The consumption of plant-based bioactive compounds modulates the gut microbiota and interacts with the innate and adaptive immune responses associated with metabolic disorders. The present study aimed to evaluate the effect of cranberry polyphenols (CP), rich in flavonoids, and agavins (AG), a highly branched agave-derived neo-fructans, on cardiometabolic response, gut microbiota composition, metabolic endotoxemia, and mucosal immunomodulation of C57BL6 male mice fed an obesogenic high-fat and high-sucrose (HFHS) diet for 9 weeks. Interestingly, CP+AG-fed mice had improved glucose homeostasis. Oral supplementation with CP selectively and robustly (five-fold) increases the relative abundance of Akkermansia muciniphila, a beneficial bacteria associated with metabolic health. AG, either alone or combined with CP (CP+AG), mainly stimulated the glycan-degrading bacteria Muribaculum intestinale, Faecalibaculum rodentium, Bacteroides uniformis, and Bacteroides acidifaciens. This increase of glycan-degrading bacteria was consistent with a significantly increased level of butyrate in obese mice receiving AG, as compared to untreated counterparts. CP+AG-supplemented HFHS-fed mice had significantly lower levels of plasma LBP than HFHS-fed controls, suggesting blunted metabolic endotoxemia and improved intestinal barrier function. Gut microbiota and derived metabolites interact with the immunological factors to improve intestinal epithelium barrier function. Oral administration of CP and AG to obese mice contributed to dampen the pro-inflammatory immune response through different signaling pathways. CP and AG, alone or combined, increased toll-like receptor (TLR)-2 (Tlr2) expression, while decreasing the expression of interleukin 1ss (ILss1) in obese mice. Moreover, AG selectively promoted the anti-inflammatory marker Foxp3, while CP increased the expression of NOD-like receptor family pyrin domain containing 6 (Nlrp6) inflammasome. The intestinal immune system was also shaped by dietary factor recognition. Indeed, the combination of CP+AG significantly increased the expression of aryl hydrocarbon receptors (Ahr). Altogether, both CP and AG can shape gut microbiota composition and regulate key mucosal markers involved in the repair of epithelial barrier integrity, thereby attenuating obesity-associated gut dysbiosis and metabolic inflammation and improving glucose homeostasis.

Simple Summary Microbes present in the large intestine of humans and companion animals produce bioactive metabolites from host-ingested food. These bioactive metabolites can influence host health. A prior study in dogs that were healthy or had chronic enteritis/gastroenteritis showed that stool quality improved when they ate food containing a fiber bundle made from fibers of pecan shells, flax seed, cranberry, citrus, and beet. In addition, eating food containing the fiber bundle resulted in the gut bacteria shifting from digesting mainly protein to digesting mainly carbohydrates. The present study tested the impact of the fiber bundle at a lower range of concentrations in dogs. Fecal levels of several bioactive metabolites with beneficial antioxidant or anti-inflammatory properties increased after dogs consumed food with the fiber bundle, though no changes in the bacteria or their functional pathways were observed. Stool quality remained in the acceptable range. These results suggest that the gut bacteria were able to digest the fiber bundle to produce beneficial bioactive metabolites to improve host health. This study assessed changes in canine fecal metabolites and microbiota with the consumption of foods with increasing concentrations of a fiber bundle including pecan shells, flax seed, and powders of cranberry, citrus, and beet that was previously shown (at 14% w/w) to improve stool quality, shift fecal bacterial metabolism from proteolysis to saccharolysis, increase abundance of saccharolytic bacteria, and decrease abundance of proteolytic bacteria. In this study, 48 healthy adult dogs were split evenly to consume different inclusion levels (0%, 1%, 2%, and 4%) of the fiber bundle for a 31-day period following a 28-day pre-feed period. Increases from baseline in the fecal short-chain fatty acids butyric acid, valeric acid, and hexanoic acid were observed only in the dogs that consumed the food with the 4% fiber bundle. With addition of any level of the fiber bundle, increases were seen in the polyphenols hesperidin, hesperetin, ponciretin, secoisolariciresinol diglucoside, secoisolariciresinol, and enterodiol. However, fecal microbiota and their metabolism, and stool scores were largely unaffected by the fiber bundle. Overall, addition of the fiber bundle appeared to increase bioactive metabolites of increased antioxidant and anti-inflammatory potency for beneficial to health and, at levels >= 4%, shifted gut bacterial metabolism toward saccharolysis.

Polyphenol-rich cranberry extracts decrease intestinal inflammation, alter gut microbiota, and decrease intestinal permeability in obese mice, but the effect has not been investigated in adults who are obese. The purpose of this randomized double-blind, cross-over feeding study in obese (BMI = 37.4 +or- 1.2 kg/m2) but otherwise healthy adults (n = 36) 35.4 +or- 1.3 years was to determine the effects of consuming 480 mL of a high polyphenolic cranberry or control beverage daily for 2 weeks on gastrointestinal permeability, markers of inflammation and immune function, and gut microbiota. An acute aspirin challenge was administered prior to assessing intestinal permeability to determine resistance to barrier function compromise. The cranberry beverage did not affect markers of gastrointestinal permeability, inflammation, or immune function. However, fecal Faecalibacterium prausnitzii and Eggerthella lenta increased with consumption of the cranberry beverage. Data suggest that the intervention impacted bacterial communities. A longer intervention may be required to observe beneficial effects on inflammation and gastrointestinal barrier function.