Capsaicin Improves Glucose Tolerance and Insulin Sensitivity Through Modulation of the Gut Microbiota‐Bile Acid‐FXR Axis in Type 2 Diabetic db/db Mice

Abstract

Scope Previous studies have linked dietary capsaicin (CAP) intake to improved glucose homeostasis and insulin sensitivity. However, the underlying mechanisms remain unclear. Methods and results Type 2 diabetic db/db mice are fed a chow diet with or without CAP treatment for 8 weeks. CAP administration markedly improves glucose tolerance and insulin sensitivity through decreasing gluconeogenesis and increasing glycogen synthesis in the liver. Furthermore, CAP inhibits the increase in abundance of the genus Lactobacillus and its bile salt hydrolase (BSH) activity compared with levels in chow‐fed mice, thereby leading to the accumulation of tauro‐β‐muricholic acid (TβMCA), a natural antagonist of the farnesoid X receptor (FXR) that is involved in the regulation of BA and glucose metabolism. CAP‐induced suppression of enterohepatic FXR‐fibroblast growth factor 15 (FGF15) signaling contributes to the increased BA pool size, followed by increases in the expression of cholesterol 7α‐hydroxylase (CYP7A1) and hepatic BA synthesis. Additionally, depleting gut microbiota by antibiotics administration abolishes the beneficial effects of CAP on BA metabolism and glucose homeostasis. Conclusions CAP‐induced improvements in BA and glucose metabolism are partially mediated by the gut microbiota‐BA‐enterohepatic FXR axis in db/db mice.

Capsaicin and Gut Microbiota in Health and Disease

“…CAP intervention increased the ratio of conjugated/unconjugated BA (in accordance with the increased level of BSH a ), most likely due to a marked increase in TβMCA (1.5-fold). We wonder what is the mechanism of TβMCA augmentation, especially as it appears to have the largest variation compared to all other tested conjugated-BA [94]. Probably, because taurine, a semi-essential amino acid, which has been shown to have numerous beneficial effects in the human body [105][106][107][108], also targets the intestine and it is known to regulate gut microbiota by inhibiting harmful bacteria, reducing bacterial lipopolysaccharide (LPS) level, and accelerating short-chain fatty acids (SCFA) production [109,110].…”

“…CAP has also been proven to increase L-lactate in bacterial culture, by enhancing the metabolic activity of Lactobacillus acidophilus [93]. In another study conducted in spontaneous diabetic male mice with a genetic mutation (db/db, leptin receptor-deficient diabetic mice), a CAP-enriched diet (at a low dose of 0.01%, for 8 weeks) mitigated insulin resistance and improved glucose homeostasis, an effect that was associated with the CAP-induced repression of the increased abundance of the genus Lactobacillus [94].…”

Antidiabetic Effect of Casein Glycomacropeptide Hydrolysates on High-Fat Diet and STZ-Induced Diabetic Mice via Regulating Insulin Signaling in Skeletal Muscle and Modulating Gut Microbiota

“…Transplantation of intestinal microbiota from healthy, lean donors improved insulin signaling in participants with metabolic syndrome [13], suggesting that modulating gut microbiota is helpful for ameliorating T2D. Diet supplementations with some natural bioactive ingredients were found to improve glucose metabolism partially by modifying gut microbiome [14,15], providing evidence for alleviating T2D by regulating gut microbiota.…”

Hypoglycemic Effect of Prolamin from Cooked Foxtail Millet (Setaria italic) on Streptozotocin-Induced Diabetic Mice

“…After 5 weeks’ treatment, an oral glucose tolerance test (OGTT) was performed as follows. Briefly, mice were fasted for 6 h and 1 g/kg BW glucose solution was injected into mice by gavage, and blood glucose (BG) was measured at 0 min, 30 min, 60 min and 120 min [ 32 ]. The area under curve (AUC) over 120 min was calculated following the trapezoidal rule.…”