Microbiomic and Metabolomic Analyses Unveil the Protective Effect of Saffron in a Mouse Colitis Model

Abstract

Despite the existence of effective drugs used to treat inflammatory bowel disease (IBD), many patients fail to respond or lose response over time. Further, many drugs can carry serious adverse effects, including increased risk of infections and malignancies. Saffron (Crocus sativus) has been reported to have anti-inflammatory properties. Its protective role in IBD and how the microbiome and metabolome play a role has not been explored extensively. We aimed to establish whether saffron treatment modulates the host microbiome and metabolic profile in experimental colitis. Colitis was induced in C57BL/6 mice with 3% DSS and treated with either saffron in a dose of 20 mg/kg body weight or vehicle through daily gavage. On day 10, stool pellets from mice were collected and analyzed to assess saffron’s effect on fecal microbiota and metabolites through 16S rRNA sequencing and untargeted primary metabolite analysis. Saffron treatment maintained gut microbiota homeostasis by counter-selecting pro-inflammatory bacteria and maintained Firmicutes/Bacteroides ratio, which was otherwise disturbed by DSS treatment. Several metabolites (uric acid, cholesterol, 2 hydroxyglutaric acid, allantoic acid, 2 hydroxyhexanoic acid) were altered significantly with saffron treatment in DSS-treated mice, and this might play a role in mediating saffron’s colitis-mitigating effects. These data demonstrate saffron’s therapeutic potential, and its protective role is modulated by gut microbiota, potentially acting through changes in metabolites.

Mechanism of Antitumor Effects of Saffron in Human Prostate Cancer Cells

“…We are currently conducting a clinical trial that stems from a successful in vitro and in vivo data extrapolation to humans with ulcerative colitis [ 12 , 17 ]. In this clinical trial, we used two saffron concentrations after extrapolating from mice findings to human body weight [ 13 ]. We are assessing the presence of saffron compounds in the plasma of the recruited patients.…”

“…Several reviews have reported the anti-inflammatory effects of saffron treatment in gastrointestinal disorders and saffron’s antitumor effects on gastric cancer, colorectal cancer, liver cancer, and pancreatic cancer [ 12 , 13 ]. In prostate cancer, preclinical studies of the oral treatment of saffron and its major metabolites crocetin (CCT) and crocin (CR) in aggressive-PCa-cell-line xenografts in male nude mice also showed antitumor effects [ 14 ].…”

Saffron, a Potential Bridge between Nutrition and Disease Therapeutics: Global Health Challenges and Therapeutic Opportunities

“…Despite a huge number of drugs being designed to treat numerous diseases, the adverse effects such as decreasing the beneficial gut microbiome, risk of infection, toxicity, and malignancies diminish their applicability in humans. Saffron and its derivative compounds are alternatives to eliminating the pro-inflammatory bacteria and regulating the beneficial microbes such as Firmicutes/Bacteroides in mouse models [ 173 ]. These studies also demonstrated the role of saffron in regulating microbiome-associated metabolites such as 2 hydroxyglutaric acid, cholesterol, uric acid, 2-hydroxyhexanoic acid, and allantoic acid.…”

“…These studies also demonstrated the role of saffron in regulating microbiome-associated metabolites such as 2 hydroxyglutaric acid, cholesterol, uric acid, 2-hydroxyhexanoic acid, and allantoic acid. In conclusion, saffron plays a pivotal role in maintaining the homeostatic balance in regulating the gut microbiome and healthy state of the gut [ 173 ]. Recently, Pontifex et al [ 174 ] reported that the saffron extract reduces anxiety-related behavior in a rat model of low-grade inflammation via modulating the microbiota and gut metabolites.…”