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Gut Microbes Volume 16, 2024 - Issue 1
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Research Paper

Gut enterotype-dependent modulation of gut microbiota and their metabolism in response to xanthohumol supplementation in healthy adults

Paige E. Jamiesona College of Health, Oregon State University, Corvallis, OR, USA;b Linus Pauling Institute, Oregon State University, Corvallis, OR, USAORCID Iconhttps://orcid.org/0009-0006-1492-8063View further author information
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Eli B. Smartb Linus Pauling Institute, Oregon State University, Corvallis, OR, USA;c Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR, USAView further author information
,
John A. Bouranisa College of Health, Oregon State University, Corvallis, OR, USA;b Linus Pauling Institute, Oregon State University, Corvallis, OR, USAORCID Iconhttps://orcid.org/0000-0002-5533-7570View further author information
ORCID Icon,
Jaewoo Choib Linus Pauling Institute, Oregon State University, Corvallis, OR, USAORCID Iconhttps://orcid.org/0000-0001-6376-3089View further author information
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Robert E. Danczakd Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA, USAORCID Iconhttps://orcid.org/0000-0003-1396-192XView further author information
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Carmen P. Wongb Linus Pauling Institute, Oregon State University, Corvallis, OR, USAORCID Iconhttps://orcid.org/0000-0001-8294-2584View further author information
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Ines L. Paraisob Linus Pauling Institute, Oregon State University, Corvallis, OR, USA;e Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, USAORCID Iconhttps://orcid.org/0000-0001-8796-6702View further author information
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Claudia S. Maierb Linus Pauling Institute, Oregon State University, Corvallis, OR, USA;f Department of Chemistry, Oregon State University, Corvallis, OR, USAORCID Iconhttps://orcid.org/0000-0003-0743-8956View further author information
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Emily Hoa College of Health, Oregon State University, Corvallis, OR, USA;b Linus Pauling Institute, Oregon State University, Corvallis, OR, USAORCID Iconhttps://orcid.org/0000-0002-7687-2820View further author information
ORCID Icon,
Thomas J. Sharptong Department of Statistics, Oregon State University, Corvallis, OR, USA;h Department of Microbiology, Oregon State University, Corvallis, OR, USAORCID Iconhttps://orcid.org/0000-0002-5996-7764View further author information
ORCID Icon,
Thomas O. Metzd Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA, USAORCID Iconhttps://orcid.org/0000-0001-6049-3968View further author information
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Ryan Bradleyi Helfgott Research Institute, National University of Natural Medicine, Portland, OR, USA;j Herbert Wertheim School of Public Health, University of California, San Diego, La Jolla, CA, USAORCID Iconhttps://orcid.org/0000-0002-8073-3671View further author information
ORCID Icon &
Jan F. Stevensb Linus Pauling Institute, Oregon State University, Corvallis, OR, USA;e Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, USA;i Helfgott Research Institute, National University of Natural Medicine, Portland, OR, USACorrespondence[email protected]
ORCID Iconhttps://orcid.org/0000-0002-6348-9347View further author information
ORCID Icon show all
Article: 2315633 | Received 02 Nov 2023, Accepted 02 Feb 2024, Published online: 15 Feb 2024

References

  • Schönberger C, Kostelecky T. 125th anniversary review: the role of hops in brewing. J Inst Brew. 2011;117(3):259–19. doi:10.1002/j.2050-0416.2011.tb00471.x.
  • Gao X, Deeb D, Liu Y, Gautam S, Dulchavsky SA, Gautam SC. Immunomodulatory activity of xanthohumol: inhibition of T cell proliferation, cell-mediated cytotoxicity and Th1 cytokine production through suppression of NF-κB. Immunopharmacol Immunotoxicol. 2009 Sep 1;31(3):477–484. doi:10.1080/08923970902798132.
  • Lee IS, Lim J, Gal J, Kang JC, Kim HJ, Kang BY, Choi, HJ. Anti-inflammatory activity of xanthohumol involves heme oxygenase-1 induction via NRF2-ARE signaling in microglial BV2 cells. Neurochem Int. 2011 Feb 1;58(2):153–160. doi:10.1016/j.neuint.2010.11.008.
  • Miranda CL, Elias VD, Hay JJ, Choi J, Reed RL, Stevens JF. Xanthohumol improves dysfunctional glucose and lipid metabolism in diet-induced obese C57BL/6J mice. Arch Biochem Biophys. 2016 Jun 1;599:22–30. doi:10.1016/j.abb.2016.03.008.
  • Miranda CL, Johnson LA, de Montgolfier O, Elias VD, Ullrich LS, Hay JJ, Paraiso IL, Choi J, Reed RL, Revel JS. et al. Non-estrogenic xanthohumol derivatives mitigate insulin resistance and cognitive impairment in high-fat diet-induced obese mice. Sci Rep. 2018 Jan 12;8(1):613. doi:10.1038/s41598-017-18992-6.
  • Paraiso IL, Tran TQ, Magana AA, Kundu P, Choi J, Maier CS, Bobe G, Raber J, Kioussi C, Stevens JF. Xanthohumol ameliorates Diet-Induced Liver Dysfunction via Farnesoid X Receptor-Dependent and Independent Signaling. Front Pharmacol. 2021;12. doi:10.3389/fphar.2021.643857.
  • Zhang Y, Bobe G, Revel JS, Rodrigues RR, Sharpton TJ, Fantacone ML, Raslan K, Miranda CL, Lowry MB, Blakemore PR. et al. Improvements in metabolic syndrome by Xanthohumol derivatives are linked to altered gut microbiota and bile acid metabolism. Mol Nutr Food Res. 2020;64(1):1900789. doi:10.1002/mnfr.201900789.
  • Colgate EC, Miranda CL, Stevens JF, Bray TM, Ho E. Xanthohumol, a prenylflavonoid derived from hops induces apoptosis and inhibits NF-kappaB activation in prostate epithelial cells. Cancer Lett. 2007 Feb 8;246(1):201–209. doi:10.1016/j.canlet.2006.02.015.
  • Legette L, Karnpracha C, Reed RL, Choi J, Bobe G, Christensen JM, Rodriguez‐Proteau R, Purnell JQ, Stevens JF. Human pharmacokinetics of xanthohumol, an antihyperglycemic flavonoid from hops. Mol Nutr Food Res. 2014;58(2):248–255. doi:10.1002/mnfr.201300333.
  • Legette L, Ma L, Reed RL, Miranda CL, Christensen JM, Rodriguez-Proteau R, Stevens JF. Pharmacokinetics of xanthohumol and metabolites in rats after oral and intravenous administration. Mol Nutr Food Res. 2012;56(3):466–474. doi:10.1002/mnfr.201100554.
  • Logan IE, Shulzhenko N, Sharpton TJ, Bobe G, Liu K, Nuss S, Jones ML, Miranda CL, Vasquez‐Perez S, Pennington JM. et al. Xanthohumol requires the intestinal microbiota to improve glucose metabolism in diet-induced obese mice. Mol Nutr Food Res. 2021;65(21):2100389. doi:10.1002/mnfr.202100389.
  • Cermak P, Olsovska J, Mikyska A, Dusek M, Kadleckova Z, Vanicek J, Nyc O, Sigler K, Bostikova V, Bostik P. et al. Strong antimicrobial activity of xanthohumol and other derivatives from hops (Humulus lupulus L.) on gut anaerobic bacteria. APMIS. 2017;125(11):1033–1038. doi:10.1111/apm.12747.
  • Possemiers S, Heyerick A, Robbens V, De Keukeleire D, Verstraete W. Activation of proestrogens from hops (Humulus lupulus L.) by intestinal microbiota; conversion of Isoxanthohumol into 8-prenylnaringenin. J Agric Food Chem. 2005 Aug 1;53(16):6281–6288. doi:10.1021/jf0509714.
  • Possemiers S, Bolca S, Grootaert C, Heyerick A, Decroos K, Dhooge W, De Keukeleire D, Rabot S, Verstraete W, Van de Wiele T. et al. The prenylflavonoid isoxanthohumol from hops (Humulus lupulus L.) is activated into the potent phytoestrogen 8-prenylnaringenin in vitro and in the human intestine. J Nutr. 2006 Jul 1;136(7):1862–1867. doi:10.1093/jn/136.7.1862.
  • Paraiso IL, Plagmann LS, Yang L, Zielke R, Gombart AF, Maier CS, Sikora AE, Blakemore PR, Stevens JF. Reductive metabolism of Xanthohumol and 8-prenylnaringenin by the intestinal bacterium eubacterium ramulus. Mol Nutr Food Res. 2019;63(2):1800923. doi:10.1002/mnfr.201800923.
  • Paraiso IL, Revel JS, Choi J, Miranda CL, Lak P, Kioussi C, Bobe G, Gombart AF, Raber J, Maier CS. et al. Targeting the Liver-Brain axis with hop-derived flavonoids improves lipid metabolism and cognitive performance in mice. Mol Nutr Food Res. 2020;64(15):2000341. doi:10.1002/mnfr.202000341.
  • Possemiers S, Rabot S, Espín JC, Bruneau A, Philippe C, González-Sarrías A, Heyerick A, Tomás-Barberán FA, De Keukeleire D, Verstraete W. et al. Eubacterium limosum activates isoxanthohumol from hops (Humulus lupulus L.) into the potent phytoestrogen 8-prenylnaringenin in vitro and in rat intestine. J Nutr. 2008 Jul 1;138(7):1310–1316. doi:10.1093/jn/138.7.1310.
  • Milligan SR, Kalita JC, Heyerick A, Rong H, De Cooman L, De Keukeleire D. Identification of a Potent Phytoestrogen in Hops (Humulus lupulus L.) and Beer. J Clin Endocr Metab. 1999 Jun 1;84(6):2249. doi:10.1210/jcem.84.6.5887.
  • Milligan SR, Kalita JC, Pocock V, Van De Kauter V, Stevens JF, Deinzer ML, Rong H, De Keukeleire D. The Endocrine Activities of 8-Prenylnaringenin and Related Hop (Humulus lupulus L.) Flavonoids. J Clin Endocr Metab. 2000 Dec 1;85(12):4912–4915. doi:10.1210/jcem.85.12.7168.
  • Bradley R, Langley BO, Ryan JJ, Phipps J, Hanes DA, Stack E, Jansson JK, Metz TO, Stevens JF. Xanthohumol microbiome and signature in healthy adults (the XMaS trial): a phase I triple-masked, placebo-controlled clinical trial. Trials. 2020 Oct 7;21(1):835. doi:10.1186/s13063-020-04769-2.
  • Langley BO, Ryan JJ, Hanes D, Phipps J, Stack E, Metz TO, Stevens JF, Bradley R. Xanthohumol microbiome and signature in healthy adults (the XMaS trial): safety and tolerability results of a phase I triple-masked, placebo-controlled clinical trial. Mol Nutr Food Res. 2021;65(8):2001170. doi:10.1002/mnfr.202001170.
  • Stompor M, Żarowska B. Antimicrobial activity of Xanthohumol and its selected structural analogues. Molecules. 2016 May;21(5):608. doi:10.3390/molecules21050608.
  • Rozalski M, Micota B, Sadowska B, Stochmal A, Jedrejek D, Wieckowska-Szakiel M, Rozalska B. Antiadherent and Antibiofilm Activity of Humulus lupulus L. Derived Products: New Pharmacological Properties. Biomed Res Int. 2013 Sep 23;2013:1–7. doi:10.1155/2013/101089.
  • Gerhäuser C. Broad spectrum antiinfective potential of xanthohumol from hop (humulus lupulus L.) in comparison with activities of other hop constituents and xanthohumol metabolites. Mol Nutr Food Res. 2005;49(9):827–831. doi:10.1002/mnfr.200500091.
  • Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto J-M. et al. Enterotypes of the human gut microbiome. Nature. 2011 May;473(7346):174–180. doi:10.1038/nature09944.
  • Costea PI, Hildebrand F, Arumugam M, Bäckhed F, Blaser MJ, Bushman FD, de Vos WM, Ehrlich S, Fraser CM, Hattori M. et al. Enterotypes in the landscape of gut microbial community composition. Nat Microbiol. 2018 Jan;3(1):8–16. doi:10.1038/s41564-017-0072-8.
  • Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, Bewtra M, Knights D, Walters WA, Knight R. et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334(6052):105–108. doi:10.1126/science.1208344.
  • Zhang H, DiBaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y, Parameswaran P, Crowell MD, Wing R, Rittmann BE. et al. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci USA. 2009;106(7):2365–2370. doi:10.1073/pnas.0812600106.
  • Song EJ, Han K, Lim TJ, Lim S, Chung MJ, Nam MH, Kim H, Nam Y-D. Effect of probiotics on obesity-related markers per enterotype: a double-blind, placebo-controlled, randomized clinical trial. EPMA J. 2020 Mar 1;11(1):31–51. doi:10.1007/s13167-020-00198-y.
  • Hur HJ, Wu X, Yang HJ, Kim MJ, Lee KH, Hong M, Park S, Kim M-S. Beneficial effects of a low-glycemic diet on serum metabolites and gut microbiota in obese women with prevotella and Bacteriodes Enterotypes: a randomized clinical trial. Front Nutr. 2022;9. doi:10.3389/fnut.2022.861880.
  • Miller TL, Wolin MJ. Pathways of acetate, propionate, and butyrate formation by the human fecal microbial flora. Appl Environ Microb. 1996 May;62(5):1589–1592. doi:10.1128/aem.62.5.1589-1592.1996.
  • Clavel T, Henderson G, Engst W, Doré J, Blaut M. Phylogeny of human intestinal bacteria that activate the dietary lignan secoisolariciresinol diglucoside. FEMS Microbiol Ecol. 2006 Mar 1;55(3):471–478. doi:10.1111/j.1574-6941.2005.00057.x.
  • Clavel T, Henderson G, Alpert CA, Philippe C, Rigottier-Gois L, Doré J, Blaut M. Intestinal bacterial communities that produce active estrogen-like compounds enterodiol and enterolactone in humans. Appl Environ Microb. 2005 Oct;71(10):6077–6085. doi:10.1128/AEM.71.10.6077-6085.2005.
  • Kim M, Kim N, Han J. Metabolism of Kaempferia parviflora polymethoxyflavones by human intestinal bacterium Bautia sp. MRG-PMF1. J Agric Food Chem. 2014 Dec 24;62(51):12377–12383. doi:10.1021/jf504074n.
  • Burapan S, Kim M, Han J. Demethylation of polymethoxyflavones by human gut bacterium, Blautia sp. MRG-PMF1. J Agric Food Chem. 2017 Mar 1;65(8):1620–1629. doi:10.1021/acs.jafc.7b00408.
  • Goodrich JK, Waters JL, Poole AC, Sutter JL, Koren O, Blekhman R, Beaumont M, Van Treuren W, Knight R, Bell J. et al. Human genetics shape the gut microbiome. Cell. 2014 Nov 6;159(4):789–799. doi:10.1016/j.cell.2014.09.053.
  • Waters JL, Ley RE. The human gut bacteria christensenellaceae are widespread, heritable, and associated with health. BMC Biol. 2019 Oct 28;17(1):83. doi:10.1186/s12915-019-0699-4.
  • Beaumont M, Goodrich JK, Jackson MA, Yet I, Davenport ER, Vieira-Silva S, Debelius J, Pallister T, Mangino M, Raes J. et al. Heritable components of the human fecal microbiome are associated with visceral fat. Genome Biol. 2016 Sep 26;17(1):189. doi:10.1186/s13059-016-1052-7.
  • Fu J, Bonder MJ, Cenit MC, Tigchelaar EF, Maatman A, Dekens JAM, Brandsma E, Marczynska J, Imhann F, Weersma RK. et al. The gut microbiome contributes to a substantial proportion of the variation in blood lipids. Circ Res. 2015 Oct 9;117(9):817–824. doi:10.1161/CIRCRESAHA.115.306807.
  • Alemán JO, Bokulich NA, Swann JR, Walker JM, De Rosa JC, Battaglia T, Costabile A, Pechlivanis A, Liang Y, Breslow JL. et al. Fecal microbiota and bile acid interactions with systemic and adipose tissue metabolism in diet-induced weight loss of obese postmenopausal women. J Transl Med. 2018 Sep 3;16(1):244. doi:10.1186/s12967-018-1619-z.
  • Lim MY, You HJ, Yoon HS, Kwon B, Lee JY, Lee S, Song Y-M, Lee K, Sung J, Ko G. et al. The effect of heritability and host genetics on the gut microbiota and metabolic syndrome. Gut. 2017 Jun 1;66(6):1031–1038. doi:10.1136/gutjnl-2015-311326.
  • He Y, Wu W, Wu S, Zheng HM, Li P, Sheng HF, Chen M-X, Chen Z-H, Ji G-Y, Zheng ZDX. et al. Linking gut microbiota, metabolic syndrome and economic status based on a population-level analysis. Microbiome. 2018 Sep 24;6(1):172. doi:10.1186/s40168-018-0557-6.
  • Gevers D, Kugathasan S, Denson LA, Vázquez-Baeza Y, Van Treuren W, Ren B, Schwager E, Knights D, Song S, Yassour M. et al. The treatment-naive microbiome in New-Onset Crohn’s disease. Cell Host Microbe. 2014 Mar 12;15(3):382–392. doi:10.1016/j.chom.2014.02.005.
  • Imhann F, Vich Vila A, Bonder MJ, Fu J, Gevers D, Visschedijk MC, Spekhorst LM, Alberts R, Franke L, van Dullemen HM. et al. Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease. Gut. 2018 Jan;67(1):108–119. doi:10.1136/gutjnl-2016-312135.
  • Pascal V, Pozuelo M, Borruel N, Casellas F, Campos D, Santiago A. et al. A microbial signature for Crohn’s disease. Gut. 2017 May;66(5):813–822. doi:10.1136/gutjnl-2016-313235.
  • Sun L, Xie C, Wang G, Wu Y, Wu Q, Wang X, Liu J, Deng Y, Xia J, Chen B. et al. Gut microbiota and intestinal FXR mediate the clinical benefits of metformin. Nat Med. 2018 Dec;24(12):1919–1929. doi:10.1038/s41591-018-0222-4.
  • Sun L, Cai J, Gonzalez FJ. The role of farnesoid X receptor in metabolic diseases, and gastrointestinal and liver cancer. Nat Rev Gastroenterol Hepatol. 2021 May;18(5):335–347. doi:10.1038/s41575-020-00404-2.
  • Rath S, Rud T, Karch A, Pieper DH, Vital M. Pathogenic functions of host microbiota. Microbiome. 2018 Sep 28;6(1):174. doi:10.1186/s40168-018-0542-0.
  • Kim KH, Park D, Jia B, Baek JH, Hahn Y, Jeon CO, Chu H. Identification and characterization of Major bile acid 7α-dehydroxylating bacteria in the human gut. mSystems. mSystems. 2022 Jun 23;7(4):e00455–22. doi:10.1128/msystems.00455-22.
  • Vital M, Rud T, Rath S, Pieper DH, Schlüter D. Diversity of bacteria exhibiting bile acid-inducible 7α-dehydroxylation genes in the human gut. Comput Struct Biotechnol J. 2019 Jan 1;17:1016–1019. doi:10.1016/j.csbj.2019.07.012.
  • Tap J, Lejzerowicz F, Cotillard A, Pichaud M, McDonald D, Song SJ, Knight R, Veiga P, Derrien M. Global branches and local states of the human gut microbiome define associations with environmental and intrinsic factors. Nat Commun. 2023 Jun 20;14(1):3310. doi:10.1038/s41467-023-38558-7.
  • Boekhorst J, Venlet N, Procházková N, Hansen ML, Lieberoth CB, Bahl MI, Lauritzen L, Pedersen O, Licht TR, Kleerebezem M. et al. Stool energy density is positively correlated to intestinal transit time and related to microbial enterotypes. Microbiome. 2022 Dec 12;10(1):223. doi:10.1186/s40168-022-01418-5.
  • Ryan JJ, Hanes DA, Bradley RD, Contractor N. Effect of a nutrition support formula in adults with inflammatory bowel disease: a pilot study. Glob Adv Health Med. 2019 Jan 1;8:2164956119867251. doi:10.1177/2164956119867251.
  • Caporaso JG, Lauber CL, Walters WA, Berg-Lyons D, Huntley J, Fierer N, Owens SM, Betley J, Fraser L, Bauer M. et al. Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. ISME J. 2012 Aug;6(8):1621–1624. doi:10.1038/ismej.2012.8.
  • Illumina 16S Sample Preparation Guide [Internet]. [accessed 2023 Jun 30]. https://support.illumina.com/documents/documentation/chemistry_documentation/16s/16s-metagenomic-library-prep-guide-15044223-b.pdf
  • Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJA, Holmes SP. DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods. 2016 Jul;13(7):581–583. doi:10.1038/nmeth.3869.
  • Quast C, Pruesse E, Yilmaz P, Gerken J, Schweer T, Yarza P, Peplies J, Glöckner FO. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res. 2013 Jan 1;41(D1):D590–6. doi:10.1093/nar/gks1219.
  • McMurdie PJ, Holmes S, Watson M. Phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PloS One. 2013 Apr 22;8(4):e61217. doi:10.1371/journal.pone.0061217.
  • Wickham H. ggplo 2. WIREs Computational Stats. 2011;3(2):180–185. doi:10.1002/wics.147.
  • Oksanen J, Kindt R, Legendre P, O’Hara B, Stevens MHH, Oksanen MJ, Suggests, MA. The vegan package. Commun Eco Package. 2007;10(631–637):719.
  • Brooks ME, Kristensen K, van Benthem KJ, Magnusson A, Berg CW, Nielsen A, Skaug, HJ, Maechler M, Bolker, BM. Modeling zero-inflated count data with glmmTMB. bioRxiv. 2017;132753.
  • Magnusson A, Skaug H, Nielsen A, Berg C, Kristensen K, Maechler M, van Bentham K, Bolker B, Brooks M, Brooks, MM. glmmTMB: generalized linear mixed models using template model builder. R Package Version 0 1 3. 2017;25.
  • Hothorn T, Bretz F, Westfall P. Simultaneous inference in general parametric models. Biom J: J Maths Methods In Bioscie. 2008;50(3):346–363. doi:10.1002/bimj.200810425.
  • Maechler M, Rousseeuw P, Struyf A, Hubert M, Hornik K, Studer M, Roudier P, Gonzalez J. Package ‘cluster. Dosegljivo na. 2013.
  • Rohart F, Gautier B, Singh A, Cao KAL, Schneidman D. mixOmics: An R package for ‘omics feature selection and multiple data integration. PLoS Comput Biol. 2017 Nov 3;13(11):e1005752. doi:10.1371/journal.pcbi.1005752.
  • Gloor GB, Macklaim JM, Pawlowsky-Glahn V, Egozcue JJ. Microbiome datasets are compositional: and this is not optional. Front Microbiol [Internet]. 2017;8: 2224. doi:10.3389/fmicb.2017.02224.
  • Cao KAL, Rossouw D, Robert-Granié C, Besse P . A sparse PLS for variable selection when integrating omics data. Stat Appl Genet Mol Biol. 2008;7(1). doi:10.2202/1544-6115.1390.
  • Han J, Lin K, Sequeira C, Borchers CH. An isotope-labeled chemical derivatization method for the quantitation of short-chain fatty acids in human feces by liquid chromatography–tandem mass spectrometry. Anal Chim Acta. 2015 Jan 7;854:86–94. doi:10.1016/j.aca.2014.11.015.
  • Kuznetsova A, Brockhoff PB, Christensen RHB. Package ‘lmertest’. R Package Version. 2015;2(0):734.

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