O.I. Akinrimisi¹ , J.L. Scheijen^2,3 , A.S. Meijnikman¹, B. Voermans¹ , Y. Acherman⁴ , S. Bruin⁴ , V.E.A. Gerdes^1,4 , M. Nieuwdorp^1,5 , C.G. Schalkwijk^2,3 , N.M.J.Hanssen^1,5

¹Department of Experimental Vascular and Internal Medicine, Amsterdam UMC, Amsterdam, Netherlands, ²Department of Internal Medicine, Maastricht University Medical Center, Maastricht, Netherlands, ³Cardiovascular Research Institute Maastricht

(CARIM), Maastricht, Netherlands, ⁴Department of Surgery, Spaarne Gasthuis,Hoofddorp, Netherlands, ⁵Diabeter Center Amsterdam, Amsterdam, Netherlands.

Introduction :

Methylglyoxal (MGO) is a compound formed as a byproduct of glucose metabolism and is known to be cytotoxic. Its formation and metabolism by prokaryotic cells has remained relatively neglected in the setting of human diseases. This study investigates the relationship between the human gut microbiome and MGO to eventually find new therapeutic targets to lower MGO.

Methods :

A subset of the BARIA cohort was used which included 292 patients (76 % female , mean age 47 ± 10 years) with morbid obesity. Fecal metagenomics alongside targeted metabolomics (UPLC-MS/MS , MGO analysis) was used to explore the association between the gut microbiome and plasma MGO levels

Results :

Plasma MGO was significantly higher in individuals with diabetes (295 ± 60 nmol/L) compared to individuals without diabetes (252 ± 71 nmol/L) (P = 0.001). A correlation was observed between Lactobacillus delbrueckii abundance and plasma MGO in the individuals with diabetes (Spearman rho = 0.37, P-adjusted =0.02). which persisted after adjusting for age and sex . Lactobacillus delbrueckii formed the closest clusters with Streptococcus thermophilus in both groups of individuals with and without diabetes.

Conclusion :

Plasma MGO was higher in diabetes. Higher abundance of Lactobacillus delbrueckii was associated with higher plasma MGO in individuals with diabetes. In vitro experiments will be conducted to explore the causal direction of these findings.