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Intestinal changes associated with fluoride exposure in rats: Integrative morphological, proteomic and microbiome analyses
Gastrointestinal signs and symptoms are the first signs of toxicity due to exposure to fluoride (F). This suggests the possibility that lower levels of subchronic F exposure may affect the gut. The aim of this study was to evaluate changes in the morphology, proteome and microbiome of the ileum of r...
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Published in: | Chemosphere (Oxford) 2021-06, Vol.273, p.129607-129607, Article 129607 |
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creator | Dionizio, Aline Uyghurturk, Dawud Abduweli Melo, Carina Guimarães Souza Sabino-Arias, Isabela Tomazini Araujo, Tamara Teodoro Ventura, Talita Mendes Silva Perles, Juliana Vanessa Colombo Martins Zanoni, Jacqueline Nelisis Den Besten, Pamela Buzalaf, Marília Afonso Rabelo |
description | Gastrointestinal signs and symptoms are the first signs of toxicity due to exposure to fluoride (F). This suggests the possibility that lower levels of subchronic F exposure may affect the gut. The aim of this study was to evaluate changes in the morphology, proteome and microbiome of the ileum of rats, after subchronic exposure to F. Male rats ingested water with 0, 10, or 50 mgF/L for thirty days. Treatment with F, regardless of the dose, significantly decreased the density of HuC/D-IR neurons, whereas CGRP-IR and SP-IR varicosities were significantly increased compared to the control group. Increased VIP-IR varicosities were significantly increased only in the group treated with 50 mgF/L. A significant increase in thickness of the tunica muscularis, as well as in the total thickness of the ileum wall was observed at both F doses when compared to controls. In proteomics analysis, myosin isoforms were increased, and Gastrotopin was decreased in F-exposed mice. In the microbiome metagenomics analysis, Class Clostridia was significantly reduced upon exposure to 10 mgF/L. At the higher F dose of 50 mg/L, genus Ureaplasma was significantly reduced in comparison with controls. Morphological and proteomics alterations induced by F were marked by changes associated with inflammation, and alterations in the gut microbiome. Further studies are needed to determine whether F exposure increases inflammation with secondary effects of the gut microbiome, and/or whether primary effects of F on the gut microbiome enhance changes associated with inflammation.
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•Fluoridated water increases the thickness of the ileum wall.•Fluoridated water increases CGRP-IR and SP-IR varicosities in the ileum.•Proteomic changes induced by fluoride have similarity with Crohn’s disease.•Microbiomic changes induced by fluoride are associated with inflammation. |
doi_str_mv | 10.1016/j.chemosphere.2021.129607 |
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[Display omitted]
•Fluoridated water increases the thickness of the ileum wall.•Fluoridated water increases CGRP-IR and SP-IR varicosities in the ileum.•Proteomic changes induced by fluoride have similarity with Crohn’s disease.•Microbiomic changes induced by fluoride are associated with inflammation.</description><identifier>ISSN: 0045-6535</identifier><identifier>EISSN: 1879-1298</identifier><identifier>DOI: 10.1016/j.chemosphere.2021.129607</identifier><identifier>PMID: 33508686</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Crohn’s disease ; Firmicutes ; Fluoride ; Fluorides - toxicity ; Gastrointestinal Microbiome ; Gastrointestinal symptoms ; Ileum ; Male ; Mice ; Microbiome ; Proteome ; Proteomics ; Rats</subject><ispartof>Chemosphere (Oxford), 2021-06, Vol.273, p.129607-129607, Article 129607</ispartof><rights>2021 Elsevier Ltd</rights><rights>Copyright © 2021 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-453390c398c0019e9446559c434fd4844bc5c89188cd1011a1a1c1a421bdcca73</citedby><cites>FETCH-LOGICAL-c483t-453390c398c0019e9446559c434fd4844bc5c89188cd1011a1a1c1a421bdcca73</cites><orcidid>0000-0002-2892-5123 ; 0000-0002-5985-3951 ; 0000-0002-2107-6229 ; 0000-0002-7560-9051</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33508686$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dionizio, Aline</creatorcontrib><creatorcontrib>Uyghurturk, Dawud Abduweli</creatorcontrib><creatorcontrib>Melo, Carina Guimarães Souza</creatorcontrib><creatorcontrib>Sabino-Arias, Isabela Tomazini</creatorcontrib><creatorcontrib>Araujo, Tamara Teodoro</creatorcontrib><creatorcontrib>Ventura, Talita Mendes Silva</creatorcontrib><creatorcontrib>Perles, Juliana Vanessa Colombo Martins</creatorcontrib><creatorcontrib>Zanoni, Jacqueline Nelisis</creatorcontrib><creatorcontrib>Den Besten, Pamela</creatorcontrib><creatorcontrib>Buzalaf, Marília Afonso Rabelo</creatorcontrib><title>Intestinal changes associated with fluoride exposure in rats: Integrative morphological, proteomic and microbiome analyses</title><title>Chemosphere (Oxford)</title><addtitle>Chemosphere</addtitle><description>Gastrointestinal signs and symptoms are the first signs of toxicity due to exposure to fluoride (F). This suggests the possibility that lower levels of subchronic F exposure may affect the gut. The aim of this study was to evaluate changes in the morphology, proteome and microbiome of the ileum of rats, after subchronic exposure to F. Male rats ingested water with 0, 10, or 50 mgF/L for thirty days. Treatment with F, regardless of the dose, significantly decreased the density of HuC/D-IR neurons, whereas CGRP-IR and SP-IR varicosities were significantly increased compared to the control group. Increased VIP-IR varicosities were significantly increased only in the group treated with 50 mgF/L. A significant increase in thickness of the tunica muscularis, as well as in the total thickness of the ileum wall was observed at both F doses when compared to controls. In proteomics analysis, myosin isoforms were increased, and Gastrotopin was decreased in F-exposed mice. In the microbiome metagenomics analysis, Class Clostridia was significantly reduced upon exposure to 10 mgF/L. At the higher F dose of 50 mg/L, genus Ureaplasma was significantly reduced in comparison with controls. Morphological and proteomics alterations induced by F were marked by changes associated with inflammation, and alterations in the gut microbiome. Further studies are needed to determine whether F exposure increases inflammation with secondary effects of the gut microbiome, and/or whether primary effects of F on the gut microbiome enhance changes associated with inflammation.
[Display omitted]
•Fluoridated water increases the thickness of the ileum wall.•Fluoridated water increases CGRP-IR and SP-IR varicosities in the ileum.•Proteomic changes induced by fluoride have similarity with Crohn’s disease.•Microbiomic changes induced by fluoride are associated with inflammation.</description><subject>Animals</subject><subject>Crohn’s disease</subject><subject>Firmicutes</subject><subject>Fluoride</subject><subject>Fluorides - toxicity</subject><subject>Gastrointestinal Microbiome</subject><subject>Gastrointestinal symptoms</subject><subject>Ileum</subject><subject>Male</subject><subject>Mice</subject><subject>Microbiome</subject><subject>Proteome</subject><subject>Proteomics</subject><subject>Rats</subject><issn>0045-6535</issn><issn>1879-1298</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNqNkU1vGyEQhlGVqnHT_oWI3LMuGFhDDpEiqx-RIvXSnhEexl6s3WUF2En664vlNkpvFYdhxLzvDPMQcsXZnDPeftrNocMh5qnDhPMFW_A5X5iWLd-QGddL09RMn5EZY1I1rRLqnLzPecdYFSvzjpwLoZhudTsjv-7HgrmE0fUUOjduMVOXc4TgCnr6GEpHN_0-puCR4tMU8z4hDSNNruQbelRv6zUckA4xTV3s4zaA66_plGLBOASgbvS0xhTXIQ5YU9c_Z8wfyNuN6zN-_BMvyM8vn3-svjUP37_er-4eGpBalEYqIQwDYTTU-Q0aKVulDEghN15qKdegQBuuNfi6He7qAe7kgq89gFuKC3J78p326wE94FiS6-2UwuDSs40u2H9fxtDZbTxYzZYtM6oamJNB_ULOCTcvWs7sEYjd2VdA7BGIPQGp2svXzV-UfwnUgtWpAOsKDgGTzRBwBPQhIRTrY_iPNr8BuLenCg</recordid><startdate>20210601</startdate><enddate>20210601</enddate><creator>Dionizio, Aline</creator><creator>Uyghurturk, Dawud Abduweli</creator><creator>Melo, Carina Guimarães Souza</creator><creator>Sabino-Arias, Isabela Tomazini</creator><creator>Araujo, Tamara Teodoro</creator><creator>Ventura, Talita Mendes Silva</creator><creator>Perles, Juliana Vanessa Colombo Martins</creator><creator>Zanoni, Jacqueline Nelisis</creator><creator>Den Besten, Pamela</creator><creator>Buzalaf, Marília Afonso Rabelo</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>5PM</scope><orcidid>https://orcid.org/0000-0002-2892-5123</orcidid><orcidid>https://orcid.org/0000-0002-5985-3951</orcidid><orcidid>https://orcid.org/0000-0002-2107-6229</orcidid><orcidid>https://orcid.org/0000-0002-7560-9051</orcidid></search><sort><creationdate>20210601</creationdate><title>Intestinal changes associated with fluoride exposure in rats: Integrative morphological, proteomic and microbiome analyses</title><author>Dionizio, Aline ; Uyghurturk, Dawud Abduweli ; Melo, Carina Guimarães Souza ; Sabino-Arias, Isabela Tomazini ; Araujo, Tamara Teodoro ; Ventura, Talita Mendes Silva ; Perles, Juliana Vanessa Colombo Martins ; Zanoni, Jacqueline Nelisis ; Den Besten, Pamela ; Buzalaf, Marília Afonso Rabelo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-453390c398c0019e9446559c434fd4844bc5c89188cd1011a1a1c1a421bdcca73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Crohn’s disease</topic><topic>Firmicutes</topic><topic>Fluoride</topic><topic>Fluorides - toxicity</topic><topic>Gastrointestinal Microbiome</topic><topic>Gastrointestinal symptoms</topic><topic>Ileum</topic><topic>Male</topic><topic>Mice</topic><topic>Microbiome</topic><topic>Proteome</topic><topic>Proteomics</topic><topic>Rats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dionizio, Aline</creatorcontrib><creatorcontrib>Uyghurturk, Dawud Abduweli</creatorcontrib><creatorcontrib>Melo, Carina Guimarães Souza</creatorcontrib><creatorcontrib>Sabino-Arias, Isabela Tomazini</creatorcontrib><creatorcontrib>Araujo, Tamara Teodoro</creatorcontrib><creatorcontrib>Ventura, Talita Mendes Silva</creatorcontrib><creatorcontrib>Perles, Juliana Vanessa Colombo Martins</creatorcontrib><creatorcontrib>Zanoni, Jacqueline Nelisis</creatorcontrib><creatorcontrib>Den Besten, Pamela</creatorcontrib><creatorcontrib>Buzalaf, Marília Afonso Rabelo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Chemosphere (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dionizio, Aline</au><au>Uyghurturk, Dawud Abduweli</au><au>Melo, Carina Guimarães Souza</au><au>Sabino-Arias, Isabela Tomazini</au><au>Araujo, Tamara Teodoro</au><au>Ventura, Talita Mendes Silva</au><au>Perles, Juliana Vanessa Colombo Martins</au><au>Zanoni, Jacqueline Nelisis</au><au>Den Besten, Pamela</au><au>Buzalaf, Marília Afonso Rabelo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intestinal changes associated with fluoride exposure in rats: Integrative morphological, proteomic and microbiome analyses</atitle><jtitle>Chemosphere (Oxford)</jtitle><addtitle>Chemosphere</addtitle><date>2021-06-01</date><risdate>2021</risdate><volume>273</volume><spage>129607</spage><epage>129607</epage><pages>129607-129607</pages><artnum>129607</artnum><issn>0045-6535</issn><eissn>1879-1298</eissn><abstract>Gastrointestinal signs and symptoms are the first signs of toxicity due to exposure to fluoride (F). This suggests the possibility that lower levels of subchronic F exposure may affect the gut. The aim of this study was to evaluate changes in the morphology, proteome and microbiome of the ileum of rats, after subchronic exposure to F. Male rats ingested water with 0, 10, or 50 mgF/L for thirty days. Treatment with F, regardless of the dose, significantly decreased the density of HuC/D-IR neurons, whereas CGRP-IR and SP-IR varicosities were significantly increased compared to the control group. Increased VIP-IR varicosities were significantly increased only in the group treated with 50 mgF/L. A significant increase in thickness of the tunica muscularis, as well as in the total thickness of the ileum wall was observed at both F doses when compared to controls. In proteomics analysis, myosin isoforms were increased, and Gastrotopin was decreased in F-exposed mice. In the microbiome metagenomics analysis, Class Clostridia was significantly reduced upon exposure to 10 mgF/L. At the higher F dose of 50 mg/L, genus Ureaplasma was significantly reduced in comparison with controls. Morphological and proteomics alterations induced by F were marked by changes associated with inflammation, and alterations in the gut microbiome. Further studies are needed to determine whether F exposure increases inflammation with secondary effects of the gut microbiome, and/or whether primary effects of F on the gut microbiome enhance changes associated with inflammation.
[Display omitted]
•Fluoridated water increases the thickness of the ileum wall.•Fluoridated water increases CGRP-IR and SP-IR varicosities in the ileum.•Proteomic changes induced by fluoride have similarity with Crohn’s disease.•Microbiomic changes induced by fluoride are associated with inflammation.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>33508686</pmid><doi>10.1016/j.chemosphere.2021.129607</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-2892-5123</orcidid><orcidid>https://orcid.org/0000-0002-5985-3951</orcidid><orcidid>https://orcid.org/0000-0002-2107-6229</orcidid><orcidid>https://orcid.org/0000-0002-7560-9051</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Animals Crohn’s disease Firmicutes Fluoride Fluorides - toxicity Gastrointestinal Microbiome Gastrointestinal symptoms Ileum Male Mice Microbiome Proteome Proteomics Rats |
title | Intestinal changes associated with fluoride exposure in rats: Integrative morphological, proteomic and microbiome analyses |
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