Keywords
soybean
cardiovascular disease
type 2 diabetes
Akkermansia muciniphila
How to Cite
Abstract
Bioactive compounds (proteins and isoflavones) in soy have been linked to a reduced incidence of obesity-related diseases including cardiovascular disease (CVD) and type 2 diabetes (T2D). Therefore, the development of functional foods containing these compounds is a promising strategy to promote health and prevent obesity-related conditions. However, their efficacy and safety require further clinical evaluation. This study assessed the effects of consuming a functional food formulated with soy flour and cornstarch (extruded snack) on metabolic parameters and the gut microbiota in individuals with overweight or obesity. A paired, eight-week intervention study was conducted in adults (n = 16) with a body mass index (BMI) ≥25 kg/m². Anthropometric and nutritional assessments were performed every 15 days, and blood and fecal samples were collected at the beginning and end of the intervention. The results showed significant reductions in low-density lipoprotein (LDL p = 0.041), waist circumference (p = 0.002), and blood glucose levels (p = 0.012). Additionally, fecal Akkermansia muciniphila concentration increased from 2.78 ± 1.72 to 3.19 ± 1.57 log DNA copies/g feces. These findings suggest that the consumption of the evaluated functional food may contribute to the prevention of CVD and T2D in individuals with overweight or obesity by improving key metabolic parameters.
References
Abioye, A. O., Ajala, A. S., Bolarinwa, I. F. & Duduyemi, O. (2016). Effect of Extrusion Conditions on Cassava/Soybean Extrudates. MOJ Food Processing & Technology, 3(1), 237–245. https://doi.org/10.15406/mojfpt.2016.03.00062
Ahmad, S. R. (2022). Plant-based diet for obesity treatment. Frontiers in Nutrition, 9, 952553. DOI:10.3389/fnut.2022.952553
AOAC (2012). In W. Horwitz & G. W. Latimer (Eds.), Association of official analytical chemists, official methods of analysis (18th ed.). Gathersburg, MD: AOAC International.
Carrão-Panizzi, M. C., Pedroso de Goés, F. S. & Kikuchi, A. (2002). Extraction Time for Soybean Isoflavone Determination. Brazilian Archives of Biology and Technology, 45(4), 515–518. DOI: 10.1590/S1516-89132002000600015
Chen, Z., Liang, N., Zhang, H., Li, H., Guo, J., Zhang, Y., Chen, Y., Wang, Y. & Shi, N. (2024). Resistant starch and the gut microbiome: Exploring beneficial interactions and dietary impacts. Food Chemistry: X, 21, 101118. https://doi.org/10.1016/j.fochx.2024.101118
Collado, M. C., Derrien, M., Isolauri, E., de Vos, W. M. & Salminen, S. (2007). Intestinal Integrity and Akkermansia muciniphila, a Mucin-Degrading Member of the Intestinal Microbiota Present in Infants, Adults, and the Elderly. Applied and Environmental Microbiology, 73(23), 7767–7770. DOI:10.1128/AEM.01477-07
Cook, R. J., Dickens, B. M. & Fathalla, M. F. (2011). ‘World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects’, Reproductive Health and Human Rights: Integrating Medicine, Ethics, and Law (Oxford, 2003; online edn, Oxford Academic, 3 Oct. 2011), https://doi.org/10.1093/acprof:oso/9780199241323.003.0025
Dao, M. C., Everard, A., Aron-Wisnewsky, J., Sokolovska, N., Prifti, E., Verger, E. O., Kayser, B. D., Levenez, F., Chilloux, J., Hoyles, L., Consortium, M., Dumas, M., Rizkalla, S. W., Doré, J., Cani, P. D. & Clément, K. (2016). Akkermansia muciniphila, and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut, 65(3), 426–436. DOI:10.1136/gutjnl-2014-308778
Depommier, C., Everard, A., Druart, C., Plovier, H., Van Hul, M., Vieira-silva, S., Falony, G., Raes, J., Maiter, D., Delzanne, N. M., de Barsy, M., Loumaye, A., Hermans, M. P., Thissen, J. P., de Vos, W. M. & Cani, P. D. (2019). Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nature Medicine, 25, 1096–1103. https://doi.org/10.1038/s41591-019-0495-2
Everard, A. & Cani, P. D. (2014). Gut Microbiota and GLP-1. Endocrine and Metabolic Disorders, 15, 189–196. https://doi.org/10.1007/s11154-014-9288-6
Fernandez-Raudales, D., Hoeflinger, J. L., Bringe, N. A., Cox, S. B., Dowd, S. E., Miller, M. J. & Gonzalez de Mejia, E. (2012). Consumption of different soymilk formulations differentially affects the gut microbiomes of overweight and obese men. Gut Microbes, 3(6), 490–500. https://doi.org/10.4161/gmic.21578
General Assembly of the World Medical Association. (2014).World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. Journal of the American College of Dentists, 81(3),14-18. PMID: 25951678.
Gobierno de México (2017). “NORMA Oficial Mexicana NOM-008-SSA3-2010 Para el tratamiento integral del sobrepeso y la obe-sidad,” Retrieved from https://www.gob.mx/cms/uploads/attachment/file/35879/NOM-008-SSA3-2010.pdf
Gress, T. W., Denvir, J. & Shapiro, J. I. (2022). Effect of removing outliers on statistical inference: implications to interpretation of experimental data in medical research. Marshall Journal of Medicine, 4(2), 9. DOI: 10.18590/mjm.2018.vol4.iss2.9
Guevara-Cruz, M., Godinez-Salas, E. T., Sanchez-Tapia, M., Torres-Villalobos, G., Pichardo-Ontiveros, E., Guizar-Heredia, R., Arteaga-Sanchez, L., Gamba, G., Mojica-Espinosa, R., Schcolnik-Cabrera, A., Granados, O., López-Barradas, A., Vargas-Castillo, A., Torre-Villalvazo, I., Noriega, L. G., Torres, N. & Tovar, A. R. (2020). Genistein stimulates insulin sensitivity through gut microbiota reshaping and skeletal muscle AMPK activation in obese subjects. BMJ Open Diabetes Research & Care, 8(1), 1–9. DOI:10.1136/bmjdrc-2019-000948
Haghighat, N., Ashtary-Larky, D., Bagheri, R., Wong, A., Cheraghloo, N., Moradpour, G., Nordvall, M., Asbaghi, O., Moeinvaziri, N., Amini, M., Sohrabi, Z. & Dutheil, F. (2021). Effects of 6 Months of Soy-Enriched High Protein Compared to Intake , and Body Composition in Normal-Weight Obese Women : A Randomized Controlled Trial. Nutrients, 13(7), 2266. https://doi.org/10.3390/nu13072266
Hou, K., Wu, Z. X., Chen, X. Y., Wang, J. Q., Zhang, D., Xiao, C., Zhu, D., Koya, J. B., Wei, L., Li, J. & Chen, Z.S. (2022). Microbiota in health and diseases. Signal Transduction and Targeted Therapy, 7, 135. https://doi.org/10.1038/s41392-022-00974-4
Huang, H., Krishnan, H. B., Pham, Q., Yu, L. L. & Wang, T. T. Y. (2016). Soy and Gut Microbiota: Interaction and Implication for Human Health. Journal of Agricultural and Food Chemistry, 64(46), 8695–8709. https://doi.org/10.1021/acs.jafc.6b03725
Iino, C., Shimoyama, T., Iino, K., Yokoyama, Y., Chinda, D., Sakuraba, H., Fukuda, S. & Nakaji, S. (2019). Daidzein Intake Is Associated with Equol Producing Status through an Increase in the Intestinal Bacteria Responsible for Equol Production. Nutrients, 11(2), 433. https://doi.org/10.3390/nu11020433
Jenkins, D. J. A., Mejia, S. B., Chiavaroli, L., Viguiliouk, E., Li, S. S., Kendall, C. W. C., Vuksan, V. & Sievenpiper, J. L. (2019). Cumulative meta-analysis of the soy effect over time. Journal of the American Heart Association, 8(13). https://doi.org/10.1161/JAHA.119.012458
Jin, X., Qiu, T., Li, L., Yu, R., Chen, X., Li, C., Proud, C. G. & Jiang, T. (2023). Pathophysiology of obesity and its associated diseases. Acta Pharmaceutica Sinica B, 13(6), 2403–2424. https://doi.org/10.1016/j.apsb.2023.01.012
Kurina, I., Popenko, A., Klimenko, N., Koshechkin, S., Chuprikova, L., Filipenko, M., Tyakht, A. & Alexeev, D. (2020). Development of qPCR platform with probes for quantifying prevalent and biomedically relevant human gut microbial taxa. Molecular and Cellular Probes, 52, 101570. https://doi.org/10.1016/j.mcp.2020.101570
Lin, K., Zhu, L. & Yang, L. (2022). Gut and obesity / metabolic disease : Focus on microbiota metabolites. MedComm, 3(3), e171. https://doi.org/10.1002/mco2.171
López, P., Sánchez, M., Perez-Cruz, C., Velázquez-Villegas, L. A., Syeda, T., Aguilar-López, M., Rocha-Viggiano, A. K., Silva-Lucero, M. C., Torre-Villalvazo, I., Noriega, L.G., Torres, N. & Tovar, A. R. (2018). Long-Term Genistein Consumption Modifies Gut Microbiota, Improving Glucose Metabolism, Metabolic Endotoxemia, and Cognitive Function in Mice Fed a High-Fat Diet. Molecular Nutrition & Food Research, 62(16), 1800313. DOI:10.1002/mnfr.201800313
Moradi, M., Daneshzad, E. & Azadbakht, L. (2020). The effects of isolated soy protein, isolated soy isoflavones, and soy protein containing isoflavones on serum lipids in postmenopausal women: A systematic review and meta-analysis. Critical Reviews in Food Science and Nutrition, 60(20), 3414–3428. DOI:10.1080/10408398.2019.1689097
Mayo, B., Vázquez, L. & Flórez, A. B. (2019). Equol: A Bacterial Metabolite from The Daidzein Isoflavone and Its Presumed Beneficial Health Effects. Nutrients, 11(9), 2231. https://doi: 10.3390/nu11092231
Naito, Y., Uchiyama, K. & Takagi, T. (2018). A next-generation beneficial microbe: Akkermansia muciniphila. Journal of Clinical Biochemistry and Nutrition, 63(1), 33-35. https://doi:10.3164/jcbn.18-57
Nakatsu, C. H., Armstrong, A., Clavijo, A. P., Martin, B. R., Barnes, S. & Weaver, C. M. (2014). Fecal Bacterial Community Changes Associated with Isoflavone Metabolites in Postmenopausal Women after Soy Bar Consumption. PLoS ONE, 9, e108924. DOI:10.1371/journal.pone.0108924
Norton, K. I. (2018). Standards for Anthropometry Assessment. DOI:10.4324/9781315385662-4.
Orozco-Angelino, X., Espinosa-Ramírez, J. & Serna-Saldívar, S. O. Extrusion as a tool to enhance the nutritional and bioactive potential of cereal and legume by-products. Food Research International, 169, 112889. https://doi.org/10.1016/j.foodres.2023.112889.
Razmifard, F., Barzeghari, A., Farrin, N., Safaiyan, A., Ghaem-Maghami, S. J., Mobasseri, M., Sodabi, S. M., Saleh-Ghadimi, S. & Ostadrahimi, A. (2019). Changes in Akkermansia muciniphila and its relationship with dietary habits in type 2 diabetic obese patients. Progress in Nutrition, 21(1-S), 130–137. https://doi.org/10.23751/pn.v21i1-S.5812
Rowland, I., Gibson, G., Heinken, A., Scott, K., Swann, J., Thiele, I. & Tuohy, K. (2018). Gut microbiota functions : metabolism of nutrients and other food components. European Journal of Nutrition, 57(1), 1–24. https://doi.org/10.1007/s00394-017-1445-8
Shih, C. T., Yeh, Y. T., Lin, C. C., Yang, L. Y. & Chiang, C. P. (2020). Akkermansia muciniphila is negatively correlated with hemoglobin a1c in refractory diabetes. Microorganisms, 8(9), 1–13. https://doi.org/10.3390/microorganisms8091360
Torres-Fuentes, C., Schellekens, H., Dinan, T. G. & Cryan, J. F. (2017). The microbiota–gut–brain axis in obesity. Lancet Gastroenterology & Hepatology, 2(10), 747–756. DOI:10.1016/S2468-1253(17)30147-4
Willson, K. & Situ, C. (2017). Systematic Review on Effects of Diet on Gut Microbiota in Relation to Metabolic Syndromes. Journal of Clinical Nutrition and Metabolism, 1(2), 1–12.
Xu, Y., Jia, F., Wu, Y., Jiang, J., Zheng, T., Zheng, H. & Yang, Y. (2025). The Impact of Extrusion Cooking on the Physical Properties, Functional Components, and Pharmacological Activities of Natural Medicinal and Edible Plants: A Review. Foods, 14(11). 1869. https://doi.org/10.3390/foods14111869
Yarahmadi, A., Afkhami, H., Javadi, A. & Kashfi, M. (2024). Understanding the complex function of gut microbiota : its impact on the pathogenesis of obesity and beyond : a comprehensive review. Diabetology & Metabolic Syndrome, 16(1), 308. DOI: 10.1186/s13098-024-01561-z
Zhang, L., Shi, M., Tian, M., Wang, X., Ji, J., Liao, X., Hu, X. & Chen, F. (2020). Guidelines for Absolute Quantitative Real-time PCR for Microbial Determination in Vitro Gastrointestinal Digestion. Food Frontiers, 1(2), 200–204. https://doi.org/10.1002/fft2.31
Zhou, Q., Zhang, Y., Wang, X., Yang, R., Zhu, X., Zhang, Y., Chen, C., Yuan, H., Yang, Z. & Sun, L. (2020). Gut Bacteria Akkermansia Is Associated with Reduced Risk of Obesity: Evidence from the American Gut Project. Nutrition & Metabolism, 17(90), 1–9. https://doi.org/10.1186/s12986-020-00516-1
TIP Magazine Specialized in Chemical-Biological Sciences, distributed under Creative Commons License: Attribution + Noncommercial + NoDerivatives 4.0 International.