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Ferulic acid improves intestinal barrier function through altering gut microbiota composition in high-fat diet-induced mice

  • Original Contribution
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European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

A high-fat diet (HFD) induces gut microbiota (GM) disorders, leading to intestinal barrier dysfunction and inflammation. Ferulic acid (FA) has shown anti-obesity effects, e.g., reducing body weight and food intake. However, the mechanism linking the anti-obesity effects of FA and GM modulation remains obscure. The present study aimed to clarify the mechanism underlying the anti-obesity effects of FA and modulation of the GM.

Methods

C57BL/6 J mice were fed by a low-fat diet (LFD) and HFD with or without FA at a dose of 100 mg/kg of body weight by oral gavage for 12 weeks. Using high-throughput sequencing, gas chromatography, real-time fluorescence quantitative PCR and immunohistochemical staining, the attenuation of obesity by FA were assessed via intestinal barrier integrity, inflammation, and the GM.

Results

FA reduced weight gain, improved HFD-induced GM imbalance, significantly enhanced intestinal short-chain fatty acid (SCFA)-producing bacteria (e.g., Olsenella, Eisenbergiella, Dubosiella, Clostridiales_unclassified, and Faecalibaculum) along with SCFA accumulation and its receptors’ expression, decreased endotoxin-producing bacteria or obesity-related bacterial genera, and serum endotoxin (lipopolysaccharides), and inhibited the colonic TLR4/NF-κB pathway. Thus, FA can mitigate colonic barrier dysfunction and intestinal inflammation, induce the production of SCFAs and inhibit endotoxins by modulating the GM.

Conclusion

These results indicate that enhancement of intestinal barrier by altering the GM may be an anti-obesity target of FA and that FA can be used as a functional compound with great developmental values.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

FA:

Ferulic acid

GM:

Gut microbiota

HFD:

High-fat diet

IECs:

Intestinal epithelial cells

LEfSe:

Linear discriminant analysis effect size analysis

LPS:

Lipopolysaccharide

NF-κB:

Nuclear factor Kappa-B

OTUs:

Operational taxonomic units

SCFA:

Short-chain fatty acid

TJs:

Tight junctions

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Acknowledgements

This work was sponsored by Zhejiang Provincial Key Research and Development Program (2022C04036, 2019C02100, 2019C02074 and 2019C02040) and the Cooperative Project Fund of the Zhejiang University of Technology and Zhejiang Institute of Modern TCM and Natural Medicine Co., Ltd. (KYY-HX-20211132). We sincerely thank Zhixin Luo (Northwest A&F University) for animal feeding and management.

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Authors and Affiliations

  1. College of Food Science and Technology, Zhejiang University of Technology, Chaowang Road 18, Hangzhou, 310014, People’s Republic of China

    Baoming Tian, Yan Geng, Peiyi Wang, Ming Cai, Jing Neng, Kai Yang & Peilong Sun

  2. Zhejiang Institute of Modern TCM and Natural Medicine Co., Ltd., Hangzhou, 310052, People’s Republic of China

    Baoming Tian & Jiangning Hu

  3. School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China

    Baoming Tian & Daozong Xia

  4. Zhejiang Conba Pharmaceutical Co., Ltd., Hangzhou, 310052, People’s Republic of China

    Wangli Cao

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Contributions

Conceptualization, BT and YG; methodology, BT and PW; software, MC and JH; validation and formal analysis, BT and DX; data curation, BT and WC; writing-original draft preparation, BT; writing-review and editing, JN and KY; project administration, BT and PS; and funding acquisition, KY.

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Correspondence to Kai Yang.

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394_2022_2927_MOESM1_ESM.docx

Supplementary Information The e-component of this article contains supplementary materials in several parts: 1) Primer sequences used for real-time quantitative PCR; 2)The average body weight changes of mice; 3)The feed intake curve of mice; 4) Alpha diversity analysis of intestinal microbiota in mice; 5) The gut microbial taxonomic profiling at the phylum and genus levels (DOCX 735 KB)

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Tian, B., Geng, Y., Wang, P. et al. Ferulic acid improves intestinal barrier function through altering gut microbiota composition in high-fat diet-induced mice. Eur J Nutr 61, 3767–3783 (2022). https://doi.org/10.1007/s00394-022-02927-7

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