Isoflavones Effects on Vascular and Endothelial Outcomes: How Is the Gut Microbiota Involved?

Samuele Laudani¹, Justyna Godos¹, Giovanni Luca Romano², Lucia Gozzo³, Federica Martina Di Domenico¹, Irma Dominguez Azpíroz^{4

5

6}, Raquel Martínez Diaz^{4

7

8}, Francesca Giampieri^{4

9}, José L Quiles^{4

10

11}, Maurizio Battino^{4

9

12}, Filippo Drago¹, Fabio Galvano¹, Giuseppe Grosso^{1

13}

Affiliations

¹ Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.
² Department of Medicine and Surgery, University of Enna "Kore", 94100 Enna, Italy.
³ Clinical Pharmacology Unit/Regional Pharmacovigilance Centre, Azienda Ospedaliero Universitaria Policlinico "G. Rodolico-S. Marco", 95123 Catania, Italy.
⁴ Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Isabel Torres 21, 39011 Santander, Spain.
⁵ Universidade Internacional do Cuanza, Cuito EN250, Angola.
⁶ Universidad de La Romana, La Romana 22000, Dominican Republic.
⁷ Universidad Internacional Iberoamericana, Campeche 24560, Mexico.
⁸ Universidad Internacional Iberoamericana, Arecibo 00613, Puerto Rico.
⁹ Department of Clinical Sciences, Università Politecnica delle Marche, 60131 Ancona, Italy.
¹⁰ Department of Physiology, Institute of Nutrition and Food Technology "José Mataix", Biomedical Research Center, University of Granada, 18016 Granada, Spain.
¹¹ Research and Development Functional Food Centre (CIDAF), Health Science Technological Park, Avenida del Conocimiento 37, 18016 Granada, Spain.
¹² International Joint Research Laboratory of Intelligent Agriculture and Agri-Products Processing, Jiangsu University, Zhenjiang 212013, China.
¹³ Center for Human Nutrition and Mediterranean Foods (NUTREA), University of Catania, 95123 Catania, Italy.

PMID: 38399451
PMCID: PMC10891971
DOI: 10.3390/ph17020236

Review

Isoflavones Effects on Vascular and Endothelial Outcomes: How Is the Gut Microbiota Involved?

Samuele Laudani et al. Pharmaceuticals (Basel). 2024.

. 2024 Feb 11;17(2):236.

doi: 10.3390/ph17020236.

Authors

Affiliations

¹ Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.
² Department of Medicine and Surgery, University of Enna "Kore", 94100 Enna, Italy.
³ Clinical Pharmacology Unit/Regional Pharmacovigilance Centre, Azienda Ospedaliero Universitaria Policlinico "G. Rodolico-S. Marco", 95123 Catania, Italy.
⁴ Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Isabel Torres 21, 39011 Santander, Spain.
⁵ Universidade Internacional do Cuanza, Cuito EN250, Angola.
⁶ Universidad de La Romana, La Romana 22000, Dominican Republic.
⁷ Universidad Internacional Iberoamericana, Campeche 24560, Mexico.
⁸ Universidad Internacional Iberoamericana, Arecibo 00613, Puerto Rico.
⁹ Department of Clinical Sciences, Università Politecnica delle Marche, 60131 Ancona, Italy.
¹⁰ Department of Physiology, Institute of Nutrition and Food Technology "José Mataix", Biomedical Research Center, University of Granada, 18016 Granada, Spain.
¹¹ Research and Development Functional Food Centre (CIDAF), Health Science Technological Park, Avenida del Conocimiento 37, 18016 Granada, Spain.
¹² International Joint Research Laboratory of Intelligent Agriculture and Agri-Products Processing, Jiangsu University, Zhenjiang 212013, China.
¹³ Center for Human Nutrition and Mediterranean Foods (NUTREA), University of Catania, 95123 Catania, Italy.

PMID: 38399451
PMCID: PMC10891971
DOI: 10.3390/ph17020236

Abstract

Isoflavones are a group of (poly)phenols, also defined as phytoestrogens, with chemical structures comparable with estrogen, that exert weak estrogenic effects. These phytochemical compounds have been targeted for their proven antioxidant and protective effects. Recognizing the increasing prevalence of cardiovascular diseases (CVD), there is a growing interest in understanding the potential cardiovascular benefits associated with these phytochemical compounds. Gut microbiota may play a key role in mediating the effects of isoflavones on vascular and endothelial functions, as it is directly implicated in isoflavones metabolism. The findings from randomized clinical trials indicate that isoflavone supplementation may exert putative effects on vascular biomarkers among healthy individuals, but not among patients affected by cardiometabolic disorders. These results might be explained by the enzymatic transformation to which isoflavones are subjected by the gut microbiota, suggesting that a diverse composition of the microbiota may determine the diverse bioavailability of these compounds. Specifically, the conversion of isoflavones in equol-a microbiota-derived metabolite-seems to differ between individuals. Further studies are needed to clarify the intricate molecular mechanisms behind these contrasting results.

Keywords: equol; gut microbiota; isoflavones; phytoestrogens; polyphenols; vascular.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

**Figure 1**
Gut-microbiota derived metabolites involved in cardiovascular disease. High protein intake leads to an increased production of TMA and p-cresol that negatively impacts gut permeability leading to systemic low-grade inflammation. IL-1beta (Interleukin-1 beta), ICAM (Intercellular Adhesion Molecule 1), NF-kB (Nuclear factor kappa B), TMA (Trimethylamine), TMAO (Trimethylamine N-Oxide), TNF-alpha (Tumor necrosis factor alpha), VCAM (Vascular cell adhesion protein). ↑ denotes increase.

**Figure 2**
Main equol mechanisms of action in equol-producers. Equol can increase eNOS activity resulting in higher levels of NO. This can react with superoxide producing peroxynitrite and increasing Nrf2 levels leading to upregulation of antioxidant genes. ARE (antioxidant response elements), CAT (Catalase), eNOS (Endothelial nitric oxide synthase), EC (Endothelial cell), ERK (Extracellular signal-regulated kinases), GPx (Glutathione peroxidase), HO-1 (Heme oxygenase 1), NO (Nitric oxide), PI3K (Phosphatidylinositol 3-kinase), NADPH (Nicotinamide adenine dinucleotide phosphate), SOD (Superoxide dismutase). ↑ denotes increase, ↓ denotes decrease.

See this image and copyright information in PMC

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J.G. was supported by the co-financing of the European Union—FSE-REACT-EU, PON Research and Innovation 2014–2020 DM1062/2021; CUP: E65F21002560001.

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Isoflavones Effects on Vascular and Endothelial Outcomes: How Is the Gut Microbiota Involved?

Affiliations

Isoflavones Effects on Vascular and Endothelial Outcomes: How Is the Gut Microbiota Involved?

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

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References

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