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High fat diet is associated with gut microbiota dysbiosis and decreased gut microbial derived metabolites related to metabolic health in young Göttingen Minipigs

High fat diet is associated with gut microbiota dysbiosis and decreased gut microbial derived metabolites related to metabolic health in young Göttingen Minipigs
High fat diet is associated with gut microbiota dysbiosis and decreased gut microbial derived metabolites related to metabolic health in young Göttingen Minipigs

The objectives were 1) to characterize a Göttingen Minipig model of metabolic syndrome regarding its colon microbiota and circulating microbial products, and 2) to assess whether ovariectomized female and castrated male minipigs show similar phenotypes. Twenty-four nine-week-old Göttingen Minipigs were allocated to four groups based on sex and diet: ovariectomized females and castrated males fed either chow or high-fat diet (HFD) for 12 weeks. At study end, body composition and plasma biomarkers were measured, and a mixed meal tolerance test (MMT) and an intravenous glucose tolerance test (IVGTT) were performed. The HFD groups had significantly higher weight gain, fat percentage, fasting plasma insulin and glucagon compared to the chow groups. Homeostatic model assessment of insulin resistance index (HOMA-IR) was increased and glucose effectiveness derived from the IVGTT and Matsuda´s insulin sensitivity index from the MMT were decreased in the HFD groups. The HFD groups displayed dyslipidemia, with significantly increased total-, LDL- and HDL-cholesterol, and decreased HDL/non-HDL cholesterol ratio. The colon microbiota of HFD minipigs clearly differed from the lean controls (GuniFrac distance matrix). The main bacteria families driving this separation were Clostridiaceae, Fibrobacteraceae, Flavobacteriaceae and Porphyromonadaceae. Moreover, the species richness was significantly decreased by HFD. In addition, HFD decreased the circulating level of short chain fatty acids and beneficial microbial metabolites hippuric acid, xanthine and trigonelline, while increasing the level of branched chain amino acids. Six and nine metabolically relevant genes were differentially expressed between chow-fed and HFD-fed animals in liver and omental adipose tissue, respectively. The HFD-fed pigs presented with metabolic syndrome, gut microbial dysbiosis and a marked decrease in healthy gut microbial products and thus displayed marked parallels to human obesity and insulin resistance.

1932-6203
Lützhøft, Ditte Olsen
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Bækgård, Cecilie
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Wimborne, Elizabeth
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Straarup, Ellen Marie
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Pedersen, Karen Margrethe
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Swann, Jonathan R.
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Pedersen, Henrik Duelund
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Kristensen, Kim
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Morgills, Line
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Nielsen, Dennis Sandris
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Hansen, Axel Kornerup
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Bracken, Marianne Kronborg
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Cirera, Susanna
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Christoffersen, Berit Østergaard
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Lützhøft, Ditte Olsen
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Bækgård, Cecilie
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Wimborne, Elizabeth
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Straarup, Ellen Marie
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Pedersen, Karen Margrethe
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Swann, Jonathan R.
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Pedersen, Henrik Duelund
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Kristensen, Kim
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Morgills, Line
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Nielsen, Dennis Sandris
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Hansen, Axel Kornerup
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Bracken, Marianne Kronborg
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Cirera, Susanna
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Christoffersen, Berit Østergaard
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Lützhøft, Ditte Olsen, Bækgård, Cecilie, Wimborne, Elizabeth, Straarup, Ellen Marie, Pedersen, Karen Margrethe, Swann, Jonathan R., Pedersen, Henrik Duelund, Kristensen, Kim, Morgills, Line, Nielsen, Dennis Sandris, Hansen, Axel Kornerup, Bracken, Marianne Kronborg, Cirera, Susanna and Christoffersen, Berit Østergaard (2024) High fat diet is associated with gut microbiota dysbiosis and decreased gut microbial derived metabolites related to metabolic health in young Göttingen Minipigs. PLoS ONE, 19 (3 March), [e0298602]. (doi:10.1371/journal.pone.0298602).

Record type: Article

Abstract

The objectives were 1) to characterize a Göttingen Minipig model of metabolic syndrome regarding its colon microbiota and circulating microbial products, and 2) to assess whether ovariectomized female and castrated male minipigs show similar phenotypes. Twenty-four nine-week-old Göttingen Minipigs were allocated to four groups based on sex and diet: ovariectomized females and castrated males fed either chow or high-fat diet (HFD) for 12 weeks. At study end, body composition and plasma biomarkers were measured, and a mixed meal tolerance test (MMT) and an intravenous glucose tolerance test (IVGTT) were performed. The HFD groups had significantly higher weight gain, fat percentage, fasting plasma insulin and glucagon compared to the chow groups. Homeostatic model assessment of insulin resistance index (HOMA-IR) was increased and glucose effectiveness derived from the IVGTT and Matsuda´s insulin sensitivity index from the MMT were decreased in the HFD groups. The HFD groups displayed dyslipidemia, with significantly increased total-, LDL- and HDL-cholesterol, and decreased HDL/non-HDL cholesterol ratio. The colon microbiota of HFD minipigs clearly differed from the lean controls (GuniFrac distance matrix). The main bacteria families driving this separation were Clostridiaceae, Fibrobacteraceae, Flavobacteriaceae and Porphyromonadaceae. Moreover, the species richness was significantly decreased by HFD. In addition, HFD decreased the circulating level of short chain fatty acids and beneficial microbial metabolites hippuric acid, xanthine and trigonelline, while increasing the level of branched chain amino acids. Six and nine metabolically relevant genes were differentially expressed between chow-fed and HFD-fed animals in liver and omental adipose tissue, respectively. The HFD-fed pigs presented with metabolic syndrome, gut microbial dysbiosis and a marked decrease in healthy gut microbial products and thus displayed marked parallels to human obesity and insulin resistance.

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journal.pone.0298602
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Accepted/In Press date: 26 January 2024
Published date: 1 March 2024
Additional Information: Publisher Copyright: © 2024 Lützhøft et al. This is an open access article distributed under the terms of the Creative Commons Attribution License,

Identifiers

Local EPrints ID: 494319
URI: http://eprints.soton.ac.uk/id/eprint/494319
ISSN: 1932-6203
PURE UUID: 8af39740-48fa-4ecf-8937-bcaca492c118
ORCID for Elizabeth Wimborne: ORCID iD orcid.org/0000-0001-8471-4489
ORCID for Jonathan R. Swann: ORCID iD orcid.org/0000-0002-6485-4529

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Date deposited: 03 Oct 2024 16:43
Last modified: 05 Oct 2024 02:09

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Contributors

Author: Ditte Olsen Lützhøft
Author: Cecilie Bækgård
Author: Elizabeth Wimborne ORCID iD
Author: Ellen Marie Straarup
Author: Karen Margrethe Pedersen
Author: Henrik Duelund Pedersen
Author: Kim Kristensen
Author: Line Morgills
Author: Dennis Sandris Nielsen
Author: Axel Kornerup Hansen
Author: Marianne Kronborg Bracken
Author: Susanna Cirera
Author: Berit Østergaard Christoffersen

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