The Habitat Filters of Microbiota-Nourishing Immunity

Literature Cited

1. 1. 

   Kisseleva EP. 2014. Innate immunity underlies symbiotic relationships. Biochemistry 79:1273–85
   [Google Scholar]
2. 2. 

   Costello EK, Stagaman K, Dethlefsen L, Bohannan BJ, Relman DA. 2012. The application of ecological theory toward an understanding of the human microbiome. Science 336:1255–62
   [Google Scholar]
3. 3. 

   Litvak Y, Baumler AJ. 2019. Microbiota-nourishing immunity: a guide to understanding our microbial self. Immunity 51:214–24
   [Google Scholar]
4. 4. 

   Byndloss MX, Litvak Y, Baumler AJ. 2019. Microbiota-nourishing immunity and its relevance for ulcerative colitis. Inflamm. Bowel Dis. 25:5811–15
   [Google Scholar]
5. 5. 

   Litvak Y, Baumler AJ. 2019. The founder hypothesis: a basis for microbiota resistance, diversity in taxa carriage, and colonization resistance against pathogens. PLOS Pathog 15:e1007563
   [Google Scholar]
6. 6. 

   Tiffany CR, Baumler AJ. 2019. Dysbiosis: from fiction to function. Am. J. Physiol. Gastrointest. Liver Physiol. 317:G602–8
   [Google Scholar]
7. 7. 

   Cani PD. 2017. Gut microbiota—at the intersection of everything?. Nat. Rev. Gastroenterol. Hepatol. 14:6321–22
   [Google Scholar]
8. 8. 

   Shreiner A, Huffnagle GB, Noverr MC. 2008. The “Microflora Hypothesis” of allergic disease. Adv. Exp. Med. Biol. 635:113–34
   [Google Scholar]
9. 9. 

   Packey CD, Sartor RB. 2009. Commensal bacteria, traditional and opportunistic pathogens, dysbiosis and bacterial killing in inflammatory bowel diseases. Curr. Opin. Infect. Dis. 22:292–301
   [Google Scholar]
10. 10. 

    Round JL, Mazmanian SK. 2009. The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 9:313–23
    [Google Scholar]
11. 11. 

    Bjorksten B. 2009. The hygiene hypothesis: Do we still believe in it?. Nestle Nutr. Workshop Ser. Pediatr. Program. 64:11–18
    [Google Scholar]
12. 12. 

    Gagliardi A, Totino V, Cacciotti F, Iebba V, Neroni B et al. 2018. Rebuilding the gut microbiota ecosystem. Int. J. Environ. Res. Public Health 15:81679
    [Google Scholar]
13. 13. 

    Kumar V, Fischer M. 2019. Expert opinion on fecal microbiota transplantation for the treatment of Clostridioides difficile infection and beyond. Expert Opin. Biol. Ther. 20:173–81
    [Google Scholar]
14. 14. 

    Chen CC, Chen YN, Liou JM, Wu MS, Taiwan Gastrointest. Dis. Helicobacter Consort. 2019. From germ theory to germ therapy. Kaohsiung J. Med. Sci 35:73–82
    [Google Scholar]
15. 15. 

    Marshall BJ, Warren JR. 1984. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 323:1311–15
    [Google Scholar]
16. 16. 

    Bik EM, Eckburg PB, Gill SR, Nelson KE, Purdom EA et al. 2006. Molecular analysis of the bacterial microbiota in the human stomach. PNAS 103:732–37
    [Google Scholar]
17. 17. 

    Bassis CM, Erb-Downward JR, Dickson RP, Freeman CM, Schmidt TM et al. 2015. Analysis of the upper respiratory tract microbiotas as the source of the lung and gastric microbiotas in healthy individuals. mBio 6:e00037
    [Google Scholar]
18. 18. 

    Zoetendal EG, Raes J, van den Bogert B, Arumugam M, Booijink CC et al. 2012. The human small intestinal microbiota is driven by rapid uptake and conversion of simple carbohydrates. ISME J 6:1415–26
    [Google Scholar]
19. 19. 

    Bures J, Cyrany J, Kohoutova D, Forstl M, Rejchrt S et al. 2010. Small intestinal bacterial overgrowth syndrome. World J. Gastroenterol. 16:2978–90
    [Google Scholar]
20. 20. 

    Sarker SA, Ahmed T, Brussow H. 2017. Hunger and microbiology: Is a low gastric acid-induced bacterial overgrowth in the small intestine a contributor to malnutrition in developing countries?. Microb. Biotechnol. 10:1025–30
    [Google Scholar]
21. 21. 

    Trespi E, Ferrieri A. 1999. Intestinal bacterial overgrowth during chronic pancreatitis. Curr. Med. Res. Opin. 15:47–52
    [Google Scholar]
22. 22. 

    Stenwall A, Ingvast S, Skog O, Korsgren O. 2019. Characterization of host defense molecules in the human pancreas. Islets 11:89–101
    [Google Scholar]
23. 23. 

    Ahuja M, Schwartz DM, Tandon M, Son A, Zeng M et al. 2017. Orai1-mediated antimicrobial secretion from pancreatic acini shapes the gut microbiome and regulates gut innate immunity. Cell Metab 25:635–46
    [Google Scholar]
24. 24. 

    Minelli EB, Benini A, Bassi C, Abbas H, Falconi M et al. 1996. Antimicrobial activity of human pancreatic juice and its interaction with antibiotics. Antimicrob. Agents Chemother. 40:2099–105
    [Google Scholar]
25. 25. 

    Kongara KR, Soffer EE. 2000. Intestinal motility in small bowel diverticulosis: a case report and review of the literature. J. Clin. Gastroenterol. 30:84–86
    [Google Scholar]
26. 26. 

    Pignata C, Budillon G, Monaco G, Nani E, Cuomo R et al. 1990. Jejunal bacterial overgrowth and intestinal permeability in children with immunodeficiency syndromes. Gut 31:879–82
    [Google Scholar]
27. 27. 

    Fan X, Sellin JH. 2009. Review article: small intestinal bacterial overgrowth, bile acid malabsorption and gluten intolerance as possible causes of chronic watery diarrhoea. Aliment. Pharmacol. Ther. 29:1069–77
    [Google Scholar]
28. 28. 

    Bouhnik Y, Alain S, Attar A, Flourie B, Raskine L et al. 1999. Bacterial populations contaminating the upper gut in patients with small intestinal bacterial overgrowth syndrome. Am. J. Gastroenterol. 94:1327–31
    [Google Scholar]
29. 29. 

    Dickson RP, Erb-Downward JR, Freeman CM, McCloskey L, Beck JM et al. 2015. Spatial variation in the healthy human lung microbiome and the adapted island model of lung biogeography. Ann. Am. Thorac. Soc. 12:821–30
    [Google Scholar]
30. 30. 

    Charlson ES, Bittinger K, Haas AR, Fitzgerald AS, Frank I et al. 2011. Topographical continuity of bacterial populations in the healthy human respiratory tract. Am. J. Respir. Crit. Care Med. 184:957–63
    [Google Scholar]
31. 31. 

    Budden KF, Gellatly SL, Wood DL, Cooper MA, Morrison M et al. 2017. Emerging pathogenic links between microbiota and the gut-lung axis. Nat. Rev. Microbiol. 15:55–63
    [Google Scholar]
32. 32. 

    Boutin S, Depner M, Stahl M, Graeber SY, Dittrich SA et al. 2017. Comparison of oropharyngeal microbiota from children with asthma and cystic fibrosis. Mediators Inflamm 2017:5047403
    [Google Scholar]
33. 33. 

    Kerem B, Rommens JM, Buchanan JA, Markiewicz D, Cox TK et al. 1989. Identification of the cystic fibrosis gene: genetic analysis. Science 245:1073–80
    [Google Scholar]
34. 34. 

    Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R et al. 1989. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245:1066–73
    [Google Scholar]
35. 35. 

    Rommens JM, Iannuzzi MC, Kerem B, Drumm ML, Melmer G et al. 1989. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 245:1059–65
    [Google Scholar]
36. 36. 

    Shukla SD, Budden KF, Neal R, Hansbro PM. 2017. Microbiome effects on immunity, health and disease in the lung. Clin. Transl. Immunol. 6:e133
    [Google Scholar]
37. 37. 

    Gibson RL, Burns JL, Ramsey BW. 2003. Pathophysiology and management of pulmonary infections in cystic fibrosis. Am. J. Respir. Crit. Care Med. 168:918–51
    [Google Scholar]
38. 38. 

    Miah KM, Hyde SC, Gill DR. 2019. Emerging gene therapies for cystic fibrosis. Expert Rev. Respir. Med. 13:709–25
    [Google Scholar]
39. 39. 

    Yan Z, McCray PB Jr., Engelhardt JF. 2019. Advances in gene therapy for cystic fibrosis lung disease. Hum. Mol. Genet. 28:R88–94
    [Google Scholar]
40. 40. 

    Petersen C, Round JL. 2014. Defining dysbiosis and its influence on host immunity and disease. Cell Microbiol 16:1024–33
    [Google Scholar]
41. 41. 

    Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS et al. 2011. Vaginal microbiome of reproductive-age women. PNAS 108:Suppl. 14680–87
    [Google Scholar]
42. 42. 

    Chen C, Song X, Wei W, Zhong H, Dai J et al. 2017. The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat. Commun. 8:875
    [Google Scholar]
43. 43. 

    Spear GT, French AL, Gilbert D, Zariffard MR, Mirmonsef P et al. 2014. Human alpha-amylase present in lower-genital-tract mucosal fluid processes glycogen to support vaginal colonization by Lactobacillus. J. Infect. Dis. 210:1019–28
    [Google Scholar]
44. 44. 

    Mirmonsef P, Hotton AL, Gilbert D, Burgad D, Landay A et al. 2014. Free glycogen in vaginal fluids is associated with Lactobacillus colonization and low vaginal pH. PLOS ONE 9:e102467
    [Google Scholar]
45. 45. 

    Nasioudis D, Beghini J, Bongiovanni AM, Giraldo PC, Linhares IM, Witkin SS. 2015. Alpha-amylase in vaginal fluid: association with conditions favorable to dominance of Lactobacillus. Reprod. Sci. 22:1393–98
    [Google Scholar]
46. 46. 

    Brotman RM, Shardell MD, Gajer P, Fadrosh D, Chang K et al. 2014. Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy. Menopause 21:450–58
    [Google Scholar]
47. 47. 

    Thoma ME, Gray RH, Kiwanuka N, Aluma S, Wang MC et al. 2011. Longitudinal changes in vaginal microbiota composition assessed by Gram stain among never sexually active pre- and postmenarcheal adolescents in Rakai. Uganda. J. Pediatr. Adolesc. Gynecol. 24:42–47
    [Google Scholar]
48. 48. 

    Miller L, Patton DL, Meier A, Thwin SS, Hooton TM, Eschenbach DA. 2000. Depomedroxyprogesterone-induced hypoestrogenism and changes in vaginal flora and epithelium. Obstet. Gynecol. 96:431–39
    [Google Scholar]
49. 49. 

    Wessels JM, Lajoie J, Cooper M, Omollo K, Felker AM et al. 2019. Medroxyprogesterone acetate alters the vaginal microbiota and microenvironment in women and increases susceptibility to HIV-1 in humanized mice. Dis. Model. Mech. 12:10dmm039669
    [Google Scholar]
50. 50. 

    David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE et al. 2014. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505:559–63
    [Google Scholar]
51. 51. 

    Singh RK, Chang HW, Yan D, Lee KM, Ucmak D et al. 2017. Influence of diet on the gut microbiome and implications for human health. J. Transl. Med. 15:73
    [Google Scholar]
52. 52. 

    El Kaoutari A, Armougom F, Gordon JI, Raoult D, Henrissat B. 2013. The abundance and variety of carbohydrate-active enzymes in the human gut microbiota. Nat. Rev. Microbiol. 11:497–504
    [Google Scholar]
53. 53. 

    Shepherd ES, DeLoache WC, Pruss KM, Whitaker WR, Sonnenburg JL. 2018. An exclusive metabolic niche enables strain engraftment in the gut microbiota. Nature 557:434–38
    [Google Scholar]
54. 54. 

    Kearney SM, Gibbons SM, Erdman SE, Alm EJ. 2018. Orthogonal dietary niche enables reversible engraftment of a gut bacterial commensal. Cell Rep 24:1842–51
    [Google Scholar]
55. 55. 

    Sonnenburg ED, Smits SA, Tikhonov M, Higginbottom SK, Wingreen NS, Sonnenburg JL. 2016. Diet-induced extinctions in the gut microbiota compound over generations. Nature 529:212–15
    [Google Scholar]
56. 56. 

    Sonnenburg JL, Xu J, Leip DD, Chen CH, Westover BP et al. 2005. Glycan foraging in vivo by an intestine-adapted bacterial symbiont. Science 307:1955–59
    [Google Scholar]
57. 57. 

    Moeller AH, Caro-Quintero A, Mjungu D, Georgiev AV, Lonsdorf EV et al. 2016. Cospeciation of gut microbiota with hominids. Science 353:380–82
    [Google Scholar]
58. 58. 

    Reddel S, Putignani L, Del Chierico F. 2019. The impact of low-FODMAPs, gluten-free, and ketogenic diets on gut microbiota modulation in pathological conditions. Nutrients 11:2373
    [Google Scholar]
59. 59. 

    Sela DA, Chapman J, Adeuya A, Kim JH, Chen F et al. 2008. The genome sequence of Bifidobacterium longum subsp. infantis reveals adaptations for milk utilization within the infant microbiome. PNAS 105:18964–69
    [Google Scholar]
60. 60. 

    Ward RE, Ninonuevo M, Mills DA, Lebrilla CB, German JB. 2006. In vitro fermentation of breast milk oligosaccharides by Bifidobacterium infantis and Lactobacillus gasseri. Appl. Environ. Microbiol. 72:4497–99
    [Google Scholar]
61. 61. 

    LoCascio RG, Desai P, Sela DA, Weimer B, Mills DA. 2010. Broad conservation of milk utilization genes in Bifidobacterium longum subsp. infantis as revealed by comparative genomic hybridization. Appl. Environ. Microbiol. 76:7373–81
    [Google Scholar]
62. 62. 

    Sela DA, Garrido D, Lerno L, Wu S, Tan K et al. 2012. Bifidobacterium longum subsp. infantis ATCC 15697 alpha-fucosidases are active on fucosylated human milk oligosaccharides. Appl. Environ. Microbiol. 78:795–803
    [Google Scholar]
63. 63. 

    Sela DA, Mills DA. 2010. Nursing our microbiota: molecular linkages between bifidobacteria and milk oligosaccharides. Trends Microbiol 18:298–307
    [Google Scholar]
64. 64. 

    Garrido D, Dallas DC, Mills DA. 2013. Consumption of human milk glycoconjugates by infant-associated bifidobacteria: mechanisms and implications. Microbiology 159:649–64
    [Google Scholar]
65. 65. 

    Mackie RI, Sghir A, Gaskins HR. 1999. Developmental microbial ecology of the neonatal gastrointestinal tract. Am. J. Clin. Nutr. 69:1035S–45S
    [Google Scholar]
66. 66. 

    Kelly CJ, Zheng L, Campbell EL, Saeedi B, Scholz CC et al. 2015. Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function. Cell Host Microbe 17:662–71
    [Google Scholar]
67. 67. 

    Rigottier-Gois L. 2013. Dysbiosis in inflammatory bowel diseases: the oxygen hypothesis. ISME J 7:1256–61
    [Google Scholar]
68. 68. 

    Rivera-Chavez F, Lopez CA, Baumler AJ. 2017. Oxygen as a driver of gut dysbiosis. Free Radic. Biol. Med. 105:93–101
    [Google Scholar]
69. 69. 

    Litvak Y, Byndloss MX, Tsolis RM, Baumler AJ. 2017. Dysbiotic Proteobacteria expansion: a microbial signature of epithelial dysfunction. Curr. Opin. Microbiol. 39:1–6
    [Google Scholar]
70. 70. 

    Litvak Y, Byndloss MX, Baumler AJ. 2018. Colonocyte metabolism shapes the gut microbiota. Science 362:6418eaat9076
    [Google Scholar]
71. 71. 

    Shin NR, Whon TW, Bae JW. 2015. Proteobacteria: microbial signature of dysbiosis in gut microbiota. Trends Biotechnol 33:496–503
    [Google Scholar]
72. 72. 

    Dubinkina VB, Tyakht AV, Odintsova VY, Yarygin KS, Kovarsky BA et al. 2017. Links of gut microbiota composition with alcohol dependence syndrome and alcoholic liver disease. Microbiome 5:141
    [Google Scholar]
73. 73. 

    Vollaard EJ, Clasener HA, Janssen AJ. 1992. Co-trimoxazole impairs colonization resistance in healthy volunteers. J. Antimicrob. Chemother. 30:685–91
    [Google Scholar]
74. 74. 

    Wang Z, Wang Q, Wang X, Zhu L, Chen J et al. 2019. Gut microbial dysbiosis is associated with development and progression of radiation enteritis during pelvic radiotherapy. J. Cell Mol. Med. 23:3747–56
    [Google Scholar]
75. 75. 

    Pham TA, Clare S, Goulding D, Arasteh JM, Stares MD et al. 2014. Epithelial IL-22RA1-mediated fucosylation promotes intestinal colonization resistance to an opportunistic pathogen. Cell Host Microbe 16:504–16
    [Google Scholar]
76. 76. 

    Mueller S, Saunier K, Hanisch C, Norin E, Alm L et al. 2006. Differences in fecal microbiota in different European study populations in relation to age, gender, and country: a cross-sectional study. Appl. Environ. Microbiol. 72:1027–33
    [Google Scholar]
77. 77. 

    Frank DN, St. Amand AL, Feldman RA, Boedeker EC, Harpaz N Pace NR. 2007. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. PNAS 104:13780–85
    [Google Scholar]
78. 78. 

    Arthur JC, Perez-Chanona E, Muhlbauer M, Tomkovich S, Uronis JM et al. 2012. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 338:120–23
    [Google Scholar]
79. 79. 

    Normann E, Fahlen A, Engstrand L, Lilja HE. 2013. Intestinal microbial profiles in extremely preterm infants with and without necrotizing enterocolitis. Acta Paediatr 102:129–36
    [Google Scholar]
80. 80. 

    Vujkovic-Cvijin I, Dunham RM, Iwai S, Maher MC, Albright RG et al. 2013. Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism. Sci. Transl. Med. 5:193ra91
    [Google Scholar]
81. 81. 

    Fredricks DN. 2019. The gut microbiota and graft-versus-host disease. J. Clin. Investig. 129:1808–17
    [Google Scholar]
82. 82. 

    Braun T, Di Segni A, BenShoshan M, Asaf R, Squires JE et al. 2017. Fecal microbial characterization of hospitalized patients with suspected infectious diarrhea shows significant dysbiosis. Sci. Rep. 7:1088
    [Google Scholar]
83. 83. 

    Krogius-Kurikka L, Lyra A, Malinen E, Aarnikunnas J, Tuimala J et al. 2009. Microbial community analysis reveals high level phylogenetic alterations in the overall gastrointestinal microbiota of diarrhoea-predominant irritable bowel syndrome sufferers. BMC Gastroenterol 9:95
    [Google Scholar]
84. 84. 

    Carroll IM, Ringel-Kulka T, Siddle JP, Ringel Y. 2012. Alterations in composition and diversity of the intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol. Motil. 24:521–30.e248
    [Google Scholar]
85. 85. 

    Hughes ER, Winter MG, Duerkop BA, Spiga L, Furtado de Carvalho T et al. 2017. Microbial respiration and formate oxidation as metabolic signatures of inflammation-associated dysbiosis. Cell Host Microbe 21:208–19
    [Google Scholar]
86. 86. 

    Cevallos SA, Lee JY, Tiffany CR, Byndloss AJ, Johnston L et al. 2019. Increased epithelial oxygenation links colitis to an expansion of tumorigenic bacteria. mBio 10:e02244–19
    [Google Scholar]
87. 87. 

    Byndloss MX, Olsan EE, Rivera-Chávez F, Tiffany CR, Cevallos SA et al. 2017. Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion. Science 357:570–75
    [Google Scholar]
88. 88. 

    Rivera-Chávez F, Zhang LF, Faber F, Lopez CA, Byndloss MX et al. 2016. Depletion of butyrate-producing Clostridia from the gut microbiota drives an aerobic luminal expansion of Salmonella. Cell Host Microbe 19:443–54
    [Google Scholar]
89. 89. 

    Lopez CA, Miller BM, Rivera-Chávez F, Velazquez EM, Byndloss MX et al. 2016. Virulence factors enhance Citrobacter rodentium expansion through aerobic respiration. Science 353:1249–53
    [Google Scholar]
90. 90. 

    Winter SE, Winter MG, Xavier MN, Thiennimitr P, Poon V et al. 2013. Host-derived nitrate boosts growth of E. coli in the inflamed gut. Science 339:708–11
    [Google Scholar]
91. 91. 

    Lopez CA, Winter SE, Rivera-Chávez F, Xavier MN, Poon V et al. 2012. Phage-mediated acquisition of a type III secreted effector protein boosts growth of Salmonella by nitrate respiration. mBio 3:e00143–12
    [Google Scholar]
92. 92. 

    Lopez CA, Rivera-Chavez F, Byndloss MX, Baumler AJ. 2015. The periplasmic nitrate reductase NapABC supports luminal growth of Salmonella enterica serovar Typhimurium during colitis. Infect. Immun. 83:3470–78
    [Google Scholar]
93. 93. 

    McLaughlin PA, Bettke JA, Tam JW, Leeds J, Bliska JB et al. 2019. Inflammatory monocytes provide a niche for Salmonella expansion in the lumen of the inflamed intestine. PLOS Pathog 15:e1007847
    [Google Scholar]
94. 94. 

    Thursby E, Juge N. 2017. Introduction to the human gut microbiota. Biochem. J. 474:1823–36
    [Google Scholar]
95. 95. 

    Byndloss MX, Baumler AJ. 2018. The germ-organ theory of non-communicable diseases. Nat. Rev. Microbiol. 16:103–10
    [Google Scholar]
96. 96. 

    Carson D, Barry R, Hopkins EGD, Roumeliotis TI, Garcia-Weber D et al. 2019. Citrobacter rodentium induces rapid and unique metabolic and inflammatory responses in mice suffering from severe disease. Cell. Microbiol. 22:1e13126
    [Google Scholar]
97. 97. 

    Gillis CC, Winter MG, Chanin RB, Zhu W, Spiga L, Winter SE. 2019. Host-derived metabolites modulate transcription of Salmonella genes involved in l-lactate utilization during gut colonization. Infect. Immun. 87:4e00773–18
    [Google Scholar]
98. 98. 

    Gillis CC, Hughes ER, Spiga L, Winter MG, Zhu W et al. 2018. Dysbiosis-associated change in host metabolism generates lactate to support Salmonella growth. Cell Host Microbe 23:54–64.e6
    [Google Scholar]
99. 99. 

    Rivera-Chavez F, Mekalanos JJ. 2019. Cholera toxin promotes pathogen acquisition of host-derived nutrients. Nature 572:244–48
    [Google Scholar]
100. 100. 

     Roediger WE. 1980. The colonic epithelium in ulcerative colitis: an energy-deficiency disease?. Lancet 2:712–15
     [Google Scholar]
101. 101. 

     Dubuquoy L, Jansson EA, Deeb S, Rakotobe S, Karoui M et al. 2003. Impaired expression of peroxisome proliferator-activated receptor γ in ulcerative colitis. Gastroenterology 124:1265–76
     [Google Scholar]
102. 102. 

     Azad Khan AK, Piris J, Truelove SC 1977. An experiment to determine the active therapeutic moiety of sulphasalazine. Lancet 2:892–95
     [Google Scholar]
103. 103. 

     Iacucci M, de Silva S, Ghosh S 2010. Mesalazine in inflammatory bowel disease: a trendy topic once again?. Can. J. Gastroenterol. 24:127–33
     [Google Scholar]
104. 104. 

     Criscuoli V, Modesto I, Orlando A, Cottone M 2013. Mesalazine for the treatment of inflammatory bowel disease. Expert Opin. Pharmacother. 14:1669–78
     [Google Scholar]
105. 105. 

     Rousseaux C, El-Jamal N, Fumery M, Dubuquoy C, Romano O et al. 2013. The 5-aminosalicylic acid antineoplastic effect in the intestine is mediated by PPARγ. Carcinogenesis 34:2580–86
     [Google Scholar]
106. 106. 

     Giralt A, Hondares E, Villena JA, Ribas F, Diaz-Delfin J et al. 2011. Peroxisome proliferator-activated receptor-γ coactivator-1α controls transcription of the Sirt3 gene, an essential component of the thermogenic brown adipocyte phenotype. J. Biol. Chem. 286:16958–66
     [Google Scholar]
107. 107. 

     Finley LW, Haas W, Desquiret-Dumas V, Wallace DC, Procaccio V et al. 2011. Succinate dehydrogenase is a direct target of sirtuin 3 deacetylase activity. PLOS ONE 6:e23295
     [Google Scholar]
108. 108. 

     Hirschey MD, Shimazu T, Goetzman E, Jing E, Schwer B et al. 2010. SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature 464:121–25
     [Google Scholar]
109. 109. 

     Ahn BH, Kim HS, Song S, Lee IH, Liu J et al. 2008. A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. PNAS 105:14447–52
     [Google Scholar]
110. 110. 

     Xu J, Chen N, Wu Z, Song Y, Zhang Y et al. 2018. 5-Aminosalicylic acid alters the gut bacterial microbiota in patients with ulcerative colitis. Front. Microbiol. 9:1274
     [Google Scholar]
111. 111. 

     Johansson ME, Phillipson M, Petersson J, Velcich A, Holm L, Hansson GC 2008. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. PNAS 105:15064–69
     [Google Scholar]
112. 112. 

     Johansson ME, Gustafsson JK, Holmen-Larsson J, Jabbar KS, Xia L et al. 2014. Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis. Gut 63:281–91
     [Google Scholar]
113. 113. 

     van der Post S, Jabbar KS, Birchenough G, Arike L, Akhtar N et al. 2019. Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis. Gut 68:122142–51
     [Google Scholar]
114. 114. 

     Li H, Limenitakis JP, Fuhrer T, Geuking MB, Lawson MA et al. 2015. The outer mucus layer hosts a distinct intestinal microbial niche. Nat. Commun. 6:8292
     [Google Scholar]
115. 115. 

     Albenberg L, Esipova TV, Judge CP, Bittinger K, Chen J et al. 2014. Correlation between intraluminal oxygen gradient and radial partitioning of intestinal microbiota. Gastroenterology 147:1055–63.e8
     [Google Scholar]
116. 116. 

     Matziouridou C, Rocha SDC, Haabeth OA, Rudi K, Carlsen H, Kielland A. 2018. iNOS- and NOX1-dependent ROS production maintains bacterial homeostasis in the ileum of mice. Mucosal Immunol 11:774–84
     [Google Scholar]
117. 117. 

     Aviello G, Singh AK, O'Neill S, Conroy E, Gallagher W et al. 2019. Colitis susceptibility in mice with reactive oxygen species deficiency is mediated by mucus barrier and immune defense defects. Mucosal Immunol 12:1316–26
     [Google Scholar]
118. 118. 

     Schwerd T, Bryant RV, Pandey S, Capitani M, Meran L et al. 2018. NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease. Mucosal Immunol 11:562–74
     [Google Scholar]
119. 119. 

     Johansson ME, Sjovall H, Hansson GC. 2013. The gastrointestinal mucus system in health and disease. Nat. Rev. Gastroenterol. Hepatol. 10:352–61
     [Google Scholar]
120. 120. 

     Cullender TC, Chassaing B, Janzon A, Kumar K, Muller CE et al. 2013. Innate and adaptive immunity interact to quench microbiome flagellar motility in the gut. Cell Host Microbe 14:571–81
     [Google Scholar]
121. 121. 

     Salzman NH, Hung K, Haribhai D, Chu H, Karlsson-Sjoberg J et al. 2010. Enteric defensins are essential regulators of intestinal microbial ecology. Nat. Immunol. 11:76–83
     [Google Scholar]
122. 122. 

     Vaishnava S, Yamamoto M, Severson KM, Ruhn KA, Yu X et al. 2011. The antibacterial lectin RegIIIγ promotes the spatial segregation of microbiota and host in the intestine. Science 334:255–58
     [Google Scholar]
123. 123. 

     Bevins CL, Stange EF, Wehkamp J. 2009. Decreased Paneth cell defensin expression in ileal Crohn's disease is independent of inflammation, but linked to the NOD2 1007fs genotype. Gut 58:882–83
     [Google Scholar]
124. 124. 

     Wehkamp J, Salzman NH, Porter E, Nuding S, Weichenthal M et al. 2005. Reduced Paneth cell α-defensins in ileal Crohn's disease. PNAS 102:18129–34
     [Google Scholar]
125. 125. 

     Wehkamp J, Harder J, Weichenthal M, Schwab M, Schaffeler E et al. 2004. NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal α-defensin expression. Gut 53:1658–64
     [Google Scholar]
126. 126. 

     Darfeuille-Michaud A, Boudeau J, Bulois P, Neut C, Glasser AL et al. 2004. High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease. Gastroenterology 127:412–21
     [Google Scholar]
127. 127. 

     Salzman NH, Bevins CL. 2013. Dysbiosis—a consequence of Paneth cell dysfunction. Semin. Immunol. 25:334–41
     [Google Scholar]
128. 128. 

     Nadjsombati MS, McGinty JW, Lyons-Cohen MR, Jaffe JB, DiPeso L et al. 2018. Detection of succinate by intestinal tuft cells triggers a type 2 innate immune circuit. Immunity 49:33–41.e7
     [Google Scholar]
129. 129. 

     Morita N, Umemoto E, Fujita S, Hayashi A, Kikuta J et al. 2019. GPR31-dependent dendrite protrusion of intestinal CX3CR1+ cells by bacterial metabolites. Nature 566:110–14
     [Google Scholar]
130. 130. 

     Miller CA 3rd 1997. Expression of the human aryl hydrocarbon receptor complex in yeast. Activation of transcription by indole compounds. J. Biol. Chem. 272:32824–29
     [Google Scholar]
131. 131. 

     Heath-Pagliuso S, Rogers WJ, Tullis K, Seidel SD, Cenijn PH et al. 1998. Activation of the Ah receptor by tryptophan and tryptophan metabolites. Biochemistry 37:11508–15
     [Google Scholar]
132. 132. 

     Zelante T, Iannitti RG, Cunha C, De Luca A, Giovannini G et al. 2013. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity 39:372–85
     [Google Scholar]
133. 133. 

     Monteleone I, Rizzo A, Sarra M, Sica G, Sileri P et al. 2011. Aryl hydrocarbon receptor-induced signals up-regulate IL-22 production and inhibit inflammation in the gastrointestinal tract. Gastroenterology 141:237–48.e1
     [Google Scholar]
134. 134. 

     Fukumoto S, Toshimitsu T, Matsuoka S, Maruyama A, Oh-Oka K et al. 2014. Identification of a probiotic bacteria-derived activator of the aryl hydrocarbon receptor that inhibits colitis. Immunol. Cell Biol. 92:5460–65
     [Google Scholar]
135. 135. 

     Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J et al. 2013. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504:451–55
     [Google Scholar]
136. 136. 

     Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T et al. 2011. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331:337–41
     [Google Scholar]
137. 137. 

     Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G et al. 2013. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504:446–50
     [Google Scholar]
138. 138. 

     Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA et al. 2013. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341:569–73
     [Google Scholar]
139. 139. 

     Singh N, Gurav A, Sivaprakasam S, Brady E, Padia R et al. 2014. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 40:128–39
     [Google Scholar]
140. 140. 

     Alex S, Lange K, Amolo T, Grinstead JS, Haakonsson AK et al. 2013. Short-chain fatty acids stimulate angiopoietin-like 4 synthesis in human colon adenocarcinoma cells by activating peroxisome proliferator-activated receptor γ. Mol. Cell. Biol. 33:1303–16
     [Google Scholar]
141. 141. 

     Chang PV, Hao L, Offermanns S, Medzhitov R 2014. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. PNAS 111:2247–52
     [Google Scholar]
142. 142. 

     Hooper LV, Gordon JI. 2001. Commensal host-bacterial relationships in the gut. Science 292:1115–18
     [Google Scholar]
143. 143. 

     Human Microbiome Project Consort 2012. Structure, function and diversity of the healthy human microbiome. Nature 486:207–14
     [Google Scholar]
144. 144. 

     Integrative Hum. Microbiome Proj. Res. Netw. Consort 2019. The Integrative Human Microbiome Project. Nature 569:641–48
     [Google Scholar]
145. 145. 

     Proctor L. 2019. Priorities for the next 10 years of human microbiome research. Nature 569:623–25
     [Google Scholar]
146. 146. 

     Tipton L, Darcy JL, Hynson NA. 2019. A developing symbiosis: enabling cross-talk between ecologists and microbiome scientists. Front. Microbiol. 10:292
     [Google Scholar]
147. 147. 

     Foster KR, Schluter J, Coyte KZ, Rakoff-Nahoum S. 2017. The evolution of the host microbiome as an ecosystem on a leash. Nature 548:43–51
     [Google Scholar]
148. 148. 

     Byndloss MX, Pernitzsch SR, Baumler AJ. 2018. Healthy hosts rule within: ecological forces shaping the gut microbiota. Mucosal. Immunol. 11:51299–305
     [Google Scholar]
149. 149. 

     Mills EL, Kelly B, O'Neill LAJ. 2017. Mitochondria are the powerhouses of immunity. Nat. Immunol. 18:488–98
     [Google Scholar]
150. 150. 

     Quie PG. 1986. Lung defense against infection. J. Pediatr. 108:813–16
     [Google Scholar]
151. 151. 

     Borges S, Silva J, Teixeira P. 2014. The role of lactobacilli and probiotics in maintaining vaginal health. Arch. Gynecol. Obstet. 289:479–89
     [Google Scholar]
152. 152. 

     Johansson ME, Gustafsson JK, Sjoberg KE, Petersson J, Holm L et al. 2010. Bacteria penetrate the inner mucus layer before inflammation in the dextran sulfate colitis model. PLOS ONE 5:e12238
     [Google Scholar]
153. 153. 

     Colomer V, Lal K, Hoops TC, Rindler MJ. 1994. Exocrine granule specific packaging signals are present in the polypeptide moiety of the pancreatic granule membrane protein GP2 and in amylase: implications for protein targeting to secretory granules. EMBO J 13:3711–19
     [Google Scholar]
154. 154. 

     Yu S, Lowe AW. 2009. The pancreatic zymogen granule membrane protein, GP2, binds Escherichia coli type 1 Fimbriae. BMC Gastroenterol 9:58
     [Google Scholar]