Endocrine properties of microbiota

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Microbiota and the macroorganism are in constant interaction with each other. Symbiotic microbiota participates in a number of important physiological, biochemical and neuroendocrine functions of the macroorganism. Metabolic activity of microbiota in the gastrointestinal tract (GIT) helps to digest food, absorb nutrients and extract energy. GIT microbiota participates in the metabolic processes of protein, fat and carbohydrate metabolism, in gluconeogenesis and glycogenolysis, and also affects the feeling of hunger and satiety. In addition, microbiota is often considered as a metabolically active "organ", since the power of metabolic reactions of the intestinal microbiota is comparable to that of the liver of the host organism. Microbiota produces autoinducers (quorum-sensing substances), hormones, neurotransmitters, short-chain fatty acids (SCFA), secondary bile acids, growth factors, gaseous molecules and many other active substances. Microbial metabolites provide the main communication between the host organism and its microbial community and are of great importance for the normal functioning of the macroorganism, starting from intrauterine development and ending with the aging process. Moreover, changes in metabolic activity and/or the ratio of different types of microorganisms can lead to various metabolic disorders of the host organism. Conversely, a metabolic disorder of the host organism can lead to a change in the species composition of the microbiota. This review describes the influence of the microbiota and its metabolites on the neuroendocrine functions of the macroorganism and describes the corresponding mechanisms of this influence.

Full Text

Restricted Access

About the authors

K. V. Sobol

Sechenov Institute of Evolutionary Physiology and Biochemistry, RAS

Author for correspondence.
Email: peep9@yandex.ru
Russian Federation, St-Petersburg

References

  1. Олескин АВ, Шендеров БА, Роговский ВС (2020) Социальность микроорганизмов и взаимоотношения в системе микробиота – хозяин: роль нейромедиаторов. М. Изд-во Моск. ун-та. [Oleskin AV, Shenderov BA, Rogovsky VS (2020) Microbial sociality and microbiota-host relationships: the role of neurotransmitters. M. Moscow Univer Publ. (In Russ)].
  2. Cryan JF, Dinan TG (2012) Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 13: 701–712. https://doi.org/10.1038/nrn3346
  3. Cryan JF, O'Riordan KJ, Cowan CSM, Sandhu KV, Bastiaanssen TFS, Boehme M, Codagnone MG, Cussotto S, Fulling C, Golubeva AV, Guzzetta KE, Jaggar M, Long-Smith CM, Lyte JM, Martin JA, Molinero-Perez A, Moloney G, Morelli E, Morillas E, O'Connor R, Cruz-Pereira JS, Peterson VL, Rea K, Ritz NL, Sherwin E, Spichak S, Teichman EM, van de Wouw M, Ventura-Silva AP, Wallace- Fitzsimons SE, Hyland N, Clarke G, Dinan TG (2019) The Microbiota-Gut-Brain-Axis. Physiol Rev 99: 1877–2013. https://doi.org/10.1152/physrev.00018.2018
  4. Forsythe P, Sudo N, Dinan T, Taylor VH, Bienenstock J (2010) Mood and gut feelings. Brain Behav Immun 24: 9—16. https://doi.org/10.1016/j.bbi.2009.05.058
  5. Han S, Van Treuren W, Fischer CR, Merrill BD, DeFelice BC, Sanchez JM, Higginbottom SK, Guthrie L, Fall LA, Dodd D, Fischbach MA, Sonnenburg JL (2021) A metabolomics pipeline for the mechanistic interrogation of the gut microbiome. Nature 595(7867): 415–420. https://doi.org/10.1038/s41586-021-03707-9
  6. Olofsson LE, Bäckhed F (2022) The Metabolic Role and Therapeutic Potential of the Microbiome. Endocr Rev 43(5): 907–926. https://doi.org/10.1210/endrev/bnac004
  7. Rastelli M, Cani PD, Knauf C (2019) The Gut Microbiome Influences Host Endocrine Functions. Endocr Rev 40 (5): 1271–1284. https://doi.org/10.1210/er.2018-00280
  8. Shenderov BA, Sinitsa AV, Zakharchenko MM, Lang C (2020) Metabiotics, Present State, Challenges and Perspectives. Springer Nature Switzerland AG.
  9. Tsafarova B, Hodzhev Y, Yordanov G, Tolchkov V, Kalfin R, Panaiotov S (2023) Morphology of blood microbiota in healthy individuals assessed by light and electron microscopy. Front Cell Infect Microbiol 12: 1091341. https://doi.org/10.3389/fcimb.2022.1091341
  10. Ley RE, Peterson DA, Gordon JI (2006) Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124: 837—848. https://doi.org/10.1016/j.cell.2006.02.017
  11. Xu J, Mahowald MA, Ley RE, Lozupone CA, Hamady M, Martens EC, Henrissat B, Coutinho PM, Minx P, Latreille P, Cordum H, Van Brunt A, Kim K, Fulton RS, Fulton LA, Clifton SW, Wilson RK, Knight RD, Gordon JI (2007) Evolution of symbiotic bacteria in the distal human intestine. PLoS Biol 5: e156. https://doi.org/10.1371/journal.pbio.0050156
  12. Tremaroli V, Bäckhed F (2012) Functional interactions between the gut microbiota and host metabolism. Nature 489(7415): 242–249. https://doi.org/10.1038/nature11552
  13. Demidova TY, Lobanova KG, Oynotkinova OS (2020) Gut microbiota is an endocrine organ. Obesity and Metabol 17(3): 299–306. (In Russ). https://doi.org/10.14341/omet12457
  14. Donia MS, Fischbach MA (2015) Small molecules from the human microbiota. Science 349(6246): 1254766. https://doi.org/10.1126/science.1254766
  15. Martin CR, Osadchiy V, Kalani A, Mayer EA (2018) The Brain-Gut-Microbiome Axis. Cell Mol Gastroenterol Hepatol 6: 133–148. https://doi.org/10.1016/j.jcmgh.2018.04.003
  16. Morais LH, Schreiber HL, Mazmanian SK (2021) The gut microbiota-brain axis in behaviour and brain disorders. Nat Rev Microbiol 19(4): 241–255. https://doi.org/10.1038/s41579-020-00460-0
  17. Jones LA, Sun EW, Martin AM, Keating DJ (2020) The ever-changing roles of serotonin. Int J Biochem Cell Biol 125: 105776. https://doi.org/10.1016/j.biocel.2020.105776
  18. Natochin YV, Orlova OG, Rybalchenko OV, Shakhmatova EI (2022) Vasopressin and Oxytocin Secretion by Microorganisms. Microbiology (Russ Feder) 91(1): 104–106. https://doi.org/10.1134/s0026261721060102.
  19. Clarke MB, Hughes DT, Zhu C, Boedeker EC, Sperandio V (2006) The QseC sensor kinase: a bacterial adrenergic receptor. Proc Natl Acad Sci U S A 103(27): 10420–10425. https://doi.org/10.1073/pnas.0604343103
  20. Sobol CV (2017) A new class of pharmabiotics with unique properties. In: Grumezescu AM, Holban AM (Eds). Soft Chemistry and Food Fermentation. Elsevier. 79–107. https://doi.org/10.1016/B978-0-12-811412-4.00004-7
  21. Roshchina VV (2010) Evolutionary considerations of neurotransmitters in microbial, plant, and animal cells. Microbial Endocrinology: Interkingdom Signaling in Infectious Disease and Health. Eds. Lyte M, Freestone PPE (eds). Springer. New York. 17–52.
  22. Wall R, Cryan JF, Ross RP, Fitzgerald GF, Dinan TG, Stanton C (2014) Bacterial neuroactive compounds produced by psychobiotics. Adv Exp Med Biol 817: 221–239. https://doi.org/10.1007/978-1-4939-0897-4_10
  23. Liu J, Tan Y, Cheng H, Zhang D, Feng W, Peng C (2022) Functions of Gut Microbiota Metabolites, Current Status and Future Perspectives. Aging Dis 13(4): 1106–1126. https://doi.org/10.14336/AD.2022.0104
  24. Neveu V, Nicolas G, Amara A, Salek RM, Scalbert A (2023) The human microbial exposome: expanding the Exposome-Explorer database with gut microbial metabolites. Sci Rep 13(1): 1946. https://doi.org/10.1038/s41598-022-26366-w
  25. Gill SR, Pop M, Deboy RT, Eckburg PB, Turnbaugh PJ, Samuel BS, Gordon JI, Relman DA, Fraser-Liggett CM, Nelson KE (2006) Metagenomic analysis of the human distal gut microbiome. Science 312: 1355–1359. https://doi.org/10.1126/science.1124234
  26. Sobol CV (2018) Role of Microbiota in Neurodegenerative Diseases. Russ J Dev Biol 49: 297–313. https://doi.org/10.1134/S1062360418060061
  27. Fock E, Parnova R (2023) Mechanisms of Blood-Brain Barrier Protection by Microbiota-Derived Short-Chain Fatty Acids. Cells 12(4): 657. https://doi.org/10.3390/cells12040657
  28. Parker A, Fonseca S, Carding SR (2020) Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health. Gut Microbes 11: 135–157. https://doi.org/10.1080/19490976.2019.1638722
  29. Wynendaele E, Verbeke F, Stalmans S, Gevaert B, Janssens Y, Van De Wiele C, Peremans K, Burvenich C, De Spiegeleer B (2015) Quorum Sensing Peptides Selectively Penetrate the Blood-Brain Barrier. PLoS One 10(11): e0142071. https://doi.org/10.1371/journal.pone.0142071
  30. Witkowski M, Weeks TL, Hazen SL (2020) Gut Microbiota and Cardiovascular Disease. Circ Res 127(4): 553–570. https://doi.org/10.1161/CIRCRESAHA.120.316242
  31. Jašarević E, Bale TL (2019) Prenatal and postnatal contributions of the maternal microbiome on offspring programming. Front Neuroendocrinol 55: 100797. https://doi.org/10.1016/j.yfrne.2019.100797
  32. Bourassa MW, Alim I, Bultman SJ, Ratan RR (2016) Butyrate, neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health? Neurosci Lett 625: 56–63. https://doi.org/10.1016/j.neulet.2016.02.009
  33. Shpakov AO, Pertseva MN (2008) Signaling systems of lower eukaryotes and their evolution. Int Rev Cell Molecul Biol 269: 151–282. https://doi.org/10.1016/S1937-6448(08)01004-6
  34. Shpakov AO (2009) Bacterial autoinducing peptides. Mikrobiologiia 78(3): 291–303.
  35. Shpakov AO (2023) Allosteric Sites and Allosteric Regulators of G Protein-Coupled Receptors: Gray Cardinals of Signal Transduction. J Evol Biochem Phys 59 (Suppl 1): S1–S106. https://doi.org/10.1134/S0022093023070013
  36. Papenfort K, Bassler BL (2016) Quorum sensing signal-response systems in Gram-negative bacteria. Nat Rev Microbiol 14(9): 576–588. https://doi.org/10.1038/nrmicro.2016.89
  37. Vogt SL, Pena-Diaz J, Finlay BB (2015) Chemical communication in the gut: Effects of microbiota-generated metabolites on gastrointestinal bacterial pathogens. Anaerobe 34: 106–115. https://doi.org/10.1016/j.anaerobe.2015.05.002
  38. Whiteley M, Diggle SP, Greenberg EP (2017) Bacterial quorum sensing: the progress and promise of an emerging research area. Nature 551(7680): 313–320. https://doi.org/10.1038/nature24624
  39. Bivar Xavier K (2018) Bacterial interspecies quorum sensing in the mammalian gut microbiota. Compt Rendus Biol 341(5): 297–299. https://doi.org/10.1016/j.crvi.2018.03.006
  40. Moura-Alves P, Puyskens A, Stinn A, Klemm M, Guhlich-Bornhof U, Dorhoi A, Furkert J, Kreuchwig A, Protze J, Lozza L, Pei G, Saikali P, Perdomo C, Mollenkopf HJ, Hurwitz R, Kirschhoefer F, Brenner-Weiss G, Weiner J, Oschkinat H, Kolbe M, Krause G, Kaufmann SHE (2019) Host monitoring of quorum sensing during Pseudomonas aeruginosa infection. Science 366(6472): eaaw1629. https://doi.org/10.1126/science.aaw1629
  41. Luscombe VB, Baena-López LA, Bataille CJR, Russell AJ, Greaves DR (2023) Kinetic insights into agonist-dependent signalling bias at the pro-inflammatory G-protein coupled receptor GPR84. Eur J Pharmacol 956: 175960. https://doi.org/10.1016/j.ejphar.2023.175960
  42. Margulis L (1996) Archaeal-eubacterial mergers in the origin of Eukarya: Phylogenetic classification of life. Proc Natl Acad Sci U S A 93: 1071–1076.
  43. Brubaker SW, Bonham KS, Zanoni I, Kagan JC (2015) Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol 33: 257–290. https://doi.org/10.1146/annurev-immunol-032414-112240
  44. Troutman TD, Bazan JF, Pasare C (2012) Toll-like receptors, signaling adapters and regulation of the pro-inflammatory response by PI3K. Cell Cycle 11(19): 3559–3367. https://doi.org/10.4161/cc.21572
  45. West AP, Koblansky AA, Ghosh S (2006) Recognition and signaling by toll-like receptors. Annu Rev Cell Dev Biol 22: 409–437. https://doi.org/10.1146/annurev.cellbio.21.122303.115827
  46. Vallejo JG (2011) Role of Toll-like receptors in cardiovascular diseases. Clin Sci 121: 1–10. https://doi.org/10.1042/CS20100539
  47. Barajon I, Serrao G, Arnaboldi F, Opizzi E, Ripamonti G, Balsari A, Rumio C (2009) Toll-like receptors 3, 4, and 7 are expressed in the enteric nervous system and dorsal root ganglia. J Histochem Cytochem 57(11): 1013–1023. https://doi.org/10.1369/jhc.2009.953539
  48. Chen H, Nwe PK, Yang Y, Rosen CE, Bielecka AA, Kuchroo M, Cline GW, Kruse AC, Ring AM, Crawford JM, Palm NW (2019) A Forward Chemical Genetic Screen Reveals Gut Microbiota Metabolites That Modulate Host Physiology. Cell 177(5): 1217–1231.e18. https://doi.org/10.1016/j.cell.2019.03.036
  49. Tan J, McKenzie C, Potamitis M, Thorburn AN, Mackay CR, Macia L (2014) The role of short-chain fatty acids in health and disease. Adv Immunol 121: 91–119. https://doi.org/10.1016/B978-0-12-800100-4.00003-9
  50. Ulven T (2012) Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets. Front Endocrinol 3: 111. https://doi.org/10.3389/fendo.2012.00111
  51. Engelstoft MS, Schwartz TW (2016) Opposite Regulation of Ghrelin and Glucagon-like Peptide-1 by Metabolite G-Protein-Coupled Receptors. Trends Endocrinol Metabol 27(9): 665–675. https://doi.org/10.1016/j.tem.2016.07.001
  52. Torres-Fuentes C, Golubeva AV, Zhdanov AV, Wallace S, Arboleya S, Papkovsky DB, Aidy SE, Ross P, Roy BL, Stanton C, Dinan TG, Cryan JF, Schellekens H (2019) Short-chain fatty acids and microbiota metabolites attenuate ghrelin receptor signaling. FASEB J 33(12): 13546–13559. https://doi.org/10.1096/fj.201901433R
  53. Leeuwendaal NK, Cryan JF, Schellekens H (2021) Gut peptides and the microbiome: focus on ghrelin. Curr Opin Endocrinol Diabetes Obes 28(2): 243–252. https://doi.org/10.1097/MED.0000000000000616
  54. Sobol CV, Belostotskaya GB, Kenworthy MW (2005) Calcium signalling in rat brain neurons and differentiation of PC-12 cells induced by application of a probiotic product. Neurophysiol Ukraine 37: 284–293
  55. Amorim Neto DP, Bosque BP, Pereira de Godoy JV, Rodrigues PV, Meneses DD, Tostes K, Costa Tonoli CC, Faustino de Carvalho H, González-Billault C, de Castro Fonseca M (2022) Akkermansia muciniphila induces mitochondrial calcium overload and α –synuclein aggregation in an enteroendocrine cell line. Science 25(3): 103908. https://doi.org/10.1016/j.isci.2022.103908
  56. Cani PD, Van Hul M, Lefort C, Depommier C, Rastelli M, Everard A (2019) Microbial regulation of organismal energy homeostasis. Nat Metab 1(1): 34–46. https://doi.org/10.1038/s42255-018-0017-4
  57. Macfarlane S, Macfarlane GT (2003) Regulation of short-chain fatty acid production. Proc Nutr Soc 62: 67–72. https://doi.org/10.1079/PNS2002207
  58. Oliphant K, Allen-Vercoe E (2019) Macronutrient metabolism by the human gut microbiome: Major fermentation by-products and their impact on host health. Microbiome 7: 91. https://doi.org/10.1186/s40168-019-0704-8
  59. Islam MR, Arthur S, Haynes J, Butts MR, Nepal N, Sundaram U (2022) The Role of Gut Microbiota and Metabolites in Obesity-Associated Chronic Gastrointestinal Disorders. Nutrients 14(3): 624. https://doi.org/10.3390/nu14030624
  60. Nogal A, Valdes AM, Menni C (2021) The role of short-chain fatty acids in the interplay between gut microbiota and diet in cardio-metabolic health. Gut Microbes 13(1): 1–24. https://doi.org/10.1080/19490976.2021.1897212
  61. Duncan SH, Louis P, Flint HJ (2004) Lactate-utilizing bacteria, isolated from human feces, that produce butyrate as a major fermentation product. Appl Environ Microbiol 70(10): 5810–5817. https://doi.org/10.1128/AEM.70.10.5810-5817.2004
  62. Topping DL, Clifton PM (2001) Short-Chain Fatty Acids and Human Colonic Function: Roles of Resistant Starch and Nonstarch Polysaccharides. Physiol Rev 81: 1031–1064. https://doi.org/10.1152/physrev.2001.81.3.1031
  63. Ganapathy V, Thangaraju M, Prasad PD, Martin PM, Singh N (2013) Transporters and receptors for short-chain fatty acids as the molecular link between colonic bacteria and the host. Curr Opin Pharmacol 13: 869–874. https://doi.org/10.1016/j.coph.2013.08.006
  64. Den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM (2013) The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res 54: 2325–2340. https://doi.org/10.1194/jlr.R036012
  65. Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, Schilter HC, Rolph MS, Mackay F, Artis D, Xavier RJ, Teixeira MM, Mackay CR (2009) Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461(7268): 1282–1286. https://doi.org/10.1038/nature08530
  66. Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK, Hammer RE, Williams SC, Crowley J, Yanagisawa M, Gordon JI (2008) Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci U S A 105: 16767–16772. https://doi.org/10.1073/pnas.0808567105
  67. DeCastro M, Nankova BB, Shah P, Patel P, Mally PV, Mishra R, La Gamma EF (2005) Short chain fatty acids regulate tyrosine hydroxylase gene expression through a cAMP-dependent signaling pathway. Brain Res Mol Brain Res 142(1): 28–38. https://doi.org/10.1016/j.molbrainres.2005.09.002
  68. Shen H, Ding L, Baig M, Tian J, Wang Y, Huang W (2021) Improving glucose and lipids metabolism: drug development based on bile acid related targets. Cell Stress 5(1): 1–18. https://doi.org/10.15698/cst2021.01.239
  69. De Vadder F, Kovatcheva-Datchary P, Goncalves D, Vinera J, Zitoun C, Duchampt A, Bäckhed F, Mithieux G (2014) Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 156(1–2): 84–96. https://doi.org/10.1016/j.cell.2013.12.016
  70. Chen Y, Xu J, Chen Y (2021) Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders. Nutrients 13(6): 2099. https://doi.org/10.3390/nu13062099
  71. Loh JS, Mak WQ, Tan LKS, Ng CX, Chan HH, Yeow SH, Foo JB, Ong YS, How CW, Khaw KY (2024) Microbiota-gut-brain axis and its therapeutic applications in neurodegenerative diseases. Signal Transduct Target Ther 9(1): 37. https://doi.org/10.1038/s41392-024-01743-1
  72. Najjar SA, Hung LY, Margolis KG (2023) Serotonergic Control of Gastrointestinal Development, Motility, and Inflammation. Compr Physiol 13(3): 4851–4868. https://doi.org/10.1002/cphy.c220024
  73. Mawe GM, Hoffman JM (2013) Serotonin signalling in the gut-functions, dysfunctions and therapeutic targets. Nat Rev Gastroenterol Hepatol 10(8): 473–486. https://doi.org/10.1038/nrgastro.2013.105
  74. Gershon MD (2022) The Shaggy Dog Story of Enteric Signaling: Serotonin, a Molecular Megillah. Adv Exp Med Biol 1383: 307–318. https://doi.org/10.1007/978-3-031-05843-1_28
  75. Sanidad KZ, Rager SL, Carrow HC, Ananthanarayanan A, Callaghan R, Hart LR, Li T, Ravisankar P, Brown JA, Amir M, Jin JC, Savage AR, Luo R, Rowdo FM, Martin ML, Silver RB, Guo CJ, Krumsiek J, Inohara N, Zeng MY (2024) Gut bacteria-derived serotonin promotes immune tolerance in early life. Sci Immunol 9(93): eadj4775. https://doi.org/10.1126/sciimmunol.adj4775
  76. Yang X, Lou J, Shan W, Ding J, Jin Z, Hu Y, Du Q, Liao Q, Xie R, Xu J (2021) Pathophysiologic Role of Neurotransmitters in Digestive Diseases. Front Physiol 12: 567650. https://doi.org/10.3389/fphys.2021.567650
  77. Yabut JM, Crane JD, Green AE, Keating DJ, Khan WI, Steinberg GR (2019) Emerging Roles for Serotonin in Regulating Metabolism: New Implications for an Ancient Molecule. Endocr Rev 40(4): 1092–1107. https://doi.org/10.1210/er.2018-00283
  78. Waclawiková B, Bullock A, Schwalbe M, Aranzamendi C, Nelemans SA, van Dijk G, El Aidy S (2021) Gut bacteria-derived 5-hydroxyindole is a potent stimulant of intestinal motility via its action on L-type calcium channels. PLoS Biol 19(1): e3001070. https://doi.org/10.1371/journal.pbio.3001070
  79. Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, Nagler CR, Ismagilov RF, Mazmanian SK, Hsiao EY (2015) Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161(2): 264–276. https://doi.org/10.1016/j.cell.2015.02.047
  80. Legan TB, Lavoie B, Mawe GM (2022) Direct and indirect mechanisms by which the gut microbiota influence host serotonin systems. Neurogastroenterol Motil 34(10): e14346. https://doi.org/10.1111/nmo.14346
  81. Li N, Koester ST, Lachance DM, Dutta M, Cui JY, Dey N (2021) Microbiome-encoded bile acid metabolism modulates colonic transit times. Science 24(6): 102508. https://doi.org/10.1016/j.isci.2021.102508
  82. Ozogul F (2011) Effects of specific lactic acid bacteria species on biogenic amine production by foodborne pathogens. Int J Food Sci Technol 46(3): 478–484. https://doi.org/10.1111/j.1365-2621.2010.02511.x
  83. Roshchina VV (2016) New Trends and Perspectives in the Evolution of Neurotransmitters in Microbial, Plant, and Animal Cells. In: Lyte M (ed) Microbial Endocrinology: Interkingdom Signaling in Infectious Disease and Health. Adv Exp Med Biol 874. Springer. 25–77. https://doi.org/10.1007/978-3-319-20215-0_2
  84. Kazemi A, Noorbala AA, Azam K, Eskandari MH, Djafarian K (2019) Effect of probiotic and prebiotic vs placebo on psychological outcomes in patients with major depressive disorder: A randomized clinical trial. Clin Nutr 38: 522–528. https://doi.org/10.1016/j.clnu.2018.04.010
  85. Knecht LD, O'Connor G, Mittal R, Liu XZ, Daftarian P, Deo SK, Daunert S (2016) Serotonin Activates Bacterial Quorum Sensing and Enhances the Virulence of Pseudomonas aeruginosa in the Host. EBioMedicine 9: 161–169. https://doi.org/10.1016/j.ebiom.2016.05.037
  86. 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: 115–117 (In Russ).
  87. Shishov VA, Kirovskaia TA, Kudrin VS, Oleskin AV (2009) Prikl Biokhim Mikrobiol 45(5): 550–554. (In Russ).
  88. Lyte M, Ernst S (1992) Catecholamine induced growth of gram-negative bacteria. Life Sci 50(3): 203–212. https://doi.org/10.1016/0024-3205(92)90273-r
  89. Lyte M, Vulchanova L, Brown DR (2011) Stress at the intestinal surface: catecholamines and mucosa-bacteria interactions. Cell Tissue Res 343(1): 23–32. https://doi.org/10.1007/s00441-010-1050-0
  90. Hughes DT, Clarke MB, Yamamoto K, Rasko DA, Sperandio V (2009) The QseC adrenergic signaling cascade in Enterohemorrhagic E. coli (EHEC). PLoS Pathog 5(8): e1000553. https://doi.org/10.1371/journal.ppat.1000553
  91. Du X, Tang Z, Yan L, Zhang L, Zheng Q, Zeng X, Hu Q, Tian Q, Liang L, Zhao X, Li J, Zhao M, Fu X (2024) Norepinephrine may promote the progression of Fusobacterium nucleatum related colorectal cancer via quorum sensing signalling. Virulence 15(1): 2350904. https://doi.org/10.1080/21505594.2024.2350904
  92. 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): 8951–8956. https://doi.org/10.1073/pnas.1537100100
  93. Wessler I, Kirkpatrick CJ, Racké K (1999) The cholinergic 'pitfall': acetylcholine, a universal cell molecule in biological systems, including humans. Clin Exp Pharmacol Physiol 26(3): 198–205. https://doi.org/10.1046/j.1440-1681.1999.03016.x
  94. Stanaszek PM, Snell JF, O'Neill JJ (1977) Isolation, extraction, and measurement of acetylcholine from Lactobacillus plantarum. Appl Environ Microbiol 34(2): 237–239. https://doi.org/10.1128/aem.34.2.237-239.1977
  95. Musa NH, Mani V, Lim SM, Vidyadaran S, Abdul Majeed AB, Ramasamy K (2017) Lactobacilli-fermented cow's milk attenuated lipopolysaccharide-induced neuroinflammation and memory impairment in vitro and in vivo. J Dairy Res 84(4): 488–495. https://doi.org/10.1017/S0022029917000620
  96. Yamaguchi H, Friedman H, Yamamoto Y (2003) Involvement of nicotinic acetylcholine receptors in controlling Chlamydia pneumoniae growth in epithelial HEp-2 cells. Infect Immun 71(6): 3645–3647. https://doi.org/10.1128/IAI.71.6.3645-3647.2003
  97. Baj A, Moro E, Bistoletti M, Orlandi V, Crema F, Giaroni C (2019) Glutamatergic Signaling Along The Microbiota-Gut-Brain Axis. Int J Mol Sci 20(6): 1482. https://doi.org/10.3390/ijms20061482
  98. Mazzoli R, Pessione E (2016) The Neuro-endocrinological Role of Microbial Glutamate and GABA Signaling. Front Microbiol 7: 1934. https://doi.org/10.3389/fmicb.2016.01934
  99. Kitamura A, Tsurugizawa T, Uematsu A, Torii K, Uneyama H (2012) New therapeutic strategy for amino acid medicine: effects of dietary glutamate on gut and brain function. J Pharmacol Sci 118(2): 138–144. https://doi.org/10.1254/jphs.11r06fm
  100. Zareian M, Ebrahimpour A, Bakar FA, Mohamed AKS, Forghani B, Ab-Kadir MSB, Saari N (2012) A glutamic acid-producing lactic acid bacteria isolated from Malaysian fermented foods. Int J Mol Sci 13(5): 5482–5497. https://doi.org/10.3390/ijms13055482
  101. Watanabe M, Maemura K, Kanbara K, Tamayama T, Hayasaki H (2002) GABA and GABA receptors in the central nervous system and other organs. Int Rev Cytol 213: 1–47. https://doi.org/10.1016/s0074-7696(02)13011-7
  102. Braga JD, Thongngam M, Kumrungsee T (2024) Gamma-aminobutyric acid as a potential postbiotic mediator in the gut–brain axis. NPJ Sci Food 8: 16. https://doi.org/10.1038/s41538-024-00253-2
  103. Milon RB, Hu P, Zhang X, Hu X, Ren L (2024) Recent advances in the biosynthesis and industrial biotechnology of Gamma-amino butyric acid. Bioresour Bioproc 11(1): 32. https://doi.org/10.1186/s40643-024-00747-7
  104. Zhuang Z, Yang R, Wang W, Qi L, Huang T (2020). Associations between gut microbiota and Alzheimer's disease, major depressive disorder, and schizophrenia. J Neuroinflamm 17(1): 288. https://doi.org/10.1186/s12974-020-01961-8
  105. Ma P, Li T, Ji F, Wang H, Pang J (2015) Effect of GABA on blood pressure and blood dynamics of anesthetic rats. Int J Clin Exp Med 8(8): 14296–14302.
  106. Hyland NP, Cryan JF (2010) A gut feeling about GABA: focus on GABA(B) receptors. Front Pharmacol 1: 124. https://doi.org/10.3389/fphar.2010.00124
  107. Yogeswara IBA, Maneerat S, Haltrich D (2020) Glutamate Decarboxylase from Lactic Acid Bacteria-A Key Enzyme in GABA Synthesis. Microorganisms 8(12): 1923. https://doi.org/10.3390/microorganisms8121923
  108. Binh TT, Ju WT, Jung WJ, Park RD (2014) Optimization of γ-amino butyric acid production in a newly isolated Lactobacillus brevis. Biotechnol Lett 36(1): 93–98. https://doi.org/10.1007/s10529-013-1326-z
  109. Barrett E, Ross RP, O'Toole PW, Fitzgerald GF, Stanton C (2012) γ-Aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol 113(2): 411–417. https://doi.org/10.1111/j.1365-2672.2012.05344.x
  110. Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, Bienenstock J, Cryan JF (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): 16050–16055. https://doi.org/10.1073/pnas.1102999108
  111. Janik R, Thomason LAM, Stanisz AM, Forsythe P, Bienenstock J, Stanisz GJ (2016) Magnetic resonance spectroscopy reveals oral Lactobacillus promotion of increases in brain GABA, N-acetyl aspartate and glutamate. NeuroImage 125: 988–995. https://doi.org/10.1016/j.neuroimage.2015.11.018
  112. Yunes RA, Poluektova EU, Vasileva EV, Odorskaya MV, Marsova MV, Kovalev GI, Danilenko VN (2020) A Multi-strain Potential Probiotic Formulation of GABA-Producing Lactobacillus plantarum 90sk and Bifidobacterium adolescentis 150 with Antidepressant Effects. Probiot Antimicrob Proteins 12(3): 973–979. https://doi.org/10.1007/s12602-019-09601-1
  113. Nieto-Alamilla G, Márquez-Gómez R, García-Gálvez AM, Morales-Figueroa GE, Arias-Montaño JA (2016) The Histamine H3 Receptor: Structure, Pharmacology, and Function. Mol Pharmacol 90(5): 649–673. https://doi.org/10.1124/mol.116.104752
  114. Landete JM, De las Rivas B, Marcobal A, Muñoz R (2008) Updated molecular knowledge about histamine biosynthesis by bacteria. Crit Rev Food Sci Nutr 48(8): 697–714. https://doi.org/10.1080/10408390701639041
  115. Attaran RR, Probst F (2002) Histamine fish poisoning: a common but frequently misdiagnosed condition. Emerg Med J 19(5): 474–475. https://doi.org/10.1136/emj.19.5.474
  116. Mou Z, Yang Y, Hall AB, Jiang X (2021) The taxonomic distribution of histamine-secreting bacteria in the human gut microbiome. BMC Genom 22(1): 695. https://doi.org/10.1186/s12864-021-08004-3
  117. Thomas CM, Hong T, van Pijkeren JP, Hemarajata P, Trinh DV, Hu W, Britton RA, Kalkum M, Versalovic J (2021) Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signaling. PLoS One 7(2): e31951. https://doi.org/10.1371/journal.pone.0031951
  118. Whalen TC, Gittis AH (2018) Histamine and deep brain stimulation: the pharmacology of regularizing a brain. J Clin Invest 128(12): 5201–5202. https://doi.org/10.1172/JCI124777
  119. Albrechtsen NJW, Rehfeld JF (2021) On premises and principles for measurement of gastrointestinal peptide hormones. Peptides 141: 170545. https://doi.org/10.1016/j.peptides.2021.170545
  120. Bany Bakar R, Reimann F, Gribble FM (2023) The intestine as an endocrine organ and the role of gut hormones in metabolic regulation. Nat Rev Gastroenterol Hepatol 20(12): 784–796. https://doi.org/10.1038/s41575-023-00830-y
  121. Meyer RK, Duca FA (2023) RISING STARS: Endocrine regulation of metabolic homeostasis via the intestine and gut microbiome. J Endocrinol 258(2): e230019. https://doi.org/ 10.1530/JOE-23-0019
  122. Neuman H, Debelius JW, Knight R, Koren O (2015) Microbial endocrinology: the interplay between the microbiota and the endocrine system. FEMS Microbiol Rev 39(4): 509–521. https://doi.org/10.1093/femsre/fuu010
  123. Gribble FM, Reimann F (2019) Function and mechanisms of enteroendocrine cells and gut hormones in metabolism. Nat Rev Endocrinol 15(4): 226–237. https://doi.org/10.1038/s41574-019-0168-8
  124. Hokanson KC, Hernández C, Deitzler GE, Gaston JE, David MM (2024) Sex shapes gut-microbiota-brain communication and disease. Trends Microbiol 32(2): 151–161. https://doi.org/10.1016/j.tim.2023.08.013
  125. Tao E, Zhu Z, Hu C, Long G, Chen B, Guo R, Fang M, Jiang M (2022) Potential Roles of Enterochromaffin Cells in Early Life Stress-Induced Irritable Bowel Syndrome. Front Cell Neurosci 16: 837166. https://doi.org/10.3389/fncel.2022.837166
  126. Bohórquez DV, Shahid RA, Erdmann A, Kreger AM, Wang Y, Calakos N, Wang F, Liddle RA (2015) Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells. J Clin Invest 125(2): 782–786. https://doi.org/10.1172/JCI78361
  127. Ahlman H, Nilsson (2001) The gut as the largest endocrine organ in the body. Ann Oncol 12 Suppl 2: S63–S68. https://doi.org/10.1093/annonc/12.suppl_2.s63
  128. Covasa M, Stephens RW, Toderean R, Cobuz C (2019) Intestinal Sensing by Gut Microbiota: Targeting Gut Peptides. Front Endocrinol 10: 82. https://doi.org/10.3389/fendo.2019.00082
  129. Sobol CV (2023) Stimulatory Effect of Lactobacillus Metabolites on Colonic Contractions in Newborn Rats. Int J Mol Sci 24: 662. https://doi.org/10.3390/ijms24010662
  130. De Silva A, Bloom SR (2012) Gut Hormones and Appetite Control: A Focus on PYY and GLP-1 as Therapeutic Targets in Obesity. Gut Liver 6: 10–20. https://doi.org/10.5009/gnl.2012.6.1.10
  131. Tough IR, Forbes S, Tolhurst R, Ellis M, Herzog H, Bornstein JC, Cox HM (2011) Endogenous peptide YY and neuropeptide Y inhibit colonic ion transport, contractility and transit differentially via Y₁ and Y₂ receptors. Br J Pharmacol 164(2b): 471–484. https://doi.org/10.1111/j.1476-5381.2011.01401.x
  132. Freeland KR, Wolever TM (2010) Acute effects of intravenous and rectal acetate on glucagon-like peptide-1, peptide YY, ghrelin, adiponectin and tumour necrosis factor-alpha. Br J Nutr 103(3): 460–466. https://doi.org/10.1017/S0007114509991863
  133. Christiansen CB, Gabe MBN, Svendsen B, Dragsted LO, Rosenkilde MM, Holst JJ (2018) The impact of short-chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon. Am J Physiol 315(1): G53–G65. https://doi.org/10.1152/ajpgi.00346.2017
  134. Forny-Germano L, De Felice FG, Vieira MNDN (2019) The Role of Leptin and Adiponectin in Obesity-Associated Cognitive Decline and Alzheimer's Disease. Front Neurosc 12: 1027. https://doi.org/10.3389/fnins.2018.01027
  135. Obradovic M, Sudar-Milovanovic E, Soskic S, Essack M, Arya S, Stewart AJ, Gojobori T, Isenovic ER (2021) Leptin and Obesity: Role and Clinical Implication. Front Endocrinol 12: 585887. https://doi.org/10.3389/fendo.2021.585887
  136. Hamamah S, Covasa M (2022) Gut Microbiota Restores Central Neuropeptide Deficits in Germ-Free Mice. Int J Mol Sci 23(19): 11756. https://doi.org/10.3390/ijms231911756
  137. Kim MH, Kim H (2021) Role of Leptin in the Digestive System. Front Pharmacol 12: 660040. https://doi.org/10.3389/fphar.2021.660040
  138. Lam V, Su J, Koprowski S, Hsu A, Tweddell JS, Rafiee P, Gross GJ, Salzman NH, Baker JE (2012) Intestinal microbiota determines severity of myocardial infarction in rats. FASEB J 26(4): 1727–1735. https://doi.org/10.1096/fj.11-197921
  139. Noormohammadi M, Ghorbani Z, Löber U, Mahdavi-Roshan M, Bartolomaeus TUP, Kazemi A, Shoaibinobarian N, Forslund SK (2023) The effect of probiotic and synbiotic supplementation on appetite-regulating hormones and desire to eat: A systematic review and meta-analysis of clinical trials. Pharmacol Res 187: 106614. https://doi.org/10.1016/j.phrs.2022.106614
  140. Queipo-Ortuño MI, Seoane LM, Murri M, Pardo M, Gomez-Zumaquero JM, Cardona F, Casanueva F, Tinahones FJ (2013) Gut microbiota composition in male rat models under different nutritional status and physical activity and its association with serum leptin and ghrelin levels. PloS One 8(5): e65465. https://doi.org/10.1371/journal.pone.0065465
  141. Rajala MW, Patterson CM, Opp JS, Foltin SK, Young VB, Myers MG, Jr (2014) Leptin acts independently of food intake to modulate gut microbial composition in male mice. Endocrinology 155(3): 748–757. https://doi.org/10.1210/en.2013-1085
  142. Schalla MA, Stengel A (2020) Effects of microbiome changes on endocrine ghrelin signaling – A systematic review. Peptides 133: 170388. https://doi.org/10.1016/j.peptides.2020.170388
  143. Poinsot P, Schwarzer M, Peretti N, Leulier F (2018) The emerging connections between IGF1, the intestinal microbiome, Lactobacillus strains and bone growth. J Mol Endocrinol 61(1): T103–T113. https://doi.org/10.1530/JME-17-0292
  144. De Vadder F, Joly A, Leulier F (2021) Microbial and nutritional influence on endocrine control of growth. J Mol Endocrinol 66(3): R67–R73. https://doi.org/10.1530/JME-20-0288
  145. Schwarzer M, Gautam UK, Makki K, Lambert A, Brabec T, Joly A, Šrůtková D, Poinsot P, Novotná T, Geoffroy S, Courtin P, Hermanová PP, Matos RC, Landry JJM, Gérard C, Bulteau AL, Hudcovic T, Kozáková H, Filipp D, Chapot-Chartier MP, Šinkora M, Peretti N, Gomperts Boneca I, Chamaillard M, Vidal H, De Vadder F, Leulier F (2023) Microbe-mediated intestinal NOD2 stimulation improves linear growth of undernourished infant mice. Science 379(6634): 826–833. https://doi.org/10.1126/science.ade9767
  146. Jensen EA, Young JA, Jackson Z, Busken J, List EO, Carroll RK, Kopchick JJ, Murphy ER, Berryman DE (2020) Growth Hormone Deficiency and Excess Alter the Gut Microbiome in Adult Male Mice. Endocrinology 161(4): bqaa026. https://doi.org/10.1210/endocr/bqaa026
  147. Yan J, Charles JF (2018) Gut Microbiota and IGF-1. Calcif Tissue Int 102(4): 406–414. https://doi.org/10.1007/s00223-018-0395-3
  148. Sarubbo F, Cavallucci V, Pani G (2022) The Influence of Gut Microbiota on Neurogenesis: Evidence and Hopes. Cells 11(3): 382. https://doi.org/10.3390/cells11030382
  149. Guzzetta KE, Cryan JF, O'Leary OF (2022) Microbiota-Gut-Brain Axis Regulation of Adult Hippocampal Neurogenesis. Brain Plast 8(1): 97–119. https://doi.org/10.3233/BPL-220141
  150. Ogbonnaya ES, Clarke G, Shanahan F, Dinan TG, Cryan JF, O'Leary OF (2015) Adult Hippocampal Neurogenesis Is Regulated by the Microbiome. Biol Psychiatry 78: e7–e9. https://doi.org/10.1016/j.biopsych.2014.12.023
  151. Yang LL, Millischer V, Rodin S, MacFabe DF, Villaescusa JC, Lavebratt C (2020) Enteric short-chain fatty acids promote proliferation of human neural progenitor cells. J Neurochem 154(6): 635–646. https://doi.org/10.1111/jnc.14928
  152. Hwang D, Kim J, Kyun S, Jang I, Kim T, Park HY, Lim K (2023) Exogenous lactate augments exercise-induced improvement in memory but not in hippocampal neurogenesis. Sci Rep 13: 5838. https://doi.org/10.1038/s41598-023-33017-1
  153. Binder DK, Scharfman HE (2004) Brain-derived neurotrophic factor. Growth Factors 22: 123–131. https://doi.org/10.1080/08977190410001723308
  154. Kazim SF, Iqbal K (2016) Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer's disease. Mol Neurodegener 11: 50. https://doi.org/10.1186/s13024-016-0119-y
  155. Staley C, Weingarden AR, Khoruts A, Sadowsky MJ (2017) Interaction of gut microbiota with bile acid metabolism and its influence on disease states. Appl Microbiol Biotechnol 101(1): 47–64. https://doi.org/10.1007/s00253-016-8006-6
  156. Collins SL, Stine JG, Bisanz JE, Okafor CD, Patterson AD (2023) Bile acids and the gut microbiota: metabolic interactions and impacts on disease. Nat Rev Microbiol 21(4): 236–247. https://doi.org/10.1038/s41579-022-00805-x
  157. Giannini C, Mastromauro C, Scapaticci S, Gentile C, Chiarelli F (2022) Role of bile acids in overweight and obese children and adolescents. Front Endocrinol 13: 1011994. https://doi.org/10.3389/fendo.2022.1011994
  158. Molinaro A, Wahlström A, Marschall HU (2018) Role of bile acids in metabolic control. Trends Endocrinol Metabol 29: 31–41. https://doi.org/10.1016/ j.tem.2017.11.002
  159. Lajczak-McGinley NK, Porru E, Fallon CM, Smyth J, Curley C, McCarron PA, Tambuwala MM, Roda A, Keely SJ (2020) The secondary bile acids, ursodeoxycholic acid and lithocholic acid, protect against intestinal inflammation by inhibition of epithelial apoptosis. Physiol Rep 8(12): e14456. https://doi.org/10.14814/phy2.14456
  160. Thomas C, Pellicciari R, Pruzanski M, Auwerx J, Schoonjans K (2008) Targeting bile-acid signalling for metabolic diseases. Nature Rev Drug Discov 7(8): 678–693. https://doi.org/10.1038/nrd2619
  161. Li T, Chiang JY (2014) Bile acid signaling in metabolic disease and drug therapy. Pharmacol Rev 66(4): 948–983. https://doi.org/10.1124/pr.113.008201
  162. Ma K, Saha PK, Chan L, Moore DD (2006) Farnesoid X receptor is essential for normal glucose homeostasis. J Clin Invest 116: 1102–1109. https://doi.org/10.1172/ JCI25604
  163. Taylor SA, Green RM (2018) Bile Acids, Microbiota, and Metabolism. Hepatology 68(4): 1229–1231. https://doi.org/10.1002/hep.30078
  164. Pols TW, Noriega LG, Nomura M, Auwerx J, Schoonjans K (2011) The bile acid membrane receptor TGR5: a valuable metabolic target. Dig Dis 29(1): 37–44. https://doi.org/10.1159/000324126
  165. Guo C, Chen WD, Wang YD (2016) TGR5, Not Only a Metabolic Regulator. Front Physiol 7: 646. https://doi.org/10.3389/fphys.2016.00646
  166. Agarwal S, Patil A, Aware U, Deshmukh P, Darji B, Sasane S, Sairam KV, Priyadarsiny P, Giri P, Patel H, Giri S, Jain M, Desai RC (2015) Discovery of a Potent and Orally Efficacious TGR5 Receptor Agonist. ACS Med Chem Lett 7(1): 51–55. https://doi.org/10.1021/acsmedchemlett.5b00323
  167. Connell E, Le Gall G, Pontifex MG, Sami S, Cryan JF, Clarke G, Müller M, Vauzour D (2022) Microbial-derived metabolites as a risk factor of age-related cognitive decline and dementia. Mol Neurodegener 17(1): 43. https://doi.org/10.1186/s13024-022-00548-6
  168. Huang F, Pariante CM, Borsini A (2022) From dried bear bile to molecular investigation: A systematic review of the effect of bile acids on cell apoptosis, oxidative stress and inflammation in the brain, across pre-clinical models of neurological, neurodegenerative and neuropsychiatric disorders. Brain Behav Immun 99: 132–146. https://doi.org/10.1016/j.bbi.2021.09.021
  169. Kurdi P, Kawanishi K, Mizutani K, Yokota A (2006) Mechanism of growth inhibition by free bile acids in lactobacilli and bifidobacteria. J Bacteriol 188(5): 1979–1986. https://doi.org/10.1128/JB.188.5.1979-1986.2006
  170. Sato Y, Atarashi K, Plichta DR, Arai Y, Sasajima S, Kearney SM, Suda W, Takeshita K, Sasaki T, Okamoto S, Skelly AN, Okamura Y, Vlamakis H, Li Y, Tanoue T, Takei H, Nittono H, Narushima S, Irie J, Itoh H, Moriya K, Sugiura Y, Suematsu M, Moritoki N, Shibata Sh, Littman DR, Fischbach MA, Uwamino Y, Inoue T, Honda A, Hattori M, Murai T, Xavier RJ, Hirose N, Honda K (2021) Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians. Nature 599(7885): 458–464. https://doi.org/10.1038/s41586-021-03832-5
  171. Yoon K, Kim N (2021) Roles of Sex Hormones and Gender in the Gut Microbiota. J Neurogastroenterol Motil 27(3): 314–325. https://doi.org/10.5056/jnm20208
  172. Koren O, Goodrich JK, Cullender TC, Spor A, Laitinen K, Bäckhed HK, Gonzalez A, Werner JJ, Angenent LT, Knight R, Bäckhed F, Isolauri E, Salminen S, Ley RE (2012) Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell 150(3): 470–480. https://doi.org/10.1016/j.cell.2012.07.008
  173. Paterni I, Bertini S, Granchi C, Macchia M, Minutolo F (2013) Estrogen receptor ligands: a patent review update. Expert Opin Ther Pat 23(10): 1247–1271. https://doi.org/10.1517/13543776.2013.805206
  174. Chen KL, Madak-Erdogan Z (2016) Estrogen and Microbiota Crosstalk: Should We Pay Attention? Trends Endocrinol Metabol 27(11): 752–755. https://doi.org/10.1016/j.tem.2016.08.001
  175. Menon R, Watson SE, Thomas LN, Allred CD, Dabney A, Azcarate-Peril MA, Sturino JM (2013) Diet complexity and estrogen receptor β status affect the composition of the murine intestinal microbiota. Appl Environ Microbiol (18): 5763–5773. https://doi.org/10.1128/AEM.01182-13
  176. Mulak A, Taché Y, Larauche M (2014) Sex hormones in the modulation of irritable bowel syndrome. World J Gastroenterol 20(10): 2433–2448. https://doi.org/10.3748/wjg.v20.i10.2433
  177. Nakatsu CH, Armstrong A, Clavijo AP, Martin BR, Barnes S, Weaver CM (2014) Fecal bacterial community changes associated with isoflavone metabolites in postmenopausal women after soy bar consumption. PLoS One 9(10): e108924. https://doi.org/10.1371/journal.pone.0108924
  178. Patel J, Chaudhary H, Rajput K, Parekh B, Joshi R (2023) Assessment of gut microbial β-glucuronidase and β-glucosidase activity in women with polycystic ovary syndrome. Sci Rep 13(1): 11967. https://doi.org/10.1038/s41598-023-39168-5
  179. Colldén H, Landin A, Wallenius V, Elebring E, Fändriks L, Nilsson ME, Ryberg H, Poutanen M, Sjögren K, Vandenput L, Ohlsson C (2019) The gut microbiota is a major regulator of androgen metabolism in intestinal contents. Am J Physiol Endocrinol Metab 317(6): E1182–E1192. https://doi.org/10.1152/ajpendo.00338.2019
  180. Shin JH, Park YH, Sim M, Kim SA, Joung H, Shin DM (2019) Serum level of sex steroid hormone is associated with diversity and profiles of human gut microbiome. Res Microbiol 170(4–5): 192–201. https://doi.org/10.1016/j.resmic.2019.03.003

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Effect of microbiota and its metabolites on endocrine functions of the macroorganism. Fermentation of foods and fibers produces SCFAs and other microbiota metabolites in the intestinal lumen. SCFAs stimulate GPR-41/43 receptors, resulting in enteroendocrine L-cells (EC-L) releasing GLP-1 and PYY (see below). SCFAs can also stimulate L-cell proliferation. Enterochromaffin cells (ECs) release 5-HT as a result of stimulation of GRP-41/43. SCFAs and other microbiota metabolites, such as tryptamine, can have a prokinetic effect on the gastrointestinal tract. Unidentified microbiota products (UM) can stimulate ECs and EC-L, as well as endothelial (E) cells. Neurotransmitters (Nts) synthesized by the microbiota can affect both enteric (EN) neurons and the vagus nerve. SCFAs, UM and neurotransmitters that penetrate the epithelial barrier (1, 2 and 3, respectively) can exhibit both paracrine and endocrine effects by penetrating the hepatic portal system. The macroorganism can modulate the composition and number of microorganisms, for example, through the release of immunoglobulin A (IgA) and through the release of norepinephrine (NA) by adrenergic neurons (AN). The composition of the microbiota is also modulated by the products of microorganisms themselves, for example, SCFAs, UM and neurotransmitters, which in this case can act as mediators of quorum signaling. The complex interaction of the microbiota and immune cells, as well as the interaction with the enzymatic system of the macroorganism, including enzymes and parietal digestion, have not been shown. Legend: Microbiota – microbiota, SCFA – short chain fatty acids, UM – uncharacterized microbial products, Nts – neurotransmitters (neurotransmitters: glutamate, GABA, acetylcholine, serotonin, catecholamines, histamine), GPR-41/43 – SCFA receptors, EC-L – intestinal enteroendocrine L-type cells, ECs – enterochromaffin cells, E – endothelial cells, 5-HT – serotonin, GLP-1 – glucagon-like peptide 1, PYY – peptide YY YY), vagus – vagus nerve, EN – enteric neuron (enteric neuron) AN – adrenergic neuron (adrenergic neuron), NE – norepinephrine (norepinephrine), IgA – immunoglobulin A (immunoglobulin A). When creating the drawing, graphic elements from Servier Medical Art (https://smart.servier.com) were partially used.

Download (274KB)
Indexing metadata
3. Fig. 2. Effects of secondary bile acids and growth hormones with the participation of microbiota. Microbiota forms secondary bile acids (SBAs) from primary ones. SBAs, such as lithocholic and taurolithocholic, stimulate TGR5 to the greatest extent. As a result of TGR5 stimulation, enterochromaffin cells (ECs) release 5-HT, and L-cells (EC-L) release GLP-1 and PYY. Toxic SBAs can provoke cancer development, stimulate inflammation processes and neurodegeneration. Microbiota can influence the formation of growth hormones in the macroorganism. The formation of brain-derived neurotrophic factor (BDNF) in the macroorganism and the stimulation of neurogenesis by the microbiota and its metabolites have also been shown. Legend: SBA – secondary bile acids, GF – growth factors, TGR5 – SBA receptor, BDNF – brain-derived neurotrophic factor, NGF – nerve growth factor. Other designations are the same as in Fig. 1.

Download (144KB)
Indexing metadata

Copyright (c) 2025 Russian Academy of Sciences

Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».