An association between gut microbiota and the development of pancreatic ductal adenocarcinoma (PDAC) has been previously described. To better understand the bacterial microbiota changes accompanying PDAC promotion and progression stimulated by inflammation and fecal microbiota transplantation (FMT), we investigated stool and pancreatic microbiota by 16s RNA-based metagenomic analysis in mice with inducible acinar transgenic expressions of KrasG12D, and age- and sex-matched control mice that were exposed to inflammatory stimuli and fecal microbiota obtained from mice with PDAC. Time- and inflammatory-dependent stool and pancreatic bacterial composition alterations and stool alpha microbiota diversity reduction were observed only in mice with a Kras mutation that developed advanced pancreatic changes. Stool Actinobacteriota abundance and pancreatic Actinobacteriota and Bifidobacterium abundances increased. In contrast, stool abundance of Firmicutes, Verrucomicrobiota, Spirochaetota, Desulfobacterota, Butyricicoccus, Roseburia, Lachnospiraceae A2, Lachnospiraceae unclassified, and Oscillospiraceae unclassified decreased, and pancreatic detection of Alloprevotella and Oscillospiraceae uncultured was not observed. Furthermore, FMT accelerated tumorigenesis, gradually decreased the stool alpha diversity, and changed the pancreatic and stool microbial composition in mice with a Kras mutation. Specifically, the abundance of Actinobacteriota, Bifidobacterium and Faecalibaculum increased, while the abundance of genera such as Lachnospiraceace A2 and ASF356, Desulfovibrionaceace uncultured, and Roseburia has decreased. In conclusion, pancreatic carcinogenesis in the presence of an oncogenic Kras mutation stimulated by chronic inflammation and FMT dynamically changes the stool and pancreas microbiota. In particular, a decrease in stool microbiota diversity and abundance of bacteria known to be involved in short-fatty acids production were observed. PDAC mouse model can be used for further research on microbiota–PDAC interactions and towards more personalized and effective cancer therapies.

Risk factors for type 2 diabetes mellitus (T2DM) consist of a combination of an unhealthy, imbalanced diet and genetic factors that may interact with each other. Single nucleotide polymorphism (SNP) in the prospero homeobox 1 (PROX1) gene is a strong genetic susceptibility factor for this metabolic disorder and impaired β-cell function. As the role of this gene in T2DM development remains unclear, novel approaches are needed to advance the understanding of the mechanisms of T2DM development. Therefore, in this study, for the first time, postprandial changes in plasma metabolites were analysed by GC–MS in nondiabetic men with different PROX1 genotypes up to 5 years prior to prediabetes appearance. Eighteen contestants (12 with high risk (HR) and 6 with low risk (LR) genotype) participated in high-carbohydrate (HC) and normo-carbohydrate (NC) meal-challenge tests. Our study concluded that both meal-challenge tests provoked changes in 15 plasma metabolites (amino acids, carbohydrates, fatty acids and others) in HR, but not LR genotype carriers. Postprandial changes in the levels of some of the detected metabolites may be a source of potential specific early disturbances possibly associated with the future development of T2DM. Thus, accurate determination of these metabolites can be important for the early diagnosis of this metabolic disease.

Although brown adipose tissue (BAT) is considered to play a protective role against obesity and type 2 diabetes, the mechanisms of its activation and associations with clinical parameters are not well described. Male adults underwent a 2 h cold exposure (CE) to activate BAT and, based on the results of PET/MRI performed after the CE, were divided into BAT(+) and BAT(−) groups. During the CE procedure, blood samples were collected and alterations in plasma metabolome in both groups were investigated using LC-MS. Additionally, associations between clinical factors and BAT were examined. Moreover, levels of glucose, insulin, leptin, TNF-α, FGF21, and FABP4 were assessed in serum samples. In the BAT(+) group, levels of LPC(17:0), LPE(20:4), LPE(22:4), LPE(22:6), DHA, linoleic acid, and oleic acid increased during CE, whereas levels of sphinganine-phosphate and sphingosine-1-phosphate decreased. Levels of LPE(O-18:0), 9-HpODE, and oleic acid were elevated, while the level of LPE(20:5) was reduced in BAT(+) compared to BAT(−) subjects. AUCs of LPC(18:2), LPC(O-18:2)/LPC(P-18:1), and SM(d32:2) negatively correlated with BAT. In the BAT(+) group, the concentration of FABP4 during and after CE was decreased compared to the basal level. No alterations were observed in the BAT(−) group. In conclusion, using untargeted metabolomics, we proved that the plasma metabolome is affected by cold-induced BAT activation.

Introduction: Even though brown adipose tissue (BAT) has recently been identified as a possible target for combating obesity and type 2 diabetes, neither the mechanisms of its activation nor its relationships to clinical parameters are clearly defined. Metabolomics enables the simultaneous analysis of multiple classes of compounds, thus seems to be a perfect tool to study this topic. This study aimed to explore alterations during cold exposure (CE) associated with the activation of BAT. Materials and methods: Twenty-five healthy male adults underwent 2 hours of CE followed by PET-MRI. Afterwards, they were divided into two groups, depending on BAT presence (BATpos or BATneg). The levels of metabolites were measured in plasma samples at three time points: before, after one, and 2 hours of CE, using a standard gas chromatography-mass spectrometry (GC-MS) method for metabolite profiling. Results: In the BATpos group, the levels of linoleic, oleic, and palmitic acids were significantly increased after 120 min of CE compared to the baseline. These changes were absent in the BATneg group. When comparing the BATpos and BATneg groups, we observed that the BATpos group had significantly lower baseline level of succinic acid. After 60 min of CE, the BATpos group showed significantly increased levels of linoleic, oleic and trans-13-octadecenoic acid. The differences in oleic acid persisted for another hour. Conclusion: Between-group differences in the level of fatty acids during CE, along with the BATpos group-specific alterations during CE, suggest that the activation of BAT affects lipid metabolism.