Inter-individual variability in gut microbial metabolism and vascular response to lignans and isoflavones: the StratiPol study

Wafa Alotaibi, Paul Young Tie Yang, Wendy L. Hall, Ana Rodriguez-Mateos

Dept. of Nutritional Sciences
School of Life Courses Sciences
Faculty of Life Sciences & Medicine
King’s College London

Objectives: Evidence shows inter-individual variability in gut microbial metabolism of phytoestrogens, lignans and isoflavones, but little is known on whether this is associated with health benefits. The aim of this project is to investigate the variability in gut microbial metabolism and vascular response to lignans & isoflavones in a group of healthy individuals.

Methods: An open-label, single-arm study investigating the influence of gut microbial metabolism variability on vascular response to a (poly)phenol rich breakfast is currently ongoing in a group of healthy men and women aged 38±13 years old and with BMI 24±3 kg/m². Participants consumed a (poly)phenol rich breakfast containing 300 mg of flaxseed lignans and 22 mg of soy milk isoflavones for 3 days. Urine samples were collected for 24 hours after consumption on day 4. Flow mediated dilation, pulse wave velocity, augmentation index, blood pressure, heart rate and serum biochemistry were assessed at baseline after an overnight fast on day 1 and 24 h after the last breakfast was consumed on day 4. Urine samples were analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS) and authentic standards.

Results: Preliminary results from the first 69 volunteers (48 females vs 21 males) are presented. The main metabolites of the isoflavone daidzin (S-equol, daidzein, R,S equol 4'-sulfate, and R,S equol 7-β-D-glucuronide), and the lignan, secoisolariciresinol diglucoside ((±)-enterolactone, enterodiol, (±)-Enterolactone monosulfate and (±)-Enterolactone mono-β-D-glucuronide) gut microbial metabolites were identified and quantified in 24 h urine. In this population, 74% of the participants were non-equol producers (31% male vs 69% female) and 26% were equol producers (28% male vs 72% female). A significant decrease in systolic and diastolic blood pressure was found after 3 days isoflavone consumption only in male equol producers (120±10 to 113±8 mmHg, p=0.0046 and 77±11 to 71±12 mmHg, p=0.0024 respectively). All volunteers produced enterolactone metabolites, with a high variability in urinary levels of total and individual enterolactone metabolites. No significant differences in any vascular outcome were found between low (lower quartile ≤10 µmol, 29% men and 71% female) and high (higher quartile ≥ 44 µmol, 35% men and 65% female) enterolactone producers.

Conclusion: Sex and gut microbiota may be important factors explaining variability in the vascular response to isoflavones. More research is needed to confirm these findings, including randomised controlled trials with previous stratification by sex and polyphenol gut microbial metabotype.

Inter-individual variability in gut microbial metabolism and vascular response to lignans and isoflavones: the StratiPol study

The gastrointestinal tract is amongst the most densely populated ecosystems on earth, home to an abundant and diverse collection of microbial species, not just bacteria but also Archaea, viruses, fungi etc. Significant interest in this area has been sparked in recent years by an appreciation of the importance of the gut microbiota in the health of the host, and this has led to the microbiome of humans and animals being investigated in depth. Studies have drawn links between host nutrition, the gut microbiota and metabolic and immune functions, which in consequence affect physiology.



The first investigations of the structure of the microbiota were culture-based, however the introduction of sequencing technologies such as Sanger sequencing and subsequent development of 454 sequencing and metagenomics approaches have become the mainstay of microbiota studies. The creation of reference databases and analysis software has provided invaluable tools for assigning taxonomy to generated data. Great progress in characterising the structure of the microbiome recently has paved the way for ongoing and future studies on the functional interactions between the microbiota and the host. Studies on the function of the microbiota are critical in understanding the role of the microbiota in human homeostasis and disease pathogenesis.



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