-Derived Metabolites on Intestinal Permeability Using Simulated Gastrointestinal Digestion/Colonic Fermentation and Caco-2 Intestinal Cell Models

et al. 2021

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“…High-dose propionate has been reported to reduce LPS-induced inflammatory response in mouse endothelial cells and alveolar macrophages in a TLR-4 dependent manner ( 55 ). Another report showed the protective effect of PA against IκBα degradation and p65 translocation in LPS-treated IEC-6 cells ( 56 ), which suggests the suppression of the NF-κB/TLR-4 pathway by PA. In the present study, PA directly suppressed the HMGB-1 triggered TLR-4 activation in macrophages and suppressed TNF-α production.…”

Section: Discussionmentioning

confidence: 95%

Propionic Acid, Induced in Gut by an Inulin Diet, Suppresses Inflammation and Ameliorates Liver Ischemia and Reperfusion Injury in Mice

et al. 2022

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Liver ischemia and reperfusion injury (IRI) is one of the obstacles in liver surgery such as liver resection and transplantation. In this study, we investigated the preventive effect on mouse liver IRI by feeding mice with inulin, which is a heterogeneous blend of indigestible fructose polymer. Mice were fed either a control ordinary diet (CD) or an inulin diet (ID) containing 5% inulin in the CD, for 14 days before the ischemia and reperfusion (IR) maneuver. IR induced-liver damages were significantly ameliorated in the ID group, compared with those in the CD group. Feeding mice with an ID, but not a CD, elevated levels of Bacteroidetes among gut microbiota, and especially increased Bacteroides acidifaciens in mouse feces, which resulted in significant elevation of short-chain fatty acids (SCFAs) in the portal vein of mice. Among SCFAs, propionic acid (PA) was most significantly increased. The microbial gene functions related to PA biosynthesis were much higher in the fecal microbiome of the ID group compared to the CD. However, the action of PA on liver IRI has not been yet clarified. Direct intraperitoneal administration of PA alone prior to the ischemia strongly suppressed liver cell damages as well as inflammatory responses caused by liver IR. Furthermore, PA suppressed the secretion of inflammatory cytokines from peritoneal macrophages stimulated in vitro through TLR-4 with high-mobility group box 1 protein (HMGB-1), known to be released from apoptotic liver cells during the IR insult. The present study shows that PA may play a key role in the inulin-induced amelioration of mouse liver IRI.

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“…TLR4 plays a key role in inherent immunity by activating proinflammatory pathways in different cell types and inducing cytokine generation. The TLR4/NF-κB signaling pathway has been considered a major modulator of the inflammatory response [23]. TLR4 signaling is required for the induction of NEC in both mice and patients [24].…”

Section: Discussionmentioning

confidence: 99%

Sodium Butyrate Alleviates Intestinal Inflammation in Mice with Necrotizing Enterocolitis

Sun

Wang

et al. 2021

Mediators of Inflammation

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Objective. To determine the role of sodium butyrate in intestinal inflammation via regulation of high-mobility group box-1 (HMGB1), we analyzed the potential mechanism in necrotizing enterocolitis (NEC) in a neonatal mouse model. Methods. A NEC model was created with hypoxia and cold exposure and artificial overfeeding. C57BL/6 neonatal mice were randomized into three groups: the control, untreated NEC, and sodium butyrate (150 mM)-pretreated NEC groups. Pathological variations in ileocecal intestinal tissue were observed by HE staining and scored in a double-blind manner. The mRNA expression levels of HMGB1, Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), and inflammatory cytokines in intestinal tissues were determined by quantitative real-time PCR. The protein levels of HMGB1 and associated cytokines in intestinal tissues were evaluated using ELISA. The relative protein expression levels of TLR4 and NF-κB in intestinal tissues were quantified by western blot. Results. Sodium butyrate administration improved the body weight and survival rate of NEC mice; relieved intestinal pathological injury; reduced the intestinal expression of HMGB1, TLR4, NF-κB, interleukin- (IL-) 1β, IL-6, IL-8, and TNF-α; and increased the intestinal expression of IL-10 ( P < 0.05 ). Treatment with butyrate decreased the proportion of opportunistic Clostridium_sensu_stricto_1 and Enterococcus and increased the proportion of beneficial Firmicutes and Lactobacillus in the NEC model. Conclusions. Sodium butyrate intervention relieves intestinal inflammation and partially corrects the disrupted intestinal flora in mice with NEC.

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Propionic Acid Targets the TLR4/NF-κB Signaling Pathway and Inhibits LPS-Induced Intestinal Barrier Dysfunction: In Vitro and In Vivo Studies

Cited by 17 publications

References 37 publications

Effects of Wine and Its Microbial-Derived Metabolites on Intestinal Permeability Using Simulated Gastrointestinal Digestion/Colonic Fermentation and Caco-2 Intestinal Cell Models

Effects of Wine and Its Microbial-Derived Metabolites on Intestinal Permeability Using Simulated Gastrointestinal Digestion/Colonic Fermentation and Caco-2 Intestinal Cell Models

Propionic Acid, Induced in Gut by an Inulin Diet, Suppresses Inflammation and Ameliorates Liver Ischemia and Reperfusion Injury in Mice

Sodium Butyrate Alleviates Intestinal Inflammation in Mice with Necrotizing Enterocolitis

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