{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:16:49Z","timestamp":1789636609287,"version":"4.0.0"},"reference-count":70,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Applied Sciences and Arts Western Switzerland under the P1-HealthFood program","award":["73456\/IA-RAD17-05"],"award-info":[{"award-number":["73456\/IA-RAD17-05"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Flaxseeds are typically consumed either as whole flaxseed, ground flaxseed, flaxseed oil, partially defatted flaxseed meal, or as a milk alternative. They are considered a rich source of vitamins, minerals, proteins and peptides, lipids, carbohydrates, lignans, and dietary fiber, which have shown hypolipidemic, antiatherogenic, anticholesterolemic, and anti-inflammatory property activity. Here, an in vitro batch culture model was used to investigate the influence of whole milled flaxseed and partially defatted milled flaxseed press cake on the gut microbiota and the liberation of flaxseed bioactives. Microbial communities were profiled using 16S rRNA gene-based high-throughput sequencing with targeted mass spectrometry measuring lignan, cyclolinopeptide, and bile acid content and HPLC for short-chain fatty acid profiles. Flaxseed supplementation decreased gut microbiota richness with Firmicutes, Proteobacteria, and Bacteroidetes becoming the predominant phyla. Secoisolariciresinol, enterodiol, and enterolactone were rapidly produced with acetic acid, butyric acid, and propionic acid being the predominant acids after 24 h of fermentation. The flaxseed press cake and whole flaxseed were equivalent in microbiota changes and functionality. However, press cake may be superior as a functional additive in a variety of foods in terms of consumer acceptance as it would be more resistant to oxidative changes.<\/jats:p>","DOI":"10.3390\/ijms231810473","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T22:53:46Z","timestamp":1663023226000},"page":"10473","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Dietary Modulation of the Human Gut Microbiota and Metabolome with Flaxseed Preparations"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7718-0252","authenticated-orcid":false,"given":"Karin","family":"Kleigrewe","sequence":"first","affiliation":[{"name":"Bavarian Center for Biomolecular Mass Spectrometry, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Haack","sequence":"additional","affiliation":[{"name":"Werner Siemens-Chair of Synthetic Biotechnology, Department of Chemistry, Technical University of Munich, Garching b., 85748 M\u00fcnchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Baudin","sequence":"additional","affiliation":[{"name":"Institute of Life Technologies, School of Engineering, HES-SO University of Applied Sciences and Arts Western Switzerland Valais-Wallis, 1950 Sion, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"M\u00e9nabr\u00e9az","sequence":"additional","affiliation":[{"name":"Institute of Life Technologies, School of Engineering, HES-SO University of Applied Sciences and Arts Western Switzerland Valais-Wallis, 1950 Sion, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0467-4999","authenticated-orcid":false,"given":"Julien","family":"Crovadore","sequence":"additional","affiliation":[{"name":"Plants and Pathogens Group, Research Institute Land Nature and Environment, Geneva School of Engineering, Architecture and Landscape (HEPIA), HES-SO University of Applied Sciences and Arts Western Switzerland, 1254 Jussy, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8658-354X","authenticated-orcid":false,"given":"Mahmoud","family":"Masri","sequence":"additional","affiliation":[{"name":"Werner Siemens-Chair of Synthetic Biotechnology, Department of Chemistry, Technical University of Munich, Garching b., 85748 M\u00fcnchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0198-4385","authenticated-orcid":false,"given":"Michael","family":"Beyrer","sequence":"additional","affiliation":[{"name":"Institute of Life Technologies, School of Engineering, HES-SO University of Applied Sciences and Arts Western Switzerland Valais-Wallis, 1950 Sion, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0507-1911","authenticated-orcid":false,"given":"Wilfried","family":"Andlauer","sequence":"additional","affiliation":[{"name":"Institute of Life Technologies, School of Engineering, HES-SO University of Applied Sciences and Arts Western Switzerland Valais-Wallis, 1950 Sion, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9977-9952","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Lefort","sequence":"additional","affiliation":[{"name":"Plants and Pathogens Group, Research Institute Land Nature and Environment, Geneva School of Engineering, Architecture and Landscape (HEPIA), HES-SO University of Applied Sciences and Arts Western Switzerland, 1254 Jussy, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5342-2600","authenticated-orcid":false,"given":"Corinna","family":"Dawid","sequence":"additional","affiliation":[{"name":"Bavarian Center for Biomolecular Mass Spectrometry, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany"},{"name":"Chair of Food Chemistry and Molecular Sensory Science, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2113-6957","authenticated-orcid":false,"given":"Thomas B.","family":"Br\u00fcck","sequence":"additional","affiliation":[{"name":"Werner Siemens-Chair of Synthetic Biotechnology, Department of Chemistry, Technical University of Munich, Garching b., 85748 M\u00fcnchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4516-5146","authenticated-orcid":false,"given":"Wolfram M.","family":"Br\u00fcck","sequence":"additional","affiliation":[{"name":"Institute of Life Technologies, School of Engineering, HES-SO University of Applied Sciences and Arts Western Switzerland Valais-Wallis, 1950 Sion, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"key":"ref_1","unstructured":"Watson, R.R., and Preedy, V.R. (2013). Chapter 5\u2014Antihyperglycemic potential of secoisolaricinol diglucoside. Bioactive Food as Dietary Interventions for Diabetes, Academic Press."},{"key":"ref_2","unstructured":"Agricultural Marketing Resource Center (2021, November 04). Flax Profile. Available online: https:\/\/www.agmrc.org\/commodities-products\/grains-oilseeds\/flax-profile."},{"key":"ref_3","unstructured":"Muir, A.D., and Westcott, N.D. (2003). Flaxseed constituents and human health. Flax: The Genus Linum, Taylor & Francis."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Parikh, M., Maddaford, T.G., Austria, J.A., Aliani, M., Netticadan, T., and Pierce, G.N. (2019). Dietary flaxseed as a strategy for improving human health. Nutrients, 11.","DOI":"10.3390\/nu11051171"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"H146","DOI":"10.1152\/ajpheart.00400.2017","article-title":"Flaxseed: Its bioactive components and their cardiovascular benefits","volume":"314","author":"Parikh","year":"2018","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1007\/s13197-014-1293-y","article-title":"Flaxseed-a potential functional food source","volume":"52","author":"Kajla","year":"2015","journal-title":"J. Food Sci. Technol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Dzuvor, C.K.O., Taylor, J.T., Acquah, C., Pan, S., and Agyei, D. (2018). Bioprocessing of functional ingredients from flaxseed. Molecules, 23.","DOI":"10.3390\/molecules23102444"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7864","DOI":"10.1021\/jf071136k","article-title":"Identification of bitter off-taste compounds in the stored cold pressed linseed oil","volume":"55","author":"Fehling","year":"2007","journal-title":"J. Agric. Food Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4382","DOI":"10.1021\/acs.jafc.2c00976","article-title":"Activation spectra of human bitter taste receptors stimulated with cyclolinopeptides corresponding to fresh and aged linseed oil","volume":"70","author":"Lang","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_10","first-page":"1045","article-title":"Chemical composition and health benefits of flaxseed","volume":"2","author":"Bernacchia","year":"2014","journal-title":"Austin J. Nutr. Food Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.foodhyd.2011.12.019","article-title":"Flaxseed gum from flaxseed hulls: Extraction, fractionation, and characterization","volume":"28","author":"Qian","year":"2012","journal-title":"Food Hydrocoll."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zhou, X., Zhang, Z., Huang, F., Yang, C., and Huang, Q. (2020). In vitro digestion and fermentation by human fecal microbiota of polysaccharides from flaxseed. Molecules, 25.","DOI":"10.3390\/molecules25194354"},{"key":"ref_13","first-page":"132","article-title":"Flaxseed gum-biopolymers interactions driving rheological behaviour of oropharyngeal dysphagia-oriented products","volume":"111","author":"Vieira","year":"2020","journal-title":"Food Hydrocoll."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"E453","DOI":"10.1152\/ajpendo.00391.2018","article-title":"Microbial fermentation of flaxseed fibers modulates the transcriptome of GPR41-expressing enteroendocrine cells and protects mice against diet-induced obesity","volume":"316","author":"Arora","year":"2019","journal-title":"Am. J. Physiol. Endocrinol. Metabol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.bcdf.2015.09.006","article-title":"Short-chain fatty acid profiles from flaxseed dietary fibres after in vitro fermentation of pig colonic digesta: Structure\u2013function relationship","volume":"6","author":"Ding","year":"2015","journal-title":"Bioact. Carbohydr. Diet. Fibre"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"87","DOI":"10.2174\/2212798410901010087","article-title":"Isolation and bioactivities of furfuran type lignan compounds from edible plants","volume":"1","author":"Sok","year":"2009","journal-title":"Recent Pat. Food Nutr. Agric."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Durazzo, A., Lucarini, M., Camilli, E., Marconi, S., Gabrielli, P., Lisciani, S., Gambelli, L., Aguzzi, A., Novellino, E., and Santini, A. (2018). Dietary lignans: Definition, description and research trends in databases development. Molecules, 23.","DOI":"10.3390\/molecules23123251"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S1570-0232(02)00092-2","article-title":"Enterolignans","volume":"777","author":"Raffaelli","year":"2002","journal-title":"J. Chromatogr. B"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5216","DOI":"10.1021\/jf0005871","article-title":"HPLC method for analysis of secoisolariciresinol diglucoside in flaxseeds","volume":"48","author":"Johnsson","year":"2000","journal-title":"J. Agric. Food Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1039\/np9870400499","article-title":"Lignans, neolignans and related compounds","volume":"4","author":"Whiting","year":"1987","journal-title":"Nat. Prod. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/j.1541-4337.2009.00105.x","article-title":"Flaxseed lignans: Source, biosynthesis, metabolism, antioxidant activity, bio-active components, and health benefits","volume":"9","author":"Xueming","year":"2010","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1093\/ajcn\/nqy325","article-title":"Colonic mucosal and exfoliome transcriptomic profiling and fecal microbiome response to a flaxseed lignan extract intervention in humans","volume":"110","author":"Lampe","year":"2019","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/0960-0760(93)90022-O","article-title":"Inhibition of human aromatase by mammalian lignans and isoflavonoid phytoestrogens","volume":"44","author":"Adlercreutz","year":"1993","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/0960-0760(92)90393-W","article-title":"Enterolactone and estradiol inhibit each other\u2019s proliferative effect on MCF-7 breast cancer cells in culture","volume":"41","author":"Mousavi","year":"1992","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10041","DOI":"10.1021\/jf8020656","article-title":"Hydrolysis kinetics of secoisolariciresinol diglucoside oligomers from flaxseed","volume":"56","author":"Yuan","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1111\/j.1574-6941.2005.00057.x","article-title":"Phylogeny of human intestinal bacteria that activate the dietary lignan secoisolariciresinol diglucoside","volume":"55","author":"Clavel","year":"2006","journal-title":"FEMS Microbiol. Ecol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s00253-011-3338-8","article-title":"Role of bifidobacteria in the activation of the lignan secoisolariciresinol diglucoside","volume":"92","author":"Roncaglia","year":"2011","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1002\/mnfr.201500125","article-title":"Gut metabolites and bacterial community networks during a pilot intervention study with flaxseeds in healthy adult men","volume":"59","author":"Lagkouvardos","year":"2015","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s12934-020-01341-0","article-title":"Impact of lignans in oilseed mix on gut microbiome composition and enterolignan production in younger healthy and premenopausal women: An in vitro pilot study","volume":"19","author":"Corona","year":"2020","journal-title":"Microb. Cell Fact."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1080\/10495398.2019.1634579","article-title":"Flaxseed diet caused inflammation by altering the gut microbiota of Peking ducks","volume":"31","author":"Wu","year":"2020","journal-title":"Anim. Biotechnol."},{"key":"ref_31","first-page":"149","article-title":"An In Vitro batch-culture model to estimate the effects of interventional regimens on human fecal microbiota","volume":"31","author":"Ahmadi","year":"2019","journal-title":"J. Vis. Exp."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.fshw.2021.07.004","article-title":"Milled flaxseed-added diets ameliorated hepatic inflammation by reducing gene expression of TLR4\/NF-\u03baB pathway and altered gut microbiota in STZ-induced type 1 diabetic mice","volume":"11","author":"Xia","year":"2022","journal-title":"Food Sci. Hum. Wellness"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"112153","DOI":"10.1016\/j.jep.2019.112153","article-title":"The role of gut microbiota for the activity of medicinal plants traditionally used in the European Union for gastrointestinal disorders","volume":"245","author":"Thumann","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"G788","DOI":"10.1152\/ajpgi.00101.2018","article-title":"Ground flaxseed reverses protection of a reduced-fat diet against Citrobacter rodentium-induced colitis","volume":"315","author":"Lurz","year":"2018","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Yang, L., Wang, T., Zhang, X., Ning, Y., Zhang, G., Yan, R., Li, Y., Yu, J., He, J., and Jia, S. (2022). Exosomes derived from human placental mesenchymal stem cells ameliorate myocardial infarction via anti-inflammation and restoring gut dysbiosis. BMC Cardiovasc. Disord., 22.","DOI":"10.1186\/s12872-022-02508-w"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.3389\/fmicb.2017.01656","article-title":"Linseed oil supplementation of lambs\u2019 diet in early life leads to persistent changes in rumen microbiome structure","volume":"8","author":"Lyons","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"680101","DOI":"10.3389\/fmicb.2021.680101","article-title":"Dysbiosis of gut microbiota in patients with acute myocardial infarction","volume":"12","author":"Han","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez, M.A.G., Canfora, E.E., Jocken, J.W.E., and Blaak, E.E. (2019). The short-chain fatty acid acetate in body weight control and insulin sensitivity. Nutrients, 11.","DOI":"10.3390\/nu11081943"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1097\/MCO.0b013e32835665fa","article-title":"Butyrate: Implications for intestinal function","volume":"15","author":"Leonel","year":"2012","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1080\/19490976.2015.1134082","article-title":"Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism","volume":"7","author":"Morrison","year":"2016","journal-title":"Gut Microbes"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1002\/jsfa.6482","article-title":"Bioaccessibility of lignans from flaxseed (Linum usitatissimum L.) determined by single-batch in vitro simulation of the digestive process","volume":"94","author":"Fuentealba","year":"2014","journal-title":"J. Sci. Food Agric."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"G1042","DOI":"10.1152\/ajpgi.00253.2013","article-title":"Dietary flaxseed intake exacerbates acute colonic mucosal injury and inflammation induced by dextran sodium sulfate","volume":"306","author":"Zarepoor","year":"2014","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1111\/j.1365-2672.2005.02605.x","article-title":"Lactate is mainly fermented to butyrate by human intestinal microfloras but inter-individual variation is evident","volume":"99","author":"Bourriaud","year":"2005","journal-title":"J. Appl. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2314","DOI":"10.1099\/ijs.0.64883-0","article-title":"Acidaminococcus intestini sp. nov., isolated from human clinical samples","volume":"57","author":"Carlier","year":"2007","journal-title":"Int. J. Syst. Evol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Senizza, A., Rocchetti, G., Mosele, J.I., Patrone, V., Callegari, M.L., Morelli, L., and Lucini, L. (2020). Lignans and gut microbiota: An interplay revealing potential health implications. Molecules, 25.","DOI":"10.3390\/molecules25235709"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"108818","DOI":"10.1016\/j.jnutbio.2021.108818","article-title":"Discriminatory and cooperative effects within the mouse gut microbiota in response to flaxseed and its oil and lignan components","volume":"98","author":"Taibi","year":"2021","journal-title":"J. Nutr. Biochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"107409","DOI":"10.1016\/j.dib.2021.107409","article-title":"Data on cecal and fecal microbiota and predicted metagenomes profiles of female mice receiving whole flaxseed or its oil and secoisolariciresinol diglucoside components","volume":"38","author":"Taibi","year":"2021","journal-title":"Data Brief"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Resch, C., Parikh, M., Austria, J.A., Proctor, S.D., Netticadan, T., Blewett, H., and Pierce, G.N. (2021). The Influence of Diet and Sex on the Gut Microbiota of Lean and Obese JCR:LA-cp Rats. Microorganisms, 9.","DOI":"10.3390\/microorganisms9051037"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1016\/j.fct.2007.05.017","article-title":"Antioxidant activities of the flaxseed lignan secoisolariciresinol diglucoside, its aglycone secoisolariciresinol and the mammalian lignans enterodiol and enterolactone in vitro","volume":"45","author":"Hu","year":"2007","journal-title":"Food Chem. Toxicol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Gaya, P., Medina, M., S\u00e1nchez-Jim\u00e9nez, A., and Landete, J.M. (2016). Phytoestrogen metabolism by adult human gut microbiota. Molecules, 21.","DOI":"10.3390\/molecules21081034"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1248\/cpb.51.508","article-title":"Biotransformation of pinoresinol diglucoside to mammalian lignans by human intestinal microflora, and isolation of Enterococcus faecalis strain PDG-1 responsible for the transformation of (+)-pinoresinol to (+)-lariciresinol","volume":"51","author":"Xie","year":"2003","journal-title":"Chem. Pharm. Bull."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.cels.2019.11.007","article-title":"De novo peptide sequencing reveals a vast cyclopeptidome in human gut and other environments","volume":"10","author":"Behsaz","year":"2020","journal-title":"Cell Syst."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Navarro, S.L., Levy, L., Curtis, K.R., Elkon, I., Kahsai, O.J., Ammar, H.S., Randolph, T.W., Hong, N.N., Carnevale Neto, F., and Raftery, D. (2020). Effect of a flaxseed lignan intervention on circulating bile acids in a placebo-controlled randomized, crossover trial. Nutrients, 12.","DOI":"10.3390\/nu12061837"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Pushpass, R., Alzoufairi, S., Jackson, K., and Lovegrove, J. (2021). Circulating bile acids as a link between the gut microbiota and cardiovascular health: Impact of prebiotics, probiotics and polyphenol-rich foods. Nutr. Res. Rev., 1\u201320.","DOI":"10.1017\/S0954422421000081"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"751859","DOI":"10.1155\/2014\/751859","article-title":"Coordinated actions of FXR and LXR in metabolism: From pathogenesis to pharmacological targets for Type 2 Diabetes","volume":"2014","author":"Ding","year":"2014","journal-title":"Int. J. Endocrinol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Zheng, X., Huang, F., Zhao, A., Lei, S., Zhang, Y., Xie, G., Chen, T., Qu, C., Rajani, C., and Dong, B. (2017). Bile acid is a significant host factor shaping the gut microbiome of diet-induced obese mice. BMC Biol., 15.","DOI":"10.1186\/s12915-017-0462-7"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.foodres.2012.07.063","article-title":"Milk enhances intestinal absorption of green tea catechins in in vitro digestion\/Caco-2 cells model","volume":"53","author":"Xie","year":"2013","journal-title":"Food Res. Int."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"391S","DOI":"10.1093\/jn\/130.2.391S","article-title":"Aspects of in vitro and in vivo research approaches directed toward identifying probiotics and prebiotics for human use","volume":"130","author":"Gibson","year":"2020","journal-title":"J. Nutr."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.anifeedsci.2005.04.021","article-title":"In vitro digestion and fermentation methods, including gas production techniques, as applied to nutritive evaluation of foods in the hindgut of humans and other simple-stomached animals","volume":"123\u2013124","author":"Coles","year":"2005","journal-title":"Anim. Feed Sci. Technol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/s002489900072","article-title":"Validation of a three-stage compound continuous culture system for investigating the effect of retention time on the ecology and metabolism of bacteria in the human colon","volume":"33","author":"Macfarlane","year":"1998","journal-title":"Microb. Ecol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/nar\/gks808","article-title":"Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies","volume":"41","author":"Klindworth","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_62","unstructured":"Andrews, S. (2021, November 04). FastQC: A Quality Control Tool for High Throughput Sequence Data. Available online: http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e2836","DOI":"10.7717\/peerj.2836","article-title":"Rhea: A transparent and modular R pipeline for microbial profiling based on 16S rRNA gene amplicons","volume":"5","author":"Lagkouvardos","year":"2017","journal-title":"PeerJ"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1093\/bioinformatics\/bts342","article-title":"Associating microbiome composition with environmental covariates using generalized UniFrac distances","volume":"28","author":"Chen","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1007\/s00357-014-9161-z","article-title":"Ward\u2019s hierarchical agglomerative clustering method: Which algorithms implement Ward\u2019s criterion?","volume":"31","author":"Murtagh","year":"2014","journal-title":"J. Classif."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"D19","DOI":"10.1093\/nar\/gkq1019","article-title":"The sequence read archive","volume":"39","author":"Leinonen","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/BF00038690","article-title":"An evaluation of the relative robustness of techniques for ecological ordination","volume":"69","author":"Minchin","year":"1987","journal-title":"Vegetatio"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1021\/jf405529b","article-title":"Accurate determination of reference materials and natural isolates by means of quantitative (1)h NMR spectroscopy","volume":"62","author":"Frank","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"W388","DOI":"10.1093\/nar\/gkab382","article-title":"MetaboAnalyst 5.0: Narrowing the gap between raw spectra and functional insights","volume":"49","author":"Pang","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5238","DOI":"10.1021\/acs.jafc.1c00769","article-title":"Development of a highly sensitive ultra-high-performance liquid chromatography coupled to eectrospray ionization tandem mass spectrometry quantitation method for fecal bile acids and application on Crohn\u2019s disease studies","volume":"69","author":"Reiter","year":"2021","journal-title":"J. Agric. Food Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/18\/10473\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:28:48Z","timestamp":1760142528000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/18\/10473"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,9]]},"references-count":70,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["ijms231810473"],"URL":"https:\/\/doi.org\/10.3390\/ijms231810473","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,9]]}}}