TB-targeted regulation of intestinal microorganisms Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD) and Bacteroides acidiciens (BA) to improve glucolipid metabolism in Goto-Kakizaki rats.

Background: Although caffeine generally offers benefits to human health, its impact on bone metabolism remains unclear.Aim and Methods: This study aimed to systematically evaluate the long-term effects of caffeine administration on osteoclasts, osteoblasts, and ovariectomy-induced postmenopausal osteoporosis (OP).Results: Our in vitro findings revealed that 3.125 and 12.5 μg/mL caffeine inhibited RANKL-mediated osteoclastogenesis in RAW 264.7 cells through the MAPK and NF-κB pathways, accompanied by the inactivation of nuclear translocation of nuclear factor NFATc1. Similarly, 3.125 and 12.5 μg/mL of caffeine modulated MC3T3-E1 osteogenesis via the AKT, MAPK, and NF-κB pathways. However, 50 μg/mL of caffeine promoted the phosphorylation of IκBα, P65, JNK, P38, and AKT, followed by the activation of NFATc1 and the inactivation of Runx2 and Osterix, ultimately disrupting the balance between osteoblastogenesis and osteoclastogenesis. In vivo studies showed that gavage with 55.44 mg/kg caffeine inhibited osteoclastogenesis, promoted osteogenesis, and ameliorated bone loss in ovariectomized mice.Conclusion: Conversely, long-term intake of high-dose caffeine (110.88 mg/kg) disrupted osteogenesis activity and promoted osteoclastogenesis, thereby disturbing bone homeostasis. Collectively, these findings suggest that a moderate caffeine intake (approximately 400 mg in humans) can regulate bone homeostasis by influencing both osteoclasts and osteoblasts. However, long-term high-dose caffeine consumption (approximately 800 mg in humans) could have detrimental effects on the skeletal system.

The intestinal microbiota undergoes diurnal compositional and functional oscillations within a day, which affect the metabolic homeostasis of the host and exacerbate the occurrence of obesity. TB has the effect of reducing body weight and lipid accumulation, but the mechanism of improving obesity caused by a high-fat diet based on the circadian rhythm of intestinal microorganisms has not been clarified. In this study, we used multi-omics and imaging approaches to investigate the mechanism of TB in alleviating obesity in mice based on the circadian rhythm of gut microbiota. The results showed that TB could significantly regulate the levels and rhythmic expression of serum lipid indicators (TG, TC, LDL) and serum hormones (MT, FT3, LEP, CORT). The number of intestinal microbiota colonizing the colonic epithelium underwent daily fluctuations. TB remodeled the rhythmic oscillation of gut microbes (i.e., Lachnospiraceae_NK4A136_group, Alistipes, etc.), including the number, composition, abundance and rhythmic expression of the biogeographic localization of microbes. TB notably reduced the levels of 16 bile acids (TCA, THDCA, TCDA, GHDCA, T-α-MCA, etc.) and restored the balance of bile acid metabolism. It was found that TB may mitigate high-fat diet-induced obesity in mice by reshaping the circadian rhythm of the gut microbiome and regulating bile acid metabolism.

Epidemiological studies have reported varying associations between coffee consumption and bone mineral density. This study aims to systematically asses the pharmacological effects of prolonged coffee intake on osteoblasts, osteoclasts, and postmenopausal osteoporosis induced by ovariectomy. In vitro, experiments revealed that coffee water extract upregulated the expression of osteogenic-related proteins such as 12.5 μg/mL middle concentration group had a 1.33 fold increase in Collagen Type I Alpha 1 (COL1A1) expression, and a 1.83 fold increase in Osterix expression by inhibiting the phosphorylation of Protein Kinase B (AKT), IκBɑ, P65, and Extracellular Signal-Regulated Kinase (ERK). Additionally, it inhibited RANKL-mediated osteoclastogenesis in RAW264.7 cells though the AKT, MAPKs, and NF-κB pathways, concomitant with the inhibition of nuclear translocation of nuclear factor of activated T cells cytoplasmic 1. In vivo studies demonstrated that a medium-dose coffee sample inhibited osteoclastogenesis, stimulated osteogenesis, and ameliorated bone loss in ovariectomized mice. Molecular docking analysis validated the impact of caffeine, cholorogenic acids, and trigonelline on bone homeostasis. In summary, consumption of 4-5 cups of coffee per day in humans may attenuate OVX-associated pathological bone loss by disrupting osteoclast activity and promoting osteogenesis, while long-term consumption of high-dose coffee could disrupt bone homeostasis.