REFERENCES
1. Bäckhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science 2005;307:1915-20.
2. Gilbert JA, Blaser MJ, Caporaso JG, Jansson JK, Lynch SV, Knight R. Current understanding of the human microbiome. Nat Med 2018;24:392-400.
3. Qin J, Li R, Raes J, et al. MetaHIT Consortium. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010;464:59-65.
4. Natividad JM, Verdu EF. Modulation of intestinal barrier by intestinal microbiota: pathological and therapeutic implications. Pharmacol Res 2013;69:42-51.
5. Gensollen T, Iyer SS, Kasper DL, Blumberg RS. How colonization by microbiota in early life shapes the immune system. Science 2016;352:539-44.
6. Fischbach MA, Sonnenburg JL. Eating for two: how metabolism establishes interspecies interactions in the gut. Cell Host Microbe 2011;10:336-47.
7. Ahmad A, Yang W, Chen G, et al. Analysis of gut microbiota of obese individuals with type 2 diabetes and healthy individuals. PLoS One 2019;14:e0226372.
8. Cho I, Blaser MJ. The human microbiome: at the interface of health and disease. Nat Rev Genet 2012;13:260-70.
9. Ferrer M, Ruiz A, Lanza F, et al. Microbiota from the distal guts of lean and obese adolescents exhibit partial functional redundancy besides clear differences in community structure. Environ Microbiol 2013;15:211-26.
10. Turnbaugh PJ, Hamady M, Yatsunenko T, et al. A core gut microbiome in obese and lean twins. Nature 2009;457:480-4.
11. Zhang X, Shen D, Fang Z, et al. Human gut microbiota changes reveal the progression of glucose intolerance. PLoS One 2013;8:e71108.
12. Gevers D, Kugathasan S, Denson LA, et al. The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe 2014;15:382-92.
13. Lloyd-Price J, Arze C, Ananthakrishnan AN, et al. IBDMDB Investigators. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature 2019;569:655-62.
14. Morgan XC, Tickle TL, Sokol H, et al. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol 2012;13:R79.
15. Pascal V, Pozuelo M, Borruel N, et al. A microbial signature for Crohn’s disease. Gut 2017;66:813-22.
16. Sartor RB. The intestinal microbiota in inflammatory bowel diseases. Nestle Nutr Inst Workshop Ser 2014;79:29-39.
17. Schirmer M, Garner A, Vlamakis H, Xavier RJ. Microbial genes and pathways in inflammatory bowel disease. Nat Rev Microbiol 2019;17:497-511.
18. Baxter NT, Zackular JP, Chen GY, Schloss PD. Structure of the gut microbiome following colonization with human feces determines colonic tumor burden. Microbiome 2014;2:20.
19. Flemer B, Lynch DB, Brown JM, et al. Tumour-associated and non-tumour-associated microbiota in colorectal cancer. Gut 2017;66:633-43.
20. Zeller G, Tap J, Voigt AY, et al. Potential of fecal microbiota for early-stage detection of colorectal cancer. Mol Syst Biol 2014;10:766.
22. Kaplan GG. The global burden of IBD: from 2015 to 2025. Nat Rev Gastroenterol Hepatol 2015;12:720-7.
23. Saeedi P, Petersohn I, Salpea P, et al. IDF Diabetes Atlas Committee. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract 2019;157:107843.
24. Loos RJF, Yeo GSH. The genetics of obesity: from discovery to biology. Nat Rev Genet 2022;23:120-33.
25. Bogaert J, Prenen H. Molecular genetics of colorectal cancer. Ann Gastroenterol 2014;27:9-14. Available from:
26. Safiri S, Sepanlou SG, Ikuta KS, et al. The global, regional, and national burden of colorectal cancer and its attributable risk factors in 195 countries and territories, 1990-2017: a systematic analysis for the global burden of disease study 2017. The Lancet Gastroenterology & Hepatology 2019;4:913-33.
27. Wu S, Powers S, Zhu W, Hannun YA. Substantial contribution of extrinsic risk factors to cancer development. Nature 2016;529:43-7.
28. Guan Q. A comprehensive review and update on the pathogenesis of inflammatory bowel disease. J Immunol Res 2019;2019:7247238.
29. Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature 2011;474:307-17.
30. Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 2009;9:313-23.
31. Forslund K, Hildebrand F, Nielsen T, et al. MetaHIT Consortium. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 2015;528:262-6.
32. He Y, Wu W, Zheng HM, et al. Regional variation limits applications of healthy gut microbiome reference ranges and disease models. Nat Med 2018;24:1532-5.
33. Reitmeier S, Kiessling S, Clavel T, et al. Arrhythmic gut microbiome signatures predict risk of type 2 diabetes. Cell Host Microbe 2020;28:258-272.e6.
34. Ananthakrishnan AN, Luo C, Yajnik V, et al. Gut microbiome function predicts response to anti-integrin biologic therapy in inflammatory bowel diseases. Cell Host Microbe 2017;21:603-610.e3.
35. Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A 2007;104:13780-5.
36. Sokol H, Pigneur B, Watterlot L, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A 2008;105:16731-6.
37. Strauss J, Kaplan GG, Beck PL, et al. Invasive potential of gut mucosa-derived Fusobacterium nucleatum positively correlates with IBD status of the host. Inflamm Bowel Dis 2011;17:1971-8.
38. Ahn J, Sinha R, Pei Z, et al. Human gut microbiome and risk for colorectal cancer. J Natl Cancer Inst 2013;105:1907-11.
39. Wang T, Cai G, Qiu Y, et al. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J 2012;6:320-9.
40. Viljoen KS, Dakshinamurthy A, Goldberg P, Blackburn JM. Quantitative profiling of colorectal cancer-associated bacteria reveals associations between fusobacterium spp., enterotoxigenic Bacteroides fragilis (ETBF) and clinicopathological features of colorectal cancer. PLoS One 2015;10:e0119462.
41. Bäckhed F, Ding H, Wang T, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A 2004;101:15718-23.
42. Bäckhed F, Manchester JK, Semenkovich CF, Gordon JI. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci U S A 2007;104:979-84.
43. Fleissner CK, Huebel N, Abd El-Bary MM, Loh G, Klaus S, Blaut M. Absence of intestinal microbiota does not protect mice from diet-induced obesity. Br J Nutr 2010;104:919-29.
44. Kübeck R, Bonet-Ripoll C, Hoffmann C, et al. Dietary fat and gut microbiota interactions determine diet-induced obesity in mice. Mol Metab 2016;5:1162-74.
45. Adolph TE, Tomczak MF, Niederreiter L, et al. Paneth cells as a site of origin for intestinal inflammation. Nature 2013;503:272-6.
46. Kaser A, Lee AH, Franke A, et al. XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell 2008;134:743-56.
47. Roulis M, Bongers G, Armaka M, et al. Host and microbiota interactions are critical for development of murine Crohn’s-like ileitis. Mucosal Immunol 2016;9:787-97.
48. Schaubeck M, Clavel T, Calasan J, et al. Dysbiotic gut microbiota causes transmissible Crohn’s disease-like ileitis independent of failure in antimicrobial defence. Gut 2016;65:225-37.
49. Steck N, Hoffmann M, Sava IG, et al. Enterococcus faecalis metalloprotease compromises epithelial barrier and contributes to intestinal inflammation. Gastroenterology 2011;141:959-971.
50. Lengfelder I, Sava IG, Hansen JJ, et al. Complex bacterial consortia reprogram the colitogenic activity of Enterococcus faecalis in a gnotobiotic mouse model of chronic, immune-mediated colitis. Front Immunol 2019;10:1420.
51. Chu FF, Esworthy RS, Chu PG, et al. Bacteria-induced intestinal cancer in mice with disrupted Gpx1 and Gpx2 genes. Cancer Res 2004;64:962-8.
52. Uronis JM, Mühlbauer M, Herfarth HH, Rubinas TC, Jones GS, Jobin C. Modulation of the intestinal microbiota alters colitis-associated colorectal cancer susceptibility. PLoS One 2009;4:e6026.
53. Coleman OI, Lobner EM, Bierwirth S, et al. Activated ATF6 induces intestinal dysbiosis and innate immune response to promote colorectal tumorigenesis. Gastroenterology 2018;155:1539-1552.e12.
54. Benchimol EI, Manuel DG, To T, et al. Asthma, type 1 and type 2 diabetes mellitus, and inflammatory bowel disease amongst South Asian immigrants to Canada and their children: a population-based cohort study. PLoS One 2015;10:e0123599.
55. Britton GJ, Contijoch EJ, Mogno I, et al. Microbiotas from humans with inflammatory bowel disease alter the balance of gut Th17 and RORγt+ regulatory T cells and exacerbate colitis in mice. Immunity 2019;50:212-224.e4.
56. Goodrich JK, Waters JL, Poole AC, et al. Human genetics shape the gut microbiome. Cell 2014;159:789-99.
57. Kaiser T, Nalluri H, Zhu Z, Staley C. Donor microbiota composition and housing affect recapitulation of obese phenotypes in a human microbiota-associated murine model. Front Cell Infect Microbiol 2021;11:614218.
58. Lavoie S, Conway KL, Lassen KG, et al. The Crohn’s disease polymorphism, ATG16L1 T300A, alters the gut microbiota and enhances the local Th1/Th17 response. Elife 2019;8:e39982.
59. Li L, Li X, Zhong W, et al. Gut microbiota from colorectal cancer patients enhances the progression of intestinal adenoma in Apcmin/+ mice. EBioMedicine 2019;48:301-15.
60. Metwaly A, Dunkel A, Waldschmitt N, et al. Integrated microbiota and metabolite profiles link Crohn’s disease to sulfur metabolism. Nat Commun 2020;11:4322.
61. Nagao-Kitamoto H, Shreiner AB, Gillilland MG 3rd, et al. Functional characterization of inflammatory bowel disease-associated gut dysbiosis in gnotobiotic mice. Cell Mol Gastroenterol Hepatol 2016;2:468-81.
62. Parker KD, Maurya AK, Ibrahim H, et al. Dietary rice bran-modified human gut microbial consortia confers protection against colon carcinogenesis following fecal transfaunation. Biomedicines 2021;9:144.
63. Ridaura VK, Faith JJ, Rey FE, et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 2013;341:1241214.
64. Soderborg TK, Clark SE, Mulligan CE, et al. The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD. Nat Commun 2018;9:4462.
65. Torres J, Hu J, Seki A, et al. Infants born to mothers with IBD present with altered gut microbiome that transfers abnormalities of the adaptive immune system to germ-free mice. Gut 2020;69:42-51.
66. Wong SH, Zhao L, Zhang X, et al. Gavage of fecal samples from patients with colorectal cancer promotes intestinal carcinogenesis in germ-free and conventional mice. Gastroenterology 2017;153:1621-1633.e6.
67. Zhang L, Bahl MI, Roager HM, et al. Environmental spread of microbes impacts the development of metabolic phenotypes in mice transplanted with microbial communities from humans. ISME J 2017;11:676-90.
68. Ahmed BA, Ong FJ, Barra NG, et al. Lower brown adipose tissue activity is associated with non-alcoholic fatty liver disease but not changes in the gut microbiota. Cell Rep Med 2021;2:100397.
69. Arnoriaga-Rodríguez M, Mayneris-Perxachs J, Burokas A, et al. Obesity impairs short-term and working memory through gut microbial metabolism of aromatic amino acids. Cell Metab 2020;32:548-560.e7.
70. Fujimoto K, Kawaguchi Y, Shimohigoshi M, et al. Antigen-specific mucosal immunity regulates development of intestinal bacteria-mediated diseases. Gastroenterology 2019;157:1530-1543.e4.
71. Halatchev IG, O’Donnell D, Hibberd MC, Gordon JI. Applying indirect open-circuit calorimetry to study energy expenditure in gnotobiotic mice harboring different human gut microbial communities. Microbiome 2019;7:158.
72. Trikha SRJ, Lee DM, Ecton KE, et al. Transplantation of an obesity-associated human gut microbiota to mice induces vascular dysfunction and glucose intolerance. Gut Microbes 2021;13:1940791.
73. Walter J, Armet AM, Finlay BB, Shanahan F. Establishing or exaggerating causality for the gut microbiome: lessons from human microbiota-associated rodents. Cell 2020;180:221-32.
74. Lee M, Chang EB. Inflammatory bowel diseases (IBD) and the microbiome-searching the crime scene for clues. Gastroenterology 2021;160:524-37.
75. Leystra AA, Clapper ML. Gut microbiota influences experimental outcomes in mouse models of colorectal cancer. Genes (Basel) 2019;10:900.
76. Muscogiuri G, Cantone E, Cassarano S, et al. On Behalf of the Obesity Programs of Nutrition. Gut microbiota: a new path to treat obesity. Int J Obes Suppl 2019;9:10-9.
77. Nguyen TL, Vieira-Silva S, Liston A, Raes J. How informative is the mouse for human gut microbiota research? Dis Model Mech 2015;8:1-16.
78. Park JC, Im SH. Of men in mice: the development and application of a humanized gnotobiotic mouse model for microbiome therapeutics. Exp Mol Med 2020;52:1383-96.
79. Zihler Berner A, Fuentes S, Dostal A, et al. Novel polyfermentor intestinal model (PolyFermS) for controlled ecological studies: validation and effect of pH. PLoS One 2013;8:e77772.
80. Tanner SA, Zihler Berner A, Rigozzi E, Grattepanche F, Chassard C, Lacroix C. In vitro continuous fermentation model (PolyFermS) of the swine proximal colon for simultaneous testing on the same gut microbiota. PLoS One 2014;9:e94123.
81. Dostal A, Lacroix C, Bircher L, et al. Iron modulates butyrate production by a child gut microbiota in vitro. mBio 2015;6:e01453-15.
82. Geirnaert A, Wang J, Tinck M, et al. Interindividual differences in response to treatment with butyrate-producing butyricicoccus pullicaecorum 25-3T studied in an in vitro gut model. FEMS Microbiol Ecol 2015;91:fiv054.
83. Lacroix C, de Wouters T, Chassard C. Integrated multi-scale strategies to investigate nutritional compounds and their effect on the gut microbiota. Curr Opin Biotechnol 2015;32:149-55.
84. McDonald JA, Fuentes S, Schroeter K, et al. Simulating distal gut mucosal and luminal communities using packed-column biofilm reactors and an in vitro chemostat model. J Microbiol Methods 2015;108:36-44.
85. Payne AN, Zihler A, Chassard C, Lacroix C. Advances and perspectives in in vitro human gut fermentation modeling. Trends Biotechnol 2012;30:17-25.
86. Cinquin C, Le Blay G, Fliss I, Lacroix C. New three-stage in vitro model for infant colonic fermentation with immobilized fecal microbiota. FEMS Microbiol Ecol 2006;57:324-36.
87. Cinquin C, Le Blay G, Fliss I, Lacroix C. Immobilization of infant fecal microbiota and utilization in an in vitro colonic fermentation model. Microb Ecol 2004;48:128-38.
88. Macfarlane GT, Macfarlane S. Models for intestinal fermentation: association between food components, delivery systems, bioavailability and functional interactions in the gut. Curr Opin Biotechnol 2007;18:156-62.
89. Van den Abbeele P, Grootaert C, Marzorati M, et al. Microbial community development in a dynamic gut model is reproducible, colon region specific, and selective for bacteroidetes and clostridium cluster IX. Appl Environ Microbiol 2010;76:5237-46.
90. Pompei A, Cordisco L, Raimondi S, et al. In vitro comparison of the prebiotic effects of two inulin-type fructans. Anaerobe 2008;14:280-6.
91. Gumienna M, Lasik M, Czarnecki Z. Bioconversion of grape and chokeberry wine polyphenols during simulated gastrointestinal in vitro digestion. Int J Food Sci Nutr 2011;62:226-33.
92. Lesmes U, Beards EJ, Gibson GR, Tuohy KM, Shimoni E. Effects of resistant starch type III polymorphs on human colon microbiota and short chain fatty acids in human gut models. J Agric Food Chem 2008;56:5415-21.
93. Day-Walsh P, Shehata E, Saha S, et al. The use of an in-vitro batch fermentation (human colon) model for investigating mechanisms of TMA production from choline, L-carnitine and related precursors by the human gut microbiota. Eur J Nutr 2021;60:3987-99.
94. Macfarlane GT, Gibson GR, Cummings JH. Comparison of fermentation reactions in different regions of the human colon. J Appl Bacteriol 1992;72:57-64.
95. Macfarlane GT, Macfarlane S, Gibson GR. 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. Microb Ecol 1998;35:180-7.
96. Molly K, Vande Woestyne M, Verstraete W. Development of a 5-step multi-chamber reactor as a simulation of the human intestinal microbial ecosystem. Appl Microbiol Biotechnol 1993;39:254-8.
97. Venema K, van den Abbeele P. Experimental models of the gut microbiome. Best Pract Res Clin Gastroenterol 2013;27:115-26.
98. Sato T, Vries RG, Snippert HJ, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 2009;459:262-5.
99. Sato T, Stange DE, Ferrante M, et al. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology 2011;141:1762-72.
100. Kretzschmar K, Clevers H. Organoids: modeling development and the stem cell niche in a dish. Dev Cell 2016;38:590-600.
101. Nagpal R, Newman TM, Wang S, Jain S, Lovato JF, Yadav H. Obesity-linked gut microbiome dysbiosis associated with derangements in gut permeability and intestinal cellular homeostasis independent of diet. J Diabetes Res 2018;2018:3462092.
102. Howell KJ, Kraiczy J, Nayak KM, et al. DNA methylation and transcription patterns in intestinal epithelial cells from pediatric patients with inflammatory bowel diseases differentiate disease subtypes and associate with outcome. Gastroenterology 2018;154:585-98.
103. d’Aldebert E, Quaranta M, Sébert M, et al. Characterization of human colon organoids from inflammatory bowel disease patients. Front Cell Dev Biol 2020;8:363.
104. Nanki K, Fujii M, Shimokawa M, et al. Somatic inflammatory gene mutations in human ulcerative colitis epithelium. Nature 2020;577:254-9.
105. Fujii M, Shimokawa M, Date S, et al. A colorectal tumor organoid library demonstrates progressive loss of niche factor requirements during tumorigenesis. Cell Stem Cell 2016;18:827-38.
106. van de Wetering M, Francies HE, Francis JM, et al. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell 2015;161:933-45.
107. Vlachogiannis G, Hedayat S, Vatsiou A, et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science 2018;359:920-6.
108. Hasan NM, Johnson KF, Yin J, et al. Intestinal stem cell-derived enteroids from morbidly obese patients preserve obesity-related phenotypes: Elevated glucose absorption and gluconeogenesis. Mol Metab 2021;44:101129.
109. Mohammadi S, Morell-Perez C, Wright CW, et al. Assessing donor-to-donor variability in human intestinal organoid cultures. Stem Cell Reports 2021;16:2364-78.
110. Yin X, Farin HF, van Es JH, Clevers H, Langer R, Karp JM. Niche-independent high-purity cultures of Lgr5+ intestinal stem cells and their progeny. Nat Methods 2014;11:106-12.
111. Boonekamp KE, Dayton TL, Clevers H. Intestinal organoids as tools for enriching and studying specific and rare cell types: advances and future directions. J Mol Cell Biol 2020;12:562-8.
113. Han X, Mslati MA, Davies E, Chen Y, Allaire JM, Vallance BA. Creating a more perfect union: modeling intestinal bacteria-epithelial interactions using organoids. Cell Mol Gastroenterol Hepatol 2021;12:769-82.
114. Hentschel V, Seufferlein T, Armacki M. Intestinal organoids in coculture: redefining the boundaries of gut mucosa ex vivo modeling. Am J Physiol Gastrointest Liver Physiol 2021;321:G693-704.
115. Bartfeld S, Bayram T, van de Wetering M, et al. In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. Gastroenterology 2015;148:126-136.e6.
116. Co JY, Margalef-Català M, Li X, et al. Controlling epithelial polarity: a human enteroid model for host-pathogen interactions. Cell Rep 2019;26:2509-2520.e4.
117. Shin YC, Shin W, Koh D, et al. Three-dimensional regeneration of patient-derived intestinal organoid epithelium in a physiodynamic mucosal interface-on-a-chip. Micromachines (Basel) 2020;11:663.
118. Zhang J, Huang YJ, Yoon JY, et al. Primary human colonic mucosal barrier crosstalk with super oxygen-sensitive Faecalibacterium prausnitzii in continuous culture. Med (N Y) 2021;2:74-98.e9.
119. Morse H, Fox J. The mouse in biomedical research. 2nd ed. New York: Elsevier; 1981. Available from: https://books.google.com.hk/books?id=Vt6nUmz1yEQC&pg=PA144&lpg=PA144&dq=Morse,+H.+and+Fox,+J.,+The+mouse+in+biomedical+research.+1981:+Academic,+New+York&source=bl&ots=epxwhP32B4&sig=ACfU3U0SqkHTjy35-wpwzsLQ-LOJphIANA&hl=zh-CN&sa=X&ved=2ahUKEwjqneDDz7j3AhUDL6YKHX8HC4wQ6AF6BAgCEAM#v=onepage&q=Morse%2C%20H.%20and%20Fox%2C%20J.%2C%20The%20mouse%20in%20biomedical%20research.%201981%3A%20Academic%2C%20New%20York&f=false [Last accessed on 5 May 2022].
120. Zinkernagel RM, Doherty PC. Immunological surveillance against altered self components by sensitised T lymphocytes in lymphocytic choriomeningitis. Nature 1974;251:547-8.
121. Zinkernagel RM, Doherty PC. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature 1974;248:701-2.
122. Walburg HE Jr, Mynatt EI, Cosgrove GE, Tyndall RL, Robie DM. Microbiological evaluation of an isolation facility for the production of specific-pathogen-free mice. Lab Anim Care 1965;15:208-16.
123. Cox LM, Yamanishi S, Sohn J, et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell 2014;158:705-21.
124. Olszak T, An D, Zeissig S, et al. Microbial exposure during early life has persistent effects on natural killer T cell function. Science 2012;336:489-493.
125. Hintze KJ, Cox JE, Rompato G, et al. Broad scope method for creating humanized animal models for animal health and disease research through antibiotic treatment and human fecal transfer. Gut Microbes 2014;5:183-91.
126. Manichanh C, Reeder J, Gibert P, et al. Reshaping the gut microbiome with bacterial transplantation and antibiotic intake. Genome Res 2010;20:1411-9.
127. Wos-Oxley M, Bleich A, Oxley AP, et al. Comparative evaluation of establishing a human gut microbial community within rodent models. Gut Microbes 2012;3:234-49.
128. Gonzalez-Perez G, Hicks AL, Tekieli TM, Radens CM, Williams BL, Lamousé-Smith ES. Maternal antibiotic treatment impacts development of the neonatal intestinal microbiome and antiviral immunity. J Immunol 2016;196:3768-79.
129. Lamousé-Smith ES, Tzeng A, Starnbach MN. The intestinal flora is required to support antibody responses to systemic immunization in infant and germ free mice. PLoS One 2011;6:e27662.
130. Li F, Hao X, Chen Y, et al. The microbiota maintain homeostasis of liver-resident γδT-17 cells in a lipid antigen/CD1d-dependent manner. Nat Commun 2017;7:13839.
131. Houtkooper RH, Mouchiroud L, Ryu D, et al. Mitonuclear protein imbalance as a conserved longevity mechanism. Nature 2013;497:451-7.
133. Kalghatgi S, Spina CS, Costello JC, et al. Bactericidal antibiotics induce mitochondrial dysfunction and oxidative damage in mammalian cells. Sci Transl Med 2013;5:192ra85.
134. Rosshart SP, Vassallo BG, Angeletti D, et al. Wild mouse gut microbiota promotes host fitness and improves disease resistance. Cell 2017;171:1015-1028.e13.
135. Rosshart SP, Herz J, Vassallo BG, et al. Laboratory mice born to wild mice have natural microbiota and model human immune responses. Science 2019;365:eaaw4361.
136. Arnesen H, Hitch TCA, Steppeler C, et al. Naturalizing laboratory mice by housing in a farmyard-type habitat confers protection against colorectal carcinogenesis. Gut Microbes 2021;13:1993581.
137. Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med 2009;1:6ra14.
138. Arrieta MC, Walter J, Finlay BB. Human microbiota-associated mice: a model with challenges. Cell Host Microbe 2016;19:575-8.
139. Abarca-gómez L, Abdeen ZA, Hamid ZA, et al. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. The Lancet 2017;390:2627-42.
140. Wostmann BS, Larkin C, Moriarty A, Bruckner-Kardoss E. Dietary intake, energy metabolism, and excretory losses of adult male germfree Wistar rats. Lab Anim Sci 1983;33:46-50.
141. Hild B, Dreier MS, Oh JH, et al. Neonatal exposure to a wild-derived microbiome protects mice against diet-induced obesity. Nat Metab 2021;3:1042-57.
142. Kleinert M, Clemmensen C, Hofmann SM, et al. Animal models of obesity and diabetes mellitus. Nat Rev Endocrinol 2018;14:140-62.
143. Dalby MJ, Ross AW, Walker AW, Morgan PJ. Dietary uncoupling of gut microbiota and energy harvesting from obesity and glucose tolerance in mice. Cell Rep 2017;21:1521-33.
144. Bloom SM, Bijanki VN, Nava GM, et al. Commensal bacteroides species induce colitis in host-genotype-specific fashion in a mouse model of inflammatory bowel disease. Cell Host Microbe 2011;9:390-403.
145. Ocvirk S, Sava IG, Lengfelder I, et al. Surface-associated lipoproteins link enterococcus faecalis virulence to colitogenic activity in IL-10-deficient mice independent of their expression levels. PLoS Pathog 2015;11:e1004911.
146. Eun CS, Mishima Y, Wohlgemuth S, et al. Induction of bacterial antigen-specific colitis by a simplified human microbiota consortium in gnotobiotic interleukin-10-/- mice. Infect Immun 2014;82:2239-46.
147. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.
148. Moser AR, Pitot HC, Dove WF. A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science 1990;247:322-4.
149. De Filippo C, Cavalieri D, Di Paola M, et al. 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;107:14691-6.
150. Smith MI, Yatsunenko T, Manary MJ, et al. Gut microbiomes of malawian twin pairs discordant for kwashiorkor. Science 2013;339:548-54.
151. Subramanian S, Huq S, Yatsunenko T, et al. Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature 2014;510:417-21.
152. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006;444:1027-31.
153. Chung H, Pamp SJ, Hill JA, et al. Gut immune maturation depends on colonization with a host-specific microbiota. Cell 2012;149:1578-93.
154. Kibe R, Sakamoto M, Yokota H, et al. Movement and fixation of intestinal microbiota after administration of human feces to germfree mice. Appl Environ Microbiol 2005;71:3171-8.