Journal Home > Volume 13 , Issue 1
Food Science and Human Wellness 2024, 13(1): 90-100 https://doi.org/10.26599/FSHW.2022.9250007
Research Article | Open Access | Issue | Published: 01 June 2023

Akkermansia muciniphila-directed polyphenol chlorogenic acid intervention for obesity in mice

Show Author's Information Xiaoxiang Gaoa,b,1,  Chenbo Yuea,b,1,  Ruocen Tiana,b,  Leilei Yua,b,  Fengwei Tiana,b,  Jianxin Zhaoa,b,  Wei Chena,b,c,  Qixiao Zhaia,b,( )
State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China

1 These authors contributed equally to this study.

Peer review under responsibility of Tsinghua University Press.

Keywords:
obesity, polyphenol, Akkermansia muciniphila, chlorogenic acid
Cite this article:
Gao X, Yue C, Tian R, et al. Akkermansia muciniphila-directed polyphenol chlorogenic acid intervention for obesity in mice. Food Science and Human Wellness, 2024, 13(1): 90-100. https://doi.org/10.26599/FSHW.2022.9250007
Download citation
EndNote(RIS)
BibTeX

2080

Views

371

Downloads

Citations

8

Crossref

3

WoS

3

Scopus

0

CSCD

Abstract Full text Electronic supplementary material About this article

Akkermansia muciniphila play an important in ameliorating obesity but is not allowed for direct consumption in most countries. To date, microbiota-directed foods selectively promote the targeted human gut microbes, providing a strategy for A. muciniphila enhancement. Multiple studies have indicated the potential regulation of the polyphenol on A. muciniphila. Therefore, a polyphenol screening based on A. muciniphila upregulation was performed in mice. Chlorogenic acid (CGA) exhibited a greater response to A. muciniphila upregulation. Furthermore, we found that CGA did not directly promote A. muciniphila growth or mucin secretion. Microbiome and metabolomics revealed that the increased abundance of A. muciniphila resulted from the inhibition of CGA on Desulfovibrio and Alistipes and the influence of docosahexaenoic acid, β-hydroxybutyrate, and N-acetyl-lactosamine. Finally, to confirm the regulation of CGA on A. muciniphila under disease conditions, high-fat diet-fed mice were established. The results showed CGA promoted A. muciniphila growth, and we expectedly found that CGA suppressed the augment in body weight of mice, significantly attenuated adipose tissue abnormality, provided liver protection and improved gut barrier integrity. These results suggest that CGA inhibits the development of obesity. Overall, our results indicate that microbiota-directed food is a promising approach for the treatment of obesity.


menu
Abstract
Full text
Outline
Electronic supplementary material
About this article

Akkermansia muciniphila-directed polyphenol chlorogenic acid intervention for obesity in mice

Show Author's information Xiaoxiang Gaoa,b,1, Chenbo Yuea,b,1, Ruocen Tiana,b, Leilei Yua,b, Fengwei Tiana,b, Jianxin Zhaoa,b, Wei Chena,b,c, Qixiao Zhaia,b,( )
State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China

1 These authors contributed equally to this study.

Peer review under responsibility of Tsinghua University Press.

Highlights

1- CGA in nine polyphenols exhibits a greater response to A. muciniphila upregulation

2- CGA upregulates A. muciniphila abundance by inhibiting Desulfovibrio and Alistipes

3- CGA promotes A. muciniphila growth by the enrichment of docosahexaenoic acid, β-hydroxybutyrate, and N-acetyl-lactosamine.

4- CGA inhibits the development of obesity by increasing A. muciniphila abundance.

5- Microbiota-directed food provides an insight for diseases treatment

Abstract

Akkermansia muciniphila play an important in ameliorating obesity but is not allowed for direct consumption in most countries. To date, microbiota-directed foods selectively promote the targeted human gut microbes, providing a strategy for A. muciniphila enhancement. Multiple studies have indicated the potential regulation of the polyphenol on A. muciniphila. Therefore, a polyphenol screening based on A. muciniphila upregulation was performed in mice. Chlorogenic acid (CGA) exhibited a greater response to A. muciniphila upregulation. Furthermore, we found that CGA did not directly promote A. muciniphila growth or mucin secretion. Microbiome and metabolomics revealed that the increased abundance of A. muciniphila resulted from the inhibition of CGA on Desulfovibrio and Alistipes and the influence of docosahexaenoic acid, β-hydroxybutyrate, and N-acetyl-lactosamine. Finally, to confirm the regulation of CGA on A. muciniphila under disease conditions, high-fat diet-fed mice were established. The results showed CGA promoted A. muciniphila growth, and we expectedly found that CGA suppressed the augment in body weight of mice, significantly attenuated adipose tissue abnormality, provided liver protection and improved gut barrier integrity. These results suggest that CGA inhibits the development of obesity. Overall, our results indicate that microbiota-directed food is a promising approach for the treatment of obesity.

Keywords: obesity, polyphenol, Akkermansia muciniphila, chlorogenic acid

References(46)

[1]

S. Chen, X. Liu, C. Peng, et al., The phytochemical hyperforin triggers thermogenesis in adipose tissue via a Dlat-AMPK signaling axis to curb obesity, Cell Metab. 33 (2021) 565-580.e7. https://doi.org/10.1016/j.cmet.2021.02.007.
DOI Google Scholar
[2]

H. Plovier, A. Everard, C. Druart, et al., A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice, Nat. Med. 23 (2017) 107–113. https://doi.org/10.1038/nm.4236.
DOI Google Scholar
[3]

Y. Wang, W. Qi, X. Guo, et al., Effects of oats, tartary buckwheat, and foxtail millet supplementation on lipid metabolism, oxido-inflammatory responses, gut microbiota, and colonic SCFA composition in high-fat diet fed rats, Nutrients. 14 (2022) 2760. https://doi.org/10.3390/nu14132760.
DOI Google Scholar
[4]

C. Depommier, A. Everard, C. Druart, et al., Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study, Nat. Med. 25 (2019) 1096–1103. https://doi.org/10.1038/s41591-019-0495-2.
DOI Google Scholar
[5]

A. Palomba, A. Tanca, M. Abbondio, et al., Time-restricted feeding induces Lactobacillus-and Akkermansia-specific functional changes in the rat fecal microbiota, Npj Biofilms Microbiomes. 7 (2021) 85. https://doi.org/10.1038/s41522-021-00256-x.
DOI Google Scholar
[6]

S. Ghaffari, A. Abbasi, M.H. Somi, et al., Akkermansia muciniphila: from its critical role in human health to strategies for promoting its abundance in human gut microbiome, Crit. Rev. Food Sci. Nutr. (2022) 1–21. https://doi.org/10.1080/10408398.2022.2045894.
DOI Google Scholar
[7]

S. Keshavarz Azizi Raftar, F. Ashrafian, A. Yadegar, et al., The protective effects of live and pasteurized Akkermansia muciniphila and its extracellular vesicles against HFD/CCl4-induced liver injury, Microbiol. Spectr. 9 (2021) e00484-21. https://doi.org/10.1128/Spectrum.00484-21.
DOI Google Scholar
[8]

P.D. Cani, C. Depommier, M. Derrien, et al., Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms, Nat. Rev. Gastroenterol. Hepatol. 19 (2022) 625-637. https://doi.org/10.1038/s41575-022-00631-9.
DOI Google Scholar
[9]

F.F. Anhê, R.T. Nachbar, T.V. Varin, et al., A polyphenol-rich cranberry extract reverses insulin resistance and hepatic steatosis independently of body weight loss, Mol. Metab. 6 (2017) 1563–1573. https://doi.org/10.1016/j.molmet.2017.10.003.
DOI Google Scholar
[10]

K. Zhou, Strategies to promote abundance of Akkermansia muciniphila, an emerging probiotics in the gut, evidence from dietary intervention studies, J. Funct. Foods. 33 (2017) 194–201. https://doi.org/10.1016/j.jff.2017.03.045.
DOI Google Scholar
[11]

C. Yue, C. Chu, J. Zhao, et al., Dietary strategies to promote the abundance of intestinal Akkermansia muciniphila, a focus on the effect of plant extracts, J. Funct. Foods. 93 (2022) 105093. https://doi.org/10.1016/j.jff.2022.105093.
DOI Google Scholar
[12]

M. Peng, Z. Tabashsum, M. Anderson, et al., Effectiveness of probiotics, prebiotics, and prebiotic-like components in common functional foods, Compr. Rev. Food Sci. Food Saf. 19 (2020) 1908–1933. https://doi.org/10.1111/1541-4337.12565.
DOI Google Scholar
[13]

A. Durazzo, M. Lucarini, E.B. Souto, et al., Polyphenols: a concise overview on the chemistry, occurrence, and human health, Phytother. Res. 33 (2019) 2221–2243. https://doi.org/10.1002/ptr.6419.
DOI Google Scholar
[14]

J. Liu, Z. He, N. Ma, et al., Beneficial effects of dietary polyphenols on highfat diet-induced obesity linking with modulation of gut microbiota, J. Agric. Food Chem. 68 (2020) 33–47. https://doi.org/10.1021/acs.jafc.9b06817.
DOI Google Scholar
[15]

Z. Fan, R.P. Ross, C. Stanton, et al., Lactobacillus casei CCFM1074 alleviates collagen-induced arthritis in rats via balancing Treg/Th17 and modulating the metabolites and gut microbiota, Front. Immunol. 12 (2021) 680073. https://doi.org/10.3389/fimmu.2021.680073.
DOI Google Scholar
[16]

N. Li, F. Yan, N. Wang, et al., Distinct gut microbiota and metabolite profiles induced by different feeding methods in healthy Chinese infants, Front. Microbiol. 11 (2020) 714. https://doi.org/10.3389/fmicb.2020.00714.
DOI Google Scholar
[17]

Z. Zhang, X. Wu, S. Cao, et al., Caffeic acid ameliorates colitis in association with increased Akkermansia population in the gut microbiota of mice, Oncotarget. 7 (2016) 31790–31799. https://doi.org/10.18632/oncotarget.9306.
DOI Google Scholar
[18]

Z. Zhang, X. Wu, S. Cao, et al., Chlorogenic acid ameliorates experimental colitis by promoting growth of Akkermansia in mice, Nutrients. 9 (2017) 677. https://doi.org/10.3390/nu9070677.
DOI Google Scholar
[19]

D.E. Roopchand, R.N. Carmody, P. Kuhn, et al., Dietary polyphenols promote growth of the gut bacterium Akkermansia muciniphila and attenuate high-fat diet–induced metabolic syndrome, Diabetes. 64 (2015) 2847–2858. https://doi.org/10.2337/db14-1916.
DOI Google Scholar
[20]

L. Wang, Y. Wu, L. Zhuang, et al., Puerarin prevents high-fat diet-induced obesity by enriching Akkermansia muciniphila in the gut microbiota of mice, PLOS ONE 14 (2019) e0218490. https://doi.org/10.1371/journal.pone.0218490.
DOI Google Scholar
[21]

M.M. Sung, T.T. Kim, E. Denou, et al., Improved glucose homeostasis in obese mice treated with resveratrol is associated with alterations in the gut microbiome, Diabetes. 66 (2017) 418–425. https://doi.org/10.2337/db16-0680.
DOI Google Scholar
[22]

N. Khan, H. Mukhtar, Tea polyphenols in promotion of human health, Nutrients. 11 (2018) 39. https://doi.org/10.3390/nu11010039.
DOI Google Scholar
[23]

D. Cheng, M.Z. Xie, A review of a potential and promising probiotic candidate— Akkermansia muciniphila, J. Appl. Microbiol. 130 (2021) 1813–1822. https://doi.org/10.1111/jam.14911.
DOI Google Scholar
[24]

L. Sheng, P.K. Jena, H. Liu, et al., Obesity treatment by epigallocatechin-3-gallate-regulated bile acid signaling and its enriched Akkermansia muciniphila, FASEB J. 32 (2018) 6371–6384. https://doi.org/10.1096/fj.201800370R.
DOI Google Scholar
[25]

J. Xia, L. Lv, B. Liu, et al., Akkermansia muciniphila ameliorates acetaminophen-induced liver injury by regulating gut microbial composition and metabolism, Microbiol. Spectr. 10 (2022) e01596-21. https://doi.org/10.1128/spectrum.01596-21.
DOI Google Scholar
[26]

Z. Li, L. Zhu, G. Hu, et al., Akkermansia muciniphila fermentation culture based on a novel bionic large intestine dynamic digestion model, Food Biosci. 43 (2021) 101260. https://doi.org/10.1016/j.fbio.2021.101260.
DOI Google Scholar
[27]

S. Wang, S. Ahmadi, R. Nagpal, et al., Lipoteichoic acid from the cell wall of a heat killed Lactobacillus paracasei D3-5 ameliorates aging-related leaky gut, inflammation and improves physical and cognitive functions: from C. elegans to mice, GeroScience. 42 (2020) 333–352. https://doi.org/10.1007/s11357-019-00137-4.
DOI Google Scholar
[28]

L. García-Bayona, L.E. Comstock, Bacterial antagonism in host-associated microbial communities, Science. 361 (2018) eaat2456. https://doi.org/10.1126/science.aat2456.
DOI Google Scholar
[29]

S. Fu, C. Wu, T. Wu, et al., Preparation and characterisation of chlorogenic acid-gelatin: a type of biologically active film for coating preservation, Food Chem. 221 (2017) 657–663. https://doi.org/10.1016/j.foodchem.2016.11.123.
DOI Google Scholar
[30]

R. Jia, J.L. Tan, P. Jin, et al., Effects of biogenic H2S on the microbiologically influenced corrosion of C1018 carbon steel by sulfate reducing Desulfovibrio vulgaris biofilm, Corros. Sci. 130 (2018) 1–11. https://doi.org/10.1016/j.corsci.2017.10.023.
DOI Google Scholar
[31]

J. Zhou, C. Hou, H. Chen, et al., P16INK4a Deletion ameliorates damage of intestinal epithelial barrier and microbial dysbiosis in a stress-induced premature senescence model of Bmi-1 deficiency, Front. Cell Dev. Biol. 9(2021) 671564. https://doi.org/10.3389/fcell.2021.671564.
DOI Google Scholar
[32]

H. Earley, G. Lennon, A. Balfe, et al., A preliminary study examining the binding capacity of Akkermansia muciniphila and Desulfovibrio spp., to colonic mucin in health and ulcerative colitis, PLOS ONE 10 (2015) e0135280. https://doi.org/10.1371/journal.pone.0135280.
DOI Google Scholar
[33]

J.Q. Liang, T. Li, G. Nakatsu, et al., A novel faecal Lachnoclostridium marker for the non-invasive diagnosis of colorectal adenoma and cancer, Gut. 69 (2020) 1248–1257. https://doi.org/10.1136/gutjnl-2019-318532.
DOI Google Scholar
[34]

B.A. Daisley, R.M. Chanyi, K. Abdur-Rashid, et al., Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients, Nat. Commun. 11 (2020) 4822. https://doi.org/10.1038/s41467-020-20410-x.
DOI Google Scholar
[35]

F. Hinrichsen, J. Hamm, M. Westermann, et al., Microbial regulation of hexokinase 2 links mitochondrial metabolism and cell death in colitis, Cell Metab. 33 (2021) 2355-2366.e8. https://doi.org/10.1016/j.cmet.2021.11.004.
DOI Google Scholar
[36]

N. Haskey, J. Ye, M. Estaki, et al., A Mediterranean-like fat blend protects against the development of severe colitis in the mucin-2 deficient murine model, Gut Microbes. 14 (2022) 2055441. https://doi.org/10.1080/19490976.2022.2055441.
DOI Google Scholar
[37]

C.A. Olson, H.E. Vuong, J.M. Yano, et al., The gut microbiota mediates the anti-seizure effects of the ketogenic diet, Cell. 173 (2018) 1728-1741.e13. https://doi.org/10.1016/j.cell.2018.04.027.
DOI Google Scholar
[38]

H. Zhu, D. Bi, Y. Zhang, et al., Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations, Signal Transduct. Target. Ther. 7 (2022) 11. https://doi.org/10.1038/s41392-021-00831-w.
DOI Google Scholar
[39]

L.I. Crouch, M.V. Liberato, P.A. Urbanowicz, et al., Prominent members of the human gut microbiota express endo-acting O-glycanases to initiate mucin breakdown, Nat. Commun. 11 (2020) 4017. https://doi.org/10.1038/s41467-020-17847-5.
DOI Google Scholar
[40]

Y. Xu, N. Wang, H.Y. Tan, et al., Function of Akkermansia muciniphila in obesity: interactions with lipid metabolism, immune response and gut systems, Front. Microbiol. 11 (2020) 219. https://doi.org/10.3389/fmicb.2020.00219.
DOI Google Scholar
[41]

W.E. Kraus, M. Bhapkar, K.M. Huffman, et al., 2 years of calorie restriction and cardiometabolic risk (CALERIE): exploratory outcomes of a multicentre, phase 2, randomised controlled trial, Lancet Diabetes Endocrinol. 7 (2019) 673–683. https://doi.org/10.1016/S2213-8587(19)30151-2.
DOI Google Scholar
[42]

M.G. Xie, Y.Q. Fei, Y. Wang, et al., Chlorogenic acid alleviates colon mucosal damage induced by a high-fat diet via gut microflora adjustment to increase short-chain fatty acid accumulation in rats, Oxid. Med. Cell. Longev. 2021 (2021) 1–18. https://doi.org/10.1155/2021/3456542.
DOI Google Scholar
[43]

L. Lv, C. Yao, R. Yan, et al., Lactobacillus acidophilus LA14 alleviates liver injury, MSystems. 6 (2021) e0038421. https://doi.org/10.1128/mSystems.00384-21.
DOI Google Scholar
[44]

T. Shao, C. Zhao, F. Li, et al., Intestinal HIF-1α deletion exacerbates alcoholic liver disease through inducing intestinal dysbiosis and barrier dysfunction, J. Hepatol. 69 (2018) 886–895. https://doi.org/10.1016/j.jhep.2018.05.021.
DOI Google Scholar
[45]

Y. Ding, X. Li, Y. Liu, et al., Protection mechanisms underlying oral administration of chlorogenic acid against cadmium-induced hepatorenal injury related to regulating intestinal flora balance, J. Agric. Food Chem. 69(2021) 1675–1683. https://doi.org/10.1021/acs.jafc.0c06698.
DOI Google Scholar
[46]

M.L. Patnode, Z.W. Beller, N.D. Han, et al., Interspecies competition impacts targeted manipulation of human gut bacteria by fiber-derived glycans, Cell. 179 (2019) 59-73.e13. https://doi.org/10.1016/j.cell.2019.08.011.
DOI Google Scholar
File
fshw-2024-9250007_ESM.pdf (525.5 KB)
Publication history
Copyright
Acknowledgements
Rights and permissions

Publication history

Received: 11 August 2022
Revised: 05 September 2022
Accepted: 21 September 2022
Published: 01 June 2023
Issue date: January 2024

Copyright

© 2024 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

Acknowledgements

Acknowledgement

This work was supported by the Natural Science Foundation of Jiangsu Province [BK20200084], the National Natural Science Foundation of China [No. 32122067 and 32021005]; and the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province.

Rights and permissions

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Return