Fenugreek Counters the Effects of High Fat Diet on Gut Microbiota in Mice: Links to Metabolic Benefit

Annadora J Bruce-Keller,Jacqueline M Stephens,Sun-Ok Fernandez-Kim,J Michael Salbaum,David M Ribnicky,Richard Carmouche,Allison J Richard,Susan Newman

doi:10.1038/s41598-020-58005-7

Abstract

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.

Highlights

Obesity linked to Western-style diets is the prototypical ailment of the modern era
Fenugreek improves glucose tolerance and dyslipidemia in mice given high fat diet. Data in this manuscript is built on initial publication of the effects of whole fenugreek seed supplementation (2% w/w) on overall metabolic function in the context of a 16-week trial of high fat diet consumption[41], and previously published data are only summarized in this report
We demonstrate the robust effects of fenugreek on gut microbiota, and describe a novel combination of statistical analyses including Unifrac, iterative DESeq. 2, and pairwise correlation matrices to generate insight into the role of intestinal microbial changes in the protective effects of fenugreek

Summary

Introduction

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[2,3,4,5]. To modulate intestinal bacteria in several models[33,34,40], studies were designed to determine if fenugreek could offset the effects of a high fat diet on gut dysbiosis, and to establish the relationship of fenugreek-shaped gut microbiota to clinically relevant metrics of metabolic function. To this end, data from our previously published study on the effects of fenugreek on mice given a high fat diet were extended to include sequencing and statistical assessment of gut microbiota. Metagenomic sequencing of fecal microbiota collected from mice was conducted, and diet-related changes in gut microbiota were statistically analyzed in relation to established metrics of metabolic function

Methods

Results

Conclusion