Microbial Endocrinology and the Microbiota-Gut-Brain Axis

  • Mark LyteEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 817)


Microbial endocrinology is defined as the study of the ability of microorganisms to both produce and recognize neurochemicals that originate either within the microorganisms themselves or within the host they inhabit. As such, microbial endocrinology represents the intersection of the fields of microbiology and neurobiology. The acquisition of neurochemical-based cell-to-cell signaling mechanisms in eukaryotic organisms is believed to have been acquired due to late horizontal gene transfer from prokaryotic microorganisms. When considered in the context of the microbiota’s ability to influence host behavior, microbial endocrinology with its theoretical basis rooted in shared neuroendocrine signaling mechanisms provides for testable experiments with which to understand the role of the microbiota in host behavior and as importantly the ability of the host to influence the microbiota through neuroendocrine-based mechanisms.


Enteric Nervous System Host Behavior Neuroendocrine Hormone Neuroactive Compound Specific Bacterial Species 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Central nervous system


Enteric nervous system


Gamma aminobutyric acid


  1. 1.
    Lyte M (1993) The role of microbial endocrinology in infectious disease. J Endocrinol 137(3):343–345PubMedCrossRefGoogle Scholar
  2. 2.
    Lyte M (2010) Microbial endocrinology: a personal journey. In: Lyte M, Freestone PPE (eds) Microbial endocrinology: interkingdom signaling in infectious disease and health. Springer, New York, pp 1–16CrossRefGoogle Scholar
  3. 3.
    Lyte M (1992) The role of catecholamines in gram-negative sepsis. Med Hypotheses 37(4):255–258PubMedCrossRefGoogle Scholar
  4. 4.
    Lyte M, Ernst S (1992) Catecholamine induced growth of gram negative bacteria. Life Sci 50(3):203–212PubMedCrossRefGoogle Scholar
  5. 5.
    Lyte M (2004) Microbial endocrinology and infectious disease in the 21st century. Trends Microbiol 12(1):14–20PubMedCrossRefGoogle Scholar
  6. 6.
    Renaud M, Miget A (1930) Role favorisant des perturbations locales causees par l’ adrenaline sur le developpement des infections microbiennes. C R Seances Soc Biol Fil 103:1052–1054Google Scholar
  7. 7.
    Roshchina VV (2010) Evolutionary considerations of neurotransmitters in microbial, plant and animal cells. In: Lyte M, Freestone PP (eds) Microbial endocrinology: interkingdom signaling in infectious disease and health. Springer, New York, pp 17–52CrossRefGoogle Scholar
  8. 8.
    Tsavkelova EA, Botvinko IV, Kudrin VS, Oleskin AV (2000) Detection of neurotransmitter amines in microorganisms with the use of high-performance liquid chromatography. Dokl Biochem 372(1–6):115–117PubMedGoogle Scholar
  9. 9.
    Guerrero HY, Caceres G, Paiva CL, Marcano D (1990) Hypothalamic and telencephalic catecholamine content in the brain of the teleost fish, Pygocentrus notatus, during the annual reproductive cycle. Gen Comp Endocrinol 80:257–263PubMedCrossRefGoogle Scholar
  10. 10.
    Kulma A, Szopa J (2007) Catecholamines are active compounds in plants. Plant Sci 172(3):433–440CrossRefGoogle Scholar
  11. 11.
    Pitman RM (1971) Transmitter substances in insects: a review. Comp Gen Pharmacol 2:347–371PubMedCrossRefGoogle Scholar
  12. 12.
    Iyer LM, Aravind L, Coon SL, Klein DC, Koonin EV (2004) Evolution of cell–cell signaling in animals: did late horizontal gene transfer from bacteria have a role? Trends Genet 20(7):292–299PubMedCrossRefGoogle Scholar
  13. 13.
    Stephenson M, Rowatt E (1947) The production of acetylcholine by a strain of Lactobacillus plantarum. J Gen Microbiol 1(3):279–298PubMedCrossRefGoogle Scholar
  14. 14.
    Devalia JL, Grady D, Harmanyeri Y, Tabaqchali S, Davies RJ (1989) Histamine synthesis by respiratory tract micro-organisms: possible role in pathogenicity. J Clin Pathol 42(5):516–522PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Hsu SC, Johansson KR, Donahue MJ (1986) The bacterial flora of the intestine of Ascaris suum and 5-hydroxytryptamine production. J Parasitol 72(4):545–549PubMedCrossRefGoogle Scholar
  16. 16.
    Shahkolahi AM, Donahue MJ (1993) Bacterial flora, a possible source of serotonin in the intestine of adult female Ascaris suum. J Parasitol 79(1):17–22PubMedCrossRefGoogle Scholar
  17. 17.
    Uzbay TI (2012) The pharmacological importance of agmatine in the brain. Neurosci Biobehav Rev 36(1):502–519PubMedCrossRefGoogle Scholar
  18. 18.
    Arena ME, Manca de Nadra MC (2001) Biogenic amine production by Lactobacillus. J Appl Microbiol 90(2):158–162PubMedCrossRefGoogle Scholar
  19. 19.
    Gale EF (1940) The production of amines by bacteria: the decarboxylation of amino-acids by strains of Bacterium coli. Biochem J 34(3):392–413PubMedCentralPubMedGoogle Scholar
  20. 20.
    Holzer P, Farzi A (2014) Neuropeptides and the microbiota-gut-brain axis. In: Lyte M, Cryan JF (eds) Microbial endocrinology: the microbiota-gut-brain axis in health and disease. Springer, New York (in this volume)Google Scholar
  21. 21.
    Riley DR, Sieber KB, Robinson KM, White JR, Ganesan A, Nourbakhsh S et al (2013) Bacteria-human somatic cell lateral gene transfer is enriched in cancer samples. PLoS Comput Biol 9(6):e1003107PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Freestone PP, Sandrini SM, Haigh RD, Lyte M (2008) Microbial endocrinology: how stress influences susceptibility to infection. Trends Microbiol 16(2):55–64PubMedCrossRefGoogle Scholar
  23. 23.
    Von Roepenack-Lahaye E, Newman M, Schornack S, Hammond-Kosack K, Lahaye T, Jones J et al (2003) p-Coumaroylnoradrenaline, a novel plant metabolite implicated in tomato defense against pathogens. J Biol Chem 278(44):43373–43383CrossRefGoogle Scholar
  24. 24.
    Zacares L, Lopez-Gresa MP, Fayos J, Primo J, Belles JM, Conejero V (2007) Induction of p-coumaroyldopamine and feruloyldopamine, two novel metabolites, in tomato by the bacterial pathogen Pseudomonas syringae. Mol Plant Microbe Interact 20(11):1439–1448PubMedCrossRefGoogle Scholar
  25. 25.
    Su MS, Schlicht S, Ganzle MG (2011) Contribution of glutamate decarboxylase in Lactobacillus reuteri to acid resistance and persistence in sourdough fermentation. Microb Cell Fact 10(Suppl 1):S8Google Scholar
  26. 26.
    Foerster CW, Foerster HF (1973) Glutamic acid decarboxylase in spores of Bacillus megaterium and its possible involvement in spore germination. J Bacteriol 114(3):1090–1098PubMedCentralPubMedGoogle Scholar
  27. 27.
    Gale EF (1941) Production of amines by bacteria: the decarboxylation of amino-acids by organisms of the groups Clostridium and Proteus With an addendum by G. L. Brown, F. C. MacIntosh and P. Bruce White. Biochem J 35(1–2):66–80PubMedCentralPubMedGoogle Scholar
  28. 28.
    Krantis A (2000) GABA in the mammalian enteric nervous system. News Physiol Sci 15:284–290PubMedGoogle Scholar
  29. 29.
    Bjurstom H, Wang J, Ericsson I, Bengtsson M, Liu Y, Kumar-Mendu S et al (2008) GABA, a natural immunomodulator of T lymphocytes. J Neuroimmunol 205(1–2):44–50PubMedCrossRefGoogle Scholar
  30. 30.
    Nicholson-Guthrie CS, Guthrie GD, Daly EC, Shuck CS (1995) Determination of gamma-aminobutyric acid levels in human cerebrospinal fluid using Pseudomonas. Anal Biochem 225(2):286–290PubMedCrossRefGoogle Scholar
  31. 31.
    Guthrie GD, Nicholson-Guthrie CS, Leary HL Jr (2000) A bacterial high-affinity GABA binding protein: isolation and characterization. Biochem Biophys Res Commun 268(1):65–68PubMedCrossRefGoogle Scholar
  32. 32.
    Lyte M (2010) The microbial organ in the gut as a driver of homeostasis and disease. Med Hypotheses 74(4):634–638PubMedCrossRefGoogle Scholar
  33. 33.
    Evans DG, Miles AA, Niven JS (1948) The enhancement of bacterial infections by adrenaline. Br J Exp Pathol 29(1):20–39PubMedCentralPubMedGoogle Scholar
  34. 34.
    Traub WH, Bauer D, Wolf U (1991) Virulence of clinical and fecal isolates of Clostridium perfringens type A for outbred NMRI mice. Chemotherapy 37(6):426–435PubMedCrossRefGoogle Scholar
  35. 35.
    Sperandio V, Torres AG, Jarvis B, Nataro JP, Kaper JB (2003) Bacteria-host communication: the language of hormones. Proc Natl Acad Sci U S A 100(15):8951–8956PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Furness JB (2006) The enteric nervous system, Blackwell, Malden, MA, xiii, 274 ppGoogle Scholar
  37. 37.
    Bowdre JH, Krieg NR, Hoffman PS, Smibert RM (1976) Stimulatory effect of dihydroxyphenyl compounds on the aerotolerance of Spirillum volutans and Campylobacter fetus subspecies jejuni. Appl Environ Microbiol 31(1):127–133PubMedCentralPubMedGoogle Scholar
  38. 38.
    Lyte M, Erickson AK, Arulanandam BP, Frank CD, Crawford MA, Francis DH (1997) Norepinephrine-induced expression of the K99 pilus adhesin of enterotoxigenic Escherichia coli. Biochem Biophys Res Commun 232(3):682–686PubMedCrossRefGoogle Scholar
  39. 39.
    Lyte M, Arulanandam B, Nguyen K, Frank C, Erickson A, Francis D (1997) Norepinephrine induced growth and expression of virulence associated factors in enterotoxigenic and enterohemorrhagic strains of Escherichia coli. Adv Exp Med Biol 412:331–339PubMedCrossRefGoogle Scholar
  40. 40.
    Peterson G, Kumar A, Gart E, Narayanan S (2011) Catecholamines increase conjugative gene transfer between enteric bacteria. Microb Pathog 51(1–2):1–8PubMedCrossRefGoogle Scholar
  41. 41.
    Oneal MJ, Schafer ER, Madsen ML, Minion FC (2008) Global transcriptional analysis of Mycoplasma hyopneumoniae following exposure to norepinephrine. Microbiology 154(Pt 9):2581–2588PubMedCrossRefGoogle Scholar
  42. 42.
    Bearson BL, Bearson SM, Uthe JJ, Dowd SE, Houghton JO, Lee I et al (2008) Iron regulated genes of Salmonella enterica serovar Typhimurium in response to norepinephrine and the requirement of fepDGC for norepinephrine-enhanced growth. Microbes Infect 10(7):807–816PubMedCrossRefGoogle Scholar
  43. 43.
    Nakano M, Takahashi A, Sakai Y, Nakaya Y (2007) Modulation of pathogenicity with norepinephrine related to the type III secretion system of Vibrio parahaemolyticus. J Infect Dis 195(9):1353–1360PubMedCrossRefGoogle Scholar
  44. 44.
    Miles AA, Niven JS (1950) The enhancement of infection during shock produced by bacterial toxins and other agents. Br J Exp Pathol 31(1):73–95PubMedCentralPubMedGoogle Scholar
  45. 45.
    Miles AA, Miles EM, Burke J (1957) The value and duration of defence reactions of the skin to the primary lodgement of bacteria. Br J Exp Pathol 38(1):79–96PubMedCentralPubMedGoogle Scholar
  46. 46.
    Cooper EV (1946) Gas-gangrene following injection of adrenaline. Lancet 1(6396):459–461PubMedCrossRefGoogle Scholar
  47. 47.
    O’Donnell PM, Aviles H, Lyte M, Sonnenfeld G (2006) Enhancement of in vitro growth of pathogenic bacteria by norepinephrine: importance of inoculum density and role of transferrin. Appl Environ Microbiol 72(7):5097–5099PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Lyte M, Frank CD, Green BT (1996) Production of an autoinducer of growth by norepinephrine cultured Escherichia coli O157:H7. FEMS Microbiol Lett 139(2–3):155–159PubMedCrossRefGoogle Scholar
  49. 49.
    Freestone PP, Haigh RD, Williams PH, Lyte M (1999) Stimulation of bacterial growth by heat-stable, norepinephrine-induced autoinducers. FEMS Microbiol Lett 172(1):53–60PubMedCrossRefGoogle Scholar
  50. 50.
    Barrett E, Ross RP, O’Toole PW, Fitzgerald GF, Stanton C (2012) Gamma-aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol 113(2):411–417PubMedCrossRefGoogle Scholar
  51. 51.
    Asano Y, Hiramoto T, Nishino R, Aiba Y, Kimura T, Yoshihara K et al (2012) Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice. Am J Physiol Gastrointest Liver Physiol 303(11):G1288–G1295PubMedCrossRefGoogle Scholar
  52. 52.
    Yurdaydin C, Walsh TJ, Engler HD, Ha JH, Li Y, Jones EA et al (1995) Gut bacteria provide precursors of benzodiazepine receptor ligands in a rat model of hepatic encephalopathy. Brain Res 679(1):42–48PubMedCrossRefGoogle Scholar
  53. 53.
    Hu Y, Phelan V, Ntai I, Farnet CM, Zazopoulos E, Bachmann BO (2007) Benzodiazepine biosynthesis in Streptomyces refuineus. Chem Biol 14(6):691–701PubMedCrossRefGoogle Scholar
  54. 54.
    Polacheck I, Platt Y, Aronovitch J (1990) Catecholamines and virulence of Cryptococcus neoformans. Infect Immun 58(9):2919–2922PubMedCentralPubMedGoogle Scholar
  55. 55.
    Liu L, Wakamatsu K, Ito S, Williamson PR (1999) Catecholamine oxidative products, but not melanin, are produced by Cryptococcus neoformans during neuropathogenesis in mice. Infect Immun 67(1):108–112PubMedCentralPubMedGoogle Scholar
  56. 56.
    Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC et al (2009) Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci U S A 106(10):3698–3703PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Wood JD (2004) Enteric neuroimmunophysiology and pathophysiology. Gastroenterology 127(2):635–657PubMedCrossRefGoogle Scholar
  58. 58.
    Lyte M, Varcoe JJ, Bailey MT (1998) Anxiogenic effect of subclinical bacterial infection in mice in the absence of overt immune activation. Physiol Behav 65(1):63–68PubMedCrossRefGoogle Scholar
  59. 59.
    Goehler LE, Gaykema RPA, Opitz N, Reddaway R, Badr N, Lyte M (2005) Activation in vagal afferents and central autonomic pathways: early responses to intestinal infection with Campylobacter jejuni. Brain Behav Immun 19(4):334–344PubMedCrossRefGoogle Scholar
  60. 60.
    Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A et al (2011) Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr 105(5):755–764PubMedCrossRefGoogle Scholar
  61. 61.
    Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG et al (2011) Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A 108(38):16050–16055PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Collins SM, Kassam Z, Bercik P (2013) The adoptive transfer of behavioral phenotype via the intestinal microbiota: experimental evidence and clinical implications. Curr Opin Microbiol 16(3):240–245PubMedCrossRefGoogle Scholar
  63. 63.
    Ko CY, Lin HTV, Tsai GJ (2013) Gamma-aminobutyric acid production in black soybean milk by Lactobacillus brevis FPA 3709 and the antidepressant effect of the fermented product on a forced swimming rat model. Process Biochem 48(4):559–568CrossRefGoogle Scholar
  64. 64.
    Lyte M (2011) Probiotics function mechanistically as delivery vehicles for neuroactive compounds: microbial endocrinology in the design and use of probiotics. Bioessays 33(8):574–581PubMedCrossRefGoogle Scholar
  65. 65.
    Lyte M (2013) Microbial endocrinology and nutrition: a perspective on new mechanisms by which diet can influence gut-to-brain communication. PharmaNutrition 1(1):35–39CrossRefGoogle Scholar
  66. 66.
    Norris V, Molina F, Gewirtz AT (2013) Hypothesis: bacteria control host appetites. J Bacteriol 195(3):411–416PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Matsumoto M, Kibe R, Ooga T, Aiba Y, Kurihara S, Sawaki E et al (2012) Impact of intestinal microbiota on intestinal luminal metabolome. Sci Rep 2:233PubMedCentralPubMedGoogle Scholar
  68. 68.
    Flint HJ (2012) The impact of nutrition on the human microbiome. Nutr Rev 70(Suppl 1):S10–S13PubMedCrossRefGoogle Scholar
  69. 69.
    Mischke M, Plosch T (2013) More than just a gut instinct-the potential interplay between a baby’s nutrition, its gut microbiome, and the epigenome. Am J Physiol Regul Integr Comp Physiol 304(12):R1065–R1069PubMedCrossRefGoogle Scholar
  70. 70.
    Kovatcheva-Datchary P, Arora T (2013) Nutrition, the gut microbiome and the metabolic syndrome. Best Pract Res Clin Gastroenterol 27(1):59–72PubMedCrossRefGoogle Scholar
  71. 71.
    Parr AM, Zoutman DE, Davidson JS (1999) Antimicrobial activity of lidocaine against bacteria associated with nosocomial wound infection. Ann Plast Surg 43(3):239–245PubMedCrossRefGoogle Scholar
  72. 72.
    Lyte M, Freestone PP, Neal CP, Olson BA, Haigh RD, Bayston R et al (2003) Stimulation of Staphylococcus epidermidis growth and biofilm formation by catecholamine inotropes. Lancet 361(9352):130–135PubMedCrossRefGoogle Scholar
  73. 73.
    Neal CP, Freestone PP, Maggs AF, Haigh RD, Williams PH, Lyte M (2001) Catecholamine inotropes as growth factors for Staphylococcus epidermidis and other coagulase-negative Staphylococci. FEMS Microbiol Lett 194(2):163–169PubMedCrossRefGoogle Scholar
  74. 74.
    Brenner ED, Stahlberg R, Mancuso S, Vivanco J, Baluska F, Van Volkenburgh E (2006) Plant neurobiology: an integrated view of plant signaling. Trends Plant Sci 11(8):413–419PubMedCrossRefGoogle Scholar
  75. 75.
    Vijayakumari K, Siddhuraju P, Janardhanan K (1996) Effect of different post-harvest treatments on antinutritional factors in seeds of the tribal pulse, Mucuna pruriens (L.) DC. Int J Food Sci Nutr 47(3):263–272PubMedCrossRefGoogle Scholar
  76. 76.
    Li W, Dowd SE, Scurlock B, Acosta-Martinez V, Lyte M (2009) Memory and learning behavior in mice is temporally associated with diet-induced alterations in gut bacteria. Physiol Behav 96(4–5):557–567PubMedCrossRefGoogle Scholar
  77. 77.
    Furness JB (2012) The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol 9(5):286–294PubMedCrossRefGoogle Scholar
  78. 78.
    Hanrieder J, Ljungdahl A, Andersson M (2012) MALDI imaging mass spectrometry of neuropeptides in Parkinson’s disease. J Vis Exp (60)Google Scholar
  79. 79.
    Cryan JF, Dinan TG (2012) Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 13(10):701–712PubMedCrossRefGoogle Scholar
  80. 80.
    Al-Asmakh M, Anuar F, Zadjali F, Rafter J, Pettersson S (2012) Gut microbial communities modulating brain development and function. Gut Microbes 3(4):366–373PubMedCentralPubMedCrossRefGoogle Scholar
  81. 81.
    Forsythe P, Kunze WA (2013) Voices from within: gut microbes and the CNS. Cell Mol Life Sci 70(1):55–69PubMedCrossRefGoogle Scholar
  82. 82.
    Forsythe P, Kunze WA, Bienenstock J (2012) On communication between gut microbes and the brain. Curr Opin Gastroenterol 28(6):557–562PubMedCrossRefGoogle Scholar
  83. 83.
    Douglas-Escobar M, Elliott E, Neu J (2013) Effect of intestinal microbial ecology on the developing brain. JAMA Pediatr 167(4):374–379PubMedCrossRefGoogle Scholar
  84. 84.
    Lyte M, Bailey MT (1997) Neuroendocrine-bacterial interactions in a neurotoxin-induced model of trauma. J Surg Res 70(2):195–201PubMedCrossRefGoogle Scholar
  85. 85.
    Bailey MT, Dowd SE, Galley JD, Hufnagle AR, Allen RG, Lyte M (2011) Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation. Brain Behav Immun 25(3):397–407PubMedCentralPubMedCrossRefGoogle Scholar
  86. 86.
    McFarland LV (2008) Antibiotic-associated diarrhea: epidemiology, trends and treatment. Future Microbiol 3(5):563–578PubMedCrossRefGoogle Scholar
  87. 87.
    Lyte M (2014) Microbial endocrinology: host-microbiota neuroendocrine interactions influencing brain and behavior. Gut Microbes 5(3); PMID: 24690573;

Copyright information

© Springer New York 2014

Authors and Affiliations

  1. 1.Department of Immunotherapeutics and BiotechnologyTexas Tech University Health Sciences CenterAbileneUSA

Personalised recommendations