Diallyl Disulfide (DADS) Ameliorates Intestinal Candida albicans Infection by Modulating the Gut microbiota and Metabolites and Providing Intestinal Protection in Mice

Abstract

Diallyl disulfide (DADS), a garlic extract also known as allicin, has been reported to have numerous biological activities, including anticancer, antifungal, and inflammation-inhibiting activities, among others. Although many studies have assessed whether DADS can treat Candida albicans infection in vitro, its in vivo function and the underlying mechanism are still not clear. Accumulated evidence has implicated the gut microbiota as an important factor in the colonization and invasion of C. albicans. Thus, this study aimed to identify the mechanism by which DADS ameliorates dextran sulfate (DSS)-induced intestinal C. albicans infection based on the systematic analysis of the gut microbiota and metabolomics in mice. Here, we determined the body weight, survival, colon length, histological score, and inflammatory cytokine levels in the serum and intestines of experimental mice. Fecal samples were collected for gut microbiota and metabolite analysis by 16S rRNA gene sequencing and LC–MS metabolomics, respectively. DADS significantly alleviated DSS-induced intestinal C. albicans infection and altered the gut microbial community structure and metabolic profile in the mice. The abundances of some pathogenic bacteria, such as Proteobacteria, Escherichia–Shigella, and Streptococcus, were notably decreased after treatment with DADS. In contrast, SCFA-producing bacteria, namely, Ruminiclostridium, Oscillibacter, and Ruminococcaceae_UCG−013, greatly increased in number. The perturbance of metabolites in infectious mice was improved by DADS, with increases in secondary bile acids, arachidonic acid, indoles and their derivatives, which were highly related to the multiple differentially altered metabolic pathways, namely, bile secretion, arachidonic acid metabolism, and tryptophan metabolism. This study indicated that DADS could modulate gut microbiota and metabolites and protect the gut barrier to alleviate DSS-induced intestinal C. albicans infection in mice. Moreover, this work might also provide novel insight into the treatment of C. albicans infection using DADS.

Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis

“…Rifaximin affected Trp synthesis in the gut microbiota [ 58 ]. Diallyl disulfide (DADS) altered the gut microbial community structure and metabolic profile in mice [ 59 ].…”

Mitochondria as novel mediators linking gut microbiota to atherosclerosis that is ameliorated by herbal medicine: A review

“…Garlic is a recognized prebiotic; thus, allicin can be metabolized into diallyl disulfide (DAD) and diallyl trisulfide (DAT) to regulate gut microbiota composition and disrupt TMA production in ApoE −/− mice with high concentrations of carnitine ( Panyod et al, 2022 ). Following allicin treatment, the proportions of Bifidobacterium, Lactobacillus, Bacteroidales, and Clostridiales significantly increased in the gut ( Shi et al, 2019 ), while those in some pathogenic bacteria, such as Proteobacteria, Escherichia–Shigella, and Streptococcus, drastically reduced ( Hu et al, 2021 ). Moreover, allicin also regulates the metabolites of gut microbiota, such as upregulating SCFA, while downregulating secondary BAs, TMAO, and indoles, stimulating brown adipose tissue activation, browning in white adipose tissues ( Zhang et al, 2020 ), decline in lipid accumulation in the liver, and weight loss in obese mice ( Shi et al, 2019 ).…”

Modulating gut microbiota and metabolites with dietary fiber oat β-glucan interventions to improve growth performance and intestinal function in weaned rabbits

“…In the BG group, we also observed an increased abundance of Ruminococcaceae_UCG-007 and Ruminiclostridium_5 , which have rarely been reported previously. Ruminococcaceae is generally considered a beneficial bacterium colonized in the cecum and colon and can degrade various polysaccharides and fibers to produce SCFAs ( Huang et al, 2021 ), it also presents an effect to reduce intestinal inflammation ( Hu et al, 2021 ). Moreover, findings from prior research showed that the increase of Ruminiclostridium_5 was associated with positive health states, whereas reduced levels are associated with negative health states.…”