CE exerts beneficial metabolic effects through improving HFHS diet-induced features of the metabolic syndrome, which is associated with a proportional increase in Akkermansia spp.

Our results show that CC prevents visceral and liver fat deposition through BAT activation and increased energy expenditure, a mechanism that is dependent on the GM and linked to major changes in the BA pool size and composition.

Visceral obesity is a key risk factor for type 2 diabetes (T2D). Whereas gut dysbiosis appears to be instrumental for this relationship, whether gut-associated signatures translocate to extra-intestinal tissues and how this affects host metabolism remain elusive. Here we provide a comparative analysis of the microbial profile found in plasma, liver and in three distinct adipose tissues of individuals with morbid obesity. We explored how these tissue microbial signatures vary between individuals with normoglycaemia and those with T2D that were matched for body mass index. We identified tissue-specific signatures with higher bacterial load in the liver and omental adipose tissue. Gut commensals, but also environmental bacteria, showed tissueand T2D-specific compartmentalisation. T2D signatures were most evident in mesenteric adipose tissue, in which individuals with diabetes displayed reduced bacterial diversity concomitant with fewer Gram-positive bacteria, such as Faecalibacterium, as opposed to enhanced levels of typically opportunistic Gram-negative Enterobacteriaceae. Plasma samples of individuals with diabetes were similarly enriched in Enterobacteriaceae, including the pathobiont Escherichia-Shigella. Our work provides evidence for the presence of selective plasma and tissue microbial signatures in individuals with severe obesity and identifies new potential microbial targets and biomarkers of T2D.

ObjectivePrevious studies have reported that polyphenol-rich extracts from various sources can prevent obesity and associated gastro-hepatic and metabolic disorders in diet-induced obese (DIO) mice. However, whether such extracts can reverse obesity-linked metabolic alterations remains unknown. In the present study, we aimed to investigate the potential of a polyphenol-rich extract from cranberry (CE) to reverse obesity and associated metabolic disorders in DIO-mice.MethodsMice were pre-fed either a Chow or a High Fat-High Sucrose (HFHS) diet for 13 weeks to induce obesity and then treated either with CE (200 mg/kg, Chow + CE, HFHS + CE) or vehicle (Chow, HFHS) for 8 additional weeks.ResultsCE did not reverse weight gain or fat mass accretion in Chow- or HFHS-fed mice. However, HFHS + CE fully reversed hepatic steatosis and this was linked to upregulation of genes involved in lipid catabolism (e.g., PPARα) and downregulation of several pro-inflammatory genes (eg, COX2, TNFα) in the liver. These findings were associated with improved glucose tolerance and normalization of insulin sensitivity in HFHS + CE mice. The gut microbiota of HFHS + CE mice was characterized by lower Firmicutes to Bacteroidetes ratio and a drastic expansion of Akkermansia muciniphila and, to a lesser extent, of Barnesiella spp, as compared to HFHS controls.ConclusionsTaken together, our findings demonstrate that CE, without impacting body weight or adiposity, can fully reverse HFHS diet-induced insulin resistance and hepatic steatosis while triggering A. muciniphila blooming in the gut microbiota, thus underscoring the gut-liver axis as a primary target of cranberry polyphenols.