Metabolism Of Lignans Research Articles

Association between lignan polyphenol bioavailability and enterotypes of isoflavone metabolism: A cross-sectional analysis.

Lignan polyphenols derived from plants are metabolized by bacteria in the gut to mammalian lignans, such as enterolactone (ENL) and enterodiol (END). Mammalian lignan intake has been reported to be associated with obesity and low blood glucose levels. However, the factors that are responsible for individual differences in the metabolic capacity for ENL and END are not well understood. In the present study, the effects of enterotypes of isoflavone metabolism, equol producers (EQP) and O-desmethylangolensin producers (O-DMAP), on lignan metabolism were examined. EQP was defined by urinary daidzein (DAI) and equol concentrations as log(equol/DAI) ≥ -1.42. O-DMAP was defined by urinary DAI and O-DMA concentrations as O-DMA/DAI > 0.018. Isoflavone and lignan concentrations in urine samples from 440 Japanese women were measured by gas chromatography-mass spectrometry. Metabolic enterotypes were determined from the urinary equol and O-DMA concentrations. Urinary END and ENL concentrations were compared in four groups, combinations of EQP (+/-) and O-DMAP (+/-). The urinary lignan concentration was significantly higher in the O-DMAP/EQP group (ENL: P<0.001, END: P<0.001), and this association remained significant after adjusting for several background variables (END: β = 0.138, P = 0.00607 for EQP and β = 0.147, P = 0.00328 for O-DMAP; ENL: β = 0.312, P<0.001 for EQP and β = 0.210, P<0.001 for O-DMAP). The ENL/END ratio was also highest in the O-DMAP/EQP group, indicating that equol and O-DMA metabolizing gut bacteria may be involved in lignan metabolism. In conclusion, urinary lignan concentrations were significantly higher in groups containing either EQP or O-DMAP than in the non-EQP/non-O-DMAP group. The variables and participants in this study were limited, which the possibility of confounding by other variables cannot be ruled out. However, there are no established determinants of lignan metabolism to date. Further research is needed to determine what factors should be considered, and to examine in different settings to confirm the external validity.

Comparative Study on the Absorption and Metabolism of Pinoresinol and Pinoresinol-4-O-β-D-Glucopyranoside in Mice.

Lignans are a group of phenolic compounds commonly found in plants, often in the form of glycosides. This study investigates the differences in the digestion, absorption, and metabolism of lignans and their glucosides using pinoresinol (PIN) and pinoresinol-4-O-β-D-glucopyranoside (PMG). After oral administration mice PIN and PMG with a dose of 0.1 µmolkg-1 . The results showed that the stomach and small intestine rapidly absorbe PIN and PMG in their prototype form. After oral administration of 0.25 h, serum levels of PIN and PMG reach peak values of 61.14 and 52.97 ngmL-1 , respectively. This indicates a faster PIN absorption rate than PMG, likely due to the glycosides attach to the parent compound, with concentrations of 1574.14 and 876.75 ngg-1 , respectively. Pharmacokinetic analysis reveals that PIN has a greater area under the curve and a longer half-life than PMG in serum and liver. Moreover, mice in the PIN group exhibit higher metabolite levels in the serum and liver compared to those in the PMG group. The deglycosylation process that occurs during the pickling of white radish facilitates the absorption and metabolism of the lignans fraction in the body.

Tissue-specific transcriptome and metabolome analyses reveal candidate genes for lignan biosynthesis in the medicinal plant Schisandra sphenanthera

Schisandra sphenanthera is an extremely important medicinal plant, and its main medicinal component is bioactive lignans. The S. sphenanthera fruit is preferred by the majority of consumers, and the root, stem, and leaf are not fully used. To better understand the lignan metabolic pathway, transcriptome and metabolome analyses were performed on the four major tissues of S. sphenanthera. A total of 167,972,229 transcripts and 91,215,760 unigenes with an average length of 752 bp were identified. Tissue-specific gene analysis revealed that the root had the highest abundance of unique unigenes (9703), and the leaves had the lowest (189). Transcription factor analysis showed that MYB-, bHLH- and ERF-transcription factors, which played important roles in the regulation of secondary metabolism, showed rich expression patterns and may be involved in the regulation of processes involved in lignan metabolism. In different tissues, lignans were preferentially enriched in fruit and roots by gene expression profiles related to lignan metabolism and relative lignan compound content. Furthermore, schisandrin B is an important compound in S. sphenanthera. According to weighted gene co-expression network analysis, PAL1, C4H-2, CAD1, CYB8, OMT27, OMT57, MYB18, bHLH3, and bHLH5 can be related to the accumulation of lignans in S. sphenanthera fruit, CCR5, SDH4, CYP8, CYP20, and ERF7 can be related to the accumulation of lignans in S. sphenanthera roots. In this study, transcriptome sequencing and targeted metabolic analysis of lignans will lay a foundation for the further study of their biosynthetic genes.

IiUGT71B2 catalyzes lignan glycosylation in Isatis indigotica with substrates specificity

Lignans are a major class of secondary metabolites distributed widely in the plant kingdom that are derived from coupling of phenylpropanoid (C6-C3) units. Most lignans are 8–8'-linked, and are often found in their glycosylated forms, which are catalyzed by UDP-dependent glycosyltransferase (UGT). Up to now, all UGTs involved in lignans biosynthesis are determined with substrate promiscuity. Here, IiUGT71B2 is reported from Isatis indigotica that specific catalyzes 4-O and 4′-O glycosylation of furan (lariciresinol) and dibenzylbutyrolactone (matairesinol) type lignans. Transcriptional profile of IiUGT71B2 indicates its involvement in lignan glycosides biosynthesis, which is co-expressed with other lignan biosynthetic genes, and is consistent with metabolic distribution of lignans in organs and tissues as well. Both in vitro and in vivo experiments demonstrate IiUGT71B2 catalyzes the mono- and di- glycosylation of lariciresinol and mono-glycosylation of matairesinol. The ligand docking and site-directed mutagenesis suggest Asn261, Ser289, Ala356, and Tyr395 as key residues, which may determine its catalytic efficiency together with the narrow binding pocket of IiUGT71B2. This study provides insights into lignan metabolism and functional diversity of plant UGTs.

Identification of Human Gut Microbiome Associated with Enterolignan Production.

Dietary plant lignans are converted inside the gut to enterolignans enterodiol (ED) and enterolactone (EL), which have several biological functions, and health benefits. In this study, we characterized the gut microbiome composition associated with enterolignan production using data from a cross-sectional study in the Japanese population. We identified enterolignan producers by measuring ED and EL levels in subject's serum using liquid chromatography-tandem mass spectrometry. Enterolignan producers show more abundant proportion of Ruminococcaceae and Lachnospiraceae than non-enterolignan producers. In particular, subjects with EL in their serum had a highly diverse gut microbiome that was rich in Ruminococcaceae and Rikenellaceae. Moreover, we built a random forest classification model to classify subjects to either EL producers or not using three characteristic bacteria. In conclusion, our analysis revealed the composition of gut microbiome that is associated with lignan metabolism. We also confirmed that it can be used to classify the microbiome ability to metabolize lignan using machine learning approach.

Interaction between silver fir (Abies alba) wood water extract and lactobacilli.

Water extract from silver fir (Abies alba) wood represents a rich source of lignans and other phenols that are effective in different pathological conditions, such as diabetes, cardiovascular diseases and psoriasis. Its interaction with the gastrointestinal environment is crucial when the extract is orally administered. In this study we tested the in-vitro interaction between water extract of silver fir wood and ten different Lactobacillus species that are found in the gastrointestinal tract, vagina or are used in food industry. We tested both ways of interaction: 1) the bacterial influence on the chemical composition of the extract and 2) influence of the extract on the bacterial growth. We demonstrated that the extract is compatible with all of the bacteria and does not impair their growth. Furthermore the extract acted as a prebiotic for some bacteria including: L. paracasei, L. acidophilus, L. rhamnosus, L. gasseri, L. crispatus and L. bulgaricus, suggesting that the compounds in the extract can stimulate their growth. However, the ten lactobacilli did not show any chemical changes in lignan metabolism and the production of enterodiol and enterolactone, which are considered the final metabolic products of lignans and are produced by different gut bacteria. This study indicates that the silver fir wood extract is nutritious for some Lactobacillus bacteria and can be used as a prebiotic.

Flavone, flavanone and flavonol metabolism from soybean and flaxseed extracts by the intestinal microbiota of adults and infants.

Flaxseed and soybean are an important source of lignans and flavonoids. Previously, the metabolism of isoflavones and lignans from soybean and flaxseed extracts by the microbiota of adult individuals (n=14) and infants (n=23) was analyzed. Thus, the present study aimed to examine the metabolism of flavones, flavanones and flavonols, as well as the production of phenolic acids, by the intestinal microbiota of these individuals. Concentrations of aglycones of flavonoids, such as herbacetin, quercetin, quercetagetin, myricetin, kaempferol, apigenin and luteolin, increased for most of individuals as a consequence of deglycosylation reactions. On the other hand, a diminution in the antioxidant activity and phenolic compound concentration and an increase in the concentration of 3,4-dihydroxyphenylacetic acid, 2-(4-hydroxyphenyl)-propionic acid, protocatechuic acid and catechol was also observed. The present study found that deglycosylation reactions were the main reactions and accelerated the formation of more bioavailable flavonoids, with greater biological activity, in most of the individuals. However, other reactions also occurred, including the total or partial catabolism of flavonoids. © 2021 Society of Chemical Industry.

Metabolism of flavonoids and lignans by lactobacilli and bifidobacteria strains improves the nutritional properties of flaxseed-enriched beverages

Flaxseed (Linum usitatissimum L.) is of interest as functional food because of the presence of compounds in its composition with potential health benefits, such as fatty acid omega-3, fiber, lignans and flavonoids. The bioactivity of lignans and flavonoids depends greatly on bacterial metabolism. Previously, lactobacilli and bifidobacteria strains were described to produce enterolignans and bioactive flavonoids (herbacetin, quercetin, quercetagetin, kaempferol, naringenin and eriodictyol) from flaxseed extracts and/or from secoisolariciresinol (SECO) in culture medium. In this work, cow's milk and soy beverage were supplemented with flaxseed extracts and fermented with selected lactobacilli and bifidobacteria strains. Lacticaseibacillus rhamnosus INIA P224, Limosilactobacillus mucosae INIA P508 and Lactiplantibacillus plantarum ESI 144 were capable of producing enterolactone (ENL) in both beverages supplemented with flaxseed, in addition to matairesinol and the flavonoids daidzein, genistein, glycitein, quercetin, naringenin, kaempferol and eriodictyol. On the other hand, Bifidobacterium breve INIA P367, Bifidobacterium pseudocatenulatum INIA P815 and Bifidobacterium pseudocatenulatum INIA P946 were able to produce quercetin, quercetagetin and high concentrations of herbacetin and SECO, in addition to pinoresinol, matairesinol, daidzein, genistein, naringenin, kaempferol and eriodictyol. The co-incubation of Lacticaseibacillus paracasei INIA P74 and Ligilactobacillus salivarius INIA P183 with Lactococcus lactis MG1363 harboring the food grade vector pLEB590.gly913, facilitated the production of ENL in soy beverage enriched with flaxseed. In this work, it is demonstrated how lactobacilli and bifidobacteria strains can improve the nutritional properties of flaxseed-enriched beverages, providing metabolites of great interest for human health.

Enterolignan Production in a Flaxseed Intervention Study in Postmenopausal US Women of African Ancestry and European Ancestry.

Lignans are phytochemicals studied extensively as dietary factors in chronic disease etiology. Our goal was to examine associations between the gut microbiota and lignan metabolism and whether these associations differ by ethnicity. We conducted a flaxseed (FS) dietary intervention in 252 healthy, postmenopausal women of African ancestry (AA) and European ancestry (EA). Participants consumed ~10 g/d ground flaxseed for 6 weeks and provided overnight urine collections and fecal samples before and after intervention. The gut microbiota was characterized using 16S rRNA gene sequencing and differences in microbial community composition compared by ethnicity and intervention status. We observed a significant difference in the composition of the microbiota measured as beta diversity (p < 0.05) between AA and EA at baseline that was attenuated with FS consumption. Genera that were significantly associated with ENL production (e.g., Klebsiella, Lactobacillus, Slackia, Senegalimassilia) were unique to each group. Bacteria (e.g., Fusobacteria, Pyramidobacter and Odoribacter) previously associated with colorectal cancer and cardiovascular disease, both diet-related chronic diseases, were unique to either AA or EA and were significantly reduced in the FS intervention. This study suggests that ethnic variation in ENL metabolism may be linked to gut microbiota composition, and its impact on disease risk deserves future investigation.

Effect of a Flaxseed Lignan Intervention on Circulating Bile Acids in a Placebo-Controlled Randomized, Crossover Trial.

Plant lignans and their microbial metabolites, e.g., enterolactone (ENL), may affect bile acid (BA) metabolism through interaction with hepatic receptors. We evaluated the effects of a flaxseed lignan extract (50 mg/day secoisolariciresinol diglucoside) compared to a placebo for 60 days each on plasma BA concentrations in 46 healthy men and women (20–45 years) using samples from a completed randomized, crossover intervention. Twenty BA species were measured in fasting plasma using LC-MS. ENL was measured in 24-h urines by GC-MS. We tested for (a) effects of the intervention on BA concentrations overall and stratified by ENL excretion; and (b) cross-sectional associations between plasma BA and ENL. We also explored the overlap in bacterial metabolism at the genus level and conducted in vitro anaerobic incubations of stool with lignan substrate to identify genes that are enriched in response to lignan metabolism. There were no intervention effects, overall or stratified by ENL at FDR < 0.05. In the cross-sectional analysis, irrespective of treatment, five secondary BAs were associated with ENL excretion (FDR < 0.05). In vitro analyses showed positive associations between ENL production and bacterial gene expression of the bile acid-inducible gene cluster and hydroxysteroid dehydrogenases. These data suggest overlap in community bacterial metabolism of secondary BA and ENL.

Polyphenols in Alzheimer's Disease and in the Gut-Brain Axis.

Polyphenolic antioxidants, including dietary plant lignans, modulate the gut–brain axis, which involves transformation of these polyphenolic compounds into physiologically active and neuroprotector compounds (called human lignans) through gut bacterial metabolism. These gut bacterial metabolites exert their neuroprotective effects in various neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), and also have protective effects against other diseases, such as cardiovascular diseases, cancer, and diabetes. For example, enterolactone and enterodiol, the therapeutically relevant polyphenols, are formed as the secondary gut bacterial metabolites of lignans, the non-flavonoid polyphenolic compounds found in plant-based foods. These compounds are also acetylcholinesterase inhibitors, and thereby have potential applications as therapeutics in AD and other neurological diseases. Polyphenols are also advanced glycation end product (AGE) inhibitors (antiglycating agents), and thereby exert neuroprotective effects in cases of AD. Thus, gut bacterial metabolism of lignans and other dietary polyphenolic compounds results in the formation of neuroprotective polyphenols—some of which have enhanced blood–brain barrier permeability. It is hypothesized that gut bacterial metabolism-derived polyphenols, when combined with the nanoparticle-based blood–brain barrier (BBB)-targeted drug delivery, may prove to be effective therapeutics for various neurological disorders, including traumatic brain injury (TBI), AD, and PD. This mini-review addresses the role of polyphenolic compounds in the gut–brain axis, focusing on AD.

Full-length tran sequencing provides insight into lignan and lignin metabolism relation

Flax (Linum usitatissimum L.) is an important economic crop worldwide. The lignin content of flax stems directly determines the quality of flax fiber, and excessively high lignin content in the fiber leads to pollutant discharge by the textile industry. Flax seeds also contain lignans, a group of compounds that are structurally similar to lignin and highly beneficial for human health. The biosynthesis of lignan and lignin occurs in the same metabolic pathway. To elucidate the metabolic relationship between these two compounds and the regulatory nodes of their metabolic processes, third generation (Iso-Seq) and second generation (Illumina) sequencing technologies were used in this study to obtain the transcriptomes of a pair of flax cultivars with significant differences in lignan content. The results showed that the differentially expressed genes (DEGs) are significantly enriched in the lignin and lignan biosynthesis pathways. Ten genes with significant differences in expression (|Log2 FC|>4) were selected for quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The expression levels of these genes all were significantly different in Shuangya 4 and NEW at different stages of flax seed and stem development. We speculated that these genes were most likely closely related to the lignan and lignin metabolism. We also found that the lignan and lignin content are significantly negatively correlated with each other during flax seed and stem development. The findings of this study provide a scientific basis for the application of biotechnological methods to the development of new high-quality flax cultivars with high lignan and low lignin content.

Insights into Lignan Composition and Biosynthesis in Stinging Nettle (Urtica dioica L.).

Stinging nettle (Urtica dioica L.) has been used as herbal medicine to treat various ailments since ancient times. The biological activity of nettle is chiefly attributed to a large group of phenylpropanoid dimers, namely lignans. Despite the pharmacological importance of nettle lignans, there are no studies addressing lignan biosynthesis in this plant. We herein identified 14 genes encoding dirigent proteins (UdDIRs) and 3 pinoresinol-lariciresinol reductase genes (UdPLRs) in nettle, which are two gene families known to be associated with lignan biosynthesis. Expression profiling of these genes on different organs/tissues revealed a specific expression pattern. Particularly, UdDIR7, 12 and 13 displayed a remarkable high expression in the top internode, fibre tissues of bottom internodes and roots, respectively. The relatively high expression of UdPLR1 and UdPLR2 in the young internodes, core tissue of bottom internode and roots is consistent with the high accumulation of lariciresinol and secoisolariciresinol in these tissues. Lignan quantification showed a high abundance of pinoresinol in roots and pinoresinol diglucosides in young internodes and leaves. This study sheds light on lignan composition and biosynthesis in nettle, providing a good basis for further functional analysis of DIRs and PLRs and, ultimately, engineering lignan metabolism in planta and in cell cultures.

Colonic mucosal and exfoliome transcriptomic profiling and fecal microbiome response to a flaxseed lignan extract intervention in humans

Microbial metabolism of lignans from high-fiber plant foods produces bioactive enterolignans, such as enterolactone (ENL) and enterodiol (END). Enterolignan exposure influences cellular pathways important to cancer risk and is associated with reduced colon tumorigenesis in animal models and lower colorectal cancer risk in humans. The aim of this study was to test the effects of a flaxseed lignan supplement (50 mg secoisolariciresinol diglucoside/d) compared with placebo on host gene expression in colon biopsies and exfoliated colonocyte RNA in feces and fecal microbial community composition, and to compare responses in relation to ENL excretion. We conducted a 2-period randomized, crossover intervention in 42 healthy men and women (20-45 y). We used RNA-seq to measure differentially expressed (DE) genes in colonic mucosa and fecal exfoliated cells through the use of edgeR and functional analysis with Ingenuity Pathway Analysis. We used 16S ribosomal RNA gene (V1-V3) analysis to characterize the fecal microbiome, and measured END and ENL in 24-h urine samples by gas chromatography-mass spectrometry. We detected 32 DE genes (false discovery rate <0.05) in the exfoliome, but none in the mucosal biopsies, in response to 60 d of lignan supplement compared with placebo. Statistically significant associations were detected between ENL excretion and fecal microbiome measured at baseline and at the end of the intervention periods. Further, we detected DE genes in colonic mucosa and exfoliome between low- and high-ENL excreters. Analysis of biopsy samples indicated that several anti-inflammatory upstream regulators, including transforming growth factor β and interleukin 10 receptor, were suppressed in low-ENL excreters. Complementary analyses in exfoliated cells also suggested that low-ENL excreters may be predisposed to proinflammatory cellular events due to upregulation of nuclear transcription factor κB and NOS2, and an inhibition of the peroxisome proliferator-activated receptor γ network. These results suggest that ENL or other activities of the associated gut microbial consortia may modulate response to a dietary lignan intervention. This has important implications for dietary recommendations and chemoprevention strategies. This study was registered at clinicaltrials.gov as NCT01619020.

Serum enterolactone concentrations are low in colon but not in rectal cancer patients

The dietary lignan metabolite, enterolactone, has been suggested to have anti-cancer functions, and high serum enterolactone concentrations have been associated with decreased risk of breast and prostate cancers. We hypothesized that serum enterolactone concentrations as a marker of plant-based foods are associated with decreased risk in colorectal cancer (CRC). We measured serum enterolactone glucuronide and sulfate concentrations by liquid chromatography-tandem mass spectrometry in 115 CRC patients and 76 sex- and age-matched controls and analyzed the results with respect to tumor parameters, clinical parameters, and systemic inflammatory markers. Patients with colon cancer had significant lower serum enterolactone glucuronide and sulfate concentrations than controls (glucuronide: median 3.14 nM vs. 6.32 nM, P < 0.001; sulfate: median 0.13 nM vs. 0.17 nM, P = 0.002), whereas rectal cancer patients had similar enterolactone levels as controls (glucuronide: median 5.39 nM vs. 6.32 nM, P = 0.357; sulfate: median 0.19 nM vs. 0.17 nM, P = 0.452). High serum enterolactone concentrations were associated with low tumor grade, high serum creatinine levels, and concomitant diabetes. In summary, our results suggest that serum enterolactone concentrations are decreased in colon but not in rectal cancer. Further investigations are required to assess whether this reflects an altered lignan metabolism by the colon microbiome.

Highlights of This Issue

In a Seattle-based cohort of patients diagnosed with clinically localized prostate cancer, patients who reported vigorous physical activity at least once per week during the year before diagnosis were less likely to progress to metastatic–lethal prostate cancer compared to those who had less frequent physical activity (adjusted hazard ratio = 0.63, p-value = 0.029). Dai and colleagues identified a differentially methylated region (associated with both physical activity and metastatic–lethal progression) in the promoter region of CRACR2A, a gene encoding a calcium binding protein involved in innate immune response and neutrophil degranulation.Previous studies investigating associations of breast cancer with dietary intakes of lignans, phytoestrogens prevalent in whole grains, vegetables, fruits, and seeds, have been inconsistent. Some inconsistency may be related to genetic variation in lignan metabolism. Chang and colleagues investigated the impact of polymorphisms in 29 genes involved in steroid hormone and xenobiotic metabolism on lignan excretion after a flaxseed intervention in African American and European American healthy postmenopausal women. They identified several SNPs associated with lignan excretion, particularly among African American women. Future dietary interventions to reduce breast cancer burden may benefit from incorporating information on genetic variation in metabolism.Folic acid and vitamin-B12 play key roles in one-carbon metabolism, which has been implicated in the development of cancer. Given current considerations on folic acid fortification globally, it is essential to evaluate potential adverse effects. The aim of this study was to conduct secondary analyses on cancer incidence within the B-PROOF study, a randomized controlled trial on vitamin-B12 and folic acid supplementation on fracture risk. Oliai Araghi and colleagues found that B-vitamin supplementation increased the risk of cancer, and colorectal cancer in particular. This suggests that folic acid and vitamin-B12 supplementation should be limited to patients with proven deficiencies.Decreasing sequencing costs make population genetic screening increasingly feasible. However, the substantial infrastructure needs require thoughtful consideration of screening eligibility guidelines, which range from full-population testing to testing only those with strong personal or family histories. This study utilized a clinical risk prediction tool (BRCAPRO) to calculate BRCA1/2 carrier-probabilities for a population of Ashkenazi-Jewish women whose mutation status was known. Best and colleagues found that identifying 90% of known BRCA1/2 founder-mutations required testing only 60% of Ashkenazi-Jewish women (carrier-probability&gt;0.56%). An estimated 0.7-1.1 million U.S. Ashkenazi-Jewish women might avoid unnecessary mutation-testing. Low carrier-probability thresholds (&lt;1%) could maximize the public-health benefit of BRCA1/2 screening.

A Review of Lignan Metabolism, Milk Enterolactone Concentration, and Antioxidant Status of Dairy Cows Fed Flaxseed.

Lignans are polyphenolic compounds with a wide spectrum of biological functions including antioxidant, anti-inflammatory, and anticarcinogenic activities, therefore, there is an increasing interest in promoting the inclusion of lignan-rich foods in humans’ diets. Flaxseed is the richest source of the lignan secoisolariciresinol diglucoside—a compound found in the outer fibrous-containing layers of flax. The rumen appears to be the major site for the conversion of secoisolariciresinol diglucoside to the enterolignans enterodiol and enterolactone, but only enterolactone has been detected in milk of dairy cows fed flaxseed products (whole seeds, hulls, meal). However, there is limited information regarding the ruminal microbiota species involved in the metabolism of secoisolariciresinol diglucoside. Likewise, little is known about how dietary manipulation such as varying the nonstructural carbohydrate profile of rations affects milk enterolactone in dairy cows. Our review covers the gastrointestinal tract metabolism of lignans in humans and animals and presents an in-depth assessment of research that have investigated the impacts of flaxseed products on milk enterolactone concentration and animal health. It also addresses the pharmacokinetics of enterolactone consumed through milk, which may have implications to ruminants and humans’ health.

Influence of different lignan compounds on enterolignan production by Bifidobacterium and Lactobacillus strains

Enterolignans, i.e. enterodiol and enterolactone, are polyphenols derived from the microbial metabolism of dietary lignans. They are considered phytoestrogens because of their estrogenic/antiestrogenic activity, which confers them benefits to human health when they reach sufficient levels in plasma. Hence, there is a great interest in studying the bacteria involved in enterolignan production. In the present study, three bifidobacterial strains (Bifidobacterium bifidum INIA P466, Bifidobacterium catenulatum INIA P732 and Bifidobacterium pseudolongum INIA P2) were found capable of producing low levels of enterodiol (2–11 μM) from lignan extracts; while another one (Bifidobacterium pseudocatenulatum INIA P946) was found to produce an important increment of the lignan secoisolariciresinol (SECO). Subsequently, the three enterodiol-producing bifidobacteria and another three Lactobacillus strains previously identified as enterolignans producers (Lactobacillus gasseri INIA P508, Lactobacillus salivarius INIA P448 and Lb. salivarius INIA P183), were tested on pure lignans yielding both enterodiol and enterolactone from secoisolariciresinol (SECO), while they did not metabolised the other lignan tested (i.e. matairesinol). B. catenulatum INIA P732 and Lb. gasseri INIA P508 were the strains that transformed the greatest percentage of SECO, yielding enterolactone concentrations above 2 mM. In addition, the formation of the intermediate compound dihydroxyenterodiol was observed as part of SECO transformation by all the strains. In this work, we have demonstrated for the first time how strains of Bifidobacterium and Lactobacillus are capable of carrying out the complete enterolignan metabolism, transforming a purified lignan (SECO) into enterodiol and enterolactone. The isolation and characterization of bacteria able to metabolize lignans and produce enterolignans, especially belonging to Bifidobacterium and Lactobacillus genera, is of biotechnological interest, because of their potential application in functional foods and as probiotics.

Effect of Antibiotics and Diet on Enterolactone Concentration and Metabolome Studied by Targeted and Nontargeted LC-MS Metabolomics.

High plant lignan intake is associated with a number of health benefits, possibly induced by the lignan metabolite enterolactone (ENL). The gut microbiota plays a crucial role in converting dietary lignans into ENL, and epidemiological studies have shown that use of antibiotics is associated with lower levels of ENL. Here we investigate the link between antibiotic use and lignan metabolism in pigs using LC-MS/MS. The effect of lignan intake and antibiotic use on the gut microbial community and the pig metabolome is studied by 16S rRNA sequencing and nontargeted LC-MS. Treatment with antibiotics resulted in substantially lower concentrations of ENL compared with concentrations detected in untreated animals, whereas the plasma concentrations of plant lignans were unchanged. Both diet and antibiotic treatment affected the clustering of urinary metabolites and significantly altered the proportions of taxa in the gut microbiota. Diet, but not antibiotic treatment, affected the plasma lipid profile, and a lower concentration of LDL cholesterol was observed in the pigs fed a high lignan diet. This study provides solid support for the associations between ENL concentrations and use of antibiotics found in humans and indicates that the lower ENL concentration may be a consequence of the ecological changes in the microbiota.

Bifidobacterium adolescentis INIA P784: The first probiotic bacterium capable of producing enterodiol from lignan extracts

Lignans are phytoestrogens found in plant foods and especially in flax seeds. Although lignans present a low bioavailability, their transformation into the enterolignans enterodiol (END) and enterolactone (ENL) is associated with beneficial effects on human health. Lignan metabolism was studied in 90 lactic acid bacteria and bifidobacteria finding a wide distribution of the ability to deglycosylate secoisolariciresinol diglucoside (SDG) into secoisolariciresinol (SECO). Previous results indicate that enterolignans need a consortium of intestinal bacteria to be produced. In this paper we describe the obtaining of between 1.12μM and 4.18μM of END from lignan extracts by the action of a sole strain, Bifidobacterium adolescentis INIA P784. However, END production was not obtained from the pure lignans SECO, matairesinol and sesamin. To our knowledge, the first probiotic bacterium capable of producing END from lignan extracts is described in this work, showing potential applications in biotechnology, in functional foods and as probiotic.