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Mitochondrial DNA variants and microbiota: An experimental strategy to identify novel therapeutic potential in

Michael Olbrich1, Adina-Malin Hartmann2, Sven Künzel3

  • 1Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany; Center for Biotechnology, Khalifa University, Abu Dhabi, United Arab Emirates; University Heart Centre Lübeck, Lübeck, Germany.

Pharmacological Research
|May 30, 2024
PubMed

Insights

Mitochondrial DNA variants in B6-mtFVB mice offer protection against skin inflammation by altering metabolites and gut microbiota. D-glucosamine was identified as a potential mediator that reduces disease severity by modulating immune cell function.

Area of Science:

  • Immunology
  • Genetics
  • Metabolomics

Background:

  • Mice with FVB/NJ strain mtDNA variants (B6-mtFVB) show altered metabolites and gut microbiota, conferring partial protection against experimental skin inflammatory diseases.
  • Previous studies indicated differential disease susceptibility in mice with specific mtDNA variants.

Purpose of the Study:

  • To investigate the role of mtDNA variants in experimental skin inflammation.
  • To identify candidate mediators of disease amelioration.
  • To explore therapeutic options for chronic inflammatory diseases.

Main Methods:

  • Induction of experimental antibody-induced skin inflammatory disease in gnotobiotic mice.
  • Shotgun metagenomic sequencing of caecum contents.
  • Untargeted metabolomics of liver, CD4+ T cell, and caecum content samples.

Main Results:

  • D-glucosamine identified as a candidate mediator ameliorating disease severity in experimental antibody-induced skin inflammation.
  • D-glucosamine modulated immune cell function in T cells, neutrophils, and macrophages.
  • Mice with mtDNA variants exhibit differential susceptibility to various experimental diseases.

Conclusions:

  • Mitochondrial DNA variants influence susceptibility to inflammatory diseases.
  • D-glucosamine is a potential therapeutic target for skin inflammatory conditions.
  • This experimental approach aids in discovering novel therapies for chronic inflammatory diseases.
Keywords:
Chronic inflammationD-glucosamine (GlcN)Gnotobiotic miceMitochondrial DNA polymorphisms/variationsShotgun metagenomicsUntargeted metabolomics

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