Kinetics of imidazole propionate from orally delivered histidine in mice and humans
Imidazole Propionate (ImP), a gut-derived metabolite from histidine, affects insulin signaling in mice and is elevated in type 2 diabetes (T2D). However, the source of histidine and the role of the gut microbiota remain unclear. We conducted an intervention study in mice and humans, comparing ImP kinetics in mice on a high-fat diet with varying histidine levels and antibiotics, and assessed ImP levels in healthy and T2D subjects with histidine supplementation. Results show that dietary histidine is metabolized to ImP, with antibiotic-induced gut microbiota suppression reducing ImP levels in mice. In contrast, oral histidine supplementation resulted in increases in circulating ImP levels in humans, whereas antibiotic treatment increased ImP levels, which was associated with a bloom of several bacterial genera that have been associated with ImP production, such as Lactobacilli. Our findings highlight the gut microbiota's crucial role in regulating ImP and the complexity of translating mouse models to humans.
Authors
- Anthony Horak (ORCID: https://orcid.org/0009-0009-2024-3679)
- Sumita Dutta (ORCID: https://orcid.org/0000-0001-7538-1045)
- Albert K. Groen
- E. Marleen Kemper (ORCID: https://orcid.org/0000-0003-2275-1713)
- Elena Rampanelli (ORCID: https://orcid.org/0000-0002-7742-0092)
- Karine Clément (ORCID: https://orcid.org/0000-0002-2489-3355)
- Stanley L. Hazen (ORCID: https://orcid.org/0000-0001-7124-6639)
- William J. Massey (ORCID: https://orcid.org/0000-0002-2087-6048)
- Ina Nemet (ORCID: https://orcid.org/0000-0002-0657-7121)
- Youling Hao
- Moritz V. Warmbrunn (ORCID: https://orcid.org/0000-0003-3548-6728)
- Fredrik Bäckhed (ORCID: https://orcid.org/0000-0002-4871-8818)
- Ilias Attaye (ORCID: https://orcid.org/0000-0001-9166-3229)
- Annefleur M. Koopen
- J. Mark Brown (ORCID: https://orcid.org/0000-0003-2708-7487)
- Koen Wortelboer (ORCID: https://orcid.org/0000-0002-3582-0127)
- Hilde Herrema (ORCID: https://orcid.org/0000-0002-0112-6348)
- Mark Davids (ORCID: https://orcid.org/0000-0003-3081-9124)
- Daniël H. van Raalte (ORCID: https://orcid.org/0000-0003-2894-6124)
- Rakhee Banerjee (ORCID: https://orcid.org/0000-0002-2299-7177)
- Venkateshwari Varadharajan (ORCID: https://orcid.org/0000-0002-4557-9840)
- Judith Aron‐Wisnewsky
- Per-Olof Bergh
- Max Nieuwdorp
- Nadia R. Mohamed
Institutions
- Inserm (FR)
- Sahlgrenska University Hospital (SE)
- Cleveland Clinic Lerner College of Medicine (US)
- Sorbonne Université (FR)
- Region Västra Götaland (SE)
- Nutrition et obésité : approches systémiques (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Amsterdam Neuroscience (NL)
- Pitié-Salpêtrière Hospital (FR)
- Amsterdam University Medical Centers (NL)
- University of Gothenburg (SE)
- University of Amsterdam (NL)
Publication Details
- Journal
- npj Biofilms and Microbiomes
- Published
- 2024-11-04
- DOI
- https://doi.org/10.1038/s41522-024-00592-8
- Citations
- 4
- Primary Topic
- Amino Acid Enzymes and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 1.18