Capsaicin Ameliorates High-Fat Diet-Induced Atherosclerosis in ApoE−/− Mice via Remodeling Gut Microbiota

Dai, Zijian; Li, Siqi; Meng, Yantong; Zhao, Qingyu; Zhang, Yiyun; Suonan, Zhuoma; Sun, Yuge; Liao, Xiaojun; Xue, Yong

doi:10.3390/nu14204334

Cited by 22 publications

(13 citation statements)

References 47 publications

(62 reference statements)

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“…6 ). Previous studies have shown atherogenic role of Romboutsia 62,73 , and atheroprotective role of Akkermansia 62,68,73 Bifidobacterium 73,74 , Lactobacillus 74 and Turicibacter 75 in hyperlipidemic apoE -/- mouse model of atherosclerosis.…”

Section: Discussionmentioning

confidence: 91%

Disulfiram reduces atherosclerosis and enhances efferocytosis, autophagy, and atheroprotective gut microbiota in hyperlipidemic mice

Traughber,

Timinski,

Prince

et al. 2023

Preprint

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Pyroptosis executor Gasdermin (GsdmD) promotes atherosclerosis in mice and humans. Disulfiram (DSF) was recently shown to potently inhibit GsdmD, but the in-vivo efficacy and mechanism of DSF's anti-atherosclerotic activity is yet to be explored. We used human/mouse macrophages and a hyperlipidemic mouse model of atherosclerosis to determine DSF anti-atherosclerotic efficacy and mechanism. DSF-fed hyperlipidemic apoE-/- mice showed significantly reduced IL-1b release upon in-vivo Nlrp3 inflammasome assembly and showed smaller atherosclerotic lesions (~27% and 29% reduction in males and females, respectively). The necrotic core area was also smaller (~50% and 46% reduction in DSF-fed males and females, respectively). DSF induced autophagy in macrophages, hepatocytes/liver, and in atherosclerotic plaques. DSF modulated other atheroprotective pathways such as efferocytosis, phagocytosis, and gut microbiota. DSF-treated macrophages showed enhanced phagocytosis/efferocytosis, with a mechanism being a marked increase in cell-surface expression of efferocytic receptor MerTK. Atomic-force microscopy analysis revealed altered biophysical membrane properties of DSF treated macrophages, showing increased ordered-state of the plasma membrane and increased adhesion strength. Furthermore, the 16sRNA sequencing of DSF-fed hyperlipidemic mice showed highly significant enrichment in atheroprotective gut microbiota Akkermansia and a reduction in atherogenic Romboutsia species. Taken together, our data shows that DSF can simultaneously modulate multiple atheroprotective pathways, and thus may serve as novel adjuvant therapeutic to treat atherosclerosis.

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Section: Discussionmentioning

confidence: 91%

Disulfiram reduces atherosclerosis and enhances efferocytosis, autophagy, and atheroprotective gut microbiota in hyperlipidemic mice

Traughber,

Timinski,

Prince

et al. 2023

Preprint

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“…In the present study, calycosin decreased the abundance of the genus Desulfovibrio and Bilophila, thereby preventing abnormal bile acid metabolism. As Odoribacter is a conditional pathogenic bacteria, which is harmless when the balance of intestinal microbes, normal abundance in the intestine promotes butyrate production [35] . We found in our experiment, that the relative abundance of Odoribacter was significantly decreased in the HFD group, and it was speculated that HFD disrupted the balance of intestinal microbes, and Odoribacter could not synthesize butyrate in a timely manner to fight inflammation.…”

Section: Discussionmentioning

confidence: 99%

Calycosin improves atherosclerosis by reshaping the interaction between the gut microbiome and bile acid metabolism

Fu,

Yu,

Liang

et al. 2024

Food Science and Human Wellness

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Calycosin, Astragali Radix most prominent ingredient, has drawn more attention as a result of its ability to treat atherosclerosis(AS). However, the mechanism of action has not been fully elucidated. We investigated the effects of calycosin on bile acid (BA) metabolism and gut microbiome in ApoE -/mice fed a high-fat diet (HFD). The data showed that the aorta of ApoE -/mice treated with HFD showed significant atheromatous plaque formation and lipid accumulation, and the levels of TC, TG and LDL-C were significantly increased, while the levels of HDL-C were significantly decreased. Calycosin can substantially regulate lipid levels, thereby alleviating liver lipid deposition induced by atherosclerosis. In addition, 16S rRNA sequencing showed that calycosin treatment has reshaped the gut microbiota disturbed by HFD, in particular, increasing the ratio of Bacteroidetes/Firmicutes, and improving the relative abundance of Bilophila, Desulfovibrio, Bacteroides, Lactobacillus, etc. Meanwhile, targeted metabolomics analysis showed that calycosin treatment significantly modulated CDCA, TCA, LCA, DCA, TDCA and bile acid pool composition, which were associated with atherosclerotic plaque areas. In addition, calycosin treatment also down-regulated FXR protein levels and up-regulated CYP7A1 protein levels in the hepatic. At the same time, calycosin inhibits the ileum FXR/TGR5 signaling pathway, inhibits BA reabsorption, promotes BA excretion, and reduces hepatic cholesterol accumulation by enterohepatic circulation. In addition, we found that calycosin significantly promoted the expression of hepatic ABCA1 and ABCG1 to mediate cholesterol efflux. Meanwhile, calycosin regulates gut microbiota, and Bacteroides, Alistipes, Desulfovibrio, Lactobacillus, Bilophila and Odoribacter are closely related to specific BAs. This enables us to further understand the relationship between BA metabolism and gut microbiota. Calycosin may reduce high-fat diet-induced hepatic cholesterol accumulation in ApoE -/mice through gut microbiota and bile acid metabolism, and play a role in treating AS. Finally, we confirmed that calycosin-altered gut microbiota by fecal microbiota transplantation was sufficient to alleviate atherosclerosis. Taken together, our findings provide important insights into the pharmacological mechanisms underlying the efficacy of calycosin on atherosclerosis.

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“…As previously reported, fecal samples from each group (n = 6) were randomly selected for metabolomic analysis. [ 11 ] In brief, stool samples (50 mg) were solved in 400 µL methanol: water (4:1, v/v) solution containing 0.02 mg/mL L-2-chlorophenylalanin as internal standard. The mixtures were then ground by a tissue crusher (Wonbio-96c, Wanbo biotechnology, 50 Hz, 6 minutes, −10ºC) followed by ultrasonic homogenization (40 kHz, 30 minutes, 5ºC).…”

Section: Methodsmentioning

confidence: 99%

Changes of intestinal flora in children with febrile seizure

Yang

Tian

2023

Medicine

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Febrile seizure (FS) is a highly recurrent neuro-system disorder in children that affects their nervous system development and quality of life. However, the pathogenesis of febrile seizures remains unclear. Our study aims to investigate the potential differences in the intestinal flora and metabolomics between healthy children and those with FS. By examining the relationship between specific flora and different metabolites, we hope to shed light on the pathogenesis of FS. Fecal specimens were collected from healthy children (n = 15) and children with febrile seizures (n = 15), and 16S rDNA sequencing was conducted to characterize intestinal flora. Subsequently, fecal samples from healthy (n = 6) and febrile seizure children (n = 6) were used to characterize metabolomics using linear discriminant analysis of effect size, orthogonal partial least squares discriminant analysis, Kyoto Encyclopedia of Genes and Genomes (pathway enrichment analysis), and Kyoto encyclopedia of genes and genomes topology analysis. Liquid chromatography-mass spectrometry was used to identify metabolites in the fecal samples. The intestinal microbiome in the febrile seizure children significantly differed from that in the healthy children at the phylum level. Ten differentially accumulated metabolites (xanthosine, (S)-abscisic acid, N-palmitoylglycine, (+/−)-2-(5-methyl-5-vinyl-tetrahydrofuran-2-yl) propionaldehyde, (R)-3-hydroxybutyrylcarnitine, lauroylcarnitine, oleoylethanolamide, tetradecyl carnitine, taurine, and lysoPC [18:1 (9z)/0:0] were considered the potential febrile seizure markers. Three metabolic pathways (taurine metabolism; glycine, serine, and threonine metabolism; and arginine biosynthesis) were found essential in febrile seizure. Bacteroides were significantly correlated with the 4 differential metabolites. Adjusting the balance of intestinal flora may be an effective method for preventing and treating febrile seizures.Abbreviations: FS = febrile seizure, KEGG = Kyoto encyclopedia of genes and genomes, LC-MS = liquid chromatographymass spectrometry, LDA = linear discriminant analysis, LEfSe = linear discriminant analysis of effect size, NC = normal control, OPLS-DA = orthogonal partial least squares discriminant analysis, VIP = variable importance of the projection.

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Capsaicin Ameliorates High-Fat Diet-Induced Atherosclerosis in ApoE−/− Mice via Remodeling Gut Microbiota

Cited by 22 publications

References 47 publications

Disulfiram reduces atherosclerosis and enhances efferocytosis, autophagy, and atheroprotective gut microbiota in hyperlipidemic mice

Disulfiram reduces atherosclerosis and enhances efferocytosis, autophagy, and atheroprotective gut microbiota in hyperlipidemic mice

Calycosin improves atherosclerosis by reshaping the interaction between the gut microbiome and bile acid metabolism

Changes of intestinal flora in children with febrile seizure

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