Effects of short chain fatty acid producing bacteria on epigenetic regulation of FFAR3 in type 2 diabetes and obesity
The human gut microbiota and microbial influences on lipid and glucose metabolism, satiety, and chronic low-grade inflammation are known to be involved in metabolic syndrome. Fermentation end products, especially short chain fatty acids, are believed to engage the epigenetic regulation of inflammato...
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| Veröffentlicht in: | Gene 2014-03, Vol.537 (1), p.85-92 |
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| creator | Remely, Marlene Aumueller, Eva Merold, Christine Dworzak, Simone Hippe, Berit Zanner, Julia Pointner, Angelika Brath, Helmut Haslberger, Alexander G. |
| description | The human gut microbiota and microbial influences on lipid and glucose metabolism, satiety, and chronic low-grade inflammation are known to be involved in metabolic syndrome. Fermentation end products, especially short chain fatty acids, are believed to engage the epigenetic regulation of inflammatory reactions via FFARs (free fatty acid receptor) and other short chain fatty acid receptors.
We studied a potential interaction of the microbiota with epigenetic regulation in obese and type 2 diabetes patients compared to a lean control group over a four month intervention period. Intervention comprised a GLP-1 agonist (glucagon-like peptide 1) for type 2 diabetics and nutritional counseling for both intervention groups. Microbiota was analyzed for abundance, butyryl-CoA:acetate CoA-transferase gene and for diversity by polymerase chain reaction and 454 high-throughput sequencing. Epigenetic methylation of the promoter region of FFAR3 and LINE1 (long interspersed nuclear element 1) was analyzed using bisulfite conversion and pyrosequencing.
The diversity of the microbiota as well as the abundance of Faecalibacterium prausnitzii were significantly lower in obese and type 2 diabetic patients compared to lean individuals. Results from Clostridium cluster IV and Clostridium cluster XIVa showed a decreasing trend in type 2 diabetics in comparison to the butyryl-CoA:acetate CoA-transferase gene and according to melt curve analysis. During intervention no significant changes were observed in either intervention group.
The analysis of five CpGs in the promoter region of FFAR3 showed a significant lower methylation in obese and type 2 diabetics with an increase in obese patients over the intervention period. These results disclosed a significant correlation between a higher body mass index and lower methylation of FFAR3. LINE-1, a marker of global methylation, indicated no significant differences between the three groups or the time points, although methylation of type 2 diabetics tended to increase over time.
Our results provide evidence that a different composition of gut microbiota in obesity and type 2 diabetes affect the epigenetic regulation of genes. Interactions between the microbiota and epigenetic regulation may involve not only short chain fatty acids binding to FFARs. Therefore dietary interventions influencing microbial composition may be considered as an option in the engagement against metabolic syndrome.
-Influence of gut microbiota and according metabo |
| doi_str_mv | 10.1016/j.gene.2013.11.081 |
| format | Article |
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We studied a potential interaction of the microbiota with epigenetic regulation in obese and type 2 diabetes patients compared to a lean control group over a four month intervention period. Intervention comprised a GLP-1 agonist (glucagon-like peptide 1) for type 2 diabetics and nutritional counseling for both intervention groups. Microbiota was analyzed for abundance, butyryl-CoA:acetate CoA-transferase gene and for diversity by polymerase chain reaction and 454 high-throughput sequencing. Epigenetic methylation of the promoter region of FFAR3 and LINE1 (long interspersed nuclear element 1) was analyzed using bisulfite conversion and pyrosequencing.
The diversity of the microbiota as well as the abundance of Faecalibacterium prausnitzii were significantly lower in obese and type 2 diabetic patients compared to lean individuals. Results from Clostridium cluster IV and Clostridium cluster XIVa showed a decreasing trend in type 2 diabetics in comparison to the butyryl-CoA:acetate CoA-transferase gene and according to melt curve analysis. During intervention no significant changes were observed in either intervention group.
The analysis of five CpGs in the promoter region of FFAR3 showed a significant lower methylation in obese and type 2 diabetics with an increase in obese patients over the intervention period. These results disclosed a significant correlation between a higher body mass index and lower methylation of FFAR3. LINE-1, a marker of global methylation, indicated no significant differences between the three groups or the time points, although methylation of type 2 diabetics tended to increase over time.
Our results provide evidence that a different composition of gut microbiota in obesity and type 2 diabetes affect the epigenetic regulation of genes. Interactions between the microbiota and epigenetic regulation may involve not only short chain fatty acids binding to FFARs. Therefore dietary interventions influencing microbial composition may be considered as an option in the engagement against metabolic syndrome.
-Influence of gut microbiota and according metabolites on epigenetic regulation of genes-The role of differences in F.prausnitzii between the groups-Critical considerations of differences in the methylation of 5 CpGs in the promoter region of FFAR3 on receptor expression-Assessment of the positive correlation between FFAR3 and BMI</description><identifier>ISSN: 0378-1119</identifier><identifier>EISSN: 1879-0038</identifier><identifier>DOI: 10.1016/j.gene.2013.11.081</identifier><identifier>PMID: 24325907</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adult ; Aged ; Bacteria ; Biodiversity ; Body Mass Index ; Butyryl-CoA:acetate CoA-transferase gene ; Case-Control Studies ; Clostridium ; Coenzyme A-Transferases - genetics ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - genetics ; Diabetes Mellitus, Type 2 - microbiology ; DNA Methylation ; Epigenesis, Genetic ; Faecalibacterium prausnitzii ; Fatty Acids, Volatile - metabolism ; Feces - microbiology ; Feeding Behavior ; Female ; FFAR3 ; Gastrointestinal Tract - microbiology ; GLP-1 agonist ; Glucagon-Like Peptide 1 - agonists ; Glucagon-Like Peptide 1 - analogs & derivatives ; Glucagon-Like Peptide 1 - therapeutic use ; Gram-Positive Bacteria - physiology ; Gram-Positive Endospore-Forming Bacteria - genetics ; Humans ; LINE-1 ; Liraglutide ; Long Interspersed Nucleotide Elements ; Male ; Microbiota - physiology ; Middle Aged ; Obesity - genetics ; Obesity - microbiology ; Promoter Regions, Genetic ; Receptors, G-Protein-Coupled - genetics</subject><ispartof>Gene, 2014-03, Vol.537 (1), p.85-92</ispartof><rights>2013 Elsevier B.V.</rights><rights>Copyright © 2013 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-5d34012ad95e2774a97d20171aec1cea320f83a4fce3c8c72569012679237f603</citedby><cites>FETCH-LOGICAL-c455t-5d34012ad95e2774a97d20171aec1cea320f83a4fce3c8c72569012679237f603</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0378111913016077$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24325907$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Remely, Marlene</creatorcontrib><creatorcontrib>Aumueller, Eva</creatorcontrib><creatorcontrib>Merold, Christine</creatorcontrib><creatorcontrib>Dworzak, Simone</creatorcontrib><creatorcontrib>Hippe, Berit</creatorcontrib><creatorcontrib>Zanner, Julia</creatorcontrib><creatorcontrib>Pointner, Angelika</creatorcontrib><creatorcontrib>Brath, Helmut</creatorcontrib><creatorcontrib>Haslberger, Alexander G.</creatorcontrib><title>Effects of short chain fatty acid producing bacteria on epigenetic regulation of FFAR3 in type 2 diabetes and obesity</title><title>Gene</title><addtitle>Gene</addtitle><description>The human gut microbiota and microbial influences on lipid and glucose metabolism, satiety, and chronic low-grade inflammation are known to be involved in metabolic syndrome. Fermentation end products, especially short chain fatty acids, are believed to engage the epigenetic regulation of inflammatory reactions via FFARs (free fatty acid receptor) and other short chain fatty acid receptors.
We studied a potential interaction of the microbiota with epigenetic regulation in obese and type 2 diabetes patients compared to a lean control group over a four month intervention period. Intervention comprised a GLP-1 agonist (glucagon-like peptide 1) for type 2 diabetics and nutritional counseling for both intervention groups. Microbiota was analyzed for abundance, butyryl-CoA:acetate CoA-transferase gene and for diversity by polymerase chain reaction and 454 high-throughput sequencing. Epigenetic methylation of the promoter region of FFAR3 and LINE1 (long interspersed nuclear element 1) was analyzed using bisulfite conversion and pyrosequencing.
The diversity of the microbiota as well as the abundance of Faecalibacterium prausnitzii were significantly lower in obese and type 2 diabetic patients compared to lean individuals. Results from Clostridium cluster IV and Clostridium cluster XIVa showed a decreasing trend in type 2 diabetics in comparison to the butyryl-CoA:acetate CoA-transferase gene and according to melt curve analysis. During intervention no significant changes were observed in either intervention group.
The analysis of five CpGs in the promoter region of FFAR3 showed a significant lower methylation in obese and type 2 diabetics with an increase in obese patients over the intervention period. These results disclosed a significant correlation between a higher body mass index and lower methylation of FFAR3. LINE-1, a marker of global methylation, indicated no significant differences between the three groups or the time points, although methylation of type 2 diabetics tended to increase over time.
Our results provide evidence that a different composition of gut microbiota in obesity and type 2 diabetes affect the epigenetic regulation of genes. Interactions between the microbiota and epigenetic regulation may involve not only short chain fatty acids binding to FFARs. Therefore dietary interventions influencing microbial composition may be considered as an option in the engagement against metabolic syndrome.
-Influence of gut microbiota and according metabolites on epigenetic regulation of genes-The role of differences in F.prausnitzii between the groups-Critical considerations of differences in the methylation of 5 CpGs in the promoter region of FFAR3 on receptor expression-Assessment of the positive correlation between FFAR3 and BMI</description><subject>Adult</subject><subject>Aged</subject><subject>Bacteria</subject><subject>Biodiversity</subject><subject>Body Mass Index</subject><subject>Butyryl-CoA:acetate CoA-transferase gene</subject><subject>Case-Control Studies</subject><subject>Clostridium</subject><subject>Coenzyme A-Transferases - genetics</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Diabetes Mellitus, Type 2 - microbiology</subject><subject>DNA Methylation</subject><subject>Epigenesis, Genetic</subject><subject>Faecalibacterium prausnitzii</subject><subject>Fatty Acids, Volatile - metabolism</subject><subject>Feces - microbiology</subject><subject>Feeding Behavior</subject><subject>Female</subject><subject>FFAR3</subject><subject>Gastrointestinal Tract - microbiology</subject><subject>GLP-1 agonist</subject><subject>Glucagon-Like Peptide 1 - agonists</subject><subject>Glucagon-Like Peptide 1 - analogs & derivatives</subject><subject>Glucagon-Like Peptide 1 - therapeutic use</subject><subject>Gram-Positive Bacteria - physiology</subject><subject>Gram-Positive Endospore-Forming Bacteria - genetics</subject><subject>Humans</subject><subject>LINE-1</subject><subject>Liraglutide</subject><subject>Long Interspersed Nucleotide Elements</subject><subject>Male</subject><subject>Microbiota - physiology</subject><subject>Middle Aged</subject><subject>Obesity - genetics</subject><subject>Obesity - microbiology</subject><subject>Promoter Regions, Genetic</subject><subject>Receptors, G-Protein-Coupled - genetics</subject><issn>0378-1119</issn><issn>1879-0038</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFqGzEQhkVpaJy0L9BD0bGX3Wqk3ZUEvYQQN4FAIbRnIUsjR8bedSVtwW9fLU5zbHUZEN98w8xPyEdgLTAYvuzaLY7YcgaiBWiZgjdkBUrqhjGh3pIVE1I1AKAvyVXOO1Zf3_N35JJ3gveayRWZ70JAVzKdAs3PUyrUPds40mBLOVHroqfHNPnZxXFLN9YVTNHSaaR4jMv0Eh1NuJ33tsT6Wy3r9c2ToFVRTkeknPpoN1gwUzt6Om0wx3J6Ty6C3Wf88FKvyc_13Y_b--bx-7eH25vHxnV9X5rei44Bt173yKXsrJa-bivBogOHVnAWlLBdcCiccpL3g678IDUXMgxMXJPPZ2_d4deMuZhDzA73ezviNGcDA5d6UKrr_o92mktQWi5WfkZdmnJOGMwxxYNNJwPMLMmYnVluY5ZkDICpydSmTy_-eXNA_9ryN4oKfD0DWA_yO2Iy2UUcHfqYakLGT_Ff_j8xG54O</recordid><startdate>20140301</startdate><enddate>20140301</enddate><creator>Remely, Marlene</creator><creator>Aumueller, Eva</creator><creator>Merold, Christine</creator><creator>Dworzak, Simone</creator><creator>Hippe, Berit</creator><creator>Zanner, Julia</creator><creator>Pointner, Angelika</creator><creator>Brath, Helmut</creator><creator>Haslberger, Alexander G.</creator><general>Elsevier B.V</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><scope>7QL</scope><scope>7T7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20140301</creationdate><title>Effects of short chain fatty acid producing bacteria on epigenetic regulation of FFAR3 in type 2 diabetes and obesity</title><author>Remely, Marlene ; Aumueller, Eva ; Merold, Christine ; Dworzak, Simone ; Hippe, Berit ; Zanner, Julia ; Pointner, Angelika ; Brath, Helmut ; Haslberger, Alexander G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-5d34012ad95e2774a97d20171aec1cea320f83a4fce3c8c72569012679237f603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Bacteria</topic><topic>Biodiversity</topic><topic>Body Mass Index</topic><topic>Butyryl-CoA:acetate CoA-transferase gene</topic><topic>Case-Control Studies</topic><topic>Clostridium</topic><topic>Coenzyme A-Transferases - genetics</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Diabetes Mellitus, Type 2 - microbiology</topic><topic>DNA Methylation</topic><topic>Epigenesis, Genetic</topic><topic>Faecalibacterium prausnitzii</topic><topic>Fatty Acids, Volatile - metabolism</topic><topic>Feces - microbiology</topic><topic>Feeding Behavior</topic><topic>Female</topic><topic>FFAR3</topic><topic>Gastrointestinal Tract - microbiology</topic><topic>GLP-1 agonist</topic><topic>Glucagon-Like Peptide 1 - agonists</topic><topic>Glucagon-Like Peptide 1 - analogs & derivatives</topic><topic>Glucagon-Like Peptide 1 - therapeutic use</topic><topic>Gram-Positive Bacteria - physiology</topic><topic>Gram-Positive Endospore-Forming Bacteria - genetics</topic><topic>Humans</topic><topic>LINE-1</topic><topic>Liraglutide</topic><topic>Long Interspersed Nucleotide Elements</topic><topic>Male</topic><topic>Microbiota - physiology</topic><topic>Middle Aged</topic><topic>Obesity - genetics</topic><topic>Obesity - microbiology</topic><topic>Promoter Regions, Genetic</topic><topic>Receptors, G-Protein-Coupled - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Remely, Marlene</creatorcontrib><creatorcontrib>Aumueller, Eva</creatorcontrib><creatorcontrib>Merold, Christine</creatorcontrib><creatorcontrib>Dworzak, Simone</creatorcontrib><creatorcontrib>Hippe, Berit</creatorcontrib><creatorcontrib>Zanner, Julia</creatorcontrib><creatorcontrib>Pointner, Angelika</creatorcontrib><creatorcontrib>Brath, Helmut</creatorcontrib><creatorcontrib>Haslberger, Alexander G.</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><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Gene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Remely, Marlene</au><au>Aumueller, Eva</au><au>Merold, Christine</au><au>Dworzak, Simone</au><au>Hippe, Berit</au><au>Zanner, Julia</au><au>Pointner, Angelika</au><au>Brath, Helmut</au><au>Haslberger, Alexander G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of short chain fatty acid producing bacteria on epigenetic regulation of FFAR3 in type 2 diabetes and obesity</atitle><jtitle>Gene</jtitle><addtitle>Gene</addtitle><date>2014-03-01</date><risdate>2014</risdate><volume>537</volume><issue>1</issue><spage>85</spage><epage>92</epage><pages>85-92</pages><issn>0378-1119</issn><eissn>1879-0038</eissn><abstract>The human gut microbiota and microbial influences on lipid and glucose metabolism, satiety, and chronic low-grade inflammation are known to be involved in metabolic syndrome. Fermentation end products, especially short chain fatty acids, are believed to engage the epigenetic regulation of inflammatory reactions via FFARs (free fatty acid receptor) and other short chain fatty acid receptors.
We studied a potential interaction of the microbiota with epigenetic regulation in obese and type 2 diabetes patients compared to a lean control group over a four month intervention period. Intervention comprised a GLP-1 agonist (glucagon-like peptide 1) for type 2 diabetics and nutritional counseling for both intervention groups. Microbiota was analyzed for abundance, butyryl-CoA:acetate CoA-transferase gene and for diversity by polymerase chain reaction and 454 high-throughput sequencing. Epigenetic methylation of the promoter region of FFAR3 and LINE1 (long interspersed nuclear element 1) was analyzed using bisulfite conversion and pyrosequencing.
The diversity of the microbiota as well as the abundance of Faecalibacterium prausnitzii were significantly lower in obese and type 2 diabetic patients compared to lean individuals. Results from Clostridium cluster IV and Clostridium cluster XIVa showed a decreasing trend in type 2 diabetics in comparison to the butyryl-CoA:acetate CoA-transferase gene and according to melt curve analysis. During intervention no significant changes were observed in either intervention group.
The analysis of five CpGs in the promoter region of FFAR3 showed a significant lower methylation in obese and type 2 diabetics with an increase in obese patients over the intervention period. These results disclosed a significant correlation between a higher body mass index and lower methylation of FFAR3. LINE-1, a marker of global methylation, indicated no significant differences between the three groups or the time points, although methylation of type 2 diabetics tended to increase over time.
Our results provide evidence that a different composition of gut microbiota in obesity and type 2 diabetes affect the epigenetic regulation of genes. Interactions between the microbiota and epigenetic regulation may involve not only short chain fatty acids binding to FFARs. Therefore dietary interventions influencing microbial composition may be considered as an option in the engagement against metabolic syndrome.
-Influence of gut microbiota and according metabolites on epigenetic regulation of genes-The role of differences in F.prausnitzii between the groups-Critical considerations of differences in the methylation of 5 CpGs in the promoter region of FFAR3 on receptor expression-Assessment of the positive correlation between FFAR3 and BMI</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>24325907</pmid><doi>10.1016/j.gene.2013.11.081</doi><tpages>8</tpages></addata></record> |
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| ispartof | Gene, 2014-03, Vol.537 (1), p.85-92 |
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| subjects | Adult Aged Bacteria Biodiversity Body Mass Index Butyryl-CoA:acetate CoA-transferase gene Case-Control Studies Clostridium Coenzyme A-Transferases - genetics Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - genetics Diabetes Mellitus, Type 2 - microbiology DNA Methylation Epigenesis, Genetic Faecalibacterium prausnitzii Fatty Acids, Volatile - metabolism Feces - microbiology Feeding Behavior Female FFAR3 Gastrointestinal Tract - microbiology GLP-1 agonist Glucagon-Like Peptide 1 - agonists Glucagon-Like Peptide 1 - analogs & derivatives Glucagon-Like Peptide 1 - therapeutic use Gram-Positive Bacteria - physiology Gram-Positive Endospore-Forming Bacteria - genetics Humans LINE-1 Liraglutide Long Interspersed Nucleotide Elements Male Microbiota - physiology Middle Aged Obesity - genetics Obesity - microbiology Promoter Regions, Genetic Receptors, G-Protein-Coupled - genetics |
| title | Effects of short chain fatty acid producing bacteria on epigenetic regulation of FFAR3 in type 2 diabetes and obesity |
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