Recent rodent microbiome experiments suggest that besides Akkermansia, Parasutterella sp . are important in type 2 diabetes and obesity development. In the present translational human study, we aimed to characterize Parasutterella in our European cross-sectional FoCus cohort (n = 1,544) followed by validation of the major results in an independent Canadian cohort (n = 438). In addition, we examined Parasutterella abundance in response to a weight loss intervention (n = 55). Parasutterella was positively associated with BMI and type 2 diabetes independently of the reduced microbiome α/β diversity and low-grade inflammation commonly found in obesity. Nutritional analysis revealed a positive association with the dietary intake of carbohydrates but not with fat or protein consumption. Out of 126 serum metabolites differentially detectable by untargeted HPLC-based MS-metabolomics, L-cysteine showed the strongest reduction in subjects with high Parasutterella abundance. This is of interest, since Parasutterella is a known high L-cysteine consumer and L-cysteine is known to improve blood glucose levels in rodents. Furthermore, metabolic network enrichment analysis identified an association of high Parasutterella abundance with the activation of the human fatty acid biosynthesis pathway suggesting a mechanism for body weight gain. This is supported by a significant reduction of the Parasutterella abundance during our weight loss intervention. Together, these data indicate a role for Parasutterella in human type 2 diabetes and obesity, whereby the link to L-cysteine might be relevant in type 2 diabetes development and the link to the fatty acid biosynthesis pathway for body weight gain in response to a carbohydrate-rich diet in obesity development.

Dipeptidylpeptidase (DPP)-4 is a key regulator of the incretin system. For several years DPP-4 inhibitors in addition to GLP-1 analogues are of major importance in the clinical management of obesity and type 2 diabetes. DPP-4 is also known as CD26 and represents a membrane bound protease on the surface of several eukaryotic cell types. Of interest, DPP-4, like ACE2, has been shown to serve as a binding partner for corona-like viruses to enter host immune cells. Since metabolic diseases are major risk factors for the present COVID-19 pandemic, we examined circulating soluble DPP-4 serum concentrations in patients suffering from severe COVID-19 infection and in healthy human subjects in a case control design. In this analysis sDPP-4 levels were significantly lower in COVID-19 patients compared to controls (242.70 ± 202.12 ng/mL versus 497.70 ± 188.13 ng/mL, p = 0.02). We also examined sDPP-4 serum concentrations in patients suffering from sepsis not due to corona-like viruses. In these subjects, sDPP-4 levels were not different compared to healthy case controls (p = 0.14), which might suggest the decrease of sDPP-4 to be specific for corona-like virus infections. Currently, most data point towards membrane bound ACE2 in contrast to DPP-4 as the major binding partner for COVID-19 internalization into host immune cells. However, the finding that the circulating soluble form of DPP-4 is reduced in hospitalized patients might suggest a regulatory role for both, ACE and DPP-4, in COVID-19 infections, especially since obesity and type 2 diabetes are major risk factor for a severe course of the disease * Matthias Laudes

Our data suggest that wnt5a is important in linking inflammation to metabolism. The nutrition and the microbiome might be interesting targets to prevent and/or treat wnt5a-mediated metabolic inflammation.

Context Dipeptidylpeptidase (DPP)-4 is a key regulator of the incretin system. It exists in a membrane bound form and a soluble form (= sDPP-4). Initial human studies suggested sDPP-4 to be an adipokine involved in metabolic inflammation. However, recent mechanistic data in genetically modified mice questioned these findings. Objectives We examined circulating sDPP-4 in a cohort of n = 451 humans with different metabolic phenotypes and during three different weight loss interventions (n = 101) to further clarify its role in human physiology and metabolic diseases. Design sDPP-4 serum concentrations were measured by ELISA and related to several phenotyping data including gut microbiome analysis. Results sDPP-4 increased with age and body weight and was positively associated with insulin resistance and hypertriglyceridemia but was reduced in manifest type 2 diabetes. In addition, we found reduced serum concentrations of sDPP-4 in subjects with arterial hypertension. In contrast to earlier reports, we did not identify an association with systemic markers of inflammation. Impaired kidney and liver functions significantly altered sDPP-4 concentrations while no relation to biomarkers for heart failure was observed. Having found increased levels of sDPP-4 in obesity, we studied surgical (gastric bypass and sleeve gastrectomy) and non-surgical interventions revealing a significant association of sDPP-4 with the improvement of liver function tests but not with changes in body weight. Conclusions Our data suggest that sDPP-4 is related to hepatic abnormalities in obesity rather than primarily functioning as an adipokine and that sDPP-4 is implicated both, in glucose and lipid metabolism, but not fundamentally in systemic inflammation.

Aim Recombinant secreted frizzled‐related protein 5 (sFRP5) improved periodontal status in mice. Thus, this study aimed to investigate this finding in human periodontitis using an epidemiological approach. Materials and Methods sFRP5 and wnt5a concentrations were determined in human serum from the Food Chain Plus cohort using ELISAs. A total of 128 patients with periodontitis and tooth loss and 245 patients with periodontitis without tooth loss were compared to 373 sex‐, smoker‐, age‐ and BMI‐matched individuals in a nested case–control design. Results Systemic sFRP5 serum levels were significantly lower in patients with periodontitis and tooth loss (2.5 [0.0–10.4] ng/ml, median [IQR]) compared to patients with periodontitis without tooth loss (6.0 [2.5–15.8] ng/ml, median [IQR], p = 0.04] and matched controls (7.0 [2.5–18.3] ng/ml, median [IQR], p = 0.02). No significant differences in sFRP5 serum levels were found among patients with periodontitis without tooth loss (6.0 [2.5–15.8] ng/ml, median [IQR]) and controls (3.1 [0.0–10.6] ng/ml, median [IQR], p = 0.06). Conclusions sFRP5 might serve as a novel biomarker for periodontitis severity. Modulating the inflammatory background of severe forms of periodontitis, in the time of precision medicine, needs to be revealed in further studies.