<i>Lactobacillus plantarum</i> CCFM1180 attenuates obesity induced by estrogen deficiency by activating estrogen receptor alpha in abdominal adipose tissue and regulating gut microbiota-derived metabolites

Qian Chen; Chunxia Mei; Min Guo; Botao Wang; Haiqin Chen; Jianxin Zhao; Gang Wang; Wei Chen

doi:10.26599/FSHW.2022.9250065

Food Science and Human Wellness 2024, 13(2): 765-777 https://doi.org/10.26599/FSHW.2022.9250065

Open Access | Issue | Published: 25 September 2023

Lactobacillus plantarum CCFM1180 attenuates obesity induced by estrogen deficiency by activating estrogen receptor alpha in abdominal adipose tissue and regulating gut microbiota-derived metabolites

Show Author's Information Hide Author's Information Qian Chen^{^a^,^b^,}, Chunxia Mei^{^a^,^b}, Min Guo^{^a^,^b^,^c^,^d}, Botao Wang^{^a^,^b^,^e}, Haiqin Chen^{^a^,^b^,^c^,^d}, Jianxin Zhao^{^a^,^b^,^c^,^d}, Gang Wang^{^a^,^b^,^c^,^d}(

), Wei Chen^{^a^,^b^,^c}

State Key Laboratory of Food Science and Resources, 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

(Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China

Bloomage Biotechnology Co., Ltd., Jinan 250000, China

Peer review under responsibility of Tsinghua University Press.

Keywords:

Gut microbiota, Bile acid, Short chain fatty acid, Menopause, Ovariectomy

Cite this article:

Chen Q, Mei C, Guo M, et al. Lactobacillus plantarum CCFM1180 attenuates obesity induced by estrogen deficiency by activating estrogen receptor alpha in abdominal adipose tissue and regulating gut microbiota-derived metabolites. Food Science and Human Wellness, 2024, 13(2): 765-777. https://doi.org/10.26599/FSHW.2022.9250065

Download citation

EndNote(RIS)

BibTeX

1140

Views

157

Downloads

Citations

Crossref

WoS

Scopus

CSCD

Abstract Full text About this article

Abstract

Lipid metabolism disorders commonly occur during menopause. Estrogen deficiency has been shown to lead to excessive energy intake and abnormal lipid metabolism in ovariectomized rats, resulting in obesity. Probiotics exhibit anti-obesity properties, and their underlying mechanism has been widely reported. In this study, we demonstrated the metabolic benefits of Lactobacillus plantarum CCFM1180 in suppressing appetite, controlling body weight, correcting obesity-induced abnormalities, enhancing liver lipid metabolism, and protecting liver function in estrogen-deficient rats. The mechanisms associated with the anti-obesity and antidyslipidemia effects of CCFM1180 on estrogen-deficient rats were clarified. The results showed that CCFM1180 dramatically reduced food intake by activating the expression of estrogen receptor alpha (ERα) and increasing the level of leptin in abdominal adipose tissue. These changes, combined with the increased butyrate concentration and recovered bile acid structure, helped enhance lipid metabolism. Additionally, CCFM1180 treatment was found to be safer than exogenous estrogen supplementation. Thus, L. plantarum CCFM1180 could be considered a new therapeutic strategy for preventing and alleviating menopausal lipid abnormalities.

Full text

Abstract

Full text

Outline

About this article

Lactobacillus plantarum CCFM1180 attenuates obesity induced by estrogen deficiency by activating estrogen receptor alpha in abdominal adipose tissue and regulating gut microbiota-derived metabolites

Show Author's information Hide Author's Information Qian Chen^{^a^,^b^,}, Chunxia Mei^{^a^,^b}, Min Guo^{^a^,^b^,^c^,^d}, Botao Wang^{^a^,^b^,^e}, Haiqin Chen^{^a^,^b^,^c^,^d}, Jianxin Zhao^{^a^,^b^,^c^,^d}, Gang Wang^{^a^,^b^,^c^,^d}(

), Wei Chen^{^a^,^b^,^c}

State Key Laboratory of Food Science and Resources, 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

(Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China

Bloomage Biotechnology Co., Ltd., Jinan 250000, China

Peer review under responsibility of Tsinghua University Press.

Highlight

• CCFM1180 alleviates lipid abnormalities in ovariectomised rats.

• CCFM1180 enhances ERα expression and leptin level in abdominal adipose tissue.

• Anti-obesity effect of CCFM1180 associates with increasing colonic butyrate.

• CCFM1180 positively regulates the composition of BA pool in ovariectomised rats.

Abstract

Keywords: Gut microbiota, Bile acid, Short chain fatty acid, Menopause, Ovariectomy

References(60)

[1]

Y. Ren, M. Zhang, Y. Liu, et al., Association of menopause and type 2 diabetes mellitus, Menopause 26 (2019) 325-330. https://doi.org/10.1097/GME.0000000000001200.

DOI Google Scholar

[2]

M. Hyvärinen, H.K. Juppi, S. Taskinen, et al., Metabolic health, menopause, and physical activity—a 4-year follow-up study, Int. J. Obes. 46 (2022) 544-554. https://doi.org/10.1038/s41366-021-01022-x.

DOI Google Scholar

[3]

C.J. Chang, C.H. Wu, W.J. Yao, et al., Relationships of age, menopause and central obesity on cardiovascular disease risk factors in Chinese women, Int. J. Obes. 24 (2000) 1699-1704. https://doi.org/10.1038/sj.ijo.0801457.

DOI Google Scholar

[4]

K. Stamatelopoulos, M. Apostolakis, A. Augoulea, et al., Incident hypertension after menopause is mostly associated with obesity and insulin resistance, Maturitas 124 (2019) 139. https://doi.org/10.1016/j.maturitas.2019.04.089.

DOI Google Scholar

[5]

V. Venetsanaki, S.A. Polyzos, Menopause and non-alcoholic fatty liver disease: a review focusing on therapeutic perspectives, Curr. Vasc. Pharmacol. 17 (2019) 546-555. https://doi.org/10.2174/1570161116666180711121949.

DOI Google Scholar

[6]

P.C. Li, I. Tsai, C.Y. Hsu, et al., Risk of hyperlipidemia in women with hysterectomy-a retrospective cohort study in Taiwan, Sci. Rep. 8 (2018) 1-8. https://doi.org/10.1038/s41598-018-31347-z.

DOI Google Scholar

[7]

M. Wang, W. Gan, C. Kartsonaki, et al., Menopausal status, age at natural menopause and risk of diabetes in China: a 10-year prospective study of 300,000 women, Nutr. Metab. (Lond.). 19 (2022) 1-12. https://doi.org/10.1186/s12986-022-00643-x.

DOI Google Scholar

[8]

M.B. Sørensen, A.M. Rosenfalck, L. Højgaard, et al., Obesity and sarcopenia after menopause are reversed by sex hormone replacement therapy, Obes. Res. 9 (2001) 622-626. https://doi.org/10.1038/oby.2001.81.

DOI Google Scholar

[9]

P. Moccia, R. Belda-Montesinos, A. Monllor-Tormos, et al., Body weight and fat mass across the menopausal transition: hormonal modulators, Gynecol. Endocrinol. 38 (2022) 99-104. https://doi.org/10.1080/09513590.2021.2004395.

DOI Google Scholar

[10]

S. Della Torre, V. Benedusi, G. Pepe, et al., Dietary essential amino acids restore liver metabolism in ovariectomized mice via hepatic estrogen receptor α, Nat. Commun. 12 (2021) 6883. https://doi.org/10.1038/s41467-021-27272-x.

DOI Google Scholar

[11]

A.L. Hevener, D.J. Clegg, F. Mauvais-Jarvis, Impaired estrogen receptor action in the pathogenesis of the metabolic syndrome, Mol. Cell. Endocrinol. 418 (2015) 306-321. https://doi.org/10.1016/j.mce.2015.05.020.

DOI Google Scholar

[12]

S. Qiu, J.T. Vazquez, E. Boulger, et al., Hepatic estrogen receptor α is critical for regulation of gluconeogenesis and lipid metabolism in males, Sci. Rep. 7 (2017) 1-12. https://doi.org/10.1038/s41598-017-01937-4.

DOI Google Scholar

[13]

F. Guarner, G. Schaafsma, Probiotics, Int. J. Food Microbiol. 39 (1998) 237-238. https://doi.org/10.1016/S0168-1605(97)00136-0.

DOI Google Scholar

[14]

S. Huidrom, M.A. Beg, T. Masood, Post-menopausal osteoporosis and probiotics, Curr. Drug Targets. 22 (2021) 816-822. https://doi.org/10.2174/1389450121666201027124947.

DOI Google Scholar

[15]

J.E. Bisanz, S. Seney, A. McMillan, et al., A systems biology approach investigating the effect of probiotics on the vaginal microbiome and host responses in a double blind, placebo-controlled clinical trial of post-menopausal women, PLoS One 9 (2014) e104511. https://doi.org/10.1371/journal.pone.0104511.

DOI Google Scholar

[16]

K. Wang, M. Liao, N. Zhou, et al., Parabacteroides distasonis alleviates obesity and metabolic dysfunctions via production of succinate and secondary bile acids, Cell Rep. 26 (2019) 222-235. https://doi.org/10.1016/j.celrep.2018.12.028.

DOI Google Scholar

[17]

M. Usami, M. Miyoshi, H. Yamashita, Gut microbiota and host metabolism in liver cirrhosis, World J. Gastroenterol. 21 (2015) 11597. https://doi.org/10.3748/wjg.v21.i41.11597.

DOI Google Scholar

[18]

M. Jones, C. Martoni, S. Prakash, Cholesterol lowering and inhibition of sterol absorption by Lactobacillus reuteri NCIMB 30242: a randomized controlled trial, Eur. J. Clin. Nutr. 66 (2012) 1234-1241. https://doi.org/10.1038/ejcn.2012.126.

DOI Google Scholar

[19]

J.R. Swann, E.J. Want, F.M. Geier, et al., Systemic gut microbial modulation of bile acid metabolism in host tissue compartments, Proc. Natl. Acad. Sci. U.S.A. 108 (2011) 4523-4530. https://doi.org/10.1073/pnas.1006734107.

DOI Google Scholar

[20]

E.E. Canfora, J.W. Jocken, E.E. Blaak, Short-chain fatty acids in control of body weight and insulin sensitivity, Nat. Rev. Endocrinol. 11 (2015) 577-591. https://doi.org/10.1038/nrendo.2015.128.

DOI Google Scholar

[21]

Y. Cheng, J. Liu, Z. Ling, Short-chain fatty acids-producing probiotics: a novel source of psychobiotics, Crit. Rev. Food Sci. Nutr. (2021) 1-31. https://doi.org/10.1080/10408398.2021.1920884.

DOI Google Scholar

[22]

Q. Chen, B. Wang, S. Wang, et al., Modulation of the gut microbiota structure with probiotics and isoflavone alleviates metabolic disorder in ovariectomized mice, Nutrients 13 (2021) 1793. https://doi.org/10.3390/nu13061793.

DOI Google Scholar

[23]

C. John, P. Werner, A. Worthmann, et al., A liquid chromatography-tandem mass spectrometry-based method for the simultaneous determination of hydroxy sterols and bile acids, J. Chromatogr. A. 1371 (2014) 184-195. https://doi.org/10.1016/j.chroma.2014.10.064.

DOI Google Scholar

[24]

G. Wang, Q. Chen, P. Tian, et al., Gut microbiota dysbiosis might be responsible to different toxicity caused by di-(2-ethylhexyl) phthalate exposure in murine rodents, Environ. Pollut. 261 (2020) 114164. https://doi.org/10.1016/j.envpol.2020.114164.

DOI Google Scholar

[25]

Q. Chen, Q. Kong, P. Tian, et al., Lactic acid bacteria alleviate di-(2-ethylhexyl) phthalate-induced liver and testis toxicity via their bio-binding capacity, antioxidant capacity and regulation of the gut microbiota, Environ. Pollut. (2022) 119197. https://doi.org/10.1016/j.envpol.2022.119197.

DOI Google Scholar

[26]

M.M. Witte, D. Resuehr, A.R. Chandler, et al., Female mice and rats exhibit species-specific metabolic and behavioral responses to ovariectomy, Gen. Comp. Endocrinol. 166 (2010) 520-528. https://doi.org/10.1016/j.ygcen.2010.01.006.

DOI Google Scholar

[27]

N. Dragano, E. Milbank, M. López, Estradiol and appetite: to eat or not to eat, Mol. Metab. 42 (2020). https://doi.org/10.1016/j.molmet.2020.101061.

DOI Google Scholar

[28]

Z. Zhang, X. Liang, Y. Lv, et al., Evaluation of probiotics for improving and regulation metabolism relevant to type 2 diabetes in vitro, J. Funct. Foods 64 (2020) 103664. https://doi.org/10.1016/j.jff.2019.103664.

DOI Google Scholar

[29]

S.D. Forssten, M.Z. Korczyńska, R.M. Zwijsen, et al., Changes in satiety hormone concentrations and feed intake in rats in response to lactic acid bacteria, Appetite 71 (2013) 16-21. https://doi.org/10.1016/j.appet.2013.06.093.

DOI Google Scholar

[30]

A. De Silva, S.R. Bloom, Gut hormones and appetite control: a focus on PYY and GLP-1 as therapeutic targets in obesity, Gut Liver 6 (2012) 10. https://doi.org/10.5009/gnl.2012.6.1.10.

DOI Google Scholar

[31]

K. Wynne, S. Stanley, B. McGowan, et al., Appetite control, J. Endocrinol. 184 (2005) 291-318. https://doi.org/10.1677/joe.1.05866.

DOI Google Scholar

[32]

K.W. Yi, J.H. Shin, H.S. Seo, et al., Role of Estrogen Receptor-α and -β in regulating leptin expression in 3T3-L1 adipocytes, Obesity 16 (2008) 2393-2399. https://doi.org/10.1038/oby.2008.389.

DOI Google Scholar

[33]

M. Dieudonne, M. Leneveu, Y. Giudicelli, et al., Evidence for functional estrogen receptors α and β in human adipose cells: regional specificities and regulation by estrogens, Am. J. Physiol.-Cell Ph. 286 (2004) C655-C661. https://doi.org/10.1152/ajpcell.00321.2003.

DOI Google Scholar

[34]

F. Ahmed, P.G. Kamble, G. Fanni, et al., Role of estrogen and its receptors in adipose tissue glucose metabolism in pre-and postmenopausal women, J. Clin. Endocrinol. Metab. 107 (2022) e1879-e1889. https://doi.org/10.1210/clinem/dgac042.

DOI Google Scholar

[35]

B.T. Palmisano, L. Zhu, J.M. Stafford, Role of estrogens in the regulation of liver lipid metabolism, Sex and gender factors affecting metabolic homeostasis, diabetes and obesity. (2017) 227-256. https://doi.org/10.1007/978-3-319-70178-3_12.

DOI Google Scholar

[36]

A. Foryst-Ludwig, U. Kintscher, Metabolic impact of estrogen signalling through ERalpha and ERbeta, J. Steroid. Biochem. 122 (2010) 74-81. https://doi.org/10.1016/j.jsbmb.2010.06.012.

DOI Google Scholar

[37]

M. Mohamed, A. Abdel-Rahman, Effect of long-term ovariectomy and estrogen replacement on the expression of estrogen receptor gene in female rats, Eur. J. Endocrinol. 142 (2000) 307-314. https://doi.org/10.1530/eje.0.1420307.

DOI Google Scholar

[38]

H. Zhao, Z. Tian, J. Hao, et al., Extragonadal aromatization increases with time after ovariectomy in rats, Reprod. Biol. Endocrinol. 3 (2005) 1-9. https://doi.org/10.1186/1477-7827-3-6.

DOI Google Scholar

[39]

Y.L. Shen, L.Q. Zhang, Y. Yang, et al., Advances in the role and mechanism of lactic acid bacteria in treating obesity, Food Bioeng. (2022). https://doi.org/10.1002/fbe2.12002.

DOI Google Scholar

[40]

M.A. Stanislawski, D. Dabelea, L.A. Lange, et al., Gut microbiota phenotypes of obesity, NPJ Biofilms Microbi. 5 (2019) 1-9. https://doi.org/10.1038/s41522-019-0091-8.

DOI Google Scholar

[41]

J.A. Santos-Marcos, O.A. Rangel-Zuñiga, R. Jimenez-Lucena, et al., Influence of gender and menopausal status on gut microbiota, Maturitas 116 (2018) 43-53. https://doi.org/10.1016/j.maturitas.2018.07.008.

DOI Google Scholar

[42]

F. Magne, M. Gotteland, L. Gauthier, et al., The firmicutes/bacteroidetes ratio: a relevant marker of gut dysbiosis in obese patients? Nutrients 12 (2020) 1474. https://doi.org/10.3390/nu12051474.

DOI Google Scholar

[43]

S.J. Kallus, L.J. Brandt, The intestinal microbiota and obesity, J. Clin. Gastroenterol. 46 (2012) 16-24. https://doi.org/10.1097/MCG.0b013e31823711fd.

DOI Google Scholar

[44]

M. Ibrahim, S. Anishetty, A meta-metabolome network of carbohydrate metabolism: Interactions between gut microbiota and host, Biochem. Biophys. Res. Commun. 428 (2012) 278-284. https://doi.org/10.1016/j.bbrc.2012.10.045.

DOI Google Scholar

[45]

L. Crovesy, D. Masterson, E.L. Rosado, Profile of the gut microbiota of adults with obesity: a systematic review, Eur. J. Clin. Nutr. 74 (2020) 1251-1262. https://doi.org/10.1038/s41430-020-0607-6.

DOI Google Scholar

[46]

Q. Zeng, D. Li, Y. He, et al., Discrepant gut microbiota markers for the classification of obesity-related metabolic abnormalities, Sci. Rep. 9 (2019) 1-10. https://doi.org/10.1038/s41598-019-49462-w.

DOI Google Scholar

[47]

H.J. Hu, S.G. Park, H.B. Jang, et al., Obesity alters the microbial community profile in Korean adolescents, PLoS One 10 (2015) e0134333. https://doi.org/10.1371/journal.pone.0134333.

DOI Google Scholar

[48]

M. Rau, A. Rehman, M. Dittrich, et al., Fecal SCFAs and SCFA-producing bacteria in gut microbiome of human NAFLD as a putative link to systemic T-cell activation and advanced disease, United Eur. Gastroent. 6 (2018) 1496-1507. https://doi.org/10.1177/2050640618804444.

DOI Google Scholar

[49]

K.N. Kim, Y. Yao, S.Y. Ju, Short chain fatty acids and fecal microbiota abundance in humans with obesity: a systematic review and meta-analysis, Nutrients 11 (2019) 2512. https://doi.org/10.3390/nu11102512.

DOI Google Scholar

[50]

J.M. Baker, L. Al-Nakkash, M.M. Herbst-Kralovetz, Estrogen–gut microbiome axis: physiological and clinical implications, Maturitas 103 (2017) 45-53. https://doi.org/10.1016/j.maturitas.2017.06.025.

DOI Google Scholar

[51]

B. Yang, M. Li, S. Wang, et al., Lactobacillus ruminis alleviates DSS-induced colitis by inflammatory cytokines and gut microbiota modulation, Foods 10 (2021) 1349. https://doi.org/10.3390/foods10061349.

DOI Google Scholar

[52]

Z. Wang, C. Elekwachi, J. Jiao, et al., Changes in metabolically active bacterial community during rumen development, and their alteration by rhubarb root powder revealed by 16S rRNA amplicon sequencing, Front. Microbiol. 8 (2017) 159. https://doi.org/10.3389/fmicb.2017.00159.

DOI Google Scholar

[53]

Z. Gao, J. Yin, J. Zhang, et al., Butyrate improves insulin sensitivity and increases energy expenditure in mice, Diabetes 58 (2009) 1509-1517. https://doi.org/10.2337/db08-1637.

DOI Google Scholar

[54]

H. Lin, Y. An, H. Tang, et al., Alterations of bile acids and gut microbiota in obesity induced by high fat diet in rat model, J. Agric. Food Chem. 67 (2019) 3624-3632. https://doi.org/10.1021/acs.jafc.9b00249.

DOI Google Scholar

[55]

J.Y. Chiang, Recent advances in understanding bile acid homeostasis, F1000Res. 6 (2017). https://doi.org/10.12688/f1000research.12449.1.

DOI Google Scholar

[56]

Y. Kiriyama, H. Nochi, Physiological role of bile acids modified by the gut microbiome, Microorganisms 10 (2021) 68. https://doi.org/10.3390/microorganisms10010068.

DOI Google Scholar

[57]

A. Hofmann, The enterohepatic circulation of bile acids in health and disease, Gastrointestinal Dis. 1 (1993) 127-150.

Google Scholar

[58]

M.L. Jones, C.J. Martoni, J.G. Ganopolsky, et al., The human microbiome and bile acid metabolism: dysbiosis, dysmetabolism, disease and intervention, Expert Opin. Biol. Ther. 14 (2014) 467-482. https://doi.org/10.1517/14712598.2014.880420.

DOI Google Scholar

[59]

D.Q.H. Wang, B.A. Neuschwander-Tetri, P. Portincasa, et al., Interactions between bile acids and nuclear receptors and their effects on lipid metabolism and liver diseases, in: Hindawi, 2012. https://doi.org/10.1155/2012/560715.

DOI

[60]

H.H. Wang, M. Liu, D.J. Clegg, et al., New insights into the molecular mechanisms underlying effects of estrogen on cholesterol gallstone formation, Biochim. Biophys. Acta Bioenerg. 1791 (2009) 1037-1047. https://doi.org/10.1016/j.bbalip.2009.06.006.

DOI Google Scholar

About this article

Publication history

Acknowledgements

Rights and permissions

Publication history

Received: 29 May 2022

Revised: 23 July 2022

Accepted: 24 August 2022

Published: 25 September 2023

Issue date: March 2024

Copyright

Acknowledgements

Acknowledgment

This research was funded by the National Natural Science Foundation of China (31972052, 32021005, 31820103010), the Fundamental Research Funds for the Central Universities (JUSRP22006, JUSRP51501), the Program of Collaborative Innovation Centre 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/).