Of genes and microbes: solving the intricacies in host genomes
Received date: 06 Feb 2018
Accepted date: 28 Feb 2018
Published date: 08 Jun 2018
Copyright
Microbiome research is a quickly developing field in biomedical research, and we have witnessed its potential in understanding the physiology, metabolism and immunology, its critical role in understanding the health and disease of the host, and its vast capacity in disease prediction, intervention and treatment. However, many of the fundamental questions still need to be addressed, including the shaping forces of microbial diversity between individuals and across time. Microbiome research falls into the classical nature vs. nurture scenario, such that host genetics shape part of the microbiome, while environmental influences change the original course of microbiome development. In this review, we focus on the nature, i.e., the genetic part of the equation, and summarize the recent efforts in understanding which parts of the genome, especially the human and mouse genome, play important roles in determining the composition and functions of microbial communities, primarily in the gut but also on the skin. We aim to present an overview of different approaches in studying the intricate relationships between host genetic variations and microbes, its underlying philosophy and methodology, and we aim to highlight a few key discoveries along this exploration, as well as current pitfalls. More evidence and results will surely appear in upcoming studies, and the accumulating knowledge will lead to a deeper understanding of what we could finally term a “hologenome”, that is, the organized, closely interacting genome of the host and the microbiome.
Jun Wang , Liang Chen , Na Zhao , Xizhan Xu , Yakun Xu , Baoli Zhu . Of genes and microbes: solving the intricacies in host genomes[J]. Protein & Cell, 2018 , 9(5) : 446 -461 . DOI: 10.1007/s13238-018-0532-9
1 |
Barreiro LB, Quintana-Murci L (2010) From evolutionary genetics to human immunology: how selection shapes host defence genes. Nat Rev Genet 11:17–30
|
2 |
Barreiro LB, Laval G, Quach H, Patin E, Quintana-Murci L (2008) Natural selection has driven population differentiation in modern humans. Nat Genet 40:340–345
|
3 |
Belheouane M, Gupta Y, Kunzel S, Ibrahim S, Baines JF (2017) Improved detection of gene-microbe interactions in the mouse skin microbiota using high-resolution QTL mapping of 16S rRNA transcripts. Microbiome 5:59
|
4 |
Bennett GM, McCutcheon JP, MacDonald BR, Romanovicz D, Moran NA (2014) Differential genome evolution between companion symbionts in an insect-bacterial symbiosis. MBio 5: e01697–14
|
5 |
Benson AK (2016) The gut microbiome-an emerging complex trait. Nat Genet 48:1301–1302
|
6 |
Benson AK, Kelly SA, Legge R, Ma F, Low SJ, Kim J,Zhang M, Oh PL, Nehrenberg D, Hua K
|
7 |
Blekhman R, Goodrich JK, Huang K, Sun Q, Bukowski R, Bell JT, Spector TD, Keinan A, Ley RE, Gevers D
|
8 |
Bohn E, Bechtold O, Zahir N, Frick JS, Reimann J, Jilge B, Autenrieth IB (2006) Host gene expression in the colon of gnotobiotic interleukin-2-deficient mice colonized with commensal colitogenic or noncolitogenic bacterial strains: common patterns and bacteria strain specific signatures. Inflamm Bowel Dis 12(9):853–862
|
9 |
Bonder MJ, Kurilshikov A, Tigchelaar EF, Mujagic Z, Imhann F, Vila AV, Deelen P, Vatanen T, Schirmer M, Smeekens SP
|
10 |
Bordenstein SR, Theis KR (2015) Host biology in light of the microbiome: ten principles of holobionts and hologenomes. Plos Biol 13:e1002226
|
11 |
Brinkworth JF, Pechenkina K (2013) Primates, pathogens, and evolution. Springer, New York
|
12 |
Brucker RM, Bordenstein SR (2013) The hologenomic basis of speciation: gut bacteria cause hybrid lethality in the genus Nasonia. Science 341:667–669
|
13 |
Budden KF, Gellatly SL, Wood DL, Cooper MA, Morrison M, Hugenholtz P, Hansbro PM (2017) Emerging pathogenic links between microbiota and the gut-lung axis. Nat Rev Microbiol 15:55–63
|
14 |
Chaston JM, Dobson AJ, Newell PD, Douglas AE (2015) Host genetic control of the microbiota mediates the drosophila nutritional phenotype. Appl Environ Microbiol 82:671–679
|
15 |
Chen L, Wilson JE, Koenigsknecht MJ, Chou WC, Montgomery SA, Truax AD, Brickey WJ, Packey CD, Maharshak N, Matsushima GK, Plevy SE, Young VB, Sartor RB, Ting JP (2017a) NLRP12 attenuates colon inflammation by maintaining colonic microbial diversity and promoting protective commensal bacterial growth. Nat Immunol 18(5):541–551. https://doi.org/10.1038/ni.3690
|
16 |
Chen L, Wilson JE, Koenigsknecht MJ, Chou WC, Montgomery SA, Truax AD, Brickey WJ, Packey CD, Maharshak N, Matsushima GK, Plevy SE, Young VB, Sartor RB, Ting JP (2017b) NLRP12 attenuates colon inflammation by maintaining colonic microbial diversity and promoting protective commensal bacterial growth. Nat Immunol 18(5):541–551. https://doi.org/10.1038/ni.3690
|
17 |
Davenport ER, Cusanovich DA, Michelini K, Barreiro LB, Ober C, Gilad Y (2015) Genome-wide association studies of the human gut microbiota. PLoS One 10:e0140301
|
18 |
David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA
|
19 |
de Bruyn M, Vermeire S (2017) NOD2 and bacterial recognition as therapeutic targets for Crohn’s disease. Expert Opin Ther Targets 21(12):1123–1139. https://doi.org/10.1080/14728222.2017.1397627
|
20 |
Dewhirst FE, Chen T, Izard J,Paster BJ, Tanner AC, Yu WH, Lakshmanan A, Wade WG (2010) The human oral microbiome. J Bacteriol 192:5002–5017
|
21 |
Dickson RP, Huffnagle GB (2015) The lung microbiome: new principles for respiratory bacteriology in health and disease. PLoS Pathog 11:e1004923
|
22 |
Dobson AJ, Chaston JM, Newell PD, Donahue L, Hermann SL, Sannino DR, Westmiller S, Wong AC, Clark AG, Lazzaro BP
|
23 |
Dominianni C, Sinha R, Goedert JJ, Pei Z, Yang L, Hayes RB, Ahn J(2015) Sex, body mass index, and dietary fiber intake influence the human gut microbiome. PLoS One 10:e0124599
|
24 |
Dudbridge F (2013) Power and predictive accuracy of polygenic risk scores. Plos Genet 9:e1003348
|
25 |
Ellis JG (2017) Can plant microbiome studies lead to effective biocontrol of plant diseases? Mol Plant-Microbe Interact 30:190–193
|
26 |
Falony G, Joossens M, Vieira-Silva S, Wang J, Darzi Y, Faust K, Kurilshikov A, Bonder MJ, Valles-Colomer M, Vandeputte D
|
27 |
Foster J, Neufeld KA (2014) Gut-brain axis: How the microbiome influences anxiety and depression. Int J Neuropsychopharmacol 17:27
|
28 |
Gampa A, Engen PA, Shobar R,Mutlu EA (2017) Relationships between gastrointestinal microbiota and blood group antigens. Physiol Genom 49:473–483
|
29 |
Goodrich JK, Waters JL, Poole AC, Sutter JL, Koren O, Blekhman R, Beaumont M,Van Treuren W, Knight R, Bell JT
|
30 |
Goodrich JK, Davenport ER, Beaumont M, Jackson MA, Knight R, Ober C, Spector TD, Bell JT, Clark AG, Ley RE (2016) Genetic determinants of the gut microbiome in UK twins. Cell Host Microbe 19:731–743
|
31 |
Grice EA, Segre JA (2011) The skin microbiome. Nat Rev Microbiol 9:244–253
|
32 |
Gupta S (2016) Infectious disease: something in the water. Nature 533:S114–S115
|
33 |
Hall AB, Tolonen AC, Xavier RJ (2017) Human genetic variation and the gut microbiome in disease. Nat Rev Genet 18:690
|
34 |
Hanauer SB (2006) Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis 12(Suppl 1):S3–S9
|
35 |
Hirschhorn JN, Daly MJ (2005) Genome-wide association studies for common diseases and complex traits. Nat Rev Genet 6:95–108
|
36 |
Hooper LV, Littman DR, Macpherson AJ (2012) Interactions between the microbiota and the immune system. Science 336:1268–1273
|
37 |
Horton MW, Bodenhausen N, Beilsmith K, Meng DZ, Muegge BD, Subramanian S, Vetter MM, Vilhjalmsson BJ, Nordborg M, Gordon JI
|
38 |
Hov JR, Zhong HZ, Qin BC, Anmarkrud JA, Holm K, Franke A, Lie BA, Karlsen TH (2015) The influence of the autoimmunityassociated ancestral HLA haplotype AH8.1 on the human gut microbiota: a cross-sectional study. Plos One 10:e0133804
|
39 |
Jin D, Wu S, Zhang YG, Lu R, Xia Y, Dong H, Sun J (2015) Lack of vitamin D receptor causes dysbiosis and changes the functions of the murine intestinal microbiome. Clin Ther 37(5):996.e7–1009. e7.https://doi.org/10.1016/j.clinthera.2015.04.004
|
40 |
Jones EA, Kananurak A, Bevins CL, Hollox EJ, Bakaletz LO (2014) Copy number variation of the beta defensin gene cluster on chromosome 8p influences the bacterial microbiota within the nasopharynx of otitis-prone children. PLoS One. 9(5):e98269. https://doi.org/10.1371/journal.pone.0098269
|
41 |
Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, Lee JC, Schumm LP, Sharma Y, Anderson CA
|
42 |
Kamada N, Seo SU, Chen GY, Nunez G (2013) Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol 13:321–335
|
43 |
Kang HM, Zaitlen NA, Wade CM, Kirby A, Heckerman D, Daly MJ, Eskin E (2008) Efficient control of population structure in model organism association mapping. Genetics 178:1709–1723
|
44 |
Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI (2011) Human nutrition, the gut microbiome and the immune system. Nature 474:327–336
|
45 |
Kieser KJ, Kagan JC (2017) Multi-receptor detection of individual bacterial products by the innate immune system. Nat Rev Immunol 17:376–390
|
46 |
Kökten T, Gibot S, Lepage P, D’Alessio S, Hablot J, Ndiaye NC, Busby-Venner H, Monot C, Garnier B, Moulin D, Jouzeau JY, Hansmannel F, Danese S, Guéant JL, Muller S, Peyrin-Biroulet L (2018) TREM-1 inhibition restores impaired autophagy activity and reduces colitis in mice. J Crohns Colitis 12(2):230–244. https://doi.org/10.1093/ecco-jcc/jjx129
|
47 |
Kostic AD, Xavier RJ, Gevers D (2014) The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology 146:1489–1499
|
48 |
Kostic AD, Gevers D, Siljander H, Vatanen T,Hyotylainen T, Hamalainen AM, Peet A, Tillmann V, Poho P, Mattila I
|
49 |
Kozik AJ, Nakatsu CH, Chun H, Jones-Hall YL (2017) Age, sex, and TNF associated differences in the gut microbiota of mice and their impact on acute TNBS colitis. Exp Mol Pathol 103(3):311–319. https://doi.org/10.1016/j.yexmp.2017.11.014
|
50 |
Kubinak JL, Stephens WZ, Soto R, Petersen C, Chiaro T, Gogokhia L, Bell R, Ajami NJ, Petrosino JF, Morrison L, Potts WK, Jensen PE, O’Connell RM, Round JL (2015a) MHC variation sculpts individualized microbial communities that control susceptibility to enteric infection. Nat Commun. 23(6):8642. https://doi.org/10.1038/ncomms9642
|
51 |
Kubinak JL, Stephens WZ, Soto R, Petersen C, Chiaro T, Gogokhia L, Bell R, Ajami NJ, Petrosino JF, Morrison L
|
52 |
Kurilshikov A, Wijmenga C, Fu J, Zhernakova A (2017) Host genetics and gut microbiome: challenges and perspectives. Trends Immunol 38:633–647
|
53 |
Lahti L, Salojarvi J, Salonen A, Scheffer M, de Vos WM (2014) Tipping elements in the human intestinal ecosystem. Nat Commun.https://doi.org/10.1038/ncomms5344
|
54 |
Lamas B, Richard ML, Leducq V, Pham HP, Michel ML, Da Costa G, Bridonneau C, Jegou S, Hoffmann TW, Natividad JM, Brot L, Taleb S, Couturier-Maillard A, Nion-Larmurier I, Merabtene F, Seksik P, Bourrier A, Cosnes J, Ryffel B, Beaugerie L, Launay JM, Langella P, Xavier RJ, Sokol H (2016) CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat Med. 22(6):598–605. https://doi.org/10.1038/nm.4102
|
55 |
Larsson E, Tremaroli V, Lee YS, Koren O, Nookaew I, Fricker A, Nielsen J, Ley RE, Bäckhed F (2012) Analysis of gut microbial regulation of host gene expression along the length of the gut and regulation of gut microbial ecology through MyD88. Gut 61 (8):1124–1131. https://doi.org/10.1136/gutjnl-2011-301104
|
56 |
Leamy LJ, Kelly SA, Nietfeldt J, Legge RM, Ma F, Hua K, Sinha R, Peterson DA, Walter J, Benson AK
|
57 |
Lee SY, Yu J, Ahn KM, Kim KW, Shin YH, Lee KS, Hong SA, Jung YH, Lee E, Yang SI, Seo JH, Kwon JW, Kim BJ, Kim HB, Kim WK, Song DJ, Jang GC, Shim JY, Lee SY, Kwon JY, Choi SJ, Lee KJ, Park HJ, Won HS, Yoo HS, Kang MJ, Kim HY, Hong SJ (2014) Additive effect between IL-13 polymorphism and cesarean section delivery/prenatal antibiotics use on atopic dermatitis: a birth cohort study (COCOA). PLoS One. 9(5):e96603. https://doi.org/10.1371/journal.pone.0096603
|
58 |
Ley R, Lozupone CA, Hamady M, Knight R, Gordon JI (2008) Worlds within worlds: evolution of the vertebrate gut microbiota. Nat Rev Microbiol 6(10):776–788. https://doi.org/10.1038/nrmicro1978
|
59 |
Li D, Achkar JP, Haritunians T, Jacobs JP, Hui KY, D’Amato M, Brand S, Radford-Smith G, Halfvarson J, Niess JH, Kugathasan S, Büning C, Schumm LP, Klei L, Ananthakrishnan A, Aumais G, Baidoo L, Dubinsky M, Fiocchi C, Glas J, Milgrom R, Proctor DD, Regueiro M, Simms LA, Stempak JM, Targan SR, Törkvist L, Sharma Y, Devlin B, Borneman J, Hakonarson H, Xavier RJ, Daly M, Brant SR, Rioux JD, Silverberg MS, Cho JH, Braun J, McGovern DP, Duerr RH (2016) A pleiotropic missense variant in SLC39A8 is associated with Crohn’s Disease and human gut microbiome composition. Gastroenterology 151(4):724–732. https://doi.org/10.1053/j.gastro.2016.06.051
|
60 |
Lo Sasso G, Ryu D, Mouchiroud L, Fernando SC, Anderson CL, Katsyuba E, Piersigilli A, Hottiger MO, Schoonjans K, Auwerx J (2014) Loss of Sirt1 function improves intestinal anti-bacterial defense and protects from colitis-induced colorectal cancer. PLoS One. 9(7):e102495. https://doi.org/10.1371/journal.pone. 0102495
|
61 |
Lozupone C, Lladser ME, Knights D, Stombaugh J, Knight R (2011) UniFrac: an effective distance metric for microbial community comparison. Isme Journal 5:169–172
|
62 |
Lundberg DS, Lebeis SL, Paredes SH, Yourstone S, Gehring J, Malfatti S, Tremblay J, Engelbrektson A, Kunin V, Del Rio TG
|
63 |
McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J, Ioannidis JP, Hirschhorn JN (2008) Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet 9:356–369
|
64 |
McGovern DPB, Jones MR, Taylor KD, Marciante K, Yan XF, Dubinsky M, Ippoliti A, Vasiliauskas E, Berel D, Derkowski C
|
65 |
McKnite AM, Perez-Munoz ME, Lu L, Williams EG, Brewer S, Andreux PA, Bastiaansen JWM, Wang XS, Kachman SD, Auwerx J
|
66 |
Milot E, Pelletier F (2013) Human evolution: new playgrounds for natural selection. Curr Biol 23:R446–R448
|
67 |
Moalem S, Prince J (2008) Survival of the sickest: the surprising connections between disease and longevity. Harper, London
|
68 |
Moeller AH, Li Y, Mpoudi Ngole E, Ahuka-Mundeke S, Lonsdorf EV, Pusey AE, Peeters M, Hahn BH, Ochman H (2014) Rapid changes in the gut microbiome during human evolution. Proc Natl Acad Sci USA 111:16431–16435
|
69 |
Morgan XC, Tickle TL, Sokol H, Gevers D, Devaney KL, Ward DV, Reyes JA, Shah SA, LeLeiko N, Snapper SB
|
70 |
Moschen AR, Gerner RR, Wang J, Klepsch V, Adolph TE, Reider SJ, Hackl H, Pfister A, Schilling J, Moser PL, Kempster SL, Swidsinski A, Orth Höller D, Weiss G, Baines JF, Kaser A, Tilg H (2016) Lipocalin 2 protects from inflammation and tumorigenesis associated with gut microbiota alterations. Cell Host Microbe. 19(4):455–469. https://doi.org/10.1016/j.chom.2016.03.007
|
71 |
Nakagome S, Chinen H, Iraha A, Hokama A, Takeyama Y, Sakisaka S, Matsui T, Kidd JR, Kidd KK, Said HS, Suda W, Morita H, Hattori M, Hanihara T, Kimura R, Ishida H, Fujita J, Kinjo F, Mano S, Oota H (2017) Confounding effects of microbiome on the susceptibility of TNFSF15 to Crohn’s disease in the Ryukyu Islands. Hum Genet. 136(4):387–397. https://doi.org/10.1007/s00439-017-1764-0
|
72 |
Neefjes J, Jongsma ML, Paul P, Bakke O (2011) Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat Rev Immunol 11:823–836
|
73 |
Nester EW (2015) Agrobacterium: nature’s genetic engineer. Front Plant Sci 5:730
|
74 |
Nielsen R, Hellmann I, Hubisz M, Bustamante C, Clark AG (2007) Recent and ongoing selection in the human genome. Nat Rev Genet 8:857–868
|
75 |
Nishida AH, Ochman H (2017) Rates of gut microbiome divergence in mammals. Mol Ecol
|
76 |
Nissilä E, Korpela K, Lokki AI, Paakkanen R, Jokiranta S, de Vos WM, Lokki ML, Kolho KL, Meri S (2017) C4B gene influences intestinal microbiota through complement activation in patients with paediatric-onset inflammatory bowel disease. Clin Exp Immunol. 190(3):394–405. https://doi.org/10.1111/cei.13040
|
77 |
Novembre J, Han EJ (2012) Human population structure and the adaptive response to pathogen-induced selection pressures. Philos Trans R Soc B 367:878–886
|
78 |
Ochman H, Worobey M, Kuo CH, Ndjango JB, Peeters M, Hahn BH, Hugenholtz P (2010) Evolutionary relationships of wild hominids recapitulated by gut microbial communities. PLoS Biol 8:e1000546
|
79 |
Org E, Parks BW, Joo JW, Emert B, Schwartzman W, Kang EY, Mehrabian M, Pan C, Knight R, Gunsalus R
|
80 |
Peuker K, Muff S, Wang J, Künzel S, Bosse E, Zeissig Y, Luzzi G, Basic M, Strigli A, Ulbricht A, Kaser A, Arlt A, Chavakis T, van den Brink GR, Schafmayer C, Egberts JH, Becker T, Bianchi ME, Bleich A, Röcken C, Hampe J, Schreiber S,Baines JF , Blumberg RS, Zeissig S (2016) Epithelial calcineurin controls microbiotadependent intestinal tumor development. Nat Med. 22(5):506–515. https://doi.org/10.1038/nm.4072
|
81 |
Pohjanen VM, Koivurova OP, Niemelä SE, Karttunen RA, Karttunen TJ (2016) Role of Helicobacter pylori and interleukin 6–174 gene polymorphism in dyslipidemia: a case-control study. BMJ Open. 6 (1):e009987. https://doi.org/10.1136/bmjopen-2015-009987
|
82 |
Price AL, Zaitlen NA, Reich D, Patterson N (2010) New approaches to population stratification in genome-wide association studies. Nat Rev Genet 11:459–463
|
83 |
Prugnolle F, Manica A, Charpentier M, Guegan JF, Guernier V,Balloux F (2005) Pathogen-driven selection and worldwide HLA class I diversity. Curr Biol 15:1022–1027
|
84 |
Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T
|
85 |
Ramanan VK, Shen L, Moore JH, Saykin AJ (2012) Pathway analysis of genomic data: concepts, methods, and prospects for future development. Trends Genet 28:323–332
|
86 |
Rausch P,Rehman A, Künzel S, Häsler R, Ott SJ, Schreiber S, Rosenstiel P, Franke A, Baines JF (2011a) Colonic mucosaassociated microbiota is influenced by an interaction of Crohn disease and FUT2 (Secretor) genotype. Proc Natl Acad Sci USA 108(47):19030–19035. https://doi.org/10.1073/pnas.1106408108
|
87 |
Rausch P, Rehman A, Kunzel S, Hasler R, Ott SJ, Schreiber S, Rosenstiel P, Franke A, Baines JF (2011b) Colonic mucosaassociated microbiota is influenced by an interaction of Crohn disease and FUT2 (Secretor) genotype. Proc Natl Acad Sci USA 108:19030–19035
|
88 |
Rausch P, Steck N, Suwandi A, Seidel JA, Künzel S, Bhullar K, Basic M, Bleich A, Johnsen JM, Vallance BA, Baines JF, Grassl GA (2015) Expression of the blood-group-related gene B4galnt2 alters susceptibility to salmonella infection. PLoS Pathog 11(7): e1005008. https://doi.org/10.1371/journal.ppat.1005008
|
89 |
Rausch P, Künzel S, Suwandi A, Grassl GA, Rosenstiel P, Baines JF (2017) Multigenerational influences of the Fut2 gene on the dynamics of the gut microbiota in mice. Front Microbiol. 8:991. https://doi.org/10.3389/fmicb.2017.00991
|
90 |
Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SSK, McCulle SL, Karlebach S, Gorle R, Russell J, Tacket CO
|
91 |
Ray K (2017) Alcoholic liver disease: gut-liver axis: PPIs, enterococcus and promotion of alcoholic liver disease. Nat Rev Gastroenterol Hepatol 14:689
|
92 |
Rodriguez-Nunez I, Caluag T, Kirby K, Rudick CN, Dziarski R, Gupta D (2017) Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction. Sci Rep. 7(1):548. https://doi.org/10.1038/s41598-017-00484-2
|
93 |
Rothhammer V, Mascanfroni ID, Bunse L, Takenaka MC, Kenison JE, Mayo L, Chao CC, Patel B, Yan R, Blain M, Alvarez JI, Kébir H,Anandasabapathy N , Izquierdo G, Jung S, Obholzer N, Pochet N, Clish CB, Prinz M, Prat A, Antel J, Quintana FJ (2016) Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat Med. 22(6):586–597. https://doi.org/10.1038/nm.4106 Epub 2016 May 9
|
94 |
Ruhlemann MC, Degenhardt F, Thingholm LB, Wang J, Skieceviciene J, Rausch P, Hov JR, Lieb W, Karlsen TH, Laudes M
|
95 |
Sadaghian Sadabad M, Regeling A, de Goffau MC, Blokzijl T, Weersma RK, Penders J, Faber KN, Harmsen HJ, Dijkstra G (2015) The ATG16L1-T300A allele impairs clearance of pathosymbionts in the inflamed ileal mucosa of Crohn’s disease patients. Gut. 64(10):1546–1552. https://doi.org/10.1136/gutjnl-2014-307289
|
96 |
Santos-Cortez RL, Hutchinson DS, Ajami NJ, Reyes-Quintos MR, Tantoco ML, Labra PJ, Lagrana SM, Pedro M, Llanes EG, Gloria-Cruz TL, Chan AL, Cutiongco-de la Paz EM, Belmont JW, Chonmaitree T, Abes GT, Petrosino JF, Leal SM, Chiong CM (2016) Middle ear microbiome differences in indigenous Filipinos with chronic otitis media due to a duplication in the A2ML1 gene. Infect Dis Poverty 5(1):97
|
97 |
Sender R, Fuchs S,Milo R (2016) Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell 164:337–340
|
98 |
Sovran B, Loonen LM, Lu P, Hugenholtz F, Belzer C, Stolte EH, Boekschoten MV, van Baarlen P, Kleerebezem M, de Vos P, Dekker J, Renes IB, Wells JM (2015) IL-22-STAT3 pathway plays a key role in the maintenance of ileal homeostasis in mice lacking secreted mucus barrier. Inflamm Bowel Dis. 21(3):531–542. https://doi.org/10.1097/MIB.0000000000000319
|
99 |
Spor A, Koren O, Ley R (2011) Unravelling the effects of the environment and host genotype on the gut microbiome. Nat Rev Microbiol 9:279–290
|
100 |
Srinivas G, Moller S, Wang J, Kunzel S, Zillikens D, Baines JF, Ibrahim SM (2013) Genome-wide mapping of gene-microbiota interactions in susceptibility to autoimmune skin blistering. Nat Commun 4:2462
|
101 |
Staubach F, Kunzel S, Baines AC, Yee A, McGee BM, Backhed F, Baines JF, Johnsen JM (2012) Expression of the blood-grouprelated glycosyltransferase B4galnt2 influences the intestinal microbiota in mice. ISME J 6:1345–1355
|
102 |
Stein JM, Lammert F, Zimmer V, Granzow M, Reichert S, Schulz S, Ocklenburg C, Conrads G (2010) Clinical periodontal and microbiologic parameters in patients with Crohn’s disease with consideration of the CARD15 genotype. J Periodontol. 81(4):535–545
|
103 |
Taylor SL, Woodman RJ, Chen AC, Burr LD, Gordon DL, McGuckin MA, Wesselingh S, Rogers GB (2017) FUT2 genotype influences lung function, exacerbation frequency and airway microbiota in non-CF bronchiectasis. Thorax 72(4):304–310. https://doi.org/10.1136/thoraxjnl-2016-208775
|
104 |
Thingholm L, Rühlemann M, Wang J, Hübenthal M, Lieb W, Laudes M, Franke A, D’Amato M (2018) Sucrase-isomaltase 15Phe IBS risk variant in relation to dietary carbohydrates and faecal microbiota composition. Gut. https://doi.org/10.1136/gutjnl-2017-315841
|
105 |
Tschurtschenthaler M, Wang J, Fricke C, Fritz TM, Niederreiter L, Adolph TE, Sarcevic E, Künzel S, Offner FA, Kalinke U, Baines JF, Tilg H, Kaser A (2014) Type I interferon signalling in the intestinal epithelium affects Paneth cells, microbial ecology and epithelial regeneration. Gut. 63(12):1921–1931. https://doi.org/10.1136/gutjnl-2013-305863
|
106 |
Turpin W, Espin-Garcia O, Xu W, Silverberg MS, Kevans D, Smith MI, Guttman DS, Griffiths A, Panaccione R, Otley A
|
107 |
Vallier M, Abou Chakra M, Hindersin L, Linnenbrink M, Traulsen A, Baines JF (2017) Evaluating the maintenance of disease-associated variation at the blood group-related gene B4galnt2 in house mice. BMC Evol Biol 17:187
|
108 |
Walter J, Ley R (2011) The human gut microbiome: ecology and recent evolutionary changes. Ann Rev Microbiol 65(65):411–429
|
109 |
Wang J, Kalyan S, Steck N, Turner LM, Harr B, Kunzel S, Vallier M, Hasler R, Franke A, Oberg HH
|
110 |
Wang J, Thingholm LB, Skieceviciene J, Rausch P, Kummen M, Hov JR, Degenhardt F, Heinsen FA, Ruhlemann MC, Szymczak S
|
111 |
Ward MA, Pierre JF, Leal RF, Huang Y, Shogan B, Dalal SR, Weber CR, Leone VA, Musch MW, An GC, Rao MC, Rubin DT, Raffals LE, Antonopoulos DA, Sogin ML, Hyman NH, Alverdy JC, Chang EB (2016) Insights into the pathogenesis of ulcerative colitis from a murine model of stasis-induced dysbiosis, colonic metaplasia, and genetic susceptibility. Am J Physiol Gastrointest Liver Physiol. 310(11):G973–G988. https://doi.org/10.1152/ajpgi.00017.2016
|
112 |
Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, Stonebraker AC, Hu C, Wong FS, Szot GL, Bluestone JA
|
113 |
Wernegreen JJ (2002) Genome evolution in bacterial endosymbionts of insects. Nat Rev Genet 3:850–861
|
114 |
World Health Organization (2016) Global tuberculosis report 2016. WHO, Geneva
|
115 |
Xavier RJ, Podolsky DK (2007) Unravelling the pathogenesis of inflammatory bowel disease. Nature 448:427–434
|
116 |
Xie HL, Guo RJ, Zhong HZ, Feng Q, Lan Z, Qin BC, Ward KJ, Jackson MA, Xia Y, Chen X
|
117 |
Yassour M, Vatanen T, Siljander H, Hamalainen AM, Harkonen T, Ryhanen SJ, Franzosa EA, Vlamakis H, Huttenhower C, Gevers D
|
118 |
Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP
|
119 |
Ye Y, Carlsson G, Wondimu B, Fahlén A, Karlsson-Sjöberg J, Andersson M,Engstrand L, Yucel-Lindberg T, Modéer T, Pütsep K (2011) Mutations in the ELANE gene are associated with development of periodontitis in patients with severe congenital neutropenia. J Clin Immunol. 31(6):936–945. https://doi.org/10.1007/s10875-011-9572-0 Epub 2011 Jul 29
|
120 |
Zhao L, Wang G,Siegel P, He C, Wang H, Zhao W, Zhai Z, Tian F, Zhao J, Zhang H
|
121 |
Zhernakova A, Kurilshikov A, Bonder MJ, Tigchelaar EF, Schirmer M, Vatanen T, Mujagic Z, Vila AV, Falony G, Vieira-Silva S
|
122 |
Zhu B, Wang X, Li L (2010) Human gut microbiome: the second genome of human body. Protein Cell 1:718–725
|
123 |
Zilber-Rosenberg I, Rosenberg E (2008) Role of microorganisms in the evolution of animals and plants: the hologenome theory of evolution. FEMS Microbiol Rev 32:723–735
|
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