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Publikation Absorption and metabolism of the natural sweeteners erythritol and xylitol in humans. A dose-ranging study(MDPI, 30.08.2022) Wölnerhanssen, Bettina K.; Meyer-Gerspach, Anne Christin; Bordier, Valentine; Teysseire, Valentine; Senner, Frank; Schlotterbeck, Götz; Drewe, Jürgen; Beglinger, ChristophThe natural sweeteners erythritol and xylitol might be helpful to reduce sugar consumption and therefore prevent obesity and diabetes. The aim of the present study was to determine the absorption and metabolization into erythronate of different concentrations of erythritol and xylitol. Seventeen healthy lean participants received intragastric solutions of 10, 25, or 50 g erythritol or 7, 17, or 35 g xylitol on three study days in a randomized order. The study was double blinded with respect to the doses administered. We assessed plasma concentrations of erythritol, xylitol, and erythronate at fixed time intervals after administration with gas chromatography-mass spectrometry. We found: (i) a dose-dependent and saturable absorption of erythritol, (ii) a very low absorption of xylitol, (iii) a dose-dependent metabolization of erythritol into erythronate, and (iv) no metabolization of xylitol into erythronate. The implications of the metabolization of erythritol into erythronate for human health remain to be determined and more research in this area is needed.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Metabolomic serum abnormalities in dogs with hepatopathies(Nature, 29.03.2022) Imbery, Carolin A.; Dieterle, Frank; Ottka, Claudia; Weber, Corinna; Müller, Elisabeth; Lohi, Hannes; Giger, Urs; Schlotterbeck, GötzHepatopathies can cause major metabolic abnormalities in humans and animals. This study examined differences in serum metabolomic parameters and patterns in left-over serum samples from dogs with either congenital portosystemic shunts (cPSS, n = 24) or high serum liver enzyme activities (HLEA, n = 25) compared to control dogs (n = 64). A validated targeted proton nuclear magnetic resonance spectroscopy platform was used to assess 123 parameters. Principal component analysis of the serum metabolome demonstrated distinct clustering among individuals in each group, with the cluster of HLEA being broader compared to the other groups, presumably due to the wider spectrum of hepatic diseases represented in these samples. While younger and older adult control dogs had very similar metabolomic patterns and clusters, there were changes in many metabolites in the hepatopathy groups. Higher phenylalanine and tyrosine concentrations, lower branched-chained amino acids (BCAAs) concentrations, and altered fatty acid parameters were seen in cPSS dogs compared to controls. In contrast, dogs with HLEA had increased concentrations of BCAAs, phenylalanine, and various lipoproteins. Machine learning based solely on the metabolomics data showed excellent group classification, potentially identifying a novel tool to differentiate hepatopathies. The observed changes in metabolic parameters could provide invaluable insight into the pathophysiology, diagnosis, and prognosis of hepatopathies.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Metabolomic Abnormalities in Serum from Untreated and Treated Dogs with Hyper- and Hypoadrenocorticism(MDPI, 09.04.2022) Imbery, Carolin Anna; Dieterle, Frank; Ottka, Claudia; Weber, Corinna; Müller, Elisabeth; Lohi, Hannes; Giger, Urs; Schlotterbeck, GötzThe adrenal glands play a major role in metabolic processes, and both excess and insufficient serum cortisol concentrations can lead to serious metabolic consequences. Hyper- and hypoadrenocorticism represent a diagnostic and therapeutic challenge. Serum samples from dogs with untreated hyperadrenocorticism (n = 27), hyperadrenocorticism undergoing treatment (n = 28), as well as with untreated (n = 35) and treated hypoadrenocorticism (n = 23) were analyzed and compared to apparently healthy dogs (n = 40). A validated targeted proton nuclear magnetic resonance (1H NMR) platform was used to quantify 123 parameters. Principal component analysis separated the untreated endocrinopathies. The serum samples of dogs with untreated endocrinopathies showed various metabolic abnormalities with often contrasting results particularly in serum concentrations of fatty acids, and high- and low-density lipoproteins and their constituents, which were predominantly increased in hyperadrenocorticism and decreased in hypoadrenocorticism, while amino acid concentrations changed in various directions. Many observed serum metabolic abnormalities tended to normalize with medical treatment, but normalization was incomplete when compared to levels in apparently healthy dogs. Application of machine learning models based on the metabolomics data showed good classification, with misclassifications primarily observed in treated groups. Characterization of metabolic changes enhances our understanding of these endocrinopathies. Further assessment of the recognized incomplete reversal of metabolic alterations during medical treatment may improve disease management.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Whole-genome sequence-informed MALDI-TOF MS diagnostics reveal importance of Klebsiella oxytoca group in invasive infections: a retrospective clinical study(Springer, 2021) Cuenod, Aline; Wüthrich, Daniel; Seth-Smith, Helena; Ott, Chantal; Gehringer, Christian; Foucaul, Frederic; Mouchet, Roxanne; Kassim, Ali; Revathi, Gunturu; Vogt, Deborah; von Felten, Stefanie; Bassetti, Stefano; Tschudin-Sutter, Sarah; Hettich, Timm; Schlotterbeck, Götz; Homberger, Christina; Casanova, Carlo; Moran-Gilad, Jakob; Sagi, Orli; Rodriguez-Sanchez, Belen; Müller, Franco; Aerni, Martina; Gaia, Valeria; van Dessel, Helke; Kampinga, Greetje; Müller, Claudia; Daubenberger, Claudia; Pflüger, Valentin; Egli, AdrianBackground Klebsiella spp. are opportunistic pathogens which can cause severe infections, are often multi-drug resistant and are a common cause of hospital-acquired infections. Multiple new Klebsiella species have recently been described, yet their clinical impact and antibiotic resistance profiles are largely unknown. We aimed to explore Klebsiella group- and species-specific clinical impact, antimicrobial resistance (AMR) and virulence. Methods We analysed whole-genome sequence data of a diverse selection of Klebsiella spp. isolates and identified resistance and virulence factors. Using the genomes of 3594 Klebsiella isolates, we predicted the masses of 56 ribosomal subunit proteins and identified species-specific marker masses. We then re-analysed over 22,000 Matrix-Assisted Laser Desorption Ionization - Time Of Flight (MALDI-TOF) mass spectra routinely acquired at eight healthcare institutions in four countries looking for these species-specific markers. Analyses of clinical and microbiological endpoints from a subset of 957 patients with infections from Klebsiella species were performed using generalized linear mixed-effects models. Results Our comparative genomic analysis shows group- and species-specific trends in accessory genome composition. With the identified species-specific marker masses, eight Klebsiella species can be distinguished using MALDI-TOF MS. We identified K. pneumoniae (71.2%; n = 12,523), K. quasipneumoniae (3.3%; n = 575), K. variicola (9.8%; n = 1717), “K. quasivariicola” (0.3%; n = 52), K. oxytoca (8.2%; n = 1445), K. michiganensis (4.8%; n = 836), K. grimontii (2.4%; n = 425) and K. huaxensis (0.1%; n = 12). Isolates belonging to the K. oxytoca group, which includes the species K. oxytoca, K. michiganensis and K. grimontii, were less often resistant to 4th-generation cephalosporins than isolates of the K. pneumoniae group, which includes the species K. pneumoniae, K. quasipneumoniae, K. variicola and “K. quasivariicola” (odds ratio = 0.17, p < 0.001, 95% confidence interval [0.09,0.28]). Within the K. pneumoniae group, isolates identified as K. pneumoniae were more often resistant to 4th-generation cephalosporins than K. variicola isolates (odds ratio = 2.61, p = 0.003, 95% confidence interval [1.38,5.06]). K. oxytoca group isolates were found to be more likely associated with invasive infection to primary sterile sites than K. pneumoniae group isolates (odds ratio = 2.39, p = 0.0044, 95% confidence interval [1.05,5.53]). Conclusions Currently misdiagnosed Klebsiella spp. can be distinguished using a ribosomal marker-based approach for MALDI-TOF MS. Klebsiella groups and species differed in AMR profiles, and in their association with invasive infection, highlighting the importance for species identification to enable effective treatment options.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Effect of a chronic Intake of the natural sweeteners Xylitol and Erythritol on glucose absorption in humans with obesity(MDPI, 05.11.2021) Bordier, Valentine; Teysseire, Fabienne; Schlotterbeck, Götz; Beglinger, Christoph; Meyer-Gerspach, Anne-Christin; Wölnerhanssen, Bettina; Senner, FrankIn patients with obesity, accelerated nutrients absorption is observed. Xylitol and erythritol are of interest as alternative sweeteners, and it has been shown in rodent models that their acute in- gestion reduces intestinal glucose absorption. This study aims to investigate whether a chronic intake of xylitol and erythritol impacts glucose absorption in humans with obesity. Forty-six participants were randomized to take either 8 g of xylitol or 12 g of erythritol three times a day for five to seven weeks, or to be part of the control group (no substance). Before and after the intervention, intestinal glucose absorption was assessed during an oral glucose tolerance test with 3-Ortho-methyl-glucose (3-OMG). The effect of xylitol or erythritol intake on the area under the curve for 3-OMG concentra- tion was not significant. Neither the time (pre or post intervention), nor the group (control, xylitol, or erythritol), nor the time-by-group interaction effects were significant (p = 0.829, p = 0.821, and p = 0.572, respectively). Therefore, our results show that a chronic intake of the natural sweeteners xylitol and erythritol does not affect intestinal glucose absorption in humans with obesity01A - Beitrag in wissenschaftlicher Zeitschrift