Microbiota-Related Changes in Unconjugated Fecal Bile Acids Are Associated With Naturally Occurring, Insulin-Dependent Diabetes Mellitus in Dogs
Diabetes mellitus (DM) in humans has recently been associated with altered intestinal microbiota. The consequences of intestinal dysbiosis, such as increased intestinal permeability and altered microbial metabolites, are suspected to contribute to the host inflammatory state and peripheral insulin r...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-06-01
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| Series: | Frontiers in Veterinary Science |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fvets.2019.00199/full |
| _version_ | 1818409413682135040 |
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| author | Albert E. Jergens Blake C. Guard Alana Redfern Giacomo Rossi Jonathan P. Mochel Rachel Pilla Lawrance Chandra Yeon-Jung Seo Joerg M. Steiner Jonathan Lidbury Karin Allenspach Jan Suchodolski |
| author_facet | Albert E. Jergens Blake C. Guard Alana Redfern Giacomo Rossi Jonathan P. Mochel Rachel Pilla Lawrance Chandra Yeon-Jung Seo Joerg M. Steiner Jonathan Lidbury Karin Allenspach Jan Suchodolski |
| author_sort | Albert E. Jergens |
| collection | DOAJ |
| description | Diabetes mellitus (DM) in humans has recently been associated with altered intestinal microbiota. The consequences of intestinal dysbiosis, such as increased intestinal permeability and altered microbial metabolites, are suspected to contribute to the host inflammatory state and peripheral insulin resistance. Human diabetics have been shown to have changes in bile acid (BA) metabolism which may be detrimental to glycemic control. The purpose of this study was to examine BA metabolism in dogs with naturally-occurring, insulin-dependent DM and to relate these findings to changes in the intestinal microbiota. A prospective observational study of adult dogs with a clinical diagnosis of DM (n = 10) and healthy controls (HC, n = 10) was performed. The fecal microbiota were analyzed by 16S rRNA gene next-generation (Illumina) sequencing. Concentrations of fecal unconjugated BA (fUBA) were measured using gas chromatography and mass spectrometry. Analysis of bacterial communities showed no significant difference for any of the alpha-diversity measures between DM vs. HC dogs. Principal coordinate analysis based on unweighted Unifrac distance metric failed to show significant clustering between dog groups (ANOSIMUnweighted: R = 0.084; p = 0.114). However, linear discriminate analysis effects size (LEfSe) detected differentially abundant bacterial taxa (α = 0.01, LDA score >2.0) on various phylogenetic levels. While Enterobacteriaceae was overrepresented in dogs with DM, the proportions of Erysipelotrichia, Mogibacteriaceae, and Anaeroplasmataceae were increased in HC dogs. Dogs with DM had increased concentration of total primary fUBA compared to HC dogs (p = 0.028). The concentrations of cholic acid and the cholic acid percentage of the total fUBA were increased (p = 0.028 and p = 0.035, respectively) in the feces of DM dogs relative to HC dogs. The levels of lithocholic acid (both absolute value and percentage of the total fUBA) were decreased (p = 0.043 and p < 0.01, respectively) in DM dogs vs. HC dogs. Results indicate that dogs with DM have both intestinal dysbiosis and associated fUBA alterations. The pattern of dysbiosis and altered BA composition is similar to that seen in humans with Type 2 DM. The dog represents a novel large animal model for advancing translational medicine research efforts (e.g., investigating pathogenesis and therapeutics) in DM affecting humans. |
| first_indexed | 2024-12-14T09:59:14Z |
| format | Article |
| id | doaj.art-0c98c8baa5174313ba66f798197181af |
| institution | Directory Open Access Journal |
| issn | 2297-1769 |
| language | English |
| last_indexed | 2024-12-14T09:59:14Z |
| publishDate | 2019-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Veterinary Science |
| spelling | doaj.art-0c98c8baa5174313ba66f798197181af2022-12-21T23:07:19ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692019-06-01610.3389/fvets.2019.00199440272Microbiota-Related Changes in Unconjugated Fecal Bile Acids Are Associated With Naturally Occurring, Insulin-Dependent Diabetes Mellitus in DogsAlbert E. Jergens0Blake C. Guard1Alana Redfern2Giacomo Rossi3Jonathan P. Mochel4Rachel Pilla5Lawrance Chandra6Yeon-Jung Seo7Joerg M. Steiner8Jonathan Lidbury9Karin Allenspach10Jan Suchodolski11Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United StatesGastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United StatesDepartment of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United StatesSchool of Biosciences and Veterinary Medicine, University of Camerino, Macerata, ItalyDepartment of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United StatesGastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United StatesDepartment of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United StatesDepartment of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United StatesGastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United StatesGastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United StatesDepartment of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United StatesGastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United StatesDiabetes mellitus (DM) in humans has recently been associated with altered intestinal microbiota. The consequences of intestinal dysbiosis, such as increased intestinal permeability and altered microbial metabolites, are suspected to contribute to the host inflammatory state and peripheral insulin resistance. Human diabetics have been shown to have changes in bile acid (BA) metabolism which may be detrimental to glycemic control. The purpose of this study was to examine BA metabolism in dogs with naturally-occurring, insulin-dependent DM and to relate these findings to changes in the intestinal microbiota. A prospective observational study of adult dogs with a clinical diagnosis of DM (n = 10) and healthy controls (HC, n = 10) was performed. The fecal microbiota were analyzed by 16S rRNA gene next-generation (Illumina) sequencing. Concentrations of fecal unconjugated BA (fUBA) were measured using gas chromatography and mass spectrometry. Analysis of bacterial communities showed no significant difference for any of the alpha-diversity measures between DM vs. HC dogs. Principal coordinate analysis based on unweighted Unifrac distance metric failed to show significant clustering between dog groups (ANOSIMUnweighted: R = 0.084; p = 0.114). However, linear discriminate analysis effects size (LEfSe) detected differentially abundant bacterial taxa (α = 0.01, LDA score >2.0) on various phylogenetic levels. While Enterobacteriaceae was overrepresented in dogs with DM, the proportions of Erysipelotrichia, Mogibacteriaceae, and Anaeroplasmataceae were increased in HC dogs. Dogs with DM had increased concentration of total primary fUBA compared to HC dogs (p = 0.028). The concentrations of cholic acid and the cholic acid percentage of the total fUBA were increased (p = 0.028 and p = 0.035, respectively) in the feces of DM dogs relative to HC dogs. The levels of lithocholic acid (both absolute value and percentage of the total fUBA) were decreased (p = 0.043 and p < 0.01, respectively) in DM dogs vs. HC dogs. Results indicate that dogs with DM have both intestinal dysbiosis and associated fUBA alterations. The pattern of dysbiosis and altered BA composition is similar to that seen in humans with Type 2 DM. The dog represents a novel large animal model for advancing translational medicine research efforts (e.g., investigating pathogenesis and therapeutics) in DM affecting humans.https://www.frontiersin.org/article/10.3389/fvets.2019.00199/fullbile acidsdiabetes mellitusmicrobiotalipopolysaccharidedogT2DM |
| spellingShingle | Albert E. Jergens Blake C. Guard Alana Redfern Giacomo Rossi Jonathan P. Mochel Rachel Pilla Lawrance Chandra Yeon-Jung Seo Joerg M. Steiner Jonathan Lidbury Karin Allenspach Jan Suchodolski Microbiota-Related Changes in Unconjugated Fecal Bile Acids Are Associated With Naturally Occurring, Insulin-Dependent Diabetes Mellitus in Dogs Frontiers in Veterinary Science bile acids diabetes mellitus microbiota lipopolysaccharide dog T2DM |
| title | Microbiota-Related Changes in Unconjugated Fecal Bile Acids Are Associated With Naturally Occurring, Insulin-Dependent Diabetes Mellitus in Dogs |
| title_full | Microbiota-Related Changes in Unconjugated Fecal Bile Acids Are Associated With Naturally Occurring, Insulin-Dependent Diabetes Mellitus in Dogs |
| title_fullStr | Microbiota-Related Changes in Unconjugated Fecal Bile Acids Are Associated With Naturally Occurring, Insulin-Dependent Diabetes Mellitus in Dogs |
| title_full_unstemmed | Microbiota-Related Changes in Unconjugated Fecal Bile Acids Are Associated With Naturally Occurring, Insulin-Dependent Diabetes Mellitus in Dogs |
| title_short | Microbiota-Related Changes in Unconjugated Fecal Bile Acids Are Associated With Naturally Occurring, Insulin-Dependent Diabetes Mellitus in Dogs |
| title_sort | microbiota related changes in unconjugated fecal bile acids are associated with naturally occurring insulin dependent diabetes mellitus in dogs |
| topic | bile acids diabetes mellitus microbiota lipopolysaccharide dog T2DM |
| url | https://www.frontiersin.org/article/10.3389/fvets.2019.00199/full |
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