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Review

Employing pigs to decipher the host genetic effect on gut microbiome: advantages, challenges, and perspectives

ORCID Icon & ORCID Icon
Article: 2205410 | Received 09 Nov 2022, Accepted 11 Apr 2023, Published online: 30 Apr 2023

References

  • Berg RD. The indigenous gastrointestinal microflora. Trends Microbiol. 1996;4(11):430–20. doi:10.1016/0966-842X(96)10057-3.
  • Sender R, Fuchs S, Milo R. Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell. 2016;164(3):337–340. doi:10.1016/j.cell.2016.01.013.
  • Chen C, Zhou Y, Fu H, Xiong X, Fang S, Jiang H, Wu J, Yang H, Gao J, Huang L. Expanded catalog of microbial genes and metagenome-assembled genomes from the pig gut microbiome. Nat Commun. 2021;12(1):1106. doi:10.1038/s41467-021-21295-0.
  • Thaiss CA, Zmora N, Levy M, Elinav E. The microbiome and innate immunity. Nature. 2016;535(7610):65–74. doi:10.1038/nature18847.
  • Tremaroli V, Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012;489(7415):242–249. doi:10.1038/nature11552.
  • Sylvia KE, Demas GE. A gut feeling: microbiome-brain-immune interactions modulate social and affective behaviors. Horm Behav. 2018;99:41–49. doi:10.1016/j.yhbeh.2018.02.001.
  • Benson AK, Kelly SA, Legge R, Ma F, Low SJ, Kim J, Zhang M, Oh PL, Nehrenberg D, Hua K, et al. Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors. Proc Natl Acad Sci U S A. 2010;107(44):18933–18938. doi:10.1073/pnas.1007028107.
  • Rothschild D, Weissbrod O, Barkan E, Kurilshikov A, Korem T, Zeevi D, Costea PI, Godneva A, Kalka IN, Bar N, et al. Environment dominates over host genetics in shaping human gut microbiota. Nature. 2018;555(7695):210–215. doi:10.1038/nature25973.
  • Lopera-Maya EA, Kurilshikov A, van der Graaf A, Hu S, Andreu-Sanchez S, Chen L, Vila AV, Gacesa R, Sinha T, Collij V, et al. Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch microbiome project. Nat Genet. 2022;54(2):143–151. doi:10.1038/s41588-021-00992-y.
  • Wang J, Thingholm LB, Skieceviciene J, Rausch P, Kummen M, Hov JR, Degenhardt F, Heinsen FA, Rühlemann MC, Szymczak S, et al. Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota. Nat Genet. 2016;48(11):1396–1406. doi:10.1038/ng.3695.
  • Yang H, Wu J, Huang X, Zhou Y, Zhang Y, Liu M, Liu Q, Ke S, He M, Fu H, et al. ABO genotype alters the gut microbiota by regulating GalNAc levels in pigs. Nature. 2022;606(7913):358–367. doi:10.1038/s41586-022-04769-z.
  • Gacesa R, Kurilshikov A, Vich Vila A, Sinha T, Klaassen MAY, Bolte LA, Andreu-Sánchez S, Chen L, Collij V, Hu S, et al. Environmental factors shaping the gut microbiome in a Dutch population. Nature. 2022;604(7907):732–739. doi:10.1038/s41586-022-04567-7.
  • Wylensek D, Hitch TCA, Riedel T, Afrizal A, Kumar N, Wortmann E, Liu T, Devendran S, Lesker TR, Hernández SB, et al. A collection of bacterial isolates from the pig intestine reveals functional and taxonomic diversity. Nat Commun. 2020;11(1):6389. doi:10.1038/s41467-020-19929-w.
  • Holman DB, Brunelle BW, Trachsel J, Allen HK, Bik H. Meta-analysis to define a core microbiota in the swine gut. mSystems. 2017;2017(3):2. doi:10.1128/mSystems.00004-17.
  • Zhang L, Wu W, Lee YK, Xie J, Zhang H. Spatial heterogeneity and co-occurrence of mucosal and luminal microbiome across swine intestinal tract. Front Microbiol. 2018;9:48. doi:10.3389/fmicb.2018.00048.
  • Crespo-Piazuelo D, Estelle J, Revilla M, Criado-Mesas L, Ramayo-Caldas Y, Ovilo C, Fernández AI, Ballester M, Folch JM. Characterization of bacterial microbiota compositions along the intestinal tract in pigs and their interactions and functions. Sci Rep. 2018;8(1):12727. doi:10.1038/s41598-018-30932-6.
  • Yang H, Huang X, Fang S, Xin W, Huang L, Chen C. Uncovering the composition of microbial community structure and metagenomics among three gut locations in pigs with distinct fatness. Sci Rep. 2016;6(1):27427. doi:10.1038/srep27427.
  • Luo Y, Ren W, Smidt H, Wright AG, Yu B, Schyns G, McCormack UM, Cowieson AJ, Yu J, He J, et al. Dynamic distribution of gut microbiota in pigs at different growth stages: composition and contribution. Microbiol Spectr. 2022;10(3):e0068821. doi:10.1128/spectrum.00688-21.
  • Ke S, Fang S, He M, Huang X, Yang H, Yang B, Chen C, Huang L. Age-based dynamic changes of phylogenetic composition and interaction networks of health pig gut microbiome feeding in a uniformed condition. BMC Vet Res. 2019;15(1):172. doi:10.1186/s12917-019-1918-5.
  • Wang X, Tsai T, Deng F, Wei X, Chai J, Knapp J, Apple J, Maxwell CV, Lee JA, Li Y, et al. Longitudinal investigation of the swine gut microbiome from birth to market reveals stage and growth performance associated bacteria. Microbiome. 2019;7(1):109. doi:10.1186/s40168-019-0721-7.
  • Xiao L, Estelle J, Kiilerich P, Ramayo-Caldas Y, Xia Z, Feng Q, Liang S, Pedersen AØ, Kjeldsen NJ, Liu C, et al. A reference gene catalogue of the pig gut microbiome. Nat Microbiol. 2016;1(12):16161. doi:10.1038/nmicrobiol.2016.161.
  • Li J, Jia H, Cai X, Zhong H, Feng Q, Sunagawa S, Arumugam M, Kultima JR, Prifti E, Nielsen T, et al. An integrated catalog of reference genes in the human gut microbiome. Nat Biotechnol. 2014;32(8):834–841. doi:10.1038/nbt.2942.
  • Fassarella M, Blaak EE, Penders J, Nauta A, Smidt H, Zoetendal EG. Gut microbiome stability and resilience: elucidating the response to perturbations in order to modulate gut health. Gut. 2021;70(3):595–605. doi:10.1136/gutjnl-2020-321747.
  • Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489(7415):220–230. doi:10.1038/nature11550.
  • De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, Collini S, Pieraccini G, Lionetti P. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A. 2010;107(33):14691–14696. doi:10.1073/pnas.1005963107.
  • Fragiadakis GK, Smits SA, Sonnenburg ED, Van Treuren W, Reid G, Knight R, Manjurano A, Changalucha J, Dominguez-Bello MG, Leach J, et al. Links between environment, diet, and the hunter-gatherer microbiome. Gut Microbes. 2019;10(2):216–227. doi:10.1080/19490976.2018.1494103.
  • Daniel H, Gholami AM, Berry D, Desmarchelier C, Hahne H, Loh G, Mondot S, Lepage P, Rothballer M, Walker A, et al. High-fat diet alters gut microbiota physiology in mice. Isme J. 2014;8(2):295–308. doi:10.1038/ismej.2013.155.
  • Bian G, Ma S, Zhu Z, Su Y, Zoetendal EG, Mackie R, Liu J, Mu C, Huang R, Smidt H, et al. Age, introduction of solid feed and weaning are more important determinants of gut bacterial succession in piglets than breed and nursing mother as revealed by a reciprocal cross-fostering model. Environ Microbiol. 2016;18(5):1566–1577. doi:10.1111/1462-2920.13272.
  • Wu S, Bhat ZF, Gounder RS, Mohamed Ahmed IA, Al-Juhaimi FY, Ding Y, Bekhit AEDA. Effect of dietary protein and processing on gut microbiota-a systematic review. Nutrients. 2022;14(3):14. doi:10.3390/nu14030453.
  • Luo Y, Liu Y, Li H, Zhao Y, Wright AG, Cai J, Tian G, Mao X. Differential effect of dietary fibers in intestinal health of growing pigs: outcomes in the gut microbiota and immune-related indexes. Front Microbiol. 2022;13:843045.
  • Wu G, Tang X, Fan C, Wang L, Shen W, Ren S, Zhang L, Zhang Y. Gastrointestinal tract and dietary fiber driven alterations of gut microbiota and metabolites in durco x bamei crossbred pigs. Front Nutr. 2021;8:806646. doi:10.3389/fnut.2021.806646.
  • Zhu C, Yang J, Nie X, Wu Q, Wang L, Jiang Z. Influences of dietary vitamin e, selenium-enriched yeast, and soy isoflavone supplementation on growth performance, antioxidant capacity, carcass traits, meat quality and gut microbiota in finishing pigs. Antioxid (Basel). 2022;11(8):11. doi:10.3390/antiox11081510.
  • Zhen R, Liu C, Wei C, Luo Y, Hu X, Liu G, Yi H, Huang Y. Effect of different dosages of sodium butyrate and niacin on growth, faecal microbiota and vitamin B metabolism in weaned piglets. J Appl Microbiol. 2022;132(6):4466–4475. doi:10.1111/jam.15545.
  • Guo D, Zhang L, Zhang L, Han S, Yang K, Lin X, Wen C, Tong A, Zhang M, Yin Y, et al. Effect of dietary methylsulfonylmethane supplementation on growth performance, hair quality, fecal microbiota, and metabolome in ragdoll kittens. Front Microbiol. 2022;13:838164. doi:10.3389/fmicb.2022.838164.
  • Sarri L, Costa-Roura S, Balcells J, Seradj AR, de la Fuente G. The impact of genetics on gut microbiota of growing and fattening pigs under moderate N restriction. Animals (Basel): Open Access J MDPI. 2021;11(10):11. doi:10.3390/ani11102846.
  • Looft T, Johnson TA, Allen HK, Bayles DO, Alt DP, Stedtfeld RD, Sul WJ, Stedtfeld TM, Chai B, Cole JR, et al. In-feed antibiotic effects on the swine intestinal microbiome. Proc Natl Acad Sci U S A. 2012;109(5):1691–1696. doi:10.1073/pnas.1120238109.
  • Looft T, Allen HK, Cantarel BL, Levine UY, Bayles DO, Alt DP, Henrissat B, Stanton TB. Bacteria, phages and pigs: the effects of in-feed antibiotics on the microbiome at different gut locations. Isme J. 2014;8(8):1566–1576. doi:10.1038/ismej.2014.12.
  • Pi Y, Gao K, Peng Y, Mu CL, Zhu WY. Antibiotic-induced alterations of the gut microbiota and microbial fermentation in protein parallel the changes in host nitrogen metabolism of growing pigs. Animal. 2019;13(2):262–272. doi:10.1017/S1751731118001416.
  • Dowarah R, Verma AK, Agarwal N. The use of lactobacillus as an alternative of antibiotic growth promoters in pigs: a review. Anim Nutr. 2017;3(1):1–6. doi:10.1016/j.aninu.2016.11.002.
  • Toscano M, De Grandi R, Miniello VL, Mattina R, Drago L. Ability of lactobacillus kefiri LKF01 (DSM32079) to colonize the intestinal environment and modify the gut microbiota composition of healthy individuals. Dig Liver Dis. 2017;49(3):261–267. doi:10.1016/j.dld.2016.11.011.
  • Shin D, Chang SY, Bogere P, Won K, Choi JY, Choi YJ, Lee HK, Hur J, Park B-Y, Kim Y, et al. Beneficial roles of probiotics on the modulation of gut microbiota and immune response in pigs. Plos One. 2019;14(8):e0220843. doi:10.1371/journal.pone.0220843.
  • Dicksved J, Halfvarson J, Rosenquist M, Jarnerot G, Tysk C, Apajalahti J, Engstrand L, Jansson JK. Molecular analysis of the gut microbiota of identical twins with Crohn’s disease. Isme J. 2008;2(7):716–727. doi:10.1038/ismej.2008.37.
  • Zhang Y, Si X, Yang L, Wang H, Sun Y, Liu N. Association between intestinal microbiota and inflammatory bowel disease. Animal Model Exp Med. 2022;5(4):311–322. doi:10.1002/ame2.12255.
  • Gu W, Zhang L, Han T, Huang H, Chen J. Dynamic changes in gut microbiome of ulcerative colitis: initial study from animal model. J Inflamm Res. 2022;15:2631–2647. doi:10.2147/JIR.S358807.
  • Chung the H, Le SH. Dynamic of the human gut microbiome under infectious diarrhea. Curr Opin Microbiol. 2022;66:79–85.
  • Gresse R, Chaucheyras-Durand F, Fleury MA, Van de Wiele T, Forano E, Blanquet-Diot S. Gut microbiota dysbiosis in postweaning piglets: understanding the keys to health. Trends Microbiol. 2017;25(10):851–873. doi:10.1016/j.tim.2017.05.004.
  • Li J, Zhou J, Zhao S, Guo R, Zhong C, Xue T, Peng Q, Zhang B, Fan B, Liu C, et al. Pathogenicity, infective dose and altered gut microbiota in piglets infected with porcine deltacoronavirus. Virology. 2022;567:26–33.
  • Hu C, Niu X, Chen S, Wen J, Bao M, Mohyuddin SG, Yong Y, Liu X, Wu L, Yu Z, et al. A comprehensive analysis of the colonic flora diversity, short chain fatty acid metabolism, transcripts, and biochemical indexes in heat-stressed pigs. Front Immunol. 2021;12:717723.
  • Wen C, van Dixhoorn I, Schokker D, Woelders H, Stockhofe-Zurwieden N, Rebel JMJ, Smidt H. Environmentally enriched housing conditions affect pig welfare, immune system and gut microbiota in early life. Anim Microbiome. 2021;3(1):52. doi:10.1186/s42523-021-00115-2.
  • Markle JG, Frank DN, Mortin-Toth S, Robertson CE, Feazel LM, Rolle-Kampczyk U, von Bergen M, McCoy KD, Macpherson AJ, Danska JS, et al. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science. 2013;339(6123):1084–1088. doi:10.1126/science.1233521.
  • Yurkovetskiy L, Burrows M, Khan AA, Graham L, Volchkov P, Becker L, Antonopoulos D, Umesaki Y, Chervonsky A. Gender bias in autoimmunity is influenced by microbiota. Immunity. 2013;39:400–412.
  • He M, Gao J, Wu J, Zhou Y, Fu H, Ke S, Yang H, Chen C, Huang L. Host gender and androgen levels regulate gut bacterial taxa in pigs leading to sex-biased serum metabolite profiles. Front Microbiol. 2019;10:1359. doi:10.3389/fmicb.2019.01359.
  • Baker JM, Al-Nakkash L, Herbst-Kralovetz MM. Estrogen-gut microbiome axis: physiological and clinical implications. Maturitas. 2017;103:45–53.
  • Ervin SM, Li H, Lim L, Roberts LR, Liang X, Mani S, Redinbo MR. Gut microbial beta-glucuronidases reactivate estrogens as components of the estrobolome that reactivate estrogens. J Biol Chem. 2019;294(49):18586–18599. doi:10.1074/jbc.RA119.010950.
  • Turpin W, Espin-Garcia O, Xu W, Silverberg MS, Kevans D, Smith MI, Guttman DS, Griffiths A, Panaccione R, Otley A, et al. Association of host genome with intestinal microbial composition in a large healthy cohort. Nat Genet. 2016;48(11):1413–1417. doi:10.1038/ng.3693.
  • Kurilshikov A, Medina-Gomez C, Bacigalupe R, Radjabzadeh D, Wang J, Demirkan A, Le Roy CI, Raygoza Garay JA, Finnicum CT, Liu X, et al. Large-scale association analyses identify host factors influencing human gut microbiome composition. Nat Genet. 2021;53:156–165.
  • Chen C, Huang X, Fang S, Yang H, He M, Zhao Y, Huang L. Contribution of host genetics to the variation of microbial composition of cecum lumen and feces in pigs. Front Microbiol. 2018;9:2626.
  • Blekhman R, Goodrich JK, Huang K, Sun Q, Bukowski R, Bell JT, Spector TD, Keinan A, Ley RE, Gevers D, et al. Host genetic variation impacts microbiome composition across human body sites. Genome Biol. 2015;16(1):191. doi:10.1186/s13059-015-0759-1.
  • Wijsman EM. The role of large pedigrees in an era of high-throughput sequencing. Hum Genet. 2012;131:1555–1563.
  • Whitham TG, Bailey JK, Schweitzer JA, Shuster SM, Bangert RK, LeRoy CJ, Lonsdorf EV, Allan GJ, DiFazio SP, Potts BM, et al. A framework for community and ecosystem genetics: from genes to ecosystems. Nat Rev Genet. 2006;7(7):510–523. doi:10.1038/nrg1877.
  • van Opstal EJ, Bordenstein SR. Rethinking heritability of the microbiome. Science. 2015;349(6253):1172–1173. doi:10.1126/science.aab3958.
  • Campbell JH, Foster CM, Vishnivetskaya T, Campbell AG, Yang ZK, Wymore A, Palumbo AV, Chesler EJ, Podar M. Host genetic and environmental effects on mouse intestinal microbiota. Isme J. 2012;6(11):2033–2044. doi:10.1038/ismej.2012.54.
  • Li F, Li C, Chen Y, Liu J, Zhang C, Irving B, Fitzsimmons C, Plastow G, Guan LL. Host genetics influence the rumen microbiota and heritable rumen microbial features associate with feed efficiency in cattle. Microbiome. 2019;7(1):92. doi:10.1186/s40168-019-0699-1.
  • Fan P, Bian B, Teng L, Nelson CD, Driver J, Elzo MA, Jeong KC. Host genetic effects upon the early gut microbiota in a bovine model with graduated spectrum of genetic variation. Isme J. 2020;14(1):302–317. doi:10.1038/s41396-019-0529-2.
  • Bergamaschi M, Maltecca C, Schillebeeckx C, McNulty NP, Schwab C, Shull C, Fix J, Tiezzi F. Heritability and genome-wide association of swine gut microbiome features with growth and fatness parameters. Sci Rep. 2020;10:10134.
  • Simpson CL, Justice CM, Krishnan M, Wojciechowski R, Sung H, Cai J, Green T, Lewis D, Behneman D, Wilson AF, et al. Old lessons learned anew: family-based methods for detecting genes responsible for quantitative and qualitative traits in the genetic analysis workshop 17 mini-exome sequence data. BMC Proc. 2011;5(Suppl 9):S83.
  • Bonder MJ, Kurilshikov A, Tigchelaar EF, Mujagic Z, Imhann F, Vila AV, Deelen P, Vatanen T, Schirmer M, Smeekens SP, et al. The effect of host genetics on the gut microbiome. Nat Genet. 2016;48(11):1407–1412. doi:10.1038/ng.3663.
  • Dobson AJ, Chaston JM, Newell PD, Donahue L, Hermann SL, Sannino DR, Westmiller S, Wong ACN, Clark AG, Lazzaro BP, et al. Host genetic determinants of microbiota-dependent nutrition revealed by genome-wide analysis of drosophila melanogaster. Nat Commun. 2015;6(1):6312. doi:10.1038/ncomms7312.
  • Chaston JM, Dobson AJ, Newell PD, Douglas AE, Drake HL. Host genetic control of the microbiota mediates the drosophila nutritional phenotype. Appl Environ Microbiol. 2016;82(2):671–679. doi:10.1128/AEM.03301-15.
  • Org E, Parks BW, Joo JW, Emert B, Schwartzman W, Kang EY, Mehrabian M, Pan C, Knight R, Gunsalus R, et al. Genetic and environmental control of host-gut microbiota interactions. Genome Res. 2015;25(10):1558–1569. doi:10.1101/gr.194118.115.
  • Li J, George Markowitz RH, Brooks AW, Mallott EK, Leigh BA, Olszewski T, Zare H, Bagheri M, Smith HM, Friese KA, et al. Individuality and ethnicity eclipse a short-term dietary intervention in shaping microbiomes and viromes. PLoS Biol. 2022;20(8):e3001758. doi:10.1371/journal.pbio.3001758.
  • Davenport ER. Elucidating the role of the host genome in shaping microbiome composition. Gut Microbes. 2016;7(2):178–184. doi:10.1080/19490976.2016.1155022.
  • 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;159(4):789–799. doi:10.1016/j.cell.2014.09.053.
  • Goodrich JK, Davenport ER, Beaumont M, Jackson MA, Knight R, Ober C, Spector TD, Bell JT, Clark AG, Ley RE, et al. Genetic determinants of the gut microbiome in UK twins. Cell Host & Microbe. 2016;19(5):731–743. doi:10.1016/j.chom.2016.04.017.
  • 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;66(6):1031–1038. doi:10.1136/gutjnl-2015-311326.
  • Davenport ER, Cusanovich DA, Michelini K, Barreiro LB, Ober C, Gilad Y, White BA. Genome-wide association studies of the human gut microbiota. Plos One. 2015;10(11):e0140301. doi:10.1371/journal.pone.0140301.
  • O’Connor A, Quizon PM, Albright JE, Lin FT, Bennett BJ. Responsiveness of cardiometabolic-related microbiota to diet is influenced by host genetics. Mamm Genome. 2014;25(11–12):583–599. doi:10.1007/s00335-014-9540-0.
  • Camarinha-Silva A, Maushammer M, Wellmann R, Vital M, Preuss S, Bennewitz J. Host genome influence on gut microbial composition and microbial prediction of complex traits in pigs. Genetics. 2017;206(3):1637–1644. doi:10.1534/genetics.117.200782.
  • Visscher PM, Hill WG, Wray NR. Heritability in the genomics era–concepts and misconceptions. Nat Rev Genet. 2008;9(4):255–266. doi:10.1038/nrg2322.
  • Fan P, Nelson CD, Driver JD, Elzo MA, Penagaricano F, Jeong KC. Host genetics exerts lifelong effects upon hindgut microbiota and its association with bovine growth and immunity. Isme J. 2021;15(8):2306–2321. doi:10.1038/s41396-021-00925-x.
  • Hughes DA, Bacigalupe R, Wang J, Ruhlemann MC, Tito RY, Falony G, Joossens M, Vieira-Silva S, Henckaerts L, Rymenans L, et al. Genome-wide associations of human gut microbiome variation and implications for causal inference analyses. Nat Microbiol. 2020;5(9):1079–1087. doi:10.1038/s41564-020-0743-8.
  • Qin Y, Havulinna AS, Liu Y, Jousilahti P, Ritchie SC, Tokolyi A, Sanders JG, Valsta L, Brożyńska M, Zhu Q, et al. Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort. Nat Genet. 2022;54:134–142.
  • Ji J, Luo CL, Zou X, Lv XH, Xu YB, Shu DM, Qu H. Association of host genetics with intestinal microbial relevant to body weight in a chicken F2 resource population. Poult Sci. 2019;98:4084–4093.
  • Boulund U, Bastos DM, Ferwerda B, van den Born BJ, Pinto-Sietsma SJ, Galenkamp H, Levin E, Groen AK, Zwinderman AH, Nieuwdorp M., et al. Gut microbiome associations with host genotype vary across ethnicities and potentially influence cardiometabolic traits. Cell Host & Microbe. 2022;30(10):1464–1480.e6.
  • Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman D. Diversity of the human intestinal microbial flora. Science. 2005;308:1635–1638.
  • Reverter A, Ballester M, Alexandre PA, Marmol-Sanchez E, Dalmau A, Quintanilla R, Ramayo-Caldas Y. A gene co-association network regulating gut microbial communities in a duroc pig population. Microbiome. 2021;9:52.
  • Kuokkanen M, Kokkonen J, Enattah NS, Ylisaukko-Oja T, Komu H, Varilo T, Peltonen L, Savilahti E, Järvelä I. Mutations in the translated region of the lactase gene (LCT) underlie congenital lactase deficiency. Am J Hum Genet. 2006;78:339–344.
  • Ravcheev DA, Thiele I. Comparative genomic analysis of the human gut microbiome reveals a broad distribution of metabolic pathways for the degradation of host-synthetized mucin glycans and utilization of mucin-derived monosaccharides. Front Genet. 2017;8:111.
  • Yamamoto F, Yamamoto M. Molecular genetic basis of porcine histo-blood group AO system. Blood. 2001;97:3308–3310.
  • Nguyen DT, Choi H, Jo H, Kim JH, Dirisala VR, Lee KT, Kim TH, Park KK, Seo K, Park C. Molecular characterization of the human ABO blood group orthologus system in pigs. Anim Genet. 2011;42:325–328.
  • Choi MK, Le MT, Cho H, Yum J, Kang M, Song H, Kim JH, Chung HJ, Hong K, Park C. Determination of complete sequence information of the human ABO blood group orthologous gene in pigs and breed difference in blood type frequencies. Gene. 2018;640:1–5.
  • Peterson LW, Artis D. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat Rev Immunol. 2014;14:141–153.
  • Miro-Blanch J, Yanes O. Epigenetic regulation at the interplay netween gut microbiota and host metabolism. Front Genet. 2019;10:638.
  • LeBlanc JG, Laino JE, Del Valle MJ, Vannini V, van Sinderen D, Taranto MP, de Valdez GF, de Giori GS, Sesma F. B-group vitamin production by lactic acid bacteria–current knowledge and potential applications. J Appl Microbiol. 2011;111:1297–1309.
  • Rossi M, Amaretti A, Raimondi S. Folate production by probiotic bacteria. Nutrients. 2011;3:118–134.
  • Krautkramer KA, Kreznar JH, Romano KA, Vivas EI, Barrett-Wilt GA, Rabaglia ME, Keller MP, Attie AD, Rey FE, Denu JM. Diet-microbiota interactions mediate global epigenetic programming in multiple host tissues. Mol Cell. 2016;64:982–992.
  • Pan X, Gong D, Nguyen DN, Zhang X, Hu Q, Lu H, Fredholm M, Sangild PT, Gao F. Early microbial colonization affects DNA methylation of genes related to intestinal immunity and metabolism in preterm pigs. DNA Res. 2018;25:287–296.
  • Funkhouser LJ, Bordenstein SR. Mom knows best: the universality of maternal microbial transmission. PLoS Biol. 2013;11:e1001631.
  • Jost T, Lacroix C, Braegger CP, Rochat F, Chassard C. Vertical mother-neonate transfer of maternal gut bacteria via breastfeeding. Environ Microbiol. 2014;16:2891–2904.
  • Treichel NS, Prevorsek Z, Mrak V, Kostric M, Vestergaard G, Foesel B, Pfeiffer S, Stres B, Schöler A, Schloter M. Effect of the nursing mother on the gut microbiome of the offspring during early mouse development. Microb Ecol. 2019;78:517–527.
  • Meyer F, Fritz A, Deng ZL, Koslicki D, Lesker TR, Gurevich A, Robertson G, Alser M, Antipov D, Beghini F, et al. Critical assessment of metagenome interpretation: the second round of challenges. Nat Methods. 2022;19:429–440.
  • Klindworth A, Pruesse E, Schweer T, Peplies J, Quast C, Horn M, Glöckner FO. Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies. Nucleic Acids Res. 2013;41:e1.
  • Gohl DM, Vangay P, Garbe J, MacLean A, Hauge A, Becker A, Gould TJ, Clayton JB, Johnson TJ, Hunter R, et al. Systematic improvement of amplicon marker gene methods for increased accuracy in microbiome studies. Nat Biotechnol. 2016;34:942–949.
  • Brooks JP, Edwards DJ, Harwich MD Jr., Rivera MC, Fettweis JM, Serrano MG, Reris RA, Sheth NU, Huang B, Girerd P, et al. The truth about metagenomics: quantifying and counteracting bias in 16S rRNA studies. BMC Microbiol. 2015;15:66.
  • Bubier JA, Chesler EJ, Weinstock GM. Host genetic control of gut microbiome composition. Mamm Genome. 2021;32:263–281.