fenugreek (Trigonella foenum-graecum) is an annual herbaceous plant and a staple of traditional health remedies for metabolic conditions including high cholesterol and diabetes. While the mechanisms of the beneficial actions of fenugreek remain unknown, a role for intestinal microbiota in metabolic homeostasis is likely. To determine if fenugreek utilizes intestinal bacteria to offset the adverse effects of high fat diets, C57BL/6J mice were fed control/low fat (CD) or high fat (HFD) diets each supplemented with or without 2% (w/w) fenugreek for 16 weeks. The effects of fenugreek and HFD on gut microbiota were comprehensively mapped and then statistically assessed in relation to effects on metrics of body weight, hyperlipidemia, and glucose tolerance. 16S metagenomic analyses revealed robust and significant effects of fenugreek on gut microbiota, with alterations in both alpha and beta diversity as well as taxonomic redistribution under both CD and HFD conditions. As previously reported, fenugreek attenuated HFD-induced hyperlipidemia and stabilized glucose tolerance without affecting body weight. Finally, fenugreek specifically reversed the dysbiotic effects of HFD on numerous taxa in a manner tightly correlated with overall metabolic function. Collectively, these data reinforce the essential link between gut microbiota and metabolic syndrome and suggest that the preservation of healthy populations of gut microbiota participates in the beneficial properties of fenugreek in the context of modern Western-style diets.Obesity linked to Western-style diets is the prototypical ailment of the modern era. Obesity currently affects more than 35% of Americans 1 ; and in addition to ties with type 2 diabetes and cardiovascular disease, obesity increases the risk of all-cause mortality and exacerbates anxiety and depression 2-5 . While search for effective obesity treatments has become a priority in biomedical research, available pharmacological options for obesity are undermined by issues related to toxicity and off-target side 6 . Herbal medicine or phytotherapy has long been a source of traditional medicinal remedies, and indeed, interest in generally regarded as safe (GRAS) plant materials for the clinical treatment of obesity is growing (reviewed in 7,8 ). Fenugreek (Trigonella foenum-graecum) is an annual herbaceous plant and a staple of traditional health remedies to treat hyperlipidemia and diabetes 9-12 , as well as mood disorders 13 . Laboratory studies demonstrate protective effects of fenugreek on diabetes [14][15][16][17][18] , and suggest that potential mechanisms might include inhibition of intestinal glucose absorption 14-16 , delayed gastric emptying 15 , and/or insulinotropic activity 19,20,17,18 . Protective effects of fenugreek on cholesterol and hyperlipidemia 21 might be based on modulation of hepatic steatosis 22-26 , inflammation 26-28 , and/or oxidative stress secondary to diabetes [29][30][31][32] . While the exact mechanisms whereby fenugreek or its constituents confers metabolic resiliency are un...