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Chitosan alleviated menopausal symptoms and modulated the gut microbiota in estrogen-deficient rats

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European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

Menopause disturbs energy, glucose, and lipid metabolisms and changes the composition of the gut microbiota, but dietary fibers without phytoestrogens may ameliorate menopausal metabolic disorders. The objective of the present study was to assess whether consuming the prebiotics chitosan and citrus pectin can improve postmenopausal symptoms, possibly by modulating the gut microbiota in ovariectomized (OVX) rats, and the mechanism of action was examined.

Methods

The OVX rats were given 4.5% cellulose (OVX-Control), chitosan (OVX-Chitosan), or citrus pectin (OVX-Pectin) in a 43% fat diet and the sham rats were given the same diet as the OVX-Control for 12 weeks. Sham-operated rats had the same diet as OVX-Control (Normal-Control). Body-weight, visceral fat mass, tail skin temperature, serum 17β-estradiol, glucose intolerance, and insulin tolerance were determined. Gut microbiota in the fecal samples was measured by NGS and analyzed with PICRUSt2. Short-chain fatty acids (SCFA) and metabolomic characteristics of serum were also measured with UPLC-mass spectrometry.

Results

Chitosan and citrus pectin were selected because the incubation of rat feces with these two prebiotics in vitro had shown increased butyrate production. OVX-Chitosan reduced the weight, visceral fat content, and tail skin temperature, and OVX-Chitosan and OVX-Pectin improved glucose tolerance, compared to the OVX-Control. Both alleviated dyslipidemia, compared to the OVX-Control. OVX-Chitosan and OVX-Pectin elevated serum propionate and butyrate concentrations but only OVX-Chitosan lowered serum acetate concentrations. In PICRUSt2, chitosan upregulated the functional genes of gut microbiota involved in valine, leucine, and isoleucine biosynthesis, whereas the OVX-Control exhibited significantly upregulated lipopolysaccharide biosynthesis. OVX-Pectin exhibited increased α-diversity in the fecal bacteria. Metabolomic analysis revealed higher serum urate concentrations in the OVX-Control group than the other groups, and serum arginine and leucine concentrations were higher in the OVX-Chitosan group (P < 0.05).

Conclusion

Chitosan and citrus pectin consumptions improved menopausal symptoms by improving the diversity and composition of the gut microbiota, and serum metabolites and SCFA originating from fecal bacteria. Chitosan was more effective for improving menopausal symptoms than citrus pectin.

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Abbreviations

OVX:

Ovariectomy

OVX-Control:

OVX rats having 4.5% dextrin in a high-fat diet

OVX-Chitosan:

OVX rats having 4.5% chitosan in a high-fat diet

OVX-Pectin:

OVX rats having 4.5% citrus pectin in a high-fat diet; Normal-Control, Sham-operated rats having 4.5% dextrin in a high-fat diet

LDL:

Low-density lipoproteins; SCFA, short-chain fatty acid

OGTT:

Oral glucose tolerance test; IPITT, intraperitoneal insulin tolerance test

OPLS-DA:

Orthogonal partial least squares discriminant analysis

PICRUSt2:

Phylogenetic Investigation of Communities by Reconstruction of Unobserved States

NGS:

Next-generation sequencing

PCoA:

Principal coordinates analysis

PERMANOVA:

Permutational multivariate analysis of variance

KEGG:

Kyoto encyclopedia of genes and genomes

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Acknowledgements

This research and the study design and methods were evaluated and approved for funding by the National Research Foundation (NRF-2019R1A2C1007203), Korea.

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Authors and Affiliations

  1. Department. of Food and Nutrition, Obesity/Diabetes Research Center, Hoseo University, 165 Sechul-Ri, BaeBang-Yup, Asan-Si, ChungNam-Do, 336-795, South Korea

    Xuangao Wu & Sunmin Park

  2. Food Functional Research Division, Korea Food Research Institutes, Wanjoo, South Korea

    Min Jung Kim & Hye Jeong Yang

Authors
  1. Xuangao Wu
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  2. Min Jung Kim
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Contributions

Contributed to the experimental design: SP, XW; Conducted the animal study and biochemical assays. XW, MJK. Wrote the first draft of the manuscript: XW; Reviewed and edited the manuscript: SP; All authors reviewed the manuscript and they read and approved the final manuscript.

Corresponding author

Correspondence to Sunmin Park.

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Conflict of interest

The authors declare no conflict of interest.

Ethical standards

All experimental procedures were performed according to the guidelines for the care and use of laboratory animals from the National Research Council and with the approval of the Animal Care and Use Review Committee at Hoseo University (HSIACUC-18-231), Korea.

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Wu, X., Kim, M.J., Yang, H.J. et al. Chitosan alleviated menopausal symptoms and modulated the gut microbiota in estrogen-deficient rats. Eur J Nutr 60, 1907–1919 (2021). https://doi.org/10.1007/s00394-020-02382-2

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  • DOI: https://doi.org/10.1007/s00394-020-02382-2

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