Dietary α‐cyclodextrin reduces atherosclerosis and modifies gut flora in apolipoprotein E‐deficient mice

Sakurai, ﻿Toshihiro; Sakurai, Akiko; Chen, Ye; Vaisman, Boris; Amar, Marcelo; Pryor, Milton; Thacker, Seth G.; Zhang, Xue; Wang, Xujing; Zhang, Yubo; Zhu, Jun; Zhihong, Yang; Freeman, Lita A.; Remaley, Alan T.

doi:10.1002/mnfr.201600804

Cited by 25 publications

(24 citation statements)

References 45 publications

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“…Thus, the increases of these bacterial species by supplementation of α‐CD in obese mice may be beneficial as an antiobesity treatment. Sakurai et al reported that 1.5% of α‐CD administration decreased the Clostridium proportion in apolipoprotein E‐deficient mice, which is similar to the effect of 5.5% α‐CD on Clostridium spp. in this study.…”

Section: Discussionmentioning

confidence: 73%

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Dietary α‐cyclodextrin modifies gut microbiota and reduces fat accumulation in high‐fat‐diet‐fed obese mice

Nihei¹,

Okamoto

Furune³

et al. 2018

BioFactors

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We investigated the effect of α-cyclodextrin (α-CD) on the bacterial populations of gut microbiota, production of organic acids, and short-chain fatty acids (SCFAs), and lipid metabolism in obese mice induced by feeding a high-fat diet (HFD). Male C57BL/6J mice were assigned to three diet groups: normal diet (ND) (5% [w/w] fat), HFD (35% [w/w] fat), and HFD (35% [w/w] fat) + 5.5% (w/w) α-CD for 16 weeks. Increases in body and epididymal adipose tissue weights were observed in the HFD group compared with the ND group, which were attenuated in the HFD+α-CD group. The supplementation of α-CD increased the total number of bacteria, Bacteroides, Bifidobacterium, and Lactobacillus that were decreased in gut microbiota of mice by feeding the HFD. Importantly, α-CD administration increased the concentrations of lactic acid and SCFAs, such as acetic, propionic, and butyric acids, and decreased glucose concentrations in cecal contents. Furthermore, supplementation of α-CD upregulated the gene expression of peroxisome proliferator-activated receptor (PPAR)γ involved in adipocyte differentiation and PPARα involved in energy expenditure and downregulated that of sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase involved in fatty acid and triglyceride synthesis in adipose tissue. This study revealed that the alteration in gut microbiota and increased production of lactic acid and SCFAs by supplementation of α-CD have beneficial antiobesity effects via modulating the expression of genes related to lipid metabolism, indicating a prebiotic property of α-CD. © 2018 BioFactors, 2018.

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Section: Discussionmentioning

confidence: 73%

“…A previous study showed that Bacteroides ovatus decomposes α‐CD by producing cyclodextrinase . Recently, it was reported that addition of α‐CD (1.5% w/w) to a HFD at relatively low doses reduces atherosclerosis in apolipoprotein E‐deficient mice . This effect may be associated with gut microbiota modulation.…”

Section: Introductionmentioning

confidence: 99%

Dietary α‐cyclodextrin modifies gut microbiota and reduces fat accumulation in high‐fat‐diet‐fed obese mice

Nihei¹,

Okamoto

Furune³

et al. 2018

BioFactors

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“…In vivo, oral administration of ACD has been shown to reduce levels of proatherogenic lipoproteins and improve fatty acid profiles in LDLr-knock out (KO) mice fed a high-fat/high-cholesterolcontaining diet . Furthermore, oral administration of ACD reduced atherosclerotic lesion size, with only minimal change in plasma lipids, but was associated with potential beneficial changes in gut flora in apoE-KO mice 26 . In humans, oral intake of ACD has also been shown to have beneficial effects.…”

Section: Accepted Manuscriptmentioning

confidence: 94%

Alpha-cyclodextrin inhibits cholesterol crystal-induced complement-mediated inflammation: A potential new compound for treatment of atherosclerosis

et al. 2019

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Background and aims: Cholesterol crystal (CC)-induced inflammation is a critical step in the development of atherosclerosis. CCs activate the complement system and induce an inflammatory response resulting in phagocytosis of the CCs, production of reactive oxygen species (ROS) and release of cytokines. The cyclodextrin 2-hydroxypropyl-β-cyclodextrin has been found to reduce CC-induced complement activation and induce regression of established atherosclerotic plaques in a mouse model of atherosclerosis, thus inhibition of complement with cyclodextrins is a potential new strategy for treatment of inflammation during atherosclerosis. We hypothesized that other cyclodextrins, like α-cyclodextrin, may have related functions. Methods: The effect of cyclodextrins on CC-induced complement activation, phagocytosis, and production of ROS from granulocytes and monocytes was investigated by flow cytometry and ELISA. Results: We showed that α-cyclodextrin strongly inhibits CC-induced complement activation by inhibiting binding of the pattern recognition molecules C1q (via IgM) and ficolin-2. The reduced CC-induced complement activation mediated by α-cyclodextrin resulted in reduced phagocytosis and reduced ROS production in monocytes and granulocytes. Alpha-cyclodextrin was the most effective inhibitor of CC-induced complement activation, with the reduction in deposition of complement activation products being significantly different from the reduction induced by 2hydroxypropyl-β-cyclodextrin. We also found that α-cyclodextrin was able to dissolve CCs. Conclusions: This study identified α-cyclodextrin as a potential candidate in the search for therapeutics to prevent CC-induced inflammation in atherosclerosis.

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“…In these CDs, αCD is widely used as a water-soluble dietary fibre 8 . Addition of 1.5% αCD to mice has been shown to decrease the numbers of caecal bacteria belonging to the genus Clostridium 9 . In contrast, dextran is produced by lactic acid bacteria of the genera Leuconostoc , Streptococcus , Lactococcus , and Lactobacillus 10 .…”

Section: Introductionmentioning

confidence: 99%

Low amounts of dietary fibre increase in vitro production of short-chain fatty acids without changing human colonic microbiota structure

Sasaki

Ikuta

et al. 2018

Sci Rep

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This study investigated the effect of various prebiotics (indigestible dextrin, α-cyclodextrin, and dextran) on human colonic microbiota at a dosage corresponding to a daily intake of 6 g of prebiotics per person (0.2% of dietary intake). We used an in vitro human colonic microbiota model based on batch fermentation starting from a faecal inoculum. Bacterial 16S rRNA gene sequence analysis showed that addition of 0.2% prebiotics did not change the diversity and composition of colonic microbiota. This finding coincided with results from a clinical study showing that the microbiota composition of human faecal samples remained unchanged following administration of 6 g of prebiotics over seven days. However, compared to absence of prebiotics, their addition reduced the pH and increased the generation of acetate and propionate in the in vitro system. Thus, even at such relatively low amounts, prebiotics appear capable of activating the metabolism of colonic microbiota.

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Dietary α‐cyclodextrin reduces atherosclerosis and modifies gut flora in apolipoprotein E‐deficient mice

Cited by 25 publications

References 45 publications

Dietary α‐cyclodextrin modifies gut microbiota and reduces fat accumulation in high‐fat‐diet‐fed obese mice

Dietary α‐cyclodextrin modifies gut microbiota and reduces fat accumulation in high‐fat‐diet‐fed obese mice

Alpha-cyclodextrin inhibits cholesterol crystal-induced complement-mediated inflammation: A potential new compound for treatment of atherosclerosis

Low amounts of dietary fibre increase in vitro production of short-chain fatty acids without changing human colonic microbiota structure

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