Background
Dietary lignans belong to the group of phytoestrogens together with coumestans, stilbenes and isoflavones, and themselves do not exhibit oestrogen-like properties. Nonetheless, the gut microbiota converts them into enterolignans, which show chemical similarity to the human oestrogen molecule. One of the richest dietary sources of lignans are oilseeds, including flaxseed. The aim of this study was to determine the concentration of the main dietary lignans in an oilseed mix, and evaluate the gut microbiota-dependent production of enterolignans for oestrogen substitution in young and premenopausal women. The oilseed mix was fermented in a pH-controlled batch culture system inoculated with women’s faecal samples. The lignan content and enterolignan production were measured by ultra‐high-performance liquid chromatography – tandem mass spectrometry (UHPLC-MS/MS), and the gut-derived microbial communities were profiled by 16S rRNA gene-based next-generation sequencing.
Results
In vitro batch culture fermentation of faecal samples inoculated with oilseed mix for 24 h resulted in a substantial increase in enterolactone production in younger women and an increase in enterodiol in the premenopausal group. As for the gut microbiota, different baseline profiles were observed as well as different temporal dynamics, mainly related to Clostridiaceae, and Klebsiella and Collinsella spp.
Conclusions
Despite the small sample size, our results revealed that lignan-rich oilseeds have a strong influence on the faecal microbiota of both younger and premenopausal females, leading to a different enterolignan profile being produced. More studies are needed to evaluate the long-term effects of lignan-rich diets on the gut microbiota and find out how enterolactone-producing bacterial species could be increased. Diets rich in lignans could potentially serve as a safe supplement of oestrogen analogues to satisfy cellular needs for endogenous oestrogen and deliver numerous health benefits, provided that the premenopausal woman microbiota is capable of converting dietary precursors to enterolignans.

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Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
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On 25 Mar, 2020
On 25 Mar, 2020
On 24 Mar, 2020
On 24 Mar, 2020
Posted 13 Dec, 2019
On 25 Feb, 2020
Received 24 Feb, 2020
Received 11 Feb, 2020
On 05 Feb, 2020
Received 30 Jan, 2020
On 21 Jan, 2020
On 20 Jan, 2020
Invitations sent on 17 Jan, 2020
On 11 Dec, 2019
On 10 Dec, 2019
On 10 Dec, 2019
On 10 Dec, 2019
On 25 Mar, 2020
On 25 Mar, 2020
On 24 Mar, 2020
On 24 Mar, 2020
Posted 13 Dec, 2019
On 25 Feb, 2020
Received 24 Feb, 2020
Received 11 Feb, 2020
On 05 Feb, 2020
Received 30 Jan, 2020
On 21 Jan, 2020
On 20 Jan, 2020
Invitations sent on 17 Jan, 2020
On 11 Dec, 2019
On 10 Dec, 2019
On 10 Dec, 2019
On 10 Dec, 2019
Background
Dietary lignans belong to the group of phytoestrogens together with coumestans, stilbenes and isoflavones, and themselves do not exhibit oestrogen-like properties. Nonetheless, the gut microbiota converts them into enterolignans, which show chemical similarity to the human oestrogen molecule. One of the richest dietary sources of lignans are oilseeds, including flaxseed. The aim of this study was to determine the concentration of the main dietary lignans in an oilseed mix, and evaluate the gut microbiota-dependent production of enterolignans for oestrogen substitution in young and premenopausal women. The oilseed mix was fermented in a pH-controlled batch culture system inoculated with women’s faecal samples. The lignan content and enterolignan production were measured by ultra‐high-performance liquid chromatography – tandem mass spectrometry (UHPLC-MS/MS), and the gut-derived microbial communities were profiled by 16S rRNA gene-based next-generation sequencing.
Results
In vitro batch culture fermentation of faecal samples inoculated with oilseed mix for 24 h resulted in a substantial increase in enterolactone production in younger women and an increase in enterodiol in the premenopausal group. As for the gut microbiota, different baseline profiles were observed as well as different temporal dynamics, mainly related to Clostridiaceae, and Klebsiella and Collinsella spp.
Conclusions
Despite the small sample size, our results revealed that lignan-rich oilseeds have a strong influence on the faecal microbiota of both younger and premenopausal females, leading to a different enterolignan profile being produced. More studies are needed to evaluate the long-term effects of lignan-rich diets on the gut microbiota and find out how enterolactone-producing bacterial species could be increased. Diets rich in lignans could potentially serve as a safe supplement of oestrogen analogues to satisfy cellular needs for endogenous oestrogen and deliver numerous health benefits, provided that the premenopausal woman microbiota is capable of converting dietary precursors to enterolignans.

Figure 1

Figure 2

Figure 3

Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
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