Skip to main content

Advertisement

SpringerLink
Log in

Isoflavone consumption reduces inflammation through modulation of phenylalanine and lipid metabolism

  • Original Article
  • Published:
Metabolomics Aims and scope Submit manuscript

Abstract

Introduction

Phytoestrogens found in soy, fruits, peanuts, and other legumes, have been identified as metabolites capable of providing beneficial effects in multiple pathological conditions due to their ability to mimic endogenous estrogen. Interestingly, the health-promoting effects of some phytoestrogens, such as isoflavones, are dependent on the presence of specific gut bacteria. Specifically, gut bacteria can metabolize isoflavones into equol, which has a higher affinity for endogenous estrogen receptors compared to dietary isoflavones. We have previously shown that patients with multiple sclerosis (MS), a neuroinflammatory disease, lack gut bacteria that are able to metabolize phytoestrogen. Further, we have validated the importance of both isoflavones and phytoestrogen-metabolizing gut bacteria in disease protection utilizing an animal model of MS. Specifically, we have shown that an isoflavone-rich diet can protect from neuroinflammatory diseases, and that protection was dependent on the ability of gut bacteria to metabolize isoflavones into equol. Additionally, mice on a diet with isoflavones showed an anti-inflammatory response compared to the mice on a diet lacking isoflavones. However, it is unknown how isoflavones and/or equol mediates their protective effects, especially their effects on host metabolite levels.

Objectives

In this study, we utilized untargeted metabolomics to identify metabolites found in plasma that were modulated by the presence of dietary isoflavones.

Results

We found that the consumption of isoflavones increased anti-inflammatory monounsaturated fatty acids and beneficial polyunsaturated fatty acids while reducing pro-inflammatory glycerophospholipids, sphingolipids, phenylalanine metabolism, and arachidonic acid derivatives.

Conclusion

Isoflavone consumption alters the systemic metabolic landscape through concurrent increases in monounsaturated fatty acids and beneficial polyunsaturated fatty acids plus reduction in pro-inflammatory metabolites and pathways. This highlights a potential mechanism by which an isoflavone diet may modulate immune-mediated disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data Availability

Metabolomic data utilized for analysis is in Table S1.

References

  • Aboushanab, S. A., Khedr, S. M., Gette, I. F., Danilova, I. G., Kolberg, N. A., Ravishankar, G. A., Ambati, R. R., & Kovaleva, E. G. (2021). Isoflavones derived from plant raw materials: bioavailability, anti-cancer, anti-aging potentials, and microbiome modulation. Critical Reviews in Food Science and Nutrition. Ltd: Bellwether Publishing. https://doi.org/10.1080/10408398.2021.1946006

    Chapter  Google Scholar 

  • Akazawa, Y., Morisaki, T., Fukuda, H., Norimatsu, K., Shiota, J., Hashiguchi, K., Tabuchi, M., Kitayama, M., Matsushima, K., Yamaguchi, N., Kondo, H., Fujita, F., Takeshita, H., Nakao, K., & Takeshima, F. (2021). Significance of serum palmitoleic acid levels in inflammatory bowel disease. Scientific Reports, 11(1), https://doi.org/10.1038/s41598-021-95923-6

  • Bjørnevik, K., Chitnis, T., Ascherio, A., & Munger, K. L. (2017). Polyunsaturated fatty acids and the risk of multiple sclerosis. Multiple Sclerosis, 23(14), 1830–1838. https://doi.org/10.1177/1352458517691150

    Article  CAS  PubMed  Google Scholar 

  • Bjornevik, K., Myhr, K. M., Beiske, A., Bjerve, K. S., Holmøy, T., Hovdal, H., Midgard, R., Riise, T., Wergeland, S., & Torkildsen, Ø. (2019). α-Linolenic acid is associated with MRI activity in a prospective cohort of multiple sclerosis patients. Multiple Sclerosis Journal, 25(7), 987–993. https://doi.org/10.1177/1352458518779925

    Article  CAS  PubMed  Google Scholar 

  • Chamras, H., Barsky, S. H., Ardashian, A., Navasartian, D., Heber, D., & Glaspy, J. A. (2005). Novel Interactions of Vitamin E and Estrogen in Breast Cancer. Nutrition and Cancer, 52(1), 43–48. https://doi.org/10.1207/s15327914nc5201_6

    Article  CAS  PubMed  Google Scholar 

  • Chen, J., Chia, N., Kalari, K. R., Yao, J. Z., Novotna, M., Soldan, M. M. P., Luckey, D. H., Marietta, E., Jeraldo, P. R., Chen, X., Weinshenker, B. G., Rodriguez, M., Kantarci, O. H., Nelson, H., Murray, J. A., & Mangalam, A. K. (2016). Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Scientific Reports, 6. https://doi.org/10.1038/srep28484

  • Coll, T., Eyre, E., Rodríguez-Calvo, R., Palomer, X., Sánchez, R. M., Merlos, M., Laguna, J. C., & Vázquez-Carrera, M. (2008). Oleate reverses palmitate-induced insulin resistance and inflammation in skeletal muscle cells. Journal of Biological Chemistry, 283(17), 11107–11116. https://doi.org/10.1074/jbc.M708700200

    Article  CAS  PubMed  Google Scholar 

  • Díaz-Rubio, M. E., Pérez-Jiménez, J., Martínez-Bartolomé, M., Álvarez, I., & Saura-Calixto, F. (2015). Regular Consumption of an Antioxidant-rich Juice Improves Oxidative Status and Causes Metabolome Changes in Healthy Adults. Plant Foods for Human Nutrition, 70(1), 9–14. https://doi.org/10.1007/s11130-014-0455-4

    Article  CAS  PubMed  Google Scholar 

  • el Aidy, S., Burokas, A., Cristiano, C., Marzal, P. L., Pardo, P. P., Zheng, Y., Bek, M. K., Prince, N. Z., Marzal, P., Garssen, L. N., Perez Pardo, J., P., & Kraneveld, A. D. (2021). The Role of Bacterial-Derived Aromatic Amino Acids Metabolites Relevant in Autism Spectrum Disorders: A Comprehensive Review. https://doi.org/10.3389/fnins.2021.738220

  • François, M., Karpe, A., Liu, J. W., Beale, D., Hor, M., Hecker, J., Faunt, J., Maddison, J., Johns, S., Doecke, J., Rose, S., & Leifert, W. R. (2021). Salivaomics as a Potential Tool for Predicting Alzheimer’s Disease During the Early Stages of Neurodegeneration. Journal of Alzheimer’s Disease, 82, 1301–1313. https://doi.org/10.3233/JAD-210283

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gao, S., Quick, C., Guasch-Ferre, M., Zhuo, Z., Hutchinson, J. M., Su, L., Hu, F., Lin, X., & Christiani, D. (2021). The Association Between Inflammatory and Oxidative Stress Biomarkers and Plasma Metabolites in a Longitudinal Study of Healthy Male Welders. Journal of Inflammation Research, 14, 2825–2839. https://doi.org/10.2147/JIR.S316262

    Article  PubMed Central  PubMed  Google Scholar 

  • Ghimire, S., Cady, N. M., Lehman, P., Peterson, S. R., Shahi, S. K., Rashid, F., Giri, S., & Mangalam, A. K. (n.d.). Dietary Isoflavones Alter Gut Microbiota and Lipopolysaccharide Biosynthesis to Reduce Inflammation.Gut Microbes, 14(1),2127446. https://doi.org/10.1080/19490976.2022.2127446

  • Gryp, T., Vanholder, R., Vaneechoutte, M., & Glorieux, G. (2017). p-cresyl sulfate. Toxins, 9(2), https://doi.org/10.3390/TOXINS9020052

  • Hannun, Y. A., Gault, C. R., & Obeid, L. M. (2010). Sphingolipids as Signaling and Regulatory Molecules An Overview of Sphingolipid Metabolism: From Synthesis to Breakdown

  • Jana, A., & Pahan, K. (2010). Sphingolipids in Multiple Sclerosis. Neuromolecular Medicine. https://doi.org/10.1007/s12017-010-8128-4

    Article  PubMed Central  PubMed  Google Scholar 

  • Jensen, S. N., Cady, N. M., Shahi, S. K., Peterson, S. R., Gupta, A., Gibson-Corley, K. N., & Mangalam, A. K. (2021). Isoflavone diet ameliorates experimental autoimmune encephalomyelitis through modulation of gut bacteria depleted in patients with multiple sclerosis. In Sci. Adv (Vol. 7, Issue 9). https://doi.org/https://www.science.org

  • Jewell, D. E., & Jackson, M. I. (2022). Dietary Betaine and Fatty Acids Change Circulating Single-Carbon Metabolites and Fatty Acids in the Dog. Animals, 12(6), https://doi.org/10.3390/ani12060768

  • Johnson, E. L., Heaver, S. L., Waters, J. L., Kim, B. I., Bretin, A., Goodman, A. L., Gewirtz, A. T., Worgall, T. S., & Ley, R. E. (2020). Sphingolipids produced by gut bacteria enter host metabolic pathways impacting ceramide levels. Nature Communications, 11(1), 2471. https://doi.org/10.1038/s41467-020-16274-w

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kassambara, A. (2020). ggpubr: “ggplot2” Based Publication Ready Plots. R package version 0.4.0

  • Lee, J. S., Wang, R. X., Goldberg, M. S., Clifford, G. P., Kao, D. J., & Colgan, S. P. (2020). Microbiota-Sourced Purines Support Wound Healing and Mucous Barrier Function. IScience, 23(6), 101226. https://doi.org/10.1016/j.isci.2020.101226

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Li, Z., & Vance, D. E. (2008). Phosphatidylcholine and choline homeostasis. In Journal of Lipid Research (Vol. 49, Issue 6, pp. 1187–1194). https://doi.org/10.1194/jlr.R700019-JLR200

  • Luo, Q., Cheng, D., Huang, C., Li, Y., Lao, C., Xia, Y., Liu, W., Gong, X., Hu, D., Li, B., He, X., & Chen, Z. (2019). Improvement of Colonic Immune Function with Soy Isoflavones in High-Fat Diet-Induced Obese Rats. Molecules, 24(6), 1139. https://doi.org/10.3390/molecules24061139

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Malashree, L., Mudgil, P., Dagar, S. S., Kumar, S., & Puniya, A. K. (2012). β-Glucosidase Activity of Lactobacilli for Biotransformation of Soy Isoflavones. Food Biotechnology, 26(2), 154–163. https://doi.org/10.1080/08905436.2012.670832

    Article  CAS  Google Scholar 

  • Mangalam, A., Poisson, L., Nemutlu, E., Datta, I., Denic, A., Dzeja, P., Rodriguez, M., Rattan, R., & Giri, S. (2013). Profile of Circulatory Metabolites in an Animal Model of Multiple Sclerosis using Global Metabolomics. Journal of Clinical & Cellular Immunology, 04(03), https://doi.org/10.4172/2155-9899.1000150

  • Mangalam, A., Yadav, M., & Yadav, R. (2021). The emerging world of microbiome in autoimmune disorders: Opportunities and challenges. Indian Journal of Rheumatology (Vol, 16(1), 57–72. https://doi.org/10.4103/injr.injr_210_20. Wolters Kluwer Medknow Publications

    Article  Google Scholar 

  • Mayo, B., Vázquez, L., & Flórez, A. B. (2019a). Equol: A bacterial metabolite from the Daidzein isoflavone and its presumed beneficial health effects. Nutrients, 11(9), https://doi.org/10.3390/NU11092231

  • Mayo, B., Vázquez, L., & Flórez, A. B. (2019b). Equol: A Bacterial Metabolite from The Daidzein Isoflavone and Its Presumed Beneficial Health Effects. Nutrients, 11(9), 2231. https://doi.org/10.3390/nu11092231

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mcginley, M. P., & Cohen, J. A. (2021). Therapeutics Sphingosine 1-phosphate receptor modulators in multiple sclerosis and other conditions. The Lancet, 398, 1184–1194. https://doi.org/10.1016/S0140-6736(21)00244-0

    Article  CAS  Google Scholar 

  • Mehta, A. K., Singh, B. P., Arora, N., & Gaur, S. N. (2010). Choline attenuates immune inflammation and suppresses oxidative stress in patients with asthma. Immunobiology, 215(7), 527–534. https://doi.org/10.1016/j.imbio.2009.09.004

    Article  CAS  PubMed  Google Scholar 

  • Experimental Procedures. Metabolon Help Metabolon Inc, & Center (2022). https://doi.org/https://help.metabolon.com/docs/microbiome-smartpanel/knowledge-base/experimental-procedures/

  • Mezei, O., Li, Y., Mullen, E., Ross-Viola, J. S., & Shay, N. F. (2006). Dietary isoflavone supplementation modulates lipid metabolism via PPARalpha-dependent and -independent mechanisms. Physiological Genomics, 26(1), 8–14. https://doi.org/10.1152/physiolgenomics.00155.2005

    Article  CAS  PubMed  Google Scholar 

  • Munger, K., Bjornevik, K., Cortese, M., Edan, G., Freedman, M., Hartung, H. P., Montalban, X., Sandbrink, R., Radue, E. W., Barkhof, F., Wicklein, E. M., Kappos, L., & Ascherio, A. (2022). A Prospective Study of Serum Levels of Polyunsaturated Fatty Acids and Effects on Multiple Sclerosis Disease Activity and Progression (S40.006). In Supplement) THURSDAY (Vol. 98, Issue 7)

  • Nemazannikova, N., Mikkelsen, K., Stojanovska, L., Blatch, G. L., & Apostolopoulos, V. (2018). Is there a Link between Vitamin B and Multiple Sclerosis? Medicinal Chemistry, 14(2), https://doi.org/10.2174/1573406413666170906123857

  • Nogueras, L., Gonzalo, H., Jové, M., Sol, J., Gil-Sanchez, A., Hervás, J., Valcheva, P., Solana, M. J., peralta, S., pamplona, R., & Brieva, L. (2019). Lipid profile of cerebrospinal fluid in multiple sclerosis patients: A potential tool for diagnosis. Scientific Reports, 9, 11313. https://doi.org/10.1038/s41598-019-47906-x

  • Ntranos, A., Park, H. J., Wentling, M., Tolstikov, V., Amatruda, M., Inbar, B., Kim-Schulze, S., Frazier, C., Button, J., Kiebish, M. A., Lublin, F., Edwards, K., & Casaccia, P. (2022). Bacterial neurotoxic metabolites in multiple sclerosis cerebrospinal fluid and plasma. Brain, 145(2), 569–583. https://doi.org/10.1093/brain/awab320

    Article  PubMed  Google Scholar 

  • Oliphant, K., & Allen-Vercoe, E. (2019). Macronutrient metabolism by the human gut microbiome: major fermentation by-products and their impact on host health. Microbiome, 7(1), 91. https://doi.org/10.1186/s40168-019-0704-8

    Article  PubMed Central  PubMed  Google Scholar 

  • Pabich, M., & Materska, M. (2019). Biological effect of soy isoflavones in the prevention of civilization diseases. Nutrients, 11(7), https://doi.org/10.3390/nu11071660

  • Pang, Z., Chong, J., Zhou, G., de Lima Morais, D. A., Chang, L., Barrette, M., Gauthier, C., Jacques, P., Li, S., & Xia, J. (2021). MetaboAnalyst 5.0: Narrowing the gap between raw spectra and functional insights. Nucleic Acids Research, 49(W1), W388–W396. https://doi.org/10.1093/nar/gkab382

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pinheiro de Oliveira, F., Mendes, R. H., Dobbler, P. T., Mai, V., Pylro, V. S., Waugh, S. G., Vairo, F., Refosco, L. F., Roesch, L. F. W., & Schwartz, I. V. D. (2016). Phenylketonuria and Gut Microbiota: A Controlled Study Based on Next-Generation Sequencing. PLOS ONE, 11(6), e0157513. https://doi.org/10.1371/journal.pone.0157513

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Poisson, L. M., Suhail, H., Singh, J., Datta, I., Deni, A., Labuzek, K., Hoda, N., Shankar, A., Kumar, A., Cerghet, M., Elias, S., Mohney, R. P., Rodriguez, M., Rattan, R., Mangalam, A. K., & Giri, S. (2015). Untargeted plasma metabolomics identifies endogenous metabolite with drug-like properties in chronic animal model of multiple sclerosis. Journal of Biological Chemistry, 290(52), 30697–30712. https://doi.org/10.1074/jbc.M115.679068

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Poisson, L. M., Suhail, H., Singh, J., Datta, I., Denic, A., Labuzek, K., Hoda, M. N., Shankar, A., Kumar, A., Cerghet, M., Elias, S., Mohney, R. P., Rodriguez, M., Rattan, R., Mangalam, A. K., & Giri, S. (2015). Untargeted Plasma Metabolomics Identifies Endogenous Metabolite with Drug-like Properties in Chronic Animal Model of Multiple Sclerosis. The Journal of Biological Chemistry, 290(52), 30697–30712. https://doi.org/10.1074/jbc.M115.679068

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pompura, S. L., Wagner, A., Kitz, A., LaPerche, J., Yosef, N., Dominguez-Villar, M., & Hafler, D. A. (2021). Oleic acid restores suppressive defects in tissue-resident FOXP3 Tregs from patients with multiple sclerosis. Journal of Clinical Investigation, 131(2), https://doi.org/10.1172/JCI138519

  • R Core Team (2022). R: A Language and Environment for Statistical Computing (4.1.1)

  • Rangel-Huerta, O. D., Aguilera, C. M., Perez-de-la-Cruz, A., Vallejo, F., Tomas-Barberan, F., Gil, A., & Mesa, M. D. (2017). A serum metabolomics-driven approach predicts orange juice consumption and its impact on oxidative stress and inflammation in subjects from the BIONAOS study. Molecular Nutrition and Food Research, 61(2), https://doi.org/10.1002/mnfr.201600120

  • Ravaut, G., Légiot, A., Bergeron, K. F., & Mounier, C. (2020). Monounsaturated Fatty Acids in Obesity-Related Inflammation. International Journal of Molecular Sciences, 22(1), 330. https://doi.org/10.3390/ijms22010330

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ricciotti, E., & Fitzgerald, G. A. (2011). Prostaglandins and Inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology. https://doi.org/10.1161/ATVBAHA.110.207449

  • Sathyapalan, T., Aye, M., Rigby, A. S., Thatcher, N. J., Dargham, S. R., Kilpatrick, E. S., & Atkin, S. L. (2018). Soy isoflavones improve cardiovascular disease risk markers in women during the early menopause. Nutrition Metabolism and Cardiovascular Diseases, 28(7), 691–697. https://doi.org/10.1016/j.numecd.2018.03.007

    Article  CAS  Google Scholar 

  • Spiegel, S., & Milstien, S. (2011). The outs and the ins of sphingosine-1-phosphate in immunity. Nature Reviews Immunology (Vol, 11(6), 403–415. https://doi.org/10.1038/nri2974

    Article  CAS  Google Scholar 

  • Storm-Larsen, C., Myhr, K. M., Farbu, E., Midgard, R., Nyquist, K., Broch, L., Berg-Hansen, P., Buness, A., Holm, K., Ueland, T., Fallang, L. E., Burum-Auensen, E., Hov, J. R., & Holmøy, T. (2019). Gut microbiota composition during a 12-week intervention with delayed-release dimethyl fumarate in multiple sclerosis-a pilot trial. https://doi.org/10.1177/2055217319888767

  • Sun, Y., Tao, W., Huang, H., Ye, X., & Sun, P. (2019). Flavonoids, phenolic acids, carotenoids and antioxidant activity of fresh eating citrus fruits, using the coupled in vitro digestion and human intestinal HepG2 cells model. Food Chemistry, 279, 321–327. https://doi.org/10.1016/j.foodchem.2018.12.019

    Article  CAS  PubMed  Google Scholar 

  • Tan, J., Huang, C., Luo, Q., & Chen, Z. (2019). Soy Isoflavones Ameliorate Fatty Acid Metabolism of Visceral Adipose Tissue by Increasing the AMPK Activity in Male Rats with Diet-Induced Obesity (DIO). Molecules, 24(15), 2809. https://doi.org/10.3390/molecules24152809

    Article  PubMed Central  PubMed  Google Scholar 

  • Torres Santiago, G., Serrano Contreras, J. I., Meléndez Camargo, M. E., & Zepeda Vallejo, L. G. (2019). NMR-based metabonomic approach reveals changes in the urinary and fecal metabolome caused by resveratrol. Journal of Pharmaceutical and Biomedical Analysis, 162, 234–241. https://doi.org/10.1016/j.jpba.2018.09.025

    Article  CAS  PubMed  Google Scholar 

  • Wang, S., Li, H., Song, M., Tao, Z., Wu, T., He, Z., Zhao, X., Wu, K., & Liu, X. S. (2021). Copy number signature analysis tool and its application in prostate cancer reveals distinct mutational processes and clinical outcomes. PLOS Genetics, 17(5), e1009557. https://doi.org/10.1371/journal.pgen.1009557

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Warner, M., Huang, B., & Gustafsson, J. A. (2017). Estrogen Receptor β as a Pharmaceutical Target. Trends in Pharmacological Sciences (38 vol., pp. 92–99). Elsevier Ltd. 1https://doi.org/10.1016/j.tips.2016.10.006

  • Wickham, H. (2016). ggplot2: Elegant Graphics for Data Analysis. In ggplot2: Elegant Graphics for Data Analysis (978th-3rd-319th-24277th–4th ed.)

  • Wickham, H., Averick, M., Bryan, J., Chang, W., McGowan, L., François, R., Grolemund, G., Hayes, A., Henry, L., Hester, J., Kuhn, M., Pedersen, T., Miller, E., Bache, S., Müller, K., Ooms, J., Robinson, D., Seidel, D., Spinu, V., & Yutani, H. (2019). Welcome to the Tidyverse. Journal of Open Source Software, 4(43), 1686. https://doi.org/10.21105/joss.01686

    Article  Google Scholar 

  • Wickham, H., Francois, R., Henry, L., & Muller, K. (2022). dplyr: A Grammar of Data Manipulation. R package version 1.0.9

  • Wishart, D. S., Guo, A., Oler, E., Wang, F., Anjum, A., Peters, H., Dizon, R., Sayeeda, Z., Tian, S., Lee, B. L., Berjanskii, M., Mah, R., Yamamoto, M., Jovel, J., Torres-Calzada, C., Hiebert-Giesbrecht, M., Lui, V. W., Varshavi, D., Varshavi, D., & Gautam, V. (2022). HMDB 5.0: the Human Metabolome Database for 2022. Nucleic Acids Research, 50. https://doi.org/10.1093/nar/gkab1062

  • Xiao, C. W. (2008). Effect of soy proteins and isoflavones on lipid metabolism and involved gene expression. Frontiers in Bioscience, 13(13), 2660. https://doi.org/10.2741/2873

    Article  CAS  PubMed  Google Scholar 

  • Yu, H., Bai, S., Hao, Y., & Guan, Y. (2022). Fatty acids role in multiple sclerosis as “metabokines. Journal of Neuroinflammation, 19(1), 157. https://doi.org/10.1186/s12974-022-02502-1

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zahoor, I., Rui, B., Khan, J., Datta, I., & Giri, S. (2021). An emerging potential of metabolomics in multiple sclerosis: a comprehensive overview. Cellular and Molecular Life Sciences (78 vol., pp. 3181–3203). Springer Science and Business. https://doi.org/10.1007/s00018-020-03733-2. Media Deutschland GmbH

  • Zahoor, I., Suhail, H., Datta, I., Ahmed, M. E., Poisson, L. M., Waters, J., Rashid, F., Bin, R., Singh, J., Cerghet, M., Kumar, A., Hoda, M. N., Rattan, R., Mangalam, A. K., & Giri, S. (2022). Blood-based untargeted metabolomics in relapsing-remitting multiple sclerosis revealed the testable therapeutic target. Proceedings of the National Academy of Sciences of the United States of America, 119(25), e2123265119. https://doi.org/10.1073/pnas.2123265119

    Article  CAS  PubMed  Google Scholar 

  • Zhang, A., Sun, H., Yan, G., Wang, P., & Wang, X. (2015). Review Article Metabolomics for Biomarker Discovery: Moving to the Clinic. https://doi.org/10.1155/2015/354671

Download references

Acknowledgements

We acknowledge funding from the National Institutes of Health/NIAID 1RO1AI137075 (A.K.M), Veteran Affairs Merit Award 1I01CX002212 (A.K.M), University of Iowa Environmental Health Sciences Research Center, NIEHS/NIH P30 ES005605 (A.K.M), Gift from P. Heppelmann and M. Wacek to A.K.M and Carver Trust Pilot Grant (A.K.M). R.L.S. was supported by the Informatics Fellowship from the University of Iowa. S.N.J was supported by an institutional training grant (T32AI007485 to G. Bishop) and a diversity supplement award to A.K.M on parent 1RO1AI137075. We also thank Leeann Aguilar Meza and Stephanie Peterson (University of Iowa) for their editorial assistance on this manuscript.

Author information

Authors and Affiliations

  1. Department of Informatics, University of Iowa, Iowa City, IA, 52242, USA

    Rachel L. Shrode & Ashutosh K. Mangalam

  2. Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA

    Nicole Cady & Ashutosh K. Mangalam

  3. Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, 48109, USA

    Nicole Cady

  4. Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA, 52242, USA

    Samantha N. Jensen & Ashutosh K. Mangalam

  5. Division of Gastroenterology, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA

    Samantha N. Jensen

  6. Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA

    Samantha N. Jensen

  7. Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO, 63110, USA

    Nicholas Borcherding

  8. Iowa Institute for Oral Health Research, College of Dentistry, University of Iowa, Iowa City, IA, 52242, USA

    Ashutosh K. Mangalam

Authors
  1. Rachel L. Shrode
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicole Cady
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Samantha N. Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nicholas Borcherding
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ashutosh K. Mangalam
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualizations, Nicole Cady, Samantha N. Jensen, and Ashutosh K. Mangalam; methodology, Rachel L. Shrode., Nicole Cady, Samantha N. Jensen, Nick Borcherding, and Ashutosh K. Mangalam; validation, Rachel L. Shrode, Nick Borcherding, and Ashutosh K. Mangalam; formal analysis, investigation, resources, and data curation, Rachel L. Shrode; writing – original draft preparations Rachel L. Shrode; writing – review and editing, Rachel L. Shrode, Nicole Cady, Samantha N. Jensen, Nick Borcherding, and Ashutosh K. Mangalam; supervision Nick Borcherding, and Ashutosh K. Mangalam, funding acquisitions Ashutosh K. Mangalam. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Ashutosh K. Mangalam.

Ethics declarations

Conflict of interest

A.K.M. is one of the inventors of a technology claiming the use of Prevotella histicola to treat autoimmune diseases. A.K.M. received royalties from Mayo Clinic (paid by Evelo Biosciences). However, no funds or products from the patent were used in the present study. All other authors declare no commercial or financial relationships that could be a potential conflict of interest.

Institutional Review Board Statement

All procedures were done according to the Institutional Animal Care and Use Committee (IACUC) guidelines at the University of Iowa.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Supplementary Material 2

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shrode, R.L., Cady, N., Jensen, S.N. et al. Isoflavone consumption reduces inflammation through modulation of phenylalanine and lipid metabolism. Metabolomics 18, 84 (2022). https://doi.org/10.1007/s11306-022-01944-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11306-022-01944-1

Keywords

Search

Navigation