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

Ditte Olsen Lützhøft, Cecilie Bækgård, Elizabeth Wimborne, Ellen Marie Straarup, Karen Margrethe Pedersen, Jonathan R. Swann, Henrik Duelund Pedersen, Kim Kristensen, Line Morgills, Dennis Sandris Nielsen, Axel Kornerup Hansen, Marianne Kronborg Bracken, Susanna Cirera, Berit Østergaard Christoffersen*

*Corresponding author af dette arbejde

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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. HFD-fed Göttingen Minipig therefore represents a relevant animal model for studying host-microbiota interactions. No significant differences between the castrated and ovariectomized minipigs were observed.
OriginalsprogEngelsk
Artikelnummere0298602
TidsskriftPLoS ONE
Vol/bind19
Udgave nummer3
Antal sider27
ISSN1932-6203
DOI
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
Funding: This study was co-financed by Ellegaard Göttingen Minipigs A/S, Scantox A/S and Novo Nordisk A/S, and employees at these three companies were part of he study design, data collection and analysis, decision to publish and preparation of the manuscript. DOL was financed by the LIFEPHARM center, www.lifepharm.ku.dk.

Publisher Copyright:
© 2024 Lützhøft et al. This is an open access article distributed under the terms of the Creative Commons Attribution License,

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