Emilia Coffey

Introduction. Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder affecting the large intestines.¹ It is diagnosed in women more often than men, at a 4:1 ratio. It is estimated to affect between 8-12% of the population.² IBS is characterized by abdominal pain with altered bowel habits with no clear organic cause.¹ There are three subtypes of IBS, which are based on the predominant symptoms exhibited by the patient: IBS-D (diarrhea), IBS-C (constipation), and IBS-M (mixed).² Risk factors for IBS include female sex, family history of IBS, sexual abuse, anxiety, depression, and high stress levels.² Current treatments for IBS are vast and range from antispasmodics to opioids to antidepressants, but there is no cure.³ Researchers have been able to determine a link to estrogen, which could offer a possible method of treatment, especially for women suffering flare-ups of IBS during low-estrogen periods (late luteal phase of the menstrual cycle and post-menopause). Soy isoflavones are phytoestrogens that preferentially bind to estrogen receptor beta, the predominant estrogen receptor in the colon, responsible for modulating intestinal function and permeability.⁴ Thus, dietary soy isoflavones could potentially bind to the estrogen receptor beta, turn off transcription of tumor necrosis factor alpha (TNF-alpha), and prevent nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) from down-regulating expression of tight junctions in the epithelial tissue of the intestines. Methods. Colon tissue samples taken from healthy patients and from patients with IBS demonstrated a significant elevation in levels of estrogen receptor protein levels and inflammatory cytokines in IBS patients.¹ Blood serum analysis and completion of the Fatigue Impact Scale questionnaire in IBS patients showed that TNF-α levels were positively correlated with fatigue.⁵ Ovariectomies performed on BALB/C mice demonstrated short-term increases in intestinal permeability, which resolved after a 4-week period.⁶ A randomized clinical trial in which women with IBS aged 18-75 were allocated soy isoflavones, cholecalficerol, both, or neither (placebo) for six weeks showed a significant reduction in TNF-alpha levels, along with a corresponding decrease in NF-kB in patients that consumed soy isoflavones or soy isoflavones with cholecalciferol.⁷ Conclusion. Estrogen receptor beta is a promising target for reduction or relief of IBS symptoms. IBS predominantly effects women, who have fluctuating levels of estrogen. Soy isoflavones are phytoestrogens that have been shown to markedly reduce levels of pro-inflammatory cytokines, thus preserving gut permeability.

1. Jacenik D, Cygankiewicz AI, Fichna J, Mokrowiecka A, Małecka-Panas E, Krajewska WM. Estrogen signaling deregulation related with local immune response modulation in irritable bowel syndrome. Mol Cell Endocrinol. 2018;471:89-96. doi:10.1016/j.mce.2017.07.036
2. Pati GK, Kar C, Narayan J, et al. Irritable Bowel Syndrome and the Menstrual Cycle. Cureus. 2021;13(1):e12692. Published 2021 Jan 14. doi:10.7759/cureus.12692
3. So SY, Savidge TC. Sex-Bias in Irritable Bowel Syndrome: Linking Steroids to the Gut-Brain Axis. Front Endocrinol (Lausanne). 2021;12:684096. Published 2021 May 19. doi:10.3389/fendo.2021.684096
4. Takeuchi S, Takahashi T, Sawada Y, Iida M, Matsuda T, Kojima H. Comparative study on the nuclear hormone receptor activity of various phytochemicals and their metabolites by reporter gene assays using Chinese hamster ovary cells. Biol Pharm Bull. 2009;32(2):195-202. doi:10.1248/bpb.32.195
5. Norlin AK, Walter S, Icenhour A, et al. Fatigue in irritable bowel syndrome is associated with plasma levels of TNF-α and mesocorticolimbic connectivity. Brain Behav Immun. 2021;92:211-222. doi:10.1016/j.bbi.2020.11.035
6. Collins FL, Rios-Arce ND, Atkinson S, et al. Temporal and regional intestinal changes in permeability, tight junction, and cytokine gene expression following ovariectomy-induced estrogen deficiency. Physiol Rep. 2017;5(9):e13263. doi:10.14814/phy2.13263
7. Jalili M, Vahedi H, Poustchi H, Hekmatdoost A. Soy isoflavones and cholecalciferol reduce inflammation, and gut permeability, without any effect on antioxidant capacity in irritable bowel syndrome: A randomized clinical trial. Clin Nutr ESPEN. 2019;34:50-54. doi:10.1016/j.clnesp.2019.09.003