Cocoa diet modulates gut microbiota composition and improves intestinal health in Zucker diabetic rats

[Display omitted] •Intestinal barrier integrity is improved in diabetic rats submitted to cocoa diet.•Cocoa diet prevents intestinal inflammation in diabetic rats.•Cocoa diet modifies gut microbiota to a healthier microbial profile in diabetic rats.•Total levels of short-chain fatty acids increases...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Food research international 2020-06, Vol.132, p.109058-109058, Article 109058
Hauptverfasser: Álvarez-Cilleros, David, Ramos, Sonia, López-Oliva, María Elvira, Escrivá, Fernando, Álvarez, Carmen, Fernández-Millán, Elisa, Martín, María Ángeles
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 109058
container_issue
container_start_page 109058
container_title Food research international
container_volume 132
creator Álvarez-Cilleros, David
Ramos, Sonia
López-Oliva, María Elvira
Escrivá, Fernando
Álvarez, Carmen
Fernández-Millán, Elisa
Martín, María Ángeles
description [Display omitted] •Intestinal barrier integrity is improved in diabetic rats submitted to cocoa diet.•Cocoa diet prevents intestinal inflammation in diabetic rats.•Cocoa diet modifies gut microbiota to a healthier microbial profile in diabetic rats.•Total levels of short-chain fatty acids increases in diabetic rats fed on cocoa. Cocoa supplementation improves glucose metabolism in Zucker diabetic fatty (ZDF) rats via multiple mechanisms. Furthermore, cocoa rich-diets modify the intestinal microbiota composition both in humans and rats in healthy conditions. Accordingly, we hypothesized that cocoa could interact with the gut microbiota (GM) in ZDF rats, contributing to their antidiabetic effects. Therefore, here we investigate the effect of cocoa intake on gut health and GM in ZDF diabetic rats. Male ZDF rats were fed with standard (ZDF-C) or 10% cocoa-rich diet (ZDF-Co) during 10 weeks. Zucker Lean animals (ZL) received the standard diet. Colon tissues were obtained to determine the barrier integrity and the inflammatory status of the intestine and faeces were analysed for microbial composition, short-chain fatty acids (SCFA) and lactate levels. We found that cocoa supplementation up-regulated the levels of the tight junction protein Zonula occludens-1 (ZO-1) and the mucin glycoprotein and reduced the expression of pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1) in the colon of ZDF diabetic animals. Additionally, cocoa modulated the microbial composition of the ZDF rats to values similar to those of the lean group. Importantly, cocoa treatment increased the relative abundance of acetate-producing bacteria such as Blautia and prevented the increase in the relative amount of lactate-producing bacteria (mainly Enterococcus and Lactobacillus genera) in ZDF diabetic animals. Accordingly, the total levels of SCFA (mainly acetate) increased significantly in the faeces of ZDF-Co diabetic rats. Finally, modified GM was closely associated with improved biochemical parameters related to glucose homeostasis and intestinal integrity and inflammation. These findings demonstrate for the first time that cocoa intake modifies intestinal bacteria composition towards a healthier microbial profile in diabetic animals and suggest that these changes could be associated with the improved glucose homeostasis and gut health induced by cocoa in ZDF diabetic rats.
doi_str_mv 10.1016/j.foodres.2020.109058
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2394889858</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0963996920300831</els_id><sourcerecordid>2394889858</sourcerecordid><originalsourceid>FETCH-LOGICAL-c478t-764779259290665238458a670431ea3a15f128ec3a35fc9af0848f4cde81582a3</originalsourceid><addsrcrecordid>eNqFkEtvEzEQgC0EoqHlJ4B85LLBj_XrhFBEC1IlLnDpxZp4Z6nD7jrY3kr8exwlcOU0mtE3r4-QN5xtOeP6_WE7pjRkLFvBxKnmmLLPyIZbIzvDe_WcbJjTsnNOuyvyqpQDY0wr416SKymk5NrIDRl3KSSgQ8RK5zSsE1Qs9Mfashhy2sdUgYY0H1OJNaaFwjLQOB9zempcXBpd4wITfUSY6mOr0Ic1_MTcRsIeaww0Qy035MUIU8HXl3hNvt9--rb73N1_vfuy-3jfhd7Y2hndG-OEcsIxrZWQtlcWtGG95AgSuBq5sBgkSDUGByOzvR37MKDlygqQ1-TdeW478NfabvNzLAGnCRZMa_FCut5aZ5VtqDqj7c1SMo7-mOMM-bfnzJ8U-4O_KPYnxf6suPW9vaxY9zMO_7r-Om3AhzOA7dGniNmXEHEJOMSMofohxf-s-AMNZpAT</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2394889858</pqid></control><display><type>article</type><title>Cocoa diet modulates gut microbiota composition and improves intestinal health in Zucker diabetic rats</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Álvarez-Cilleros, David ; Ramos, Sonia ; López-Oliva, María Elvira ; Escrivá, Fernando ; Álvarez, Carmen ; Fernández-Millán, Elisa ; Martín, María Ángeles</creator><creatorcontrib>Álvarez-Cilleros, David ; Ramos, Sonia ; López-Oliva, María Elvira ; Escrivá, Fernando ; Álvarez, Carmen ; Fernández-Millán, Elisa ; Martín, María Ángeles</creatorcontrib><description>[Display omitted] •Intestinal barrier integrity is improved in diabetic rats submitted to cocoa diet.•Cocoa diet prevents intestinal inflammation in diabetic rats.•Cocoa diet modifies gut microbiota to a healthier microbial profile in diabetic rats.•Total levels of short-chain fatty acids increases in diabetic rats fed on cocoa. Cocoa supplementation improves glucose metabolism in Zucker diabetic fatty (ZDF) rats via multiple mechanisms. Furthermore, cocoa rich-diets modify the intestinal microbiota composition both in humans and rats in healthy conditions. Accordingly, we hypothesized that cocoa could interact with the gut microbiota (GM) in ZDF rats, contributing to their antidiabetic effects. Therefore, here we investigate the effect of cocoa intake on gut health and GM in ZDF diabetic rats. Male ZDF rats were fed with standard (ZDF-C) or 10% cocoa-rich diet (ZDF-Co) during 10 weeks. Zucker Lean animals (ZL) received the standard diet. Colon tissues were obtained to determine the barrier integrity and the inflammatory status of the intestine and faeces were analysed for microbial composition, short-chain fatty acids (SCFA) and lactate levels. We found that cocoa supplementation up-regulated the levels of the tight junction protein Zonula occludens-1 (ZO-1) and the mucin glycoprotein and reduced the expression of pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1) in the colon of ZDF diabetic animals. Additionally, cocoa modulated the microbial composition of the ZDF rats to values similar to those of the lean group. Importantly, cocoa treatment increased the relative abundance of acetate-producing bacteria such as Blautia and prevented the increase in the relative amount of lactate-producing bacteria (mainly Enterococcus and Lactobacillus genera) in ZDF diabetic animals. Accordingly, the total levels of SCFA (mainly acetate) increased significantly in the faeces of ZDF-Co diabetic rats. Finally, modified GM was closely associated with improved biochemical parameters related to glucose homeostasis and intestinal integrity and inflammation. These findings demonstrate for the first time that cocoa intake modifies intestinal bacteria composition towards a healthier microbial profile in diabetic animals and suggest that these changes could be associated with the improved glucose homeostasis and gut health induced by cocoa in ZDF diabetic rats.</description><identifier>ISSN: 0963-9969</identifier><identifier>EISSN: 1873-7145</identifier><identifier>DOI: 10.1016/j.foodres.2020.109058</identifier><identifier>PMID: 32331673</identifier><language>eng</language><publisher>Canada: Elsevier Ltd</publisher><subject>Animals ; Bacteria - classification ; Blood Glucose ; Cacao ; Chemokine CCL2 ; Cocoa flavanols ; Colon - microbiology ; Colon - pathology ; Diabetes Mellitus, Experimental - diet therapy ; Diabetes type 2 ; Diet ; Fatty Acids, Volatile ; Gastrointestinal Microbiome - drug effects ; Glucose homeostasis ; Glucose Tolerance Test ; Gut barrier ; Gut inflammation ; Gut microbiota ; Homeostasis - drug effects ; Hypoglycemic Agents - pharmacology ; Interleukin-6 ; Male ; Rats ; Rats, Zucker ; Tumor Necrosis Factor-alpha ; Zonula Occludens-1 Protein - metabolism</subject><ispartof>Food research international, 2020-06, Vol.132, p.109058-109058, Article 109058</ispartof><rights>2020 Elsevier Ltd</rights><rights>Copyright © 2020 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-764779259290665238458a670431ea3a15f128ec3a35fc9af0848f4cde81582a3</citedby><cites>FETCH-LOGICAL-c478t-764779259290665238458a670431ea3a15f128ec3a35fc9af0848f4cde81582a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.foodres.2020.109058$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32331673$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Álvarez-Cilleros, David</creatorcontrib><creatorcontrib>Ramos, Sonia</creatorcontrib><creatorcontrib>López-Oliva, María Elvira</creatorcontrib><creatorcontrib>Escrivá, Fernando</creatorcontrib><creatorcontrib>Álvarez, Carmen</creatorcontrib><creatorcontrib>Fernández-Millán, Elisa</creatorcontrib><creatorcontrib>Martín, María Ángeles</creatorcontrib><title>Cocoa diet modulates gut microbiota composition and improves intestinal health in Zucker diabetic rats</title><title>Food research international</title><addtitle>Food Res Int</addtitle><description>[Display omitted] •Intestinal barrier integrity is improved in diabetic rats submitted to cocoa diet.•Cocoa diet prevents intestinal inflammation in diabetic rats.•Cocoa diet modifies gut microbiota to a healthier microbial profile in diabetic rats.•Total levels of short-chain fatty acids increases in diabetic rats fed on cocoa. Cocoa supplementation improves glucose metabolism in Zucker diabetic fatty (ZDF) rats via multiple mechanisms. Furthermore, cocoa rich-diets modify the intestinal microbiota composition both in humans and rats in healthy conditions. Accordingly, we hypothesized that cocoa could interact with the gut microbiota (GM) in ZDF rats, contributing to their antidiabetic effects. Therefore, here we investigate the effect of cocoa intake on gut health and GM in ZDF diabetic rats. Male ZDF rats were fed with standard (ZDF-C) or 10% cocoa-rich diet (ZDF-Co) during 10 weeks. Zucker Lean animals (ZL) received the standard diet. Colon tissues were obtained to determine the barrier integrity and the inflammatory status of the intestine and faeces were analysed for microbial composition, short-chain fatty acids (SCFA) and lactate levels. We found that cocoa supplementation up-regulated the levels of the tight junction protein Zonula occludens-1 (ZO-1) and the mucin glycoprotein and reduced the expression of pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1) in the colon of ZDF diabetic animals. Additionally, cocoa modulated the microbial composition of the ZDF rats to values similar to those of the lean group. Importantly, cocoa treatment increased the relative abundance of acetate-producing bacteria such as Blautia and prevented the increase in the relative amount of lactate-producing bacteria (mainly Enterococcus and Lactobacillus genera) in ZDF diabetic animals. Accordingly, the total levels of SCFA (mainly acetate) increased significantly in the faeces of ZDF-Co diabetic rats. Finally, modified GM was closely associated with improved biochemical parameters related to glucose homeostasis and intestinal integrity and inflammation. These findings demonstrate for the first time that cocoa intake modifies intestinal bacteria composition towards a healthier microbial profile in diabetic animals and suggest that these changes could be associated with the improved glucose homeostasis and gut health induced by cocoa in ZDF diabetic rats.</description><subject>Animals</subject><subject>Bacteria - classification</subject><subject>Blood Glucose</subject><subject>Cacao</subject><subject>Chemokine CCL2</subject><subject>Cocoa flavanols</subject><subject>Colon - microbiology</subject><subject>Colon - pathology</subject><subject>Diabetes Mellitus, Experimental - diet therapy</subject><subject>Diabetes type 2</subject><subject>Diet</subject><subject>Fatty Acids, Volatile</subject><subject>Gastrointestinal Microbiome - drug effects</subject><subject>Glucose homeostasis</subject><subject>Glucose Tolerance Test</subject><subject>Gut barrier</subject><subject>Gut inflammation</subject><subject>Gut microbiota</subject><subject>Homeostasis - drug effects</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Interleukin-6</subject><subject>Male</subject><subject>Rats</subject><subject>Rats, Zucker</subject><subject>Tumor Necrosis Factor-alpha</subject><subject>Zonula Occludens-1 Protein - metabolism</subject><issn>0963-9969</issn><issn>1873-7145</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtvEzEQgC0EoqHlJ4B85LLBj_XrhFBEC1IlLnDpxZp4Z6nD7jrY3kr8exwlcOU0mtE3r4-QN5xtOeP6_WE7pjRkLFvBxKnmmLLPyIZbIzvDe_WcbJjTsnNOuyvyqpQDY0wr416SKymk5NrIDRl3KSSgQ8RK5zSsE1Qs9Mfashhy2sdUgYY0H1OJNaaFwjLQOB9zempcXBpd4wITfUSY6mOr0Ic1_MTcRsIeaww0Qy035MUIU8HXl3hNvt9--rb73N1_vfuy-3jfhd7Y2hndG-OEcsIxrZWQtlcWtGG95AgSuBq5sBgkSDUGByOzvR37MKDlygqQ1-TdeW478NfabvNzLAGnCRZMa_FCut5aZ5VtqDqj7c1SMo7-mOMM-bfnzJ8U-4O_KPYnxf6suPW9vaxY9zMO_7r-Om3AhzOA7dGniNmXEHEJOMSMofohxf-s-AMNZpAT</recordid><startdate>202006</startdate><enddate>202006</enddate><creator>Álvarez-Cilleros, David</creator><creator>Ramos, Sonia</creator><creator>López-Oliva, María Elvira</creator><creator>Escrivá, Fernando</creator><creator>Álvarez, Carmen</creator><creator>Fernández-Millán, Elisa</creator><creator>Martín, María Ángeles</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202006</creationdate><title>Cocoa diet modulates gut microbiota composition and improves intestinal health in Zucker diabetic rats</title><author>Álvarez-Cilleros, David ; Ramos, Sonia ; López-Oliva, María Elvira ; Escrivá, Fernando ; Álvarez, Carmen ; Fernández-Millán, Elisa ; Martín, María Ángeles</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-764779259290665238458a670431ea3a15f128ec3a35fc9af0848f4cde81582a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Bacteria - classification</topic><topic>Blood Glucose</topic><topic>Cacao</topic><topic>Chemokine CCL2</topic><topic>Cocoa flavanols</topic><topic>Colon - microbiology</topic><topic>Colon - pathology</topic><topic>Diabetes Mellitus, Experimental - diet therapy</topic><topic>Diabetes type 2</topic><topic>Diet</topic><topic>Fatty Acids, Volatile</topic><topic>Gastrointestinal Microbiome - drug effects</topic><topic>Glucose homeostasis</topic><topic>Glucose Tolerance Test</topic><topic>Gut barrier</topic><topic>Gut inflammation</topic><topic>Gut microbiota</topic><topic>Homeostasis - drug effects</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>Interleukin-6</topic><topic>Male</topic><topic>Rats</topic><topic>Rats, Zucker</topic><topic>Tumor Necrosis Factor-alpha</topic><topic>Zonula Occludens-1 Protein - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Álvarez-Cilleros, David</creatorcontrib><creatorcontrib>Ramos, Sonia</creatorcontrib><creatorcontrib>López-Oliva, María Elvira</creatorcontrib><creatorcontrib>Escrivá, Fernando</creatorcontrib><creatorcontrib>Álvarez, Carmen</creatorcontrib><creatorcontrib>Fernández-Millán, Elisa</creatorcontrib><creatorcontrib>Martín, María Ángeles</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Food research international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Álvarez-Cilleros, David</au><au>Ramos, Sonia</au><au>López-Oliva, María Elvira</au><au>Escrivá, Fernando</au><au>Álvarez, Carmen</au><au>Fernández-Millán, Elisa</au><au>Martín, María Ángeles</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cocoa diet modulates gut microbiota composition and improves intestinal health in Zucker diabetic rats</atitle><jtitle>Food research international</jtitle><addtitle>Food Res Int</addtitle><date>2020-06</date><risdate>2020</risdate><volume>132</volume><spage>109058</spage><epage>109058</epage><pages>109058-109058</pages><artnum>109058</artnum><issn>0963-9969</issn><eissn>1873-7145</eissn><abstract>[Display omitted] •Intestinal barrier integrity is improved in diabetic rats submitted to cocoa diet.•Cocoa diet prevents intestinal inflammation in diabetic rats.•Cocoa diet modifies gut microbiota to a healthier microbial profile in diabetic rats.•Total levels of short-chain fatty acids increases in diabetic rats fed on cocoa. Cocoa supplementation improves glucose metabolism in Zucker diabetic fatty (ZDF) rats via multiple mechanisms. Furthermore, cocoa rich-diets modify the intestinal microbiota composition both in humans and rats in healthy conditions. Accordingly, we hypothesized that cocoa could interact with the gut microbiota (GM) in ZDF rats, contributing to their antidiabetic effects. Therefore, here we investigate the effect of cocoa intake on gut health and GM in ZDF diabetic rats. Male ZDF rats were fed with standard (ZDF-C) or 10% cocoa-rich diet (ZDF-Co) during 10 weeks. Zucker Lean animals (ZL) received the standard diet. Colon tissues were obtained to determine the barrier integrity and the inflammatory status of the intestine and faeces were analysed for microbial composition, short-chain fatty acids (SCFA) and lactate levels. We found that cocoa supplementation up-regulated the levels of the tight junction protein Zonula occludens-1 (ZO-1) and the mucin glycoprotein and reduced the expression of pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1) in the colon of ZDF diabetic animals. Additionally, cocoa modulated the microbial composition of the ZDF rats to values similar to those of the lean group. Importantly, cocoa treatment increased the relative abundance of acetate-producing bacteria such as Blautia and prevented the increase in the relative amount of lactate-producing bacteria (mainly Enterococcus and Lactobacillus genera) in ZDF diabetic animals. Accordingly, the total levels of SCFA (mainly acetate) increased significantly in the faeces of ZDF-Co diabetic rats. Finally, modified GM was closely associated with improved biochemical parameters related to glucose homeostasis and intestinal integrity and inflammation. These findings demonstrate for the first time that cocoa intake modifies intestinal bacteria composition towards a healthier microbial profile in diabetic animals and suggest that these changes could be associated with the improved glucose homeostasis and gut health induced by cocoa in ZDF diabetic rats.</abstract><cop>Canada</cop><pub>Elsevier Ltd</pub><pmid>32331673</pmid><doi>10.1016/j.foodres.2020.109058</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0963-9969
ispartof Food research international, 2020-06, Vol.132, p.109058-109058, Article 109058
issn 0963-9969
1873-7145
language eng
recordid cdi_proquest_miscellaneous_2394889858
source MEDLINE; Elsevier ScienceDirect Journals Complete
subjects Animals
Bacteria - classification
Blood Glucose
Cacao
Chemokine CCL2
Cocoa flavanols
Colon - microbiology
Colon - pathology
Diabetes Mellitus, Experimental - diet therapy
Diabetes type 2
Diet
Fatty Acids, Volatile
Gastrointestinal Microbiome - drug effects
Glucose homeostasis
Glucose Tolerance Test
Gut barrier
Gut inflammation
Gut microbiota
Homeostasis - drug effects
Hypoglycemic Agents - pharmacology
Interleukin-6
Male
Rats
Rats, Zucker
Tumor Necrosis Factor-alpha
Zonula Occludens-1 Protein - metabolism
title Cocoa diet modulates gut microbiota composition and improves intestinal health in Zucker diabetic rats
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T14%3A50%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cocoa%20diet%20modulates%20gut%20microbiota%20composition%20and%20improves%20intestinal%20health%20in%20Zucker%20diabetic%20rats&rft.jtitle=Food%20research%20international&rft.au=%C3%81lvarez-Cilleros,%20David&rft.date=2020-06&rft.volume=132&rft.spage=109058&rft.epage=109058&rft.pages=109058-109058&rft.artnum=109058&rft.issn=0963-9969&rft.eissn=1873-7145&rft_id=info:doi/10.1016/j.foodres.2020.109058&rft_dat=%3Cproquest_cross%3E2394889858%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2394889858&rft_id=info:pmid/32331673&rft_els_id=S0963996920300831&rfr_iscdi=true