Role of microbial Agmatine in metabolic inflammation in humans

Background Recently, it was suggested that microbially produced agmatine mediates the advantageous effects of metformin on metabolism and lifespan. Additionally, our data of 1.258 human showed that agmatine production was significantly elevated in metformin-treated T2 D patients compared to untreated T2 D patients.

Methods Firstly, we determined agmatine through semi-targeted metabolomics (FT-ICR-MS) and secondly, we statistically modelled either positive counts or absence / presence of agmatine regarding metabolic and inflammatory parameters in 1.704 subjects of the FoCus cohort (two-part Hurdle model). Further, we aim to investigate agmatine in relation to human cell lines such as THP-1, Hep-G2, CaCo2 and 3T3-L1.

Results Thus far, modelling positive counts of agmatine showed an increased level of agmatine in subjects with elevated Body Mass Index (P = 3.33e-4), elevated waist (P = 2.15e-4) and elevated C-reactive protein (P = 3.56e-2) (linear model). Women with a BMI greater 25 kg / m² had an increased level of agmatine compared to a BMI lower 25 kg / m² (P = 8.47e-5). In cell culture we found in macrophages added up to 1 mM of agmatine for 24 h, that cells remained viable up to 92 %. Concentrations from 5 mM decreased viability to 52 %. NF-kB expression was decreased in macrophages added 1 mM of agmatine compared to PBS-controls (0,5 h, 2 h incubation) (n.s.).

Conclusion Our results so far suggest anti-inflammatory effects of agmatine and a positive association with obesity. It indicates that the gut microbiome tries to counteract human metabolic inflammation by producing anti-inflammatory metabolites from beneficial gut bacteria suggesting a symbiotic host-microbe interchange.

Interessenskonflikt

L. Henneke: Finanzielle Interessen: Gehaltsempfänger: SH-Exzellenz-Lehrstuhl (SH: Schleswig-Holstein) für Innere Medizin, Endokrinologie, Diabetologie und klinische Ernährungsmedizin. Nichtfinanzielle Interessen: Wissenschaftliche Mitarbeiterin, UKSH (Universitätsklinikum Schleswig-Holstein [Campus Kiel]), Klinik für Innere Medizin I & SH-Exzellenz-Lehrstuhl für Innere Medizin, Endokrinologie, Diabetologie und klinische Ernährungsmedizin.

K. Schlicht: Wissenschaftliche Mitarbeiterin, UKSH (Universitätsklinikum Schleswig-Holstein [Campus Kiel]), Klinik für Innere Medizin I & SH-Exzellenz-Lehrstuhl für Innere Medizin, Endokrinologie, Diabetologie und klinische Ernährungsmedizin.

M. Laudes: Finanzielle Interessen: Forschungsförderung zur persönlichen Verfügung: BMBF (Bundesministerium für Bildung und Forschung), DFG-Projekte (DFG: Deutsche Forschungsgemeinschaft). – Referentenhonorare: Lilly, Novo Nordisk, Boehringer Ingelheim, AstraZeneca, Sanofi. – Berater: Lilly, AstraZeneca, Novo Nordisk. Nichtfinanzielle Interessen: W3 Professor und Lehrstuhlinhaber, Leiter des Bereichs Endokrinologie, Diabetologie und klinische Ernährungsmedizin, Klinik für Innere Medizin, Universitätsklinik Schleswig-Holstein, Campus Kiel | Mitgliedschaften: DDG (Deutsche Diabetes Gesellschaft), DGE (Deutsche Gesellschaft für Ernährung), DGIM (Deutsche Gesellschaft für Innere Medizin), DAG (Deutsche Adipositas-Gesellschaft).

• Literatur

• Pryor R, Norvaisas P, Marinos G, Best L, Thingholm LB, Quintaneiro LM, De Haes W, Esser D, Waschina S, Lujan C, Smith RL, Scott TA, Martinez-Martinez D, Woodward O, Bryson K, Laudes M, Lieb W, Houtkooper RH, Franke A, Temmerman L, Bjedov I, Cochemé HM, Kaleta C, Cabreiro F. Host-Microbe-Drug-Nutrient Screen Identifies Bacterial Effectors of Metformin Therapy. Cell 2019; Sep 5; 178 (06) 1299-1312.e29. DOI: 10.1016/j.cell.2019.08.003. Epub 2019 Aug 29. PMID: 31474368; PMCID: PMC6736778..

Publication History

Article published online:
06 May 2021