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Fatty liver and alteration of the gut microbiome induced by diallyl disulfide.

ABSTRACT: Diallyl disulfide (DADS) is one of the primary components of garlic and it exhibits a broad range of biological activities. In the present study, the effects of DADS on lipid metabolism and its potential role in the modulation of the gut microbiome were determined. Hematoxylin and eosin and oil?red O staining were used to assess the liver and intestinal tissues of mice treated with DADS. The expression of lipid metabolism?associated genes was measured using reverse transcription?quantitative PCR (RT?qPCR). The effects of DADS on the gut microbiome were measured using 16S recombinant (r)DNA gene analysis. The results revealed that the serum non?esterified free fatty acids, high density lipoprotein?cholesterol, low density lipoprotein?cholesterol, serum total cholesterol, liver triglyceride and total cholesterol levels of the mice fed with a low?dose of DADS was significantly higher when compared with the control. Hematoxylin and eosin and oil?red O staining demonstrated that DADS induced fatty liver in mice. The results of the RT?qPCR revealed that the expression levels of a number of lipid metabolism?associated genes were altered in the livers of mice treated with DADS. The 16S rDNA gene analysis demonstrated that the mice fed on a normal diet treated with a low?dose of DADS had decreased levels of bacteria from the Bacteroidetes phyla and increased levels of bacteria from the Firmicutes phyla. The Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed the top 20 pathways enriched in the low?dose DADS group of mice fed with a normal diet. In the present study, low?dose DADS induced fatty liver and altered the gut microbiota, similar to the phenotype induced by a high fat diet, by regulating the expression of lipid metabolism associated genes.

SUBMITTER: Yang Y

PROVIDER: S-EPMC6777666 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Fatty liver and alteration of the gut microbiome induced by diallyl disulfide.

Yang Yanhong Y Yang Fei F Huang Miaoling M Wu Huijuan H Yang Changyuan C Zhang Xinyue X Yang Lanxiang L Chen Guibin G Li Shuqi S Wang Qianyu Q Liu Shaomin S Liu Yanyan Y Lei Yuting Y Lei Zili Z Guo Jiao J

International journal of molecular medicine 20190924 5

Diallyl disulfide (DADS) is one of the primary components of garlic and it exhibits a broad range of biological activities. In the present study, the effects of DADS on lipid metabolism and its potential role in the modulation of the gut microbiome were determined. Hematoxylin and eosin and oil‑red O staining were used to assess the liver and intestinal tissues of mice treated with DADS. The expression of lipid metabolism‑associated genes was measured using reverse transcription‑quantitative PCR ...[more]

PMID: 31573042

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Project description:BackgroundMycophenolic acid (MPA) is the most widely used immunosuppressive drug in transplantation and for autoimmune diseases. Unfortunately, more than 30% of patients experience a typical gastrointestinal adverse effect also referred to as mycophenolate-induced enteropathy. Due to its antibacterial, antifungal, and antiviral properties, MPA exposure is associated with intestinal dysbiosis characterized by a decrease in density and diversity of the microbiome regarding the main bacterial phyla (Firmicutes and Bacteroidetes). These bacterial phyla are known for their metabolic role in maintaining the homeostasis of the digestive tract, particularly through the production of short-chain fatty acids (SCFA) that could contribute to the pathophysiology of mycophenolate-induced enteropathy. Our study aimed at deciphering short-chain fatty acids (SCFA) profile alterations associated with gastrointestinal toxicity of MPA at the digestive and systemic levels in a mouse model.MethodsTen-week old C57BL/6 (SOPF) mice were randomly assigned in 2 groups of 9 subjects: control, and mycophenolate mofetil (MMF, 900 mg/kg/day). All mice were daily treated by oral gavage for 7 days. Individual faecal pellets were collected at days 0, 4 and 8 as well as plasma at day 8 for SCFA profiling. Additionally, after the sacrifice on day 8, the caecum was weighted, and colon length was measured. The proximal colon was cut for histological analysis.ResultsMMF treatment induced around 10% weight loss at the end of the protocol associated with a significant decrease in caecum weight and a slight reduction in colon length. Histological analysis showed significant architectural changes in colon epithelium. Moreover, we observed an overall decrease in SCFA concentrations in faecal samples, especially regarding acetate (at day 8, control 1040.6 ± 278.161 μM versus MMF 384.7 ± 80.5 μM, p < 0.01) and propionate (at day 8, control 185.94 ± 51.96 μM versus MMF 44.07 ± 14.66 μM, p < 0.001), and in plasma samples for butyrate (at day 8, control 0.91 ± 0.1 μM versus MMF 0.46 ± 0.1 μM, p < 0.01).ConclusionsThese results are consistent with functional impairment of the gut microbiome linked with digestive or systemic defects during MMF treatment.

Project description:BackgroundThe gut microbiome and iron status are known to play a role in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), although their complex interaction remains unclear.ResultsHere, we applied an integrative systems medicine approach (faecal metagenomics, plasma and urine metabolomics, hepatic transcriptomics) in 2 well-characterised human cohorts of subjects with obesity (discovery n = 49 and validation n = 628) and an independent cohort formed by both individuals with and without obesity (n = 130), combined with in vitro and animal models. Serum ferritin levels, as a markers of liver iron stores, were positively associated with liver fat accumulation in parallel with lower gut microbial gene richness, composition and functionality. Specifically, ferritin had strong negative associations with the Pasteurellaceae, Leuconostocaceae and Micrococcaea families. It also had consistent negative associations with several Veillonella, Bifidobacterium and Lactobacillus species, but positive associations with Bacteroides and Prevotella spp. Notably, the ferritin-associated bacterial families had a strong correlation with iron-related liver genes. In addition, several bacterial functions related to iron metabolism (transport, chelation, heme and siderophore biosynthesis) and NAFLD (fatty acid and glutathione biosynthesis) were also associated with the host serum ferritin levels. This iron-related microbiome signature was linked to a transcriptomic and metabolomic signature associated to the degree of liver fat accumulation through hepatic glucose metabolism. In particular, we found a consistent association among serum ferritin, Pasteurellaceae and Micrococcacea families, bacterial functions involved in histidine transport, the host circulating histidine levels and the liver expression of GYS2 and SEC24B. Serum ferritin was also related to bacterial glycine transporters, the host glycine serum levels and the liver expression of glycine transporters. The transcriptomic findings were replicated in human primary hepatocytes, where iron supplementation also led to triglycerides accumulation and induced the expression of lipid and iron metabolism genes in synergy with palmitic acid. We further explored the direct impact of the microbiome on iron metabolism and liver fact accumulation through transplantation of faecal microbiota into recipient's mice. In line with the results in humans, transplantation from 'high ferritin donors' resulted in alterations in several genes related to iron metabolism and fatty acid accumulation in recipient's mice.ConclusionsAltogether, a significant interplay among the gut microbiome, iron status and liver fat accumulation is revealed, with potential significance for target therapies. Video abstract.

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Fatty liver and alteration of the gut microbiome induced by diallyl disulfide.

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Fatty liver and alteration of the gut microbiome induced by diallyl disulfide.

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