1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Pathology: Mechanisms of Disease
  4. Volume 15, 2020
  5. Article

Annual Review of Pathology: Mechanisms of Disease

Volume 15, 2020

Microbial Contribution to the Human Metabolome: Implications for Health and Disease

Abstract

The human gastrointestinal tract is home to an incredibly dense population of microbes. These microbes employ unique strategies to capture energy in this largely anaerobic environment. In the process of breaking down dietary- and host-derived substrates, the gut microbiota produce a broad range of metabolic products that accumulate to high levels in the gut. Increasingly, studies are revealing that these chemicals impact host biology, either by acting on cells within the gastrointestinal tract or entering circulation and exerting their effects at distal sites within the body. Given the high level of functional diversity in the gut microbiome and the varied diets that we consume, the repertoire of microbiota-derived molecules within our bodies varies dramatically across individuals. Thus, the microbes in our gut and the metabolic end products they produce represent a phenotypic lever that we can potentially control to develop new therapeutics for personalized medicine. Here, we review current understanding of how microbes in the gastrointestinal tract contribute to the molecules within our gut and those that circulate within our bodies. We also highlight examples of how these molecules affect host physiology and discuss potential strategies for controlling their production to promote human health and to treat disease.

Keyword(s): human metabolome, human microbiome, metabolomics
Loading

Article metrics loading...

/content/journals/10.1146/annurev-pathol-020117-043559
2020-01-24
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/pathol/15/1/annurev-pathol-020117-043559.html?itemId=/content/journals/10.1146/annurev-pathol-020117-043559&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Jaffe M. 1877. Ueber die Ausscheidung des Indicans unter physiologischen und pathologischen Verhältnissen. Virchow's Arch 70:72–111
     [Google Scholar]
  2. 2. 
    Psychogios N, Hau DD, Peng J, Guo AC, Mandal R et al. 2011. The human serum metabolome. PLOS ONE 6:e16957
     [Google Scholar]
  3. 3. 
    Gates SC, Sweeley CC, Krivit W, DeWitt D, Blaisdell BE 1978. Automated metabolic profiling of organic acids in human urine. II. Analysis of urine samples from “healthy” adults, sick children, and children with neuroblastoma. Clin. Chem. 24:1680–89
     [Google Scholar]
  4. 4. 
    Gates SC, Dendramis N, Sweeley CC 1978. Automated metabolic profiling of organic acids in human urine. I. Description of methods. Clin. Chem. 24:1674–79
     [Google Scholar]
  5. 5. 
    Zlatkis A, Liebich HM. 1971. Profile of volatile metabolites in human urine. Clin. Chem. 17:592–94
     [Google Scholar]
  6. 6. 
    Horning EC, Horning MG. 1971. Metabolic profiles: gas-phase methods for analysis of metabolites. Clin. Chem. 17:802–9
     [Google Scholar]
  7. 7. 
    Mamer OA, Crawhall JC, Tjoa SS 1971. The identification of urinary acids by coupled gas chromatography–mass spectrometry. Clin. Chim. Acta 32:171–84
     [Google Scholar]
  8. 8. 
    Crawhall JC, Mamer O, Tjoa S, Claveau JC 1971. Urinary phenolic acids in tyrosinemia. Identification and quantitation by gas chromatography-mass spectrometry. Clin. Chim. Acta 34:47–54
     [Google Scholar]
  9. 9. 
    Pasquali M, Longo N. 2018. Newborn screening and inborn errors of metabolism. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics N Rifai 1697–730 St. Louis, Mo.: Elsevier. , 6th ed..
     [Google Scholar]
  10. 10. 
    Rinaldo P, Cowan TM, Matern D 2008. Acylcarnitine profile analysis. Genet. Med. 10:151–56
     [Google Scholar]
  11. 11. 
    Nyhan WL, Barshop BA, Al-Aqeel AI, Hoffmann GF 2012. Atlas of Inherited Metabolic Diseases London, UK: Hodder Arnold
  12. 12. 
    Kumps A, Duez P, Mardens Y 2002. Metabolic, nutritional, iatrogenic, and artifactual sources of urinary organic acids: a comprehensive table. Clin. Chem. 48:708–17
     [Google Scholar]
  13. 13. 
    Dridi B, Raoult D, Drancourt M 2011. Archaea as emerging organisms in complex human microbiomes. Anaerobe 17:56–63
     [Google Scholar]
  14. 14. 
    Sender R, Fuchs S, Milo R 2016. Revised estimates for the number of human and bacteria cells in the body. PLOS Biol 14:e1002533
     [Google Scholar]
  15. 15. 
    Sinha R, Abu-Ali G, Vogtmann E, Fodor AA, Ren B et al. 2017. Assessment of variation in microbial community amplicon sequencing by the Microbiome Quality Control (MBQC) project consortium. Nat. Biotechnol. 35:1077–86
     [Google Scholar]
  16. 16. 
    Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG et al. 2012. Human gut microbiome viewed across age and geography. Nature 486:222–27
     [Google Scholar]
  17. 17. 
    Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T et al. 2011. Enterotypes of the human gut microbiome. Nature 473:174–80
     [Google Scholar]
  18. 18. 
    Hum. Microbiome Proj. Consort 2012. Structure, function and diversity of the healthy human microbiome. Nature 486:207–14
     [Google Scholar]
  19. 19. 
    Qin J, Li R, Raes J, Arumugam M, Burgdorf KS et al. 2010. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464:59–65
     [Google Scholar]
  20. 20. 
    Savage DC. 1977. Microbial ecology of the gastrointestinal tract. Annu. Rev. Microbiol. 31:107–33
     [Google Scholar]
  21. 21. 
    Walter J, Ley R. 2011. The human gut microbiome: ecology and recent evolutionary changes. Annu. Rev. Microbiol. 65:411–29
     [Google Scholar]
  22. 22. 
    Heintz-Buschart A, Wilmes P. 2018. Human gut microbiome: function matters. Trends Microbiol 26:563–74
     [Google Scholar]
  23. 23. 
    Oren A, Garrity GM. 2014. Then and now: a systematic review of the systematics of prokaryotes in the last 80 years. Antonie Van Leeuwenhoek 106:43–56
     [Google Scholar]
  24. 24. 
    Belkaid Y, Hand TW. 2014. Role of the microbiota in immunity and inflammation. Cell 157:121–41
     [Google Scholar]
  25. 25. 
    Dodd D, Spitzer MH, Van Treuren W, Merrill BD, Hryckowian AJ et al. 2017. A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites. Nature 551:648–52
     [Google Scholar]
  26. 26. 
    Schwabe RF, Jobin C. 2013. The microbiome and cancer. Nat. Rev. Cancer 13:800–12
     [Google Scholar]
  27. 27. 
    Schnabl B, Brenner DA. 2014. Interactions between the intestinal microbiome and liver diseases. Gastroenterology 146:1513–24
     [Google Scholar]
  28. 28. 
    Koh A, De Vadder F, Kovatcheva-Datchary P, Bäckhed F 2016. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell 165:1332–45
     [Google Scholar]
  29. 29. 
    Flint HJ, Scott KP, Duncan SH, Louis P, Forano E 2012. Microbial degradation of complex carbohydrates in the gut. Gut Microbes 3:289–306
     [Google Scholar]
  30. 30. 
    Cummings JH, Macfarlane GT. 1991. The control and consequences of bacterial fermentation in the human colon. J. Appl. Bacteriol. 70:443–59
     [Google Scholar]
  31. 31. 
    Desai MS, Seekatz AM, Koropatkin NM, Kamada N, Hickey CA et al. 2016. A dietary fiber–deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell 167:1339–53.e21
     [Google Scholar]
  32. 32. 
    Earle KA, Billings G, Sigal M, Lichtman JS, Hansson GC et al. 2015. Quantitative imaging of gut microbiota spatial organization. Cell Host Microbe 18:478–88
     [Google Scholar]
  33. 33. 
    Macfarlane GT, Gibson GR, Cummings JH 1992. Comparison of fermentation reactions in different regions of the human colon. J. Appl. Bacteriol. 72:57–64
     [Google Scholar]
  34. 34. 
    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]
  35. 35. 
    David LA, Materna AC, Friedman J, Campos-Baptista MI, Blackburn MC et al. 2014. Host lifestyle affects human microbiota on daily timescales. Genome Biol 15:R89
     [Google Scholar]
  36. 36. 
    Flores GE, Caporaso JG, Henley JB, Rideout JR, Domogala D et al. 2014. Temporal variability is a personalized feature of the human microbiome. Genome Biol 15:531
     [Google Scholar]
  37. 37. 
    Faith JJ, Guruge JL, Charbonneau M, Subramanian S, Seedorf H et al. 2013. The long-term stability of the human gut microbiota. Science 341:1237439
     [Google Scholar]
  38. 38. 
    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]
  39. 39. 
    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]
  40. 40. 
    Dethlefsen L, Relman DA. 2011. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. PNAS 108:Suppl. 14554–61
     [Google Scholar]
  41. 41. 
    Gevers D, Kugathasan S, Denson LA, Vazquez-Baeza Y, Van Treuren W et al. 2014. The treatment-naive microbiome in new-onset Crohn's disease. Cell Host Microbe 15:382–92
     [Google Scholar]
  42. 42. 
    Walters WA, Xu Z, Knight R 2014. Meta-analyses of human gut microbes associated with obesity and IBD. FEBS Lett 588:4223–33
     [Google Scholar]
  43. 43. 
    Faith JJ, McNulty NP, Rey FE, Gordon JI 2011. Predicting a human gut microbiota's response to diet in gnotobiotic mice. Science 333:101–4
     [Google Scholar]
  44. 44. 
    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]
  45. 45. 
    Walker AW, Ince J, Duncan SH, Webster LM, Holtrop G et al. 2011. Dominant and diet-responsive groups of bacteria within the human colonic microbiota. ISME J 5:220–30
     [Google Scholar]
  46. 46. 
    Friedman ES, Bittinger K, Esipova TV, Hou L, Chau L et al. 2018. Microbes versus chemistry in the origin of the anaerobic gut lumen. PNAS 115:4170–75
     [Google Scholar]
  47. 47. 
    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
     [Google Scholar]
  48. 48. 
    de Vladar HP. 2012. Amino acid fermentation at the origin of the genetic code. Biol. Direct 7:6
     [Google Scholar]
  49. 49. 
    Canfield DE, Rosing MT, Bjerrum C 2006. Early anaerobic metabolisms. Philos. Trans. R. Soc. Lond. B 361:1819–34
     [Google Scholar]
  50. 50. 
    Fischbach MA, Sonnenburg JL. 2011. Eating for two: how metabolism establishes interspecies interactions in the gut. Cell Host Microbe 10:336–47
     [Google Scholar]
  51. 51. 
    Hoyles L, Jimenez-Pranteda ML, Chilloux J, Brial F, Myridakis A et al. 2018. Metabolic retroconversion of trimethylamine N-oxide and the gut microbiota. Microbiome 6:73
     [Google Scholar]
  52. 52. 
    Tiso M, Schechter AN. 2015. Nitrate reduction to nitrite, nitric oxide and ammonia by gut bacteria under physiological conditions. PLOS ONE 10:e0119712
     [Google Scholar]
  53. 53. 
    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]
  54. 54. 
    Nakamura N, Lin HC, McSweeney CS, Mackie RI, Gaskins HR 2010. Mechanisms of microbial hydrogen disposal in the human colon and implications for health and disease. Annu. Rev. Food Sci. Technol. 1:363–95
     [Google Scholar]
  55. 55. 
    Flint HJ, Bayer EA, Rincon MT, Lamed R, White BA 2008. Polysaccharide utilization by gut bacteria: potential for new insights from genomic analysis. Nat. Rev. Microbiol. 6:121–31
     [Google Scholar]
  56. 56. 
    Barcenilla A, Pryde SE, Martin JC, Duncan SH, Stewart CS et al. 2000. Phylogenetic relationships of butyrate-producing bacteria from the human gut. Appl. Environ. Microbiol. 66:1654–61
     [Google Scholar]
  57. 57. 
    Louis P, Flint HJ. 2009. Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Microbiol. Lett. 294:1–8
     [Google Scholar]
  58. 58. 
    Pryde SE, Duncan SH, Hold GL, Stewart CS, Flint HJ 2002. The microbiology of butyrate formation in the human colon. FEMS Microbiol. Lett. 217:133–39
     [Google Scholar]
  59. 59. 
    Vital M, Howe AC, Tiedje JM 2014. Revealing the bacterial butyrate synthesis pathways by analyzing (meta)genomic data. mBio 5:e00889
     [Google Scholar]
  60. 60. 
    Anand S, Kaur H, Mande SS 2016. Comparative in silico analysis of butyrate production pathways in gut commensals and pathogens. Front. Microbiol. 7:1945
     [Google Scholar]
  61. 61. 
    Chowdhury NP, Mowafy AM, Demmer JK, Upadhyay V, Koelzer S et al. 2014. Studies on the mechanism of electron bifurcation catalyzed by electron transferring flavoprotein (Etf) and butyryl-CoA dehydrogenase (Bcd) of Acidaminococcusfermentans. J. Biol. . Chem 289:5145–57
     [Google Scholar]
  62. 62. 
    Herrmann G, Jayamani E, Mai G, Buckel W 2008. Energy conservation via electron-transferring flavoprotein in anaerobic bacteria. J. Bacteriol. 190:784–91
     [Google Scholar]
  63. 63. 
    Buckel W, Thauer RK. 2013. Energy conservation via electron bifurcating ferredoxin reduction and proton/Na+ translocating ferredoxin oxidation. Biochim. Biophys. Acta Bioenerg. 1827:94–113
     [Google Scholar]
  64. 64. 
    Roediger WE. 1980. Role of anaerobic bacteria in the metabolic welfare of the colonic mucosa in man. Gut 21:793–98
     [Google Scholar]
  65. 65. 
    Sieber JR, McInerney MJ, Gunsalus RP 2012. Genomic insights into syntrophy: the paradigm for anaerobic metabolic cooperation. Annu. Rev. Microbiol. 66:429–52
     [Google Scholar]
  66. 66. 
    Morris BE, Henneberger R, Huber H, Moissl-Eichinger C 2013. Microbial syntrophy: interaction for the common good. FEMS Microbiol. Rev. 37:384–406
     [Google Scholar]
  67. 67. 
    Barker HA. 1939. Studies upon the methane fermentation. IV. The isolation and culture of MethanobacteriumOmelianskii. . Antonie Van Leeuwenhoek 6:201–20
     [Google Scholar]
  68. 68. 
    Bryant MP, Wolin EA, Wolin MJ, Wolfe RS 1967. Methanobacillusomelianskii, a symbiotic association of two species of bacteria. Arch. Mikrobiol. 59:20–31
     [Google Scholar]
  69. 69. 
    Iannotti EL, Kafkewitz D, Wolin MJ, Bryant MP 1973. Glucose fermentation products in Ruminococcusalbus grown in continuous culture with Vibriosuccinogenes: changes caused by interspecies transfer of H2. J. Bacteriol. 114:1231–40
     [Google Scholar]
  70. 70. 
    Samuel BS, Gordon JI. 2006. A humanized gnotobiotic mouse model of host–archaeal–bacterial mutualism. PNAS 103:10011–16
     [Google Scholar]
  71. 71. 
    Karu N, Deng L, Slae M, Guo AC, Sajed T et al. 2018. A review on human fecal metabolomics: methods, applications and the Human Fecal Metabolome Database. Anal. Chim. Acta 1030:1–24
     [Google Scholar]
  72. 72. 
    Mair RD, Sirich TL, Plummer NS, Meyer TW 2018. Characteristics of colon-derived uremic solutes. Clin. J. Am. Soc. Nephrol. 13:1398–404
     [Google Scholar]
  73. 73. 
    da Silva RR, Dorrestein PC, Quinn RA 2015. Illuminating the dark matter in metabolomics. PNAS 112:12549–50
     [Google Scholar]
  74. 74. 
    Cummings JH, Pomare EW, Branch WJ, Naylor CP, Macfarlane GT 1987. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 28:1221–27
     [Google Scholar]
  75. 75. 
    den Besten G, Lange K, Havinga R, van Dijk TH, Gerding A et al. 2013. Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids. Am. J. Physiol. Gastrointest. Liver Physiol. 305:G900–10
     [Google Scholar]
  76. 76. 
    Topping DL, Clifton PM. 2001. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol. Rev. 81:1031–64
     [Google Scholar]
  77. 77. 
    Ruppin H, Bar-Meir S, Soergel KH, Wood CM, Schmitt MG Jr 1980. Absorption of short-chain fatty acids by the colon. Gastroenterology 78:1500–7
     [Google Scholar]
  78. 78. 
    Dawson AM, Holdsworth CD, Webb J 1964. Absorption of short chain fatty acids in man. Proc. Soc. Exp. Biol. Med. 117:97–100
     [Google Scholar]
  79. 79. 
    Rechkemmer G, Ronnau K, von Engelhardt W 1988. Fermentation of polysaccharides and absorption of short chain fatty acids in the mammalian hindgut. Comp. Biochem. Physiol. A 90:563–68
     [Google Scholar]
  80. 80. 
    Bergman EN. 1990. Energy contributions of volatile fatty acids from the gastrointestinal tract in various species. Physiol. Rev. 70:567–90
     [Google Scholar]
  81. 81. 
    McNeil NI. 1984. The contribution of the large intestine to energy supplies in man. Am. J. Clin. Nutr. 39:338–42
     [Google Scholar]
  82. 82. 
    Skutches CL, Holroyde CP, Myers RN, Paul P, Reichard GA 1979. Plasma acetate turnover and oxidation. J. Clin. Investig. 64:708–13
     [Google Scholar]
  83. 83. 
    Adibi SA, Mercer DW. 1973. Protein digestion in human intestine as reflected in luminal, mucosal, and plasma amino acid concentrations after meals. J. Clin. Investig. 52:1586–94
     [Google Scholar]
  84. 84. 
    Meyer TW, Hostetter TH. 2012. Uremic solutes from colon microbes. Kidney Int 81:949–54
     [Google Scholar]
  85. 85. 
    Cummings JH, Hill MJ, Bone ES, Branch WJ, Jenkins DJ 1979. The effect of meat protein and dietary fiber on colonic function and metabolism. II. Bacterial metabolites in feces and urine. Am. J. Clin. Nutr. 32:2094–101
     [Google Scholar]
  86. 86. 
    Ross JA, Kasum CM. 2002. Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu. Rev. Nutr. 22:19–34
     [Google Scholar]
  87. 87. 
    Gonthier MP, Cheynier V, Donovan JL, Manach C, Morand C et al. 2003. Microbial aromatic acid metabolites formed in the gut account for a major fraction of the polyphenols excreted in urine of rats fed red wine polyphenols. J. Nutr. 133:461–67
     [Google Scholar]
  88. 88. 
    Clifford MN. 1999. Chlorogenic acids and other cinnamates—nature, occurrence and dietary burden. J. Sci. Food Agric. 79:362–72
     [Google Scholar]
  89. 89. 
    Scheppach W. 1994. Effects of short chain fatty acids on gut morphology and function. Gut 35:Suppl.S35–38
     [Google Scholar]
  90. 90. 
    Fleming SE, Fitch MD, DeVries S, Liu ML, Kight C 1991. Nutrient utilization by cells isolated from rat jejunum, cecum and colon. J. Nutr. 121:869–78
     [Google Scholar]
  91. 91. 
    Roediger WE. 1982. Utilization of nutrients by isolated epithelial cells of the rat colon. Gastroenterology 83:424–29
     [Google Scholar]
  92. 92. 
    Chacko A, Cummings JH. 1988. Nitrogen losses from the human small bowel: obligatory losses and the effect of physical form of food. Gut 29:809–15
     [Google Scholar]
  93. 93. 
    Smith EA, Macfarlane GT. 1997. Dissimilatory amino acid metabolism in human colonic bacteria. Anaerobe 3:327–37
     [Google Scholar]
  94. 94. 
    Elsden SR, Hilton MG. 1978. Volatile acid production from threonine, valine, leucine and isoleucine by Clostridia. Arch. Microbiol. 117:165–72
     [Google Scholar]
  95. 95. 
    Bellono NW, Bayrer JR, Leitch DB, Castro J, Zhang C et al. 2017. Enterochromaffin cells are gut chemosensors that couple to sensory neural pathways. Cell 170:185–98.e16
     [Google Scholar]
  96. 96. 
    Jakobsdottir G, Bjerregaard JH, Skovbjerg H, Nyman M 2013. Fasting serum concentration of short-chain fatty acids in subjects with microscopic colitis and celiac disease: no difference compared with controls, but between genders. Scand. J. Gastroenterol. 48:696–701
     [Google Scholar]
  97. 97. 
    Zabin I, Bloch K. 1951. Studies on the utilization of isovaleric acid in cholesterol synthesis. J. Biol. Chem. 192:267–73
     [Google Scholar]
  98. 98. 
    Gregersen N. 1979. Studies on the effects of saturated and unsaturated short-chain monocarboxylic acids on the energy metabolism of rat liver mitochondria. Pediatr. Res. 13:1227–30
     [Google Scholar]
  99. 99. 
    Heimann E, Nyman M, Palbrink AK, Lindkvist-Petersson K, Degerman E 2016. Branched short-chain fatty acids modulate glucose and lipid metabolism in primary adipocytes. Adipocyte 5:359–68
     [Google Scholar]
  100. 100. 
    Mair RD, Sirich TL, Meyer TW 2018. Uremic toxin clearance and cardiovascular toxicities. Toxins 10:226
     [Google Scholar]
  101. 101. 
    Bultman SJ. 2016. The microbiome and its potential as a cancer preventive intervention. Semin. Oncol. 43:97–106
     [Google Scholar]
  102. 102. 
    Cardona F, Andres-Lacueva C, Tulipani S, Tinahones FJ, Queipo-Ortuno MI 2013. Benefits of polyphenols on gut microbiota and implications in human health. J. Nutr. Biochem. 24:1415–22
     [Google Scholar]
  103. 103. 
    Gonthier MP, Verny MA, Besson C, Remesy C, Scalbert A 2003. Chlorogenic acid bioavailability largely depends on its metabolism by the gut microflora in rats. J. Nutr. 133:1853–59
     [Google Scholar]
  104. 104. 
    Rechner AR, Kuhnle G, Bremner P, Hubbard GP, Moore KP, Rice-Evans CA 2002. The metabolic fate of dietary polyphenols in humans. Free Radic. Biol. Med. 33:220–35
     [Google Scholar]
  105. 105. 
    Aronov PA, Luo FJ, Plummer NS, Quan Z, Holmes S et al. 2011. Colonic contribution to uremic solutes. J. Am. Soc. Nephrol. 22:1769–76
     [Google Scholar]
  106. 106. 
    Brown C, Taniguchi G, Yip K 1989. The monoamine oxidase inhibitor–tyramine interaction. J. Clin. Pharmacol. 29:529–32
     [Google Scholar]
  107. 107. 
    Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P et al. 2015. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161:264–76
     [Google Scholar]
  108. 108. 
    Pugin B, Barcik W, Westermann P, Heider A, Wawrzyniak M et al. 2017. A wide diversity of bacteria from the human gut produces and degrades biogenic amines. Microb. Ecol. Health Dis. 28:1353881
     [Google Scholar]
  109. 109. 
    Aydin S, Ugur K, Aydin S 2018. Could excessive production of tyramine by the microbiota be a reason for essential hypertension. ? Biosci. Microbiota Food Health 37:77–78
     [Google Scholar]
  110. 110. 
    Levy M, Thaiss CA, Zeevi D, Dohnalova L, Zilberman-Schapira G et al. 2015. Microbiota-modulated metabolites shape the intestinal microenvironment by regulating NLRP6 inflammasome signaling. Cell 163:1428–43
     [Google Scholar]
  111. 111. 
    Hanfrey CC, Pearson BM, Hazeldine S, Lee J, Gaskin DJ et al. 2011. Alternative spermidine biosynthetic route is critical for growth of Campylobacterjejuni and is the dominant polyamine pathway in human gut microbiota. J. Biol. Chem. 286:43301–12
     [Google Scholar]
  112. 112. 
    Perry TL, Hestrin M, MacDougall L, Hansen S 1966. Urinary amines of intestinal bacterial origin. Clin. Chim. Acta 14:116–23
     [Google Scholar]
  113. 113. 
    Lin JH, Chiba M, Baillie TA 1999. Is the role of the small intestine in first-pass metabolism overemphasized. ? Pharmacol. Rev. 51:135–58
     [Google Scholar]
  114. 114. 
    Treyer A, Musch A. 2013. Hepatocyte polarity. Compr. Physiol. 3:243–87
     [Google Scholar]
  115. 115. 
    Faber KN, Muller M, Jansen PL 2003. Drug transport proteins in the liver. Adv. Drug Deliv. Rev. 55:107–24
     [Google Scholar]
  116. 116. 
    Hinchman CA, Ballatori N. 1994. Glutathione conjugation and conversion to mercapturic acids can occur as an intrahepatic process. J. Toxicol. Environ. Health 41:387–409
     [Google Scholar]
  117. 117. 
    Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY 2004. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N. Engl. J. Med. 351:1296–305
     [Google Scholar]
  118. 118. 
    Ramezani A, Raj DS. 2014. The gut microbiome, kidney disease, and targeted interventions. J. Am. Soc. Nephrol. 25:657–70
     [Google Scholar]
  119. 119. 
    Niwa T. 1996. Organic acids and the uremic syndrome: protein metabolite hypothesis in the progression of chronic renal failure. Semin. Nephrol. 16:167–82
     [Google Scholar]
  120. 120. 
    Evenepoel P, Meijers BK, Bammens BR, Verbeke K 2009. Uremic toxins originating from colonic microbial metabolism. Kidney Int 76:Suppl. 114S12–19
     [Google Scholar]
  121. 121. 
    Saito Y, Sato T, Nomoto K, Tsuji H 2018. Identification of phenol- and p-cresol-producing intestinal bacteria by using media supplemented with tyrosine and its metabolites. FEMS Microbiol. Ecol. 94: fiy125
    [Google Scholar]
  122. 122. 
    Selvaraj B, Buckel W, Golding BT, Ullmann GM, Martins BM 2016. Structure and function of 4-hydroxyphenylacetate decarboxylase and its cognate activating enzyme. J. Mol. Microbiol. Biotechnol. 26:76–91
     [Google Scholar]
  123. 123. 
    Russell WR, Duncan SH, Scobbie L, Duncan G, Cantlay L et al. 2013. Major phenylpropanoid-derived metabolites in the human gut can arise from microbial fermentation of protein. Mol. Nutr. Food Res. 57:523–35
     [Google Scholar]
  124. 124. 
    Gryp T, Vanholder R, Vaneechoutte M, Glorieux G 2017. p-Cresyl sulfate. Toxins (Basel) 9:52
     [Google Scholar]
  125. 125. 
    Vanholder R, Schepers E, Pletinck A, Nagler EV, Glorieux G 2014. The uremic toxicity of indoxyl sulfate and p-cresyl sulfate: a systematic review. J. Am. Soc. Nephrol. 25:1897–907
     [Google Scholar]
  126. 126. 
    Wallace BD, Wang H, Lane KT, Scott JE, Orans J et al. 2010. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science 330:831–35
     [Google Scholar]
  127. 127. 
    Spanogiannopoulos P, Bess EN, Carmody RN, Turnbaugh PJ 2016. The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism. Nat. Rev. Microbiol. 14:273–87
     [Google Scholar]
  128. 128. 
    Craciun S, Balskus EP. 2012. Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme. PNAS 109:21307–12
     [Google Scholar]
  129. 129. 
    Bennett BJ, de Aguiar Vallim TQ, Wang Z, Shih DM, Meng Y et al. 2013. Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metab 17:49–60
     [Google Scholar]
  130. 130. 
    Simenhoff ML, Saukkonen JJ, Burke JF, Wesson LG, Schaedler RW 1976. Amine metabolism and the small bowel in uraemia. Lancet 2:818–21
     [Google Scholar]
  131. 131. 
    Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB et al. 2013. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 368:1575–84
     [Google Scholar]
  132. 132. 
    Tang WH, Kitai T, Hazen SL 2017. Gut microbiota in cardiovascular health and disease. Circ. Res. 120:1183–96
     [Google Scholar]
  133. 133. 
    Heianza Y, Ma W, Manson JE, Rexrode KM, Qi L 2017. Gut microbiota metabolites and risk of major adverse cardiovascular disease events and death: a systematic review and meta-analysis of prospective studies. J. Am. Heart Assoc. 6:e004947
     [Google Scholar]
  134. 134. 
    Brown JM, Hazen SL. 2018. Microbial modulation of cardiovascular disease. Nat. Rev. Microbiol. 16:171–81
     [Google Scholar]
  135. 135. 
    Zeisel SH, Warrier M. 2017. Trimethylamine N-oxide, the microbiome, and heart and kidney disease. Annu. Rev. Nutr. 37:157–81
     [Google Scholar]
  136. 136. 
    Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS et al. 2011. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472:57–63
     [Google Scholar]
  137. 137. 
    Seldin MM, Meng Y, Qi H, Zhu W, Wang Z et al. 2016. Trimethylamine N-oxide promotes vascular inflammation through signaling of mitogen-activated protein kinase and nuclear factor-κB. J. Am. Heart Assoc. 5:e002767
     [Google Scholar]
  138. 138. 
    Zhu W, Wang Z, Tang WHW, Hazen SL 2017. Gut microbe–generated trimethylamine N-oxide from dietary choline is prothrombotic in subjects. Circulation 135:1671–73
     [Google Scholar]
  139. 139. 
    Zhu W, Gregory JC, Org E, Buffa JA, Gupta N et al. 2016. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell 165:111–24
     [Google Scholar]
  140. 140. 
    Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA et al. 2009. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. PNAS 106:3698–703
     [Google Scholar]
  141. 141. 
    Chyan YJ, Poeggeler B, Omar RA, Chain DG, Frangione B et al. 1999. Potent neuroprotective properties against the Alzheimer β-amyloid by an endogenous melatonin-related indole structure, indole-3-propionic acid. J. Biol. Chem. 274:21937–42
     [Google Scholar]
  142. 142. 
    Venkatesh M, Mukherjee S, Wang H, Li H, Sun K et al. 2014. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. Immunity 41:296–310
     [Google Scholar]
  143. 143. 
    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]
  144. 144. 
    Lamas B, Richard ML, Leducq V, Pham HP, Michel ML et al. 2016. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat. Med. 22:598–605
     [Google Scholar]
  145. 145. 
    Roberts AB, Gu X, Buffa JA, Hurd AG, Wang Z et al. 2018. Development of a gut microbe–targeted nonlethal therapeutic to inhibit thrombosis potential. Nat. Med. 24:1407–17
     [Google Scholar]
  146. 146. 
    Wang Z, Roberts AB, Buffa JA, Levison BS, Zhu W et al. 2015. Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell 163:1585–95
     [Google Scholar]
  147. 147. 
    Orman M, Bodea S, Funk MA, Campo AM, Bollenbach M et al. 2018. Structure-guided identification of a small molecule that inhibits anaerobic choline metabolism by human gut bacteria. J. Am. Chem. Soc. 141:33–37
     [Google Scholar]
  148. 148. 
    Devlin AS, Marcobal A, Dodd D, Nayfach S, Plummer N et al. 2016. Modulation of a circulating uremic solute via rational genetic manipulation of the gut microbiota. Cell Host Microbe 20:709–15
     [Google Scholar]
  149. 149. 
    Kurtz CB, Millet YA, Puurunen MK, Perreault M, Charbonneau MR et al. 2019. An engineered E. coli Nissle improves hyperammonemia and survival in mice and shows dose-dependent exposure in healthy humans. Sci. Transl. Med. 11: eaau7975
    [Google Scholar]
  150. 150. 
    Isabella VM, Ha BN, Castillo MJ, Lubkowicz DJ, Rowe SE et al. 2018. Development of a synthetic live bacterial therapeutic for the human metabolic disease phenylketonuria. Nat. Biotechnol. 36:857–64
     [Google Scholar]
  151. 151. 
    Lagerlöf F, Dawes C. 1984. The volume of saliva in the mouth before and after swallowing. J. Dent. Res. 198463:618–21
     [Google Scholar]
  152. 152. 
    Gibbons RJ, Houte JV. 1975. Bacterial adherence in oral microbial ecology. Annu. Rev. Microbiol. 29:19–42
     [Google Scholar]
  153. 153. 
    Liégeois F, Albert A, Limme M 2010. Comparison between tongue volume from magnetic resonance images and tongue area from profile cephalograms. Eur. J. Orthod. 32:381–86
     [Google Scholar]
  154. 154. 
    Collins LM, Dawes C. 1987. The surface area of the adult human mouth and thickness of the salivary film covering the teeth and oral mucosa. J. Dent. Res. 66:1300–2
     [Google Scholar]
  155. 155. 
    Schiller C, Fröhlich CP, Giessmann T, Siegmund W, Mönnikes H et al. 2005. Intestinal fluid volumes and transit of dosage forms as assessed by magnetic resonance imaging. Aliment. Pharmacol. Ther. 22:971–79
     [Google Scholar]
  156. 156. 
    DeSesso JM, Jacobson CF. 2001. Anatomical and physiological parameters affecting gastrointestinal absorption in humans and rats. Food Chem. Toxicol. 39:209–28
     [Google Scholar]
  157. 157. 
    Pritchard SE, Marciani L, Garsed KC, Hoad CL, Thongborisute W et al. 2014. Fasting and postprandial volumes of the undisturbed colon: normal values and changes in diarrhea-predominant irritable bowel syndrome measured using serial MRI. Neurogastroenterol. Motil. 26:124–30
     [Google Scholar]
  158. 158. 
    Sadahiro S, Ohmura T, Yamada Y, Saito T, Taki Y 1992. Analysis of length and surface area of each segment of the large intestine according to age, sex and physique. Surg. Radiol. Anat. 14:251–57
     [Google Scholar]
  159. 159. 
    Int. Commis. Radiol. Prot 1975. Report of the Task Group on Reference Man Oxford: Pergamon Press
  160. 160. 
    Nazzal L, Roberts J, Singh P, Jhawar S, Matalon A et al. 2017. Microbiome perturbation by oral vancomycin reduces plasma concentration of two gut-derived uremic solutes, indoxyl sulfate and p-cresyl sulfate, in end-stage renal disease. Nephrol. Dial. Transplant. 32:1809–17
     [Google Scholar]
  161. 161. 
    Tanaka H, Sirich TL, Plummer NS, Weaver DS, Meyer TW 2015. An enlarged profile of uremic solutes. PLOS ONE 10:e0135657
     [Google Scholar]
  162. 162. 
    Stalmach A, Edwards CA, Wightman JD, Crozier A 2013. Colonic catabolism of dietary phenolic and polyphenolic compounds from Concord grape juice. Food Funct 4:52–62
     [Google Scholar]
  163. 163. 
    Gonzalez-Barrio R, Borges G, Mullen W, Crozier A 2010. Bioavailability of anthocyanins and ellagitannins following consumption of raspberries by healthy humans and subjects with an ileostomy. J. Agric. Food Chem. 58:3933–39
     [Google Scholar]
  164. 164. 
    Jaganath IB, Mullen W, Edwards CA, Crozier A 2006. The relative contribution of the small and large intestine to the absorption and metabolism of rutin in man. Free Radic. Res 40:1035–46
     [Google Scholar]
  165. 165. 
    Kikuchi M, Ueno M, Itoh Y, Suda W, Hattori M 2017. Uremic toxin-producing gut microbiota in rats with chronic kidney disease. Nephron 135:51–60
     [Google Scholar]
  166. 166. 
    Mishima E, Fukuda S, Mukawa C, Yuri A, Kanemitsu Y et al. 2017. Evaluation of the impact of gut microbiota on uremic solute accumulation by a CE-TOFMS–based metabolomics approach. Kidney Int 92:634–45
     [Google Scholar]
  167. 167. 
    Lee SH, An JH, Park HM, Jung BH 2012. Investigation of endogenous metabolic changes in the urine of pseudo germ-free rats using a metabolomic approach. J. Chromatogr. B 887–888:8–18
     [Google Scholar]
  168. 168. 
    Yap IK, Li JV, Saric J, Martin FP, Davies H et al. 2008. Metabonomic and microbiological analysis of the dynamic effect of vancomycin-induced gut microbiota modification in the mouse. J. Proteome Res. 7:3718–28
     [Google Scholar]
  169. 169. 
    Claus SP, Tsang TM, Wang Y, Cloarec O, Skordi E et al. 2008. Systemic multicompartmental effects of the gut microbiome on mouse metabolic phenotypes. Mol. Syst. Biol. 4:219
     [Google Scholar]
  170. 170. 
    Nicholls AW, Mortishire-Smith RJ, Nicholson JK 2003. NMR spectroscopic–based metabonomic studies of urinary metabolite variation in acclimatizing germ-free rats. Chem. Res. Toxicol. 16:1395–404
     [Google Scholar]
/content/journals/10.1146/annurev-pathol-020117-043559
Loading
Microbial Contribution to the Human Metabolome: Implications for Health and Disease
Annual Review of Pathology: Mechanisms of Disease 15, 345 (2020); https://doi.org/10.1146/annurev-pathol-020117-043559
/content/journals/10.1146/annurev-pathol-020117-043559
/content/journals/10.1146/annurev-pathol-020117-043559
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error