Alisma orientalis Beverage Treats Atherosclerosis by Regulating Gut Microbiota in ApoE-/- Mice

Abstract

Background: Alisma orientalis beverage (AOB) is a Chinese traditional medicine formulated with a diversity of medicinal plants and used for treating metabolic syndrome and atherosclerosis (AS) since time ago. Given the current limited biological research on AOB, the mechanism by which AOB treats AS is unknown. This study investigats the role of AOB-induced gut microbiota regulation in the expansion of AS. Methods: We established an AS model in male apolipoprotein E-deficient (ApoE −/−) mice that are fed with a high-fat diet (HFD), treated with numerous interventions, and evaluated the inflammatory cytokines and serum biochemical indices. The root of the aorta was stained with oil red O, and the proportion of the lesion area was quantified. Trimethylamine N-oxide (TMAO) and trimethylamine (TMA) levels in serum were evaluated through liquid chromatography with mass spectrometry. Flavin−containing monooxygenase 3 (FMO3) liver protein expression was assessed by Western blotting. 16S rDNA sequencing technique was adopted to establish the changes in the microbiota structure. Results: After 8 weeks of HFD feeding, an inflammatory cytokine, and AS development expression were significantly decreased in mice treated with AOB; the same parameters in the mice treated with the antibiotics cocktail did not change. In the gut microbiota study, mice treated with AOB had a markedly different gut microbiota than the HFD-fed mice. Additionally, AOB also decreased serum TMAO and hepatic FMO3 expression. Conclusion: The antiatherosclerotic effects of AOB were found associated with changes in the content of gut microbiota and a reduction in TMAO, a gut microbiota metabolite, suggesting that AOB has potential therapeutic value in the treatment of AS.

Lifelong dietary omega-3 fatty acid suppresses thrombotic potential through gut microbiota alteration in aged mice

“…Specifically, a total of 162 amplicon sequence variant (ASV) were differentially abundant among young and old mice ( Figure 2 B, Data S1 , FDR adjusted p values <0.05 based on DESeq2 negative binomial tests), thereby highlighting the important rearrangement of the gut microbial community with aging. Old mice showed a significant reduction in the genera Faecalibaculum , which counteracts inflammatory state and negatively associates with major proinflammatory cytokines TNF-α, IL-1β, and IL-6 ( Zhu et al., 2020a , 2020b ), Rikenellaceae_RC9_gut_group, a taxonomic group which is associated with a healthy metabolic state ( Zheng et al., 2018 ; Ijaz et al., 2018 ; Lippert et al., 2017 ), and in the butyrate-producing and anti-inflammatory Oscillospiraceae (Intestinimonas) ( Li et al., 2020 ; Bui et al., 2015 ). Importantly, lactic acid bacteria Lactococcus , known as a probiotic to correlate with anti-inflammatory and health benefits, decreased in old compared with young mice ( Cook et al., 2018 ; Luerce et al., 2014 ).…”

“…Overall, high ALA diet did not promote a community structure as similar as young mice; nevertheless, 7 ASVs (for instance, health-promoting and TMA-reducing Rikenellaceae_RC9_gut_group and Intestinimonas , which were reduced in the aging, could be partially restored by high ALA diet ( Figure S3 ). On the other hand, high ALA dramatically reduced 32 age-dependently high abundant ASVs, including TMA-producing and inflammation-driving Desulfovibrio , TMAO- and HFD-associated Clostridium genera ( Zhu et al., 2020a , 2020b ) Clostridia_sensu_stricto_1 ( Zhu et al., 2020a , 2020b ; Hoyles et al., 2018 ), Clostridium_UCG-014, and Clostridia_vadinBB60_group ( Koeth et al., 2013 ), heart failure-associated Ileibacterium , and Lachnospiraceae ( Lachnospiraceae_NK4A136_group Lachnospiraceae_UCG-006 ), which are found more abundant in a rat model of HFD ( Zhao et al., 2019 ; Data S1 and S2 ).…”

NEIL3-deficiency increases gut permeability and contributes to a pro-atherogenic metabolic phenotype

“…At genus level, Faecalibaculum was decreased, and at order level, Lactobacillales was increased, when comparing Apoe −/− Neil3 −/− mice to Apoe −/− mice. Faecalibaculum has been negatively correlated with metabolic markers of atherosclerosis 33 , and Lactobacillales has been found to correlate positively with coronary artery disease (CAD) in humans 34 . These associations have not been demonstrated to have a causal relationship.…”

Trimethylamine-N-Oxide Pathway: A Potential Target for the Treatment of MAFLD

“…In addition to the intervention strategies mentioned above, other strategies can also be used as potential approaches. Some traditional Chinese medicine are proved be able to lower TMAO concentrations, such as Alisma orientalis beverage (Zhu et al, 2020), Ginkgolide B (Lv et al, 2021), Berberine , etc. Besides, vitamins are other candidates for reducing TMAO concentrations, such as vitamin B and vitamin D (Obeid et al, 2017).…”