AIM: The metabolic performance of the gut microbiota contributes to the onset of type 2 diabetes. However, targeted dietary interventions are limited by the highly variable inter-individual response. We hypothesized (1) that the composition of the complex gut microbiome and metabolome (MIME) differ across metabolic spectra (lean-obese-diabetes); (2) that specific MIME patterns could explain the differential responses to dietary inulin; and (3) that the response can be predicted based on baseline MIME signature and clinical characteristics. METHOD: Forty-nine patients with newly diagnosed pre/diabetes (DM), 66 metabolically healthy overweight/obese (OB), and 32 healthy lean (LH) volunteers were compared in a cross-sectional case-control study integrating clinical variables, dietary intake, gut microbiome, and fecal/serum metabolomes (16 S rRNA sequencing, metabolomics profiling). Subsequently, 27 DM were recruited for a predictive study: 3 months of dietary inulin (10 g/day) intervention. RESULTS: MIME composition was different between groups. While the DM and LH groups represented opposite poles of the abundance spectrum, OB was closer to DM. Inulin supplementation was associated with an overall improvement in glycemic indices, though the response was very variable, with a shift in microbiome composition toward a more favorable profile and increased serum butyric and propionic acid concentrations. The improved glycemic outcomes of inulin treatment were dependent on better baseline glycemic status and variables related to the gut microbiota, including the abundance of certain bacterial taxa (i.e., Blautia, Eubacterium halii group, Lachnoclostridium, Ruminiclostridium, Dialister, or Phascolarctobacterium), serum concentrations of branched-chain amino acid derivatives and asparagine, and fecal concentrations of indole and several other volatile organic compounds. CONCLUSION: We demonstrated that obesity is a stronger determinant of different MIME patterns than impaired glucose metabolism. The large inter-individual variability in the metabolic effects of dietary inulin was explained by differences in baseline glycemic status and MIME signatures. These could be further validated to personalize nutritional interventions in patients with newly diagnosed diabetes.
- MeSH
- diabetes mellitus 2. typu * MeSH
- inulin * metabolismus farmakologie MeSH
- lidé MeSH
- multiomika MeSH
- nadváha metabolismus MeSH
- obezita metabolismus MeSH
- průřezové studie MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
Reactive oxygen and nitrogen species (ROS and RNS, resp.) have been traditionally perceived solely as detrimental, leading to oxidative damage of biological macromolecules and organelles, cellular demise, and ageing. However, recent data suggest that ROS/RNS also plays an integral role in intracellular signalling and redox homeostasis (redoxtasis), which are necessary for the maintenance of cellular functions. There is a complex relationship between cellular ROS/RNS content and autophagy, which represents one of the major quality control systems in the cell. In this review, we focus on redox signalling and autophagy regulation with a special interest on ageing-associated changes. In the last section, we describe the role of autophagy and redox signalling in the context of Alzheimer's disease as an example of a prevalent age-related disorder.
- MeSH
- autofagie fyziologie MeSH
- lidé MeSH
- oxidační stres fyziologie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- stárnutí fyziologie MeSH
- volné radikály metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Publikační typ
- abstrakt z konference MeSH
- MeSH
- finanční podpora výzkumu jako téma MeSH
- inzulinová rezistence fyziologie MeSH
- kosterní svaly metabolismus MeSH
- mastné kyseliny krev metabolismus MeSH
- palmitany diagnostické užití metabolismus MeSH
- poruchy metabolismu glukózy metabolismus patofyziologie MeSH
- tuková tkáň metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- MeSH
- androstadieny farmakologie MeSH
- dinoproston biosyntéza MeSH
- financování organizované MeSH
- inhibitory cyklooxygenasy MeSH
- kyseliny mastné neesterifikované krev MeSH
- ledviny enzymologie MeSH
- membránové proteiny MeSH
- obezita enzymologie MeSH
- potkani Zucker MeSH
- prostaglandinové endoperoxidy syntetické analýza MeSH
- thromboxan B2 biosyntéza MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
