scholarly journals GPR120 prevents colorectal adenocarcinoma progression by sustaining the mucosal barrier integrity

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Federica Rubbino ◽  
Valentina Garlatti ◽  
Valeria Garzarelli ◽  
Luca Massimino ◽  
Salvatore Spanò ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acids ◽  
Intestinal Permeability ◽  
Mucosal Barrier ◽  
Phenotypic Characterization ◽  
Early Event ◽  
Blue Dye ◽  
Barrier Integrity ◽  
Chain Fatty Acids

AbstractGPR120 (encoded by FFAR4 gene) is a receptor for long chain fatty acids, activated by ω-3 Polyunsaturated Fatty Acids (PUFAs), and expressed in many cell types. Its role in the context of colorectal cancer (CRC) is still puzzling with many controversial evidences. Here, we explored the involvement of epithelial GPR120 in the CRC development. Both in vitro and in vivo experiments were conducted to mimic the conditional deletion of the receptor from gut epithelium. Intestinal permeability and integrity of mucus layer were assessed by using Evans blue dye and immunofluorescence for MUC-2 protein, respectively. Microbiota composition, presence of lipid mediators and short chain fatty acids were analyzed in the stools of conditional GPR120 and wild type (WT) mice. Incidence and grade of tumors were evaluated in all groups of mice before and after colitis-associated cancer. Finally, GPR120 expression was analyzed in 9 human normal tissues, 9 adenomas, and 17 primary adenocarcinomas. Our work for the first time highlights the role of the receptor in the progression of colorectal cancer. We observed that the loss of epithelial GPR120 in the gut results into increased intestinal permeability, microbiota translocation and dysbiosis, which turns into hyperproliferation of epithelial cells, likely through the activation of β -catenin signaling. Therefore, the loss of GPR120 represents an early event of CRC, but avoid its progression as invasive cancer. these results demonstrate that the epithelial GPR120 receptor is essential to maintain the mucosal barrier integrity and to prevent CRC developing. Therefore, our data pave the way to GPR120 as an useful marker for the phenotypic characterization of CRC lesions and as new potential target for CRC prevention.

scholarly journals GPR120 Prevents Colorectal Adenocarcinoma Progression by Sustaining The Mucosal Barrier Integrity

2021 ◽  
Author(s):  
Federica Rubbino ◽  
Valentina Garlatti ◽  
Valeria Garzarelli ◽  
Luca Massimino ◽  
Salvatore Spanò ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acids ◽  
Intestinal Permeability ◽  
Mucosal Barrier ◽  
Phenotypic Characterization ◽  
Early Event ◽  
Blue Dye ◽  
Barrier Integrity ◽  
Chain Fatty Acids

Abstract Background&Aims: GPR120 (encoded by FFAR4 gene) is a receptor for long chain fatty acids, activated by ω-3 PUFAs, and expressed in many cell types. Its role in the context of colorectal cancer (CRC) is still puzzling with many controversial evidences. Here, we explored the involvement of epithelial GPR120 in the CRC development. Methods: Both in vitro and in vivo experiments were conducted to mimic the conditional deletion of the receptor from gut epithelium. Intestinal permeability and integrity of mucus layer were assessed by using Evans blue dye and immunofluorescence for MUC-2 protein, respectively. Microbiota composition, presence of lipid mediators and short chain fatty acids were analyzed in the stools of conditional GPR120 and wild type (WT) mice. Incidence and grade of tumors were evaluated in all groups of mice before and after colitis-associated cancer. Finally, GPR120 expression was analyzed in 9 human normal tissues, 9 adenomas, and 17 primary adenocarcinomas. Results: Our work for the first time highlight the role of the receptor in the progression of colorectal cancer. We observed that the loss of epithelial GPR120 in the gut results into increased intestinal permeability, microbiota translocation and dysbiosis, which turns into hyperproliferation of epithelial cells, likely through the activation of β -catenin signaling. Therefore, the loss of GPR120 represents an early event of CRC, but avoid its progression as invasive cancer. Conclusion: these results demonstrate that the epithelial GPR120 receptor is essential to maintain the mucosal barrier integrity and to prevent CRC developing. Therefore, our data pave the way to GPR120 as an useful marker for the phenotypic characterization of CRC lesions and as new potential target for CRC prevention.

scholarly journals Effect of a novel animal milk oligosaccharide biosimilar on the gut microbial communities and metabolites of in vitro incubations using feline and canine fecal inocula

2020 ◽  
Vol 98 (9) ◽  
Author(s):  
Patrícia M Oba ◽  
Sara Vidal ◽  
Romain Wyss ◽  
Yong Miao ◽  
Yemi Adesokan ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Growth Promotion ◽  
Quantitative Polymerase Chain Reaction ◽  
Random Effect ◽  
Short Chain Fatty Acids ◽  
Mucosal Barrier ◽  
Fermentation System ◽  
Animal Milk ◽  
Chain Fatty Acids

Abstract Milk oligosaccharides (MO) confer multiple potential physiological benefits, such as the selective growth promotion of beneficial microbiota, inhibition of enteric pathogen growth and adhesion to enterocytes, maturation of the gut mucosal barrier, and modulation of the gastrointestinal immune system. This study was conducted to determine the fermentation potential of GNU100, an animal MO biosimilar, in an in vitro system using healthy canine and feline fecal inocula. Single feline and single canine fecal samples were used to inoculate a batch fermentation system. Tubes containing a blank control (BNC), GNU100 at 0.5% (5 g/L; GNU1), or GNU100 at 1.0% (10 g/L; GNU2) were incubated for 48 h. Gas pressure, pH, lactate, short-chain fatty acids (SCFA; acetate, propionate, and butyrate), and branched-chain fatty acids (BCFA; isobutyrate, isovalerate, and valerate) were measured after 6, 24, and 48 h. Ammonium and microbiota (total bacteria by flow cytometry and Pet-16Seq; Lactobacillus and Bifidobacterium by quantitative polymerase chain reaction ) were measured after 24 and 48 h. Data were analyzed using the Mixed Models procedure of SAS. Substrates were considered to be a fixed effect and replicates considered to be a random effect. Tukey’s multiple comparison analysis was used to compare least squares means, with differences considered significant with P < 0.05. In feline and canine incubations, SCFA increases were greater (P < 0.0001) in GNU100 compared with BNC, with acetate making up the largest SCFA proportion (P < 0.0001). GNU100 cultures led to greater increases (P < 0.0001) in lactate and ammonium than BNC in the feline incubations. GNU100 cultures led to greater increases (P < 0.0001) in ammonium than BNC in canine incubations and greater increases (P < 0.0001) in BCFA than BNC in feline incubations. Pet-16Seq microbial profiles from the feline and canine fecal incubations exhibited a modulation after GNU100 fermentation, with a reduction of the genera Escherichia/Shigella and Salmonella. In feline incubations, Bifidobacterium populations had greater increases (P < 0.0001) in GNU100 than BNC. In feline incubations, Lactobacillus populations had greater increases (P = 0.01) in GNU100 than BNC, with GNU1 leading to greater increases (P = 0.02) in Lactobacillus than BNC tubes in canine incubations. Overall, this study demonstrated that GNU100 was fermented in an in vitro fermentation system inoculated with canine and feline microbiota, resulting in the growth of beneficial bacteria and the production of SCFA, BCFA, and ammonium.

Short-Chain Fatty Acids Prevent Diabetic Nephropathy In Vivo and In Vitro

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 92-OR ◽  
Author(s):  
WEI HUANG ◽  
YONG XU ◽  
YOUHUA XU ◽  
LUPING ZHOU ◽  
CHENLIN GAO
Keyword(s):  
Fatty Acids ◽  
Diabetic Nephropathy ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Chain Fatty Acids

PSIII-12 In vitro Evaluation of Purified Fiber Sources for Production of Short-chain Fatty Acids Using Pig Cecal Content as an Inoculum

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 177-177
Author(s):  
Gabriela E Martinez Padilla ◽  
Rajesh Jha ◽  
Vivek Fellner ◽  
Eric van Heugten
Keyword(s):  
Fatty Acids ◽  
Enzymatic Hydrolysis ◽  
Resistant Starch ◽  
Potato Starch ◽  
Short Chain ◽  
Gas Liquid Chromatography ◽  
Citrus Peel ◽  
Starch Potato ◽  
Chain Fatty Acids

Abstract This study evaluated short-chain fatty acid (SCFA) production from purified fiber sources when fermented in vitro using pig cecal contents as an inoculum. Fiber sources of interest were inulin from chicory root (native and long-chain inulin with 90 and 98% fiber, respectively), pectin from citrus peel (high methoxyl pectin), resistant starch (native starch), potato starch (commercial grade), and β-glucan (β-1,3;β-1,6 yeast-derived). Cellulose and cornstarch were used as indigestible and highly digestible carbohydrates, respectively. Triplicate samples of substrates (2 g) were subjected to enzymatic hydrolysis with pepsin and pancreatin for 6 h. Subsequently, hydrolyzed residues (200 mg) were incubated under anaerobic conditions at 39°C with 30 mL solution of cecal inoculum collected from 3 sows fed a standard commercial diet and buffered mineral solution. After 48 h of incubation, solutions from fermented samples were analyzed for pH, SCFA, and branched-chain fatty acids (BCFA) using gas-liquid chromatography. Enzymatic hydrolysis had no effect on digestion of β-glucan, but total SCFA concentration after fermentation was highest (26.13 mmol/g) followed by resistant starch (22.61 mmol/g) and potato starch (22.20 mmol/g) and was lowest for cellulose (13.91 mmol/g). In contrast, native inulin was highly digested during enzymatic hydrolysis, resulting in the lowest substrate available for fermentation (11.84% DM) and the highest pH (5.98). Enzymatic hydrolysis and fermentation of resistant starch increased (P< 0.001) concentrations of acetate (0.60 mg/g), whereas potato starch and β-glucan yielded more butyrate (0.60 and 0.54 mg/g respectively), and β-glucan resulted in greater (P< 0.001) propionate concentrations (0.69 mg/g). Pectin resulted in the highest fermentation (82.38% DM disappearance) and the lowest pH (4.03) compared to the other fiber sources (P< 0.001) and yielded the lowest BCFA concentration (1.89 mM, P< 0.001). Results suggest that fermentation of resistant starch, potato starch, and β-glucan produced higher SCFA concentrations, while pectin resulted in a decreased pH of fermentation solution.

scholarly journals The impact of long-term dietary pattern of fecal donor on in vitro fecal fermentation properties of inulin

2016 ◽  
Vol 7 (4) ◽  
pp. 1805-1813 ◽  
Author(s):  
Junyi Yang ◽  
Devin J. Rose
Keyword(s):  
Fatty Acids ◽  
Short Chain Fatty Acids ◽  
Processed Meats ◽  
Branched Chain Fatty Acids ◽  
Fiber Plant ◽  
Branched Chain ◽  
The Impact ◽  
Chain Fatty Acids

A diet high in whole grains, dry beans, and certain vegetables that contributed dietary fiber, plant protein, and B vitamins resulted in high short chain fatty acids, while a diet high in diary and processed meats that provided cholesterol and little fiber resulted in high branched chain fatty acids and ammonia during fecal fermentation of inulin.

scholarly journals Profiles of Odd- and Branched-Chain Fatty Acids and Their Correlations With Rumen Fermentation Parameters, Microbial Protein Synthesis and Bacterial Populations Based on Pure Carbohydrate Incubation in Vitro

2020 ◽  
Author(s):  
Hangshu Xin ◽  
Xin Liu ◽  
Xin Jiang ◽  
Chunlong Liu ◽  
Shuzhi Zhang ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Volatile Fatty Acids ◽  
Cellulolytic Bacteria ◽  
Bacterial Populations ◽  
Branched Chain Fatty Acids ◽  
Degrading Bacteria ◽  
Branched Chain ◽  
Fermentation Parameters ◽  
Chain Fatty Acids

Abstract Background: The objectives of this study were to evaluate the profiles of odd- and branched-chain fatty acids (OBCFA; including C15:0, iso-C15:0, anteiso-C15:0, iso-C16:0, C17:0, iso-C17:0 and anteiso-C17:0) during pure carbohydrates incubation in vitro and whether they correlated with ruminal fermentation parameters, microbial crude protein (MCP) synthesis, and bacterial populations. The pure substrates containing five different ratios of fiber and starch (F:S; 0:100, 25:75, 50:50, 75:25 and 100:0) were incubated for 6 h, 12 h, 18 h and 24 h. Results: Except iso-C17:0, OBCFA concentrations were interacted by F:S and incubation time. The highest concentration of total OBCFA was found in the fermented mixture after 24 h of incubation when the F:S = 0:100; while the lowest level was 1.65 mg/g DM produced after 6 h of incubation with F:S = 50:50. The concentrations of total volatile fatty acids (TVFA) and MCP remarkably decreased linearly as the inclusion of fiber in the substrates increased, as expected. The proportions of investigated cellulolytic bacteria in our study were increased linearly (or linearly and quadratically) while those of R. amylophilus and S. bovis were decreased as fiber inclusion increased. The correlation analysis indicated that iso-C16:0 concentration might have potential as a marker of productions of TVFA and MCP with ρ being 0.78 and 0.82 respectively. Compared to starch degrading bacteria, cellulolytic bacteria had more correlations with OBCFA profiles, and the strongest association was found on the population of R. flavefaciens with C15:0 concentration (ρ = 0.70). Conclusions: Our study shows there might be scope for iso-C16:0 to predict rumen productions of VFA and MCP. Notedly, this is the first paper reporting linkage of OBCFA with rumen function based on pure carbohydrate in vitro incubation, which would avoid confounding interference from dietary protein and fat presence. However, more in-depth experiments are needed to substantiate the current findings.

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