Research Paper|Volume 13, Issue 5|pp 6375—6405

Oral administration of Akkermansia muciniphila elevates systemic antiaging and anticancer metabolites

Claudia Grajeda-Iglesias^1,^2,³, Sylvère Durand^1,^2,³, Romain Daillère⁴, Kristina Iribarren^1,^8,^9,¹⁰, Fabien Lemaitre^1,^8,^9,¹⁰, Lisa Derosa^1,^8,^9,¹⁰, Fanny Aprahamian^1,^2,³, Noélie Bossut^1,^2,³, Nitharsshini Nirmalathasan^1,^2,³, Frank Madeo^5,^6,⁷, Laurence Zitvogel^1,^8,^9,¹⁰, Guido Kroemer^1,^2,^3,^11,^12,¹³

¹Gustave Roussy Comprehensive Cancer Institute, Villejuif, France
²Centre de Recherche des Cordeliers, Equipe labellisée Par la Ligue Contre le Cancer, Université de Paris, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France
³Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Center, Université Paris Saclay, Villejuif, France
⁴EverImmune, Villejuif, France
⁵Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria
⁶BioTechMed-Graz, Graz, Austria
⁷Field of Excellence BioHealth, University of Graz, Graz, Austria
⁸Inserm U1015, Villejuif, France
⁹Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France
¹⁰Faculty of Medicine, Université Paris Saclay, Le Kremlin-Bicêtre, France
¹¹Pôle De Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France
¹²Suzhou Institute for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China
¹³Karolinska Institute, Department of Women’s and Children’s Health, Karolinska University Hospital, Stockholm, Sweden

* Equal contribution

Received: January 21, 2021Accepted: February 19, 2021Published: March 2, 2021

https://doi.org/10.18632/aging.202739

Copyright: © 2021 Grajeda-Iglesias et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The presence of Akkermansia muciniphila (Akk) in the human gut is associated with good health, leanness and fitness. Mouse experimentation has demonstrated positive effects for Akk, which counteracts aging, mediates antiobesity and antidiabetic effects, dampens inflammation and improves anticancer immunosurveillance. Clinical trials have confirmed antidiabetic effects for Akk. Here, we investigated the time-dependent effects of oral administration of Akk (which was live or pasteurized) and other bacteria to mice on the metabolome of the ileum, colon, liver and blood plasma. Metabolomics was performed by a combination of chromatographic and mass spectrometric methods, yielding a total of 1.637.227 measurements. Akk had major effects on metabolism, causing an increase in spermidine and other polyamines in the gut and in the liver. Pasteurized Akk (Akk-past) was more efficient than live Akk in elevating the intestinal concentrations of polyamines, short-chain fatty acids, 2-hydroxybutyrate, as well multiple bile acids, which also increased in the circulation. All these metabolites have previously been associated with human health, providing a biochemical basis for the beneficial effects of Akk.