scholarly journals Gastrointestinal Digestion of a Grape Pomace Extract: Impact on Intestinal Barrier Permeability and Interaction with Gut Microbiome

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2467
Author(s):  
Diego Taladrid ◽  
Dolores González de Llano ◽  
Irene Zorraquín-Peña ◽  
Alba Tamargo ◽  
Mariana Silva ◽  
...  

Grape pomace (GP) is a winemaking by-product rich in polyphenols and fibre. Supplementation with GP extracts has shown potential benefits against oxidative stress- and inflammation-related pathologies. As a new nutritional target, this paper explores the impact of the ingestion of a grape pomace extract on intestinal barrier functionality. A GP extract was sequentially subjected to gastrointestinal and colonic digestion using the dynamic gastrointestinal simulator (simgi®). This generated two simulated fluids: intestinal-digested extract (IDE) and colonic-digested extract (CDE). The effects of these two fluids on paracellular permeability and the expression of tight junction (TJ) proteins (i.e., zonula occludens-1 (ZO-1) and occludin) were assessed in Caco-2-cell monolayers grown in Transwell® inserts. The IDE fluid significantly (p < 0.001) reduced the paracellular transport of FITC-dextran with respect to the control, whereas no significant differences (p > 0.05) were found for CDE, which could be due, at least partially, to the pro-leaky effect of the colonic digestion medium. Accordant slight increases in the mRNA levels of both ZO-1 and occludin were observed for IDE, but without statistical significance. Additionally, the colonic fermentation of the GP extract promoted the production of short-chain fatty acids (SCFA) and phenolic metabolites and led to changes in the relative abundance of some bacteria that might affect paracellular permeability. Overall, this paper reports first trends about the effects of grape pomace extracts on intestinal permeability that would require further confirmation in future experiments.

2021 ◽  
Vol 9 (7) ◽  
pp. 1378
Author(s):  
Irene Zorraquín-Peña ◽  
Diego Taladrid ◽  
Alba Tamargo ◽  
Mariana Silva ◽  
Natalia Molinero ◽  
...  

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.


1994 ◽  
Vol 267 (2) ◽  
pp. C537-C543 ◽  
Author(s):  
J. A. McRoberts ◽  
N. E. Riley

Previous studies have shown that insulin, insulin-like growth factors, and interferon-gamma cause an increase the paracellular permeability across T84 human colonic epithelial cell monolayers. The striking similarity in the time course and the structural changes in the actin cytoskeleton prompted us to test whether these factors influenced the paracellular permeability by a common mechanism. T84 cell monolayers were grown in variously modified media, and the effect of all three factors was tested by measuring the conductance of monolayers mounted in Ussing chambers. Media additions or deletions that modify cellular carbohydrate metabolism markedly influenced the response to all these peptides. In particular, the increase in conductance produced by each of the three peptides was 1) inhibited by addition of short-chain fatty acids, principally n-butyrate and propionate; 2) attenuated by the replacement of media glucose with slowly metabolized and nonmetabolized sugars; 3) potentiated by decreasing the media iron concentration; and 4) inhibited by increasing the media iron concentration. The effects of short-chain fatty acids, glucose, and iron were all shown to be dose dependent. In addition, the ability of high media iron to prevent the increase in permeability caused by all three factors was shown to require ambient oxygen. Together, these results strongly suggest that insulin, insulin-like growth factors, and interferon-gamma increase the permeability across T84 cell monolayers through a common mechanism that is modulated by glucose-derived metabolites and oxidative metabolism.


2007 ◽  
Vol 292 (3) ◽  
pp. E891-E899 ◽  
Author(s):  
Raul M. Luque ◽  
Zhi H. Huang ◽  
Bhumik Shah ◽  
Theodore Mazzone ◽  
Rhonda D. Kineman

Leptin-deficient obese mice ( ob/ob) have decreased circulating growth hormone (GH) and pituitary GH and ghrelin receptor (GHS-R) mRNA levels, whereas hypothalamic GH-releasing hormone (GHRH) and somatostatin (SST) expression do not differ from lean controls. Given the fact that GH is suppressed in diet-induced obesity (a state of hyperleptinemia), it remains to be determined whether the absence of leptin contributes to changes in the GH axis of ob/ob mice. Therefore, to study the impact of leptin replacement on the hypothalamic-pituitary GH axis of ob/ob mice, leptin was infused for 7 days (sc), resulting in circulating leptin levels that were similar to wild-type controls (∼1 ng/ml). Leptin treatment reduced food intake, body weight, and circulating insulin while elevating circulating n-octanoyl ghrelin concentrations. Leptin treatment did not alter hypothalamic GHRH, SST, or GHS-R mRNA levels compared with vehicle-treated controls. However, leptin significantly increased pituitary GH and GHRH-R expression and tended to enhance circulating GH levels, but this latter effect did not reach statistical significance. In vitro, leptin (1 ng/ml, 24 h) did not affect pituitary GH, GHRH-R, or GHS-R mRNA but did enhance GH release. The in vivo effects of leptin on circulating hormone and pituitary mRNA levels were not replicated by pair feeding ob/ob mice to match the food intake of leptin-treated mice. However, leptin did prevent the fall in hypothalamic GHRH mRNA and circulating IGF-I levels observed in pair-fed mice. These results demonstrate that leptin replacement has positive effects on multiple levels of GH axis function in ob/ob mice.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Maria Lerche Mace ◽  
Eva Gravesen ◽  
Anders Nordholm ◽  
Soeren Egstrand ◽  
Marya Morevati ◽  
...  

Abstract Background and Aims Several studies report an association between low BMD and vascular calcification (VC) in the general population and in CKD patients. Development of VC in CKD is a cell regulated process where the vascular smooth muscle cell alters phenotype to a bone-like secretory cell. Our group has previously demonstrated the expression of Wnt inhibitors in VC and so we ask if the presence of VC affects bone metabolism. Method A novel model of isogenic aorta transplantation (ATx) was developed and used in the study. Severe uremic vascular calcifications were induced in inbred Dark Aguti (DA) rats by 5/6 nephrectomy, high phosphate diet and calcitriol treatment. After 14 weeks the calcified abdominal aorta of the uremic rat was transplanted into a normal DA rat (uremic ATx, n=16). A normal aorta was transplanted into a normal DA rat as sham group (normal ATx, n=9) and age-matched normal rats were used as one more control group (control, n=6). Rats were sacrificed 4 weeks after ATx and plasma biochemistry, bone and vessels were analyzed. Data are presented as mean±SEM or median [range]. Statistical significance *p&lt;0.5,**p&lt;0.01,*** p&lt;0.001. Results The uremic donor rat suffered from severe kidney disease with disturbed mineral balance and its aorta had a high calcium content of 15.7±0.8 µg Ca/mg vs. none in the normal aorta. Uremic ATx, normal ATx and control rats had same plasma levels of creatinine, Ca2+, phosphate, PTH, FGF23 and sclerostin. The uremic ATx had significant lower bone mineral density (BMD) compared to normal ATx and control rats (1576±5 vs. 1592±5* & 1613±6* mg/cc). The impact on bone mineralization was also detected in the bone histomorphometry analysis, where the uremic ATx had less osteoid compared to normal ATx (median 3% [0,3%;8%] vs. 5% [2%;8%]*). Moreover, the uremic ATx had fewer osteoblasts and more osteoclasts. The effect on bone was supported by substantial gene analysis of several genes related to bone remodeling, mineralization and Wnt signaling. The uremic ATx rats had significant changes in mRNA levels of several genes in bone compared to normal ATX and control rats such as increased alkaline phosphatase (3.26±0.29 vs. 1.56±0.32*** & 0.86±0.12***), decreased osteoblast marker osteocalcin (0.54±0.06 vs. 0.92±0.14* & 1.19±0.06***) and increased osteoclast marker cathepsin K (2.36±0.24 vs. 1.19±0.23** & 1.01±0.07***). In addition, we found upregulation of the bone mineralization inhibitors osteopontin (1.46±0.18 vs. 0.69±0.17** & 0.49±0.06**) and progressive ankylosis protein homolog (8.10±0.60 vs. 3.21±0.74** & 2.39±0.48**) as well as collagen I (9.30 [2.73;14.81] vs. 2.30 [0.31;19.33]* & 2.78 [1.63;7.52]***). The inhibitor of bone formation sclerostin was significant increased (2.90 [1.54;13,29] vs. 1,23 [0.32;3.20]** & 0.93 [0.39;2,19]**) along with a slight downregulation of bone stimulator BMP2 (3.18±0.15 vs. 4.06±0.30* & 3.98±0.44*. Finally, the Wnt signaling pathway was affected by upregulation of β-catenin (3.15±0.25 vs. 1.28±0.26*** & 1.03±0.13***) and the downstream gene Snail1 (3.73±0.33 vs. 1.54±0.45*** & 1.04±0.12***). Conclusion These novel findings indicate the existence of a tissue crosstalk between vessels and bone. The presence of vascular calcification lowers BMD, decreases the amount of osteoid and affects several pathways in bone.


2021 ◽  
Vol 22 (13) ◽  
pp. 6728
Author(s):  
Giulia Gibiino ◽  
Martina De Siena ◽  
Monica Sbrancia ◽  
Cecilia Binda ◽  
Vittorio Sambri ◽  
...  

Diet is the first to affect our intestinal microbiota and therefore the state of eubiosis. Several studies are highlighting the potential benefits of taking certain nutritional supplements, but a dietary regime that can ensure the health of the intestinal microbiota, and the many pathways it governs, is not yet clearly defined. We performed a systematic review of the main studies concerning the impact of an omnivorous diet on the composition of the microbiota and the production of short-chain fatty acids (SCFAs). Some genera and phyla of interest emerged significantly and about half of the studies evaluated consider them to have an equally significant impact on the production of SCFAs, to be a source of nutrition for our colon cells, and many other processes. Although numerous randomized trials are still needed, the Mediterranean diet could play a valuable role in ensuring our health through direct interaction with our microbiota.


2017 ◽  
Vol 23 (5) ◽  
pp. 888-900 ◽  
Author(s):  
María del Pilar Agustín-Llach

Aims: The aim of the present paper is to look into the impact of bilingualism on lexical knowledge, lexical fluency, and lexical cross-linguistic influence (CLI). Design and methodology: To that end, Spanish monolingual (86) and Spanish–Basque bilingual (87) EFL learners were tested on lexical knowledge, lexical fluency, and (lexical) CLI by means of a task of lexical availability. Data were extracted from written sources. Data and analysis: Numerous responses were produced and instances of lexical CLI were examined and compared between monolingual and bilingual learners. Findings/Conclusions: Results point to a slight bilingual advantage in most of the measures tested but are not strong enough to reach statistical significance. Our results concur with previous studies in showing slight benefits for bilingual versus monolingual learners. Typological distance between Basque and English and the homogenization effect of schooling are thought to discard the potential benefits of bilingualism. Originality: This study shows that bilinguals are slightly better at lexical knowledge than monolingual counterparts. The comparisons of adolescent monolingual and bilingual learners learning an L3 under the same conditions are not frequent, neither is the examination of instances of lexical CLI. This is the main asset of the present study. Significance/implications: Our results suggest that teachers should encourage cross-linguistic comparison and positive lexical transfer through an increase in the use of cognates, since these can help then enhance and improve their lexical knowledge. Limitations: It is important to take into account that this study only looks at one specific aspect of lexical knowledge, other factors might also be influencing bilingual versus monolingual performance.


2018 ◽  
Vol 49 (1) ◽  
pp. 190-205 ◽  
Author(s):  
Yanhai Feng ◽  
Yu Wang ◽  
Pei Wang ◽  
Yalan Huang ◽  
Fengjun Wang

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.


2012 ◽  
Vol 142 (5) ◽  
pp. S-808-S-809
Author(s):  
Elhaseen Elamin ◽  
Daisy Jonkers ◽  
Harm-Jan Pieters ◽  
Freddy Troost ◽  
Jan Dekker ◽  
...  

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3038
Author(s):  
Alexandros Mavrommatis ◽  
Panagiotis E. Simitzis ◽  
Panagiota Kyriakaki ◽  
Elisavet Giamouri ◽  
Eleni D. Myrtsi ◽  
...  

The valorization of vinification byproducts portrays a promising bioprocess for the enrichment of animals’ diet with bioactive compounds, such as polyphenols, which could regulate the immune response. Therefore, the impact of dietary grounded grape pomace (GGP), wine lees extract (WYC), and grape stem extract (PE) on the relative transcript level of immune related genes of broiler chickens were examined. Two hundred forty, one-day-old as hatched (male/female) chicks (Ross 308) were allocated to four dietary groups, with four replicate pens each with 15 birds. Birds were fed either a basal diet (CON) or the basal diet supplemented with 2.5% GGP, or 0.2% WYC, or 0.1% PE for 42 d. The relative expression of immune-related genes was investigated using a real-time PCR platform. The mRNA levels of Toll-like Receptor 4 (TLR4) were downregulated (p = 0.039) in the liver of broilers fed the GGP-containing diet compared to the CON, while in the spleen of PE-fed broilers, TLR4 was significantly upregulated (p = 0.043). The mRNA levels of interleukin 8 (IL8) tended to upregulate (p = 0.099) in the bursa of Fabricius and were significantly increased (p = 0.036) in the spleen of broilers fed the PE diet. Vinification byproducts depict a promising sustainable source of polyphenols for the poultry feed industry, but more research is needed under field conditions.


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