ABSTRACT
SCOPE: Two hydrogenated xanthohumol (XN) derivatives, α,ß-dihydro-XN (DXN) and tetrahydro-XN (TXN), improved parameters of metabolic syndrome (MetS), a critical risk factor of cardiovascular disease (CVD) and type 2 diabetes, in a diet-induced obese murine model. It is hypothesized that improvements in obesity and MetS are linked to changes in composition of the gut microbiota, bile acid metabolism, intestinal barrier function, and inflammation. METHODS AND RESULTS: To test this hypothesis, 16S rRNA genes were sequenced and bile acids were measured in fecal samples from C57BL/6J mice fed a high-fat diet (HFD) or HFD containing XN, DXN or TXN. Expression of genes associated with epithelial barrier function, inflammation, and bile acid metabolism were measured in the colon, white adipose tissue (WAT), and liver, respectively. Administration of XN derivatives decreases intestinal microbiota diversity and abundance-specifically Bacteroidetes and Tenericutes-alters bile acid metabolism, and reduces inflammation. In WAT, TXN supplementation decreases pro-inflammatory gene expression by suppressing macrophage infiltration. Transkingdom network analysis connects changes in the microbiota to improvements in MetS in the host. CONCLUSION: Changes in the gut microbiota and bile acid metabolism may explain, in part, the improvements in obesity and MetS associated with administration of XN and its derivatives.
Subject(s)
Bile Acids and Salts/metabolism , Flavonoids/pharmacology , Gastrointestinal Microbiome/drug effects , Metabolic Syndrome/drug therapy , Propiophenones/pharmacology , Adipose Tissue, White/drug effects , Animals , Bile Acids and Salts/genetics , Diet, High-Fat/adverse effects , Feces/chemistry , Feces/microbiology , Gastrointestinal Microbiome/genetics , Gene Expression Regulation/drug effects , Male , Metabolic Syndrome/metabolism , Metabolic Syndrome/microbiology , Mice, Inbred C57BL , Obesity/drug therapy , Obesity/etiology , Panniculitis/drug therapy , Panniculitis/etiology , RNA, Ribosomal, 16SABSTRACT
Background and Objectives: Dental caries is a chronic disease affecting young children and has multi-factorial risk factors. The purpose of this work was to identify sex-specific differences in the salivary microbiota within caries-active children. Design: Saliva specimens were collected from 85 children (boys: 41; girls: 44) between the ages of 2-12 years. Salivary microbial DNA was subjected to PCR amplification using V3-V4 16S rDNA-specific primers and next-generation sequencing. Results: Significant sex differences in salivary microbiota were found between caries-active boys versus caries-active girls. Neisseria flavescens, Rothia aeria, and Haemophilus pittmaniae were found at significantly higher levels in caries-active boys. In contrast, Lactococcus lactis, Selenomonas species HOT 126, Actinobaculum species HOT 183, Veillonella parvula, and Alloprevotella species HOT 473 were found at significantly higher levels in caries-active girls. Conclusion: We have found the acid-generating, cariogenic Lactococcus lactis to be much more abundant in caries-active girls than caries-active boys, indicating that this microorganism may play a more significant role in shaping the cariogenic microbiome in girls. In addition, in caries-active girls, Alloprevotella species HOT 473 was the only species that exhibited both significant sex differences (4.4-fold difference; p=0.0003) as well as high abundance in numbers (1.85% of the total microbial population).
