Microbiota-Related Changes in Unconjugated Fecal Bile Acids Are Associated With Naturally Occurring, Insulin-Dependent Diabetes Mellitus in Dogs

dc.contributor.author Jergens, Albert
dc.contributor.author Guard, Blake
dc.contributor.author Redfern, Alana
dc.contributor.author Mochel, Jonathan
dc.contributor.author Rossi, Giacomo
dc.contributor.author Mochel, Jonathan
dc.contributor.author Pilla, Rachel
dc.contributor.author Chandra, Lawrance
dc.contributor.author Seo, Yeon-Jung
dc.contributor.author Steiner, Joerg
dc.contributor.author Lidbury, Jonathan
dc.contributor.author Allenspach, Karin
dc.contributor.author Suchodolski, Jan
dc.contributor.department Biomedical Sciences
dc.contributor.department Veterinary Clinical Sciences
dc.date 2019-08-21T14:23:24.000
dc.date.accessioned 2020-06-30T00:53:36Z
dc.date.available 2020-06-30T00:53:36Z
dc.date.copyright Tue Jan 01 00:00:00 UTC 2019
dc.date.issued 2019-06-27
dc.description.abstract <p>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 (<em>n</em> = 10) and healthy controls (HC, <em>n</em> = 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: <em>R</em> = 0.084; <em>p</em> = 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 <em>Enterobacteriaceae</em> was overrepresented in dogs with DM, the proportions of Erysipelotrichia, <em>Mogibacteriaceae</em>, and <em>Anaeroplasmataceae</em> were increased in HC dogs. Dogs with DM had increased concentration of total primary fUBA compared to HC dogs (<em>p</em> = 0.028). The concentrations of cholic acid and the cholic acid percentage of the total fUBA were increased (<em>p</em> = 0.028 and <em>p</em> = 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 (<em>p</em> = 0.043 and <em>p</em> < 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.</p>
dc.description.comments <p>This article is published as Jergens, Albert E., Blake C. Guard, Alana Redfern, Giacomo Rossi, Jonathan P. Mochel, Rachel Pilla, Lawrance Chandra, Yeon-Jung Seo, Joerg M. Steiner, Jonathan Lidbury, Karin Allenspach, and Jan Suchodolski. "Microbiota-Related Changes in Unconjugated Fecal Bile Acids are Associated with Naturally Occurring, Insulin-Dependent Diabetes Mellitus in Dogs." <em>Frontiers in Veterinary Science</em> 6 (2019): 199. DOI: <a href="http://dx.doi.org/10.3389/fvets.2019.00199" target="_blank">10.3389/fvets.2019.00199</a>. Posted with permission.</p>
dc.format.mimetype application/pdf
dc.identifier archive/lib.dr.iastate.edu/bms_pubs/70/
dc.identifier.articleid 1069
dc.identifier.contextkey 14821142
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath bms_pubs/70
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/11198
dc.language.iso en
dc.source.bitstream archive/lib.dr.iastate.edu/bms_pubs/70/2019_MochelJonathan_MicrobiotaRelated.pdf|||Sat Jan 15 01:40:40 UTC 2022
dc.source.uri 10.3389/fvets.2019.00199
dc.subject.disciplines Small or Companion Animal Medicine
dc.subject.disciplines Veterinary Pathology and Pathobiology
dc.subject.keywords bile acids
dc.subject.keywords diabetes mellitus
dc.subject.keywords microbiota
dc.subject.keywords lipopolysaccharide
dc.subject.keywords dog
dc.subject.keywords T2DM
dc.title Microbiota-Related Changes in Unconjugated Fecal Bile Acids Are Associated With Naturally Occurring, Insulin-Dependent Diabetes Mellitus in Dogs
dc.type article
dc.type.genre article
dspace.entity.type Publication
relation.isAuthorOfPublication a34180b7-6b71-4b6f-a08d-5a53c5122d9b
relation.isOrgUnitOfPublication 184db3f2-d93f-4571-8ad7-07c8a9e6a5c9
relation.isOrgUnitOfPublication 1ad68def-86ae-460b-8808-f1b1febafd0a
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