Biomarkers of Broccoli Consumption: Implications for Glutathione Metabolism and Liver Health

Abstract

Diet and lifestyle choices contribute to obesity and liver disease. Broccoli, a brassica vegetable, may mitigate negative effects of both diet and lifestyle. Currently, there are no clinically relevant, established molecular biomarkers that reflect variability in human absorption of brassica bioactives, which may be the cause of variability/inconsistencies in health benefits in the human population. Here, we focused on the plasma metabolite profile and composition of the gut microbiome in rats, a relatively homogenous population in terms of gut microbiota, genetics, sex and diet, to determine if changes in the plasma metabolite profiles caused by dietary broccoli relate to molecular changes in liver. Our aim was to identify plasma indicators that reflect how liver health is impacted by dietary broccoli. Rats were fed a 10% broccoli diet for 14 days. We examined the plasma metabolite composition by metabolomics analysis using GC–MS and gut microbiota using 16S sequencing after 0, 1, 2, 4, 7, 14 days of broccoli feeding. We identified 25 plasma metabolites that changed with broccoli consumption, including metabolites associated with hepatic glutathione synthesis, and with de novo fatty acid synthesis. Glutamine, stearic acid, and S-methyl-L-cysteine (SMC) relative abundance changes correlated with changes in gut bacteria previously implicated in metabolic disease and with validated increases in expression of hepatic NAD(P)H dehydrogenase [quinone] 1 (NQO1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), associated with elevated hepatic glutathione synthesis. Circulating biomarkers following broccoli consumption reflect gut–liver axis health.

Pathway Preferential Estrogens Prevent Hepatosteatosis Due to Ovariectomy and High-Fat Diets

“…Furthermore, GO terms associated with decreasing oxidative stress were enriched in both DIO and ob/ob models. In addition, we previously showed the metabolites in the same pathway to be upregulated by long-term broccoli feeding and correlated with improvement of liver health [25].…”

Interplay between Cruciferous Vegetables and the Gut Microbiome: A Multi-Omic Approach

“…Additionally, the microbes responsible for the metabolism of glucosinolates, and other cruciferous vegetable phytochemicals, are still unclear, representing a major gap in knowledge. Many studies have been conducted in vivo, in human and rodent models, to examine the impact of cruciferous vegetable consumption on the gut microbiome; however, these analyses are typically strictly taxonomical and do not examine specific microbe–metabolite relationships [ 26 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. Metabolomics databases, such HMDB or METLIN, typically focus on endogenous metabolites (i.e., originating from humans), so metabolomic studies, while valuable, do not provide great insight into the diverse array of microbial- and cruciferous vegetable-derived metabolites that are presumed to be present after cruciferous vegetable consumption [ 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ].…”

Targeting Metabolic Adaptations in the Breast Cancer–Liver Metastatic Niche Using Dietary Approaches to Improve Endocrine Therapy Efficacy

“…To visualize the separation between No ECM and Liver ECM groups' metabolic profiles VIP scores for the top 25 metabolites that discriminated between treatment groups were calculated and displayed using the Partial least squares discriminant analysis (PLS-DA) tool. Enrichment analysis and pathway analysis were used to identify metabolic pathways associated with enriched metabolites (fold change >2 or <0.05) as previously described (39)(40)(41)(42).…”