Abstract

Obesity currently represents a major societal and health problem worldwide. Its prevalence has reached epidemic levels, and trends continue to increase; This, in turn, reflects the need for more effective preventive measures. Dietary composition is one of the main factors that modulate the structure and function of the gut microbiota. Therefore, abnormal dietary patterns or unhealthy diets can alter gut microbiota-diet interactions and alter nutrient availability and/or microbial ligands that transmit information from the gut to the brain in response to nutrient intake, thereby disrupting energy homeostasis. Accordingly, this review aims to examine how dietary composition modulates the gut microbiota and thus the potential effects of these biological products on energy homeostasis through gut-brain based mechanisms. It also assesses the knowledge gaps and advances needed to clinically implement microbiome-based strategies to improve gut-brain axis function and therefore combat obesity.

Keywords: Microbiota, gut-brain axis, energy balance, obesity

Copyright and license

Copyright © 2024 The author(s). This is an open-access article under the terms of the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is properly cited.

How to cite

1.
Pürdik Tatık G, Baran Ö, Dağ A. Gut-brain axis: The role of gut microbiota in energy balance and body weight regulation. Clin Sci Nutr. 2024;Early View:1-8. doi:10.62210/ClinSciNutr.2024.98

References

  1. Lobstein T, Jackson-Leach R, Powis J, Brinsden H, Gray M. World obesity atlas 2023. Available at: https://www.worldobesity.org/resources/resource-library/world-obesity-atlas-2023 (Accessed on May 8, 2023).
  2. Saravanan D, Khatoon BS, Winner GJ. Unraveling the Interplay: Exploring the Links Between Gut Microbiota, Obesity, and Psychological Outcomes. Cureus. 2023;15:e49271. https://doi.org/10.7759/cureus.49271
  3. Magne F, Gotteland M, Gauthier L, et al. The Firmicutes/Bacteroidetes Ratio: A Relevant Marker of Gut Dysbiosis in Obese Patients? Nutrients. 2020;12:1474. https://doi.org/10.3390/nu12051474
  4. de Lartigue G, Diepenbroek C. Novel developments in vagal afferent nutrient sensing and its role in energy homeostasis. Curr Opin Pharmacol. 2016;31:38-43. https://doi.org/10.1016/j.coph.2016.08.007
  5. Clemmensen C, Müller TD, Woods SC, Berthoud HR, Seeley RJ, Tschöp MH. Gut-Brain Cross-Talk in Metabolic Control. Cell. 2017;168:758-774. https://doi.org/10.1016/j.cell.2017.01.025
  6. Drucker DJ. Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1. Cell Metab. 2018;27:740-756. https://doi.org/10.1016/j.cmet.2018.03.001
  7. Fan J, Yang Y, Ma C, et al. The effects and cell barrier mechanism of main dietary nutrients on intestinal barrier. Curr Opin Food Sci. 2022;48:100942. https://doi.org/10.1016/j.cofs.2022.100942
  8. Liu L, Huh JR, Shah K. Microbiota and the gut-brain-axis: Implications for new therapeutic design in the CNS. EBioMedicine. 2022;77:103908. https://doi.org/10.1016/j.ebiom.2022.103908
  9. Goldstein N, McKnight AD, Carty JRE, Arnold M, Betley JN, Alhadeff AL. Hypothalamic detection of macronutrients via multiple gut-brain pathways. Cell Metab. 2021;33:676-687.e5. https://doi.org/10.1016/j.cmet.2020.12.018
  10. Wachsmuth HR, Weninger SN, Duca FA. Role of the gut-brain axis in energy and glucose metabolism. Exp Mol Med. 2022;54:377-392. https://doi.org/10.1038/s12276-021-00677-w
  11. Psichas A, Larraufie PF, Goldspink DA, Gribble FM, Reimann F. Chylomicrons stimulate incretin secretion in mouse and human cells. Diabetologia. 2017;60:2475-2485. https://doi.org/10.1007/s00125-017-4420-2
  12. Lu WJ, Yang Q, Yang L, Lee D, D'Alessio D, Tso P. Chylomicron formation and secretion is required for lipid-stimulated release of incretins GLP-1 and GIP. Lipids. 2012;47:571-580. https://doi.org/10.1007/s11745-011-3650-1
  13. Christensen LW, Kuhre RE, Janus C, Svendsen B, Holst JJ. Vascular, but not luminal, activation of FFAR1 (GPR40) stimulates GLP-1 secretion from isolated perfused rat small intestine. Physiol Rep. 2015;3:e12551. https://doi.org/10.14814/phy2.12551
  14. Gorboulev V, Schürmann A, Vallon V, et al. Na(+)-D-glucose cotransporter SGLT1 is pivotal for intestinal glucose absorption and glucose-dependent incretin secretion. Diabetes. 2012;61:187-196. https://doi.org/10.2337/db11-1029
  15. Modvig IM, Kuhre RE, Holst JJ. Peptone-mediated glucagon-like peptide-1 secretion depends on intestinal absorption and activation of basolaterally located Calcium-Sensing Receptors. Physiol Rep. 2019;7:e14056. https://doi.org/10.14814/phy2.14056
  16. Mace OJ, Schindler M, Patel S. The regulation of K- and L-cell activity by GLUT2 and the calcium-sensing receptor CasR in rat small intestine. J Physiol. 2012;590:2917-2936. https://doi.org/10.1113/jphysiol.2011.223800
  17. Gribble FM, Reimann F. Function and mechanisms of enteroendocrine cells and gut hormones in metabolism. Nat Rev Endocrinol. 2019;15:226-237. https://doi.org/10.1038/s41574-019-0168-8
  18. Barakat GM, Ramadan W, Assi G, Khoury NBE. Satiety: a gut-brain-relationship. J Physiol Sci. 2024;74:11. https://doi.org/10.1186/s12576-024-00904-9
  19. Holst JJ, Rosenkilde MM. GIP as a Therapeutic Target in Diabetes and Obesity: Insight From Incretin Co-agonists. J Clin Endocrinol Metab. 2020;105:e2710–e2716. https://doi.org/10.1210/clinem/dgaa327
  20. Adams JM, Pei H, Sandoval DA, et al. Liraglutide Modulates Appetite and Body Weight Through Glucagon-Like Peptide 1 Receptor-Expressing Glutamatergic Neurons. Diabetes. 2018;67:1538-1548. https://doi.org/10.2337/db17-1385
  21. Cheng W, Ndoka E, Hutch C, et al. Leptin receptor-expressing nucleus tractus solitarius neurons suppress food intake independently of GLP1 in mice. JCI Insight. 2020;5:e134359. https://doi.org/10.1172/jci.insight.134359
  22. Chen W, Binbin G, Lidan S, Qiang Z, Jing H. Evolution of peptide YY analogs for the management of type 2 diabetes and obesity. Bioorg Chem. 2023;140:106808. https://doi.org/10.1016/j.bioorg.2023.106808
  23. Maljaars PW, Peters HP, Mela DJ, Masclee AA. Ileal brake: a sensible food target for appetite control. A review. Physiol Behav. 2008;95:271-281. https://doi.org/10.1016/j.physbeh.2008.07.018
  24. Larraufie P, Martin-Gallausiaux C, Lapaque N, et al. SCFAs strongly stimulate PYY production in human enteroendocrine cells. Sci Rep. 2018;8:74. https://doi.org/10.1038/s41598-017-18259-0
  25. Brooks L, Viardot A, Tsakmaki A, et al. Fermentable carbohydrate stimulates FFAR2-dependent colonic PYY cell expansion to increase satiety. Mol Metab. 2016;6:48-60. https://doi.org/10.1016/j.molmet.2016.10.011
  26. Oertel M, Ziegler CG, Kohlhaas M, et al. GLP-1 and PYY for the treatment of obesity: a pilot study on the use of agonists and antagonists in diet-induced rats. Endocr Connect. 2024;13:e230398. https://doi.org/10.1530/EC-23-0398
  27. Goswami C, Iwasaki Y, Yada T. Short-chain fatty acids suppress food intake by activating vagal afferent neurons. J Nutr Biochem. 2018;57:130-135. https://doi.org/10.1016/j.jnutbio.2018.03.009
  28. Mazhar M, Zhu Y, Qin L. The Interplay of Dietary Fibers and Intestinal Microbiota Affects Type 2 Diabetes by Generating Short-Chain Fatty Acids. Foods. 2023;12:1023. https://doi.org/10.3390/foods12051023
  29. May KS, den Hartigh LJ. Gut Microbial-Derived Short Chain Fatty Acids: Impact on Adipose Tissue Physiology. Nutrients. 2023;15:272. https://doi.org/10.3390/nu15020272
  30. De Vadder F, Kovatcheva-Datchary P, Goncalves D, et al. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell. 2014;156:84-96. https://doi.org/10.1016/j.cell.2013.12.016
  31. Yadav H, Lee JH, Lloyd J, Walter P, Rane SG. Beneficial metabolic effects of a probiotic via butyrate-induced GLP-1 hormone secretion. J Biol Chem. 2013;288:25088-25097. https://doi.org/10.1074/jbc.M113.452516
  32. Rastelli M, Knauf C, Cani PD. Gut Microbes and Health: A Focus on the Mechanisms Linking Microbes, Obesity, and Related Disorders. Obesity (Silver Spring). 2018;26:792-800. https://doi.org/10.1002/oby.22175
  33. Rehman Khan A, Awan FR. Leptin Resistance: A Possible Interface Between Obesity and Pulmonary-Related Disorders. Int J Endocrinol Metab. 2016;14:e32586. https://doi.org/10.5812/ijem.32586
  34. Izquierdo AG, Crujeiras AB, Casanueva FF, Carreira MC. Leptin, Obesity, and Leptin Resistance: Where Are We 25 Years Later? Nutrients. 2019;11:2704. https://doi.org/10.3390/nu11112704
  35. Liu J, Lai F, Hou Y, Zheng R. Leptin signaling and leptin resistance. Med Rev (2021). 2022;2:363-384. https://doi.org/10.1515/mr-2022-0017
  36. Pena-Leon V, Perez-Lois R, Villalon M, et al. Novel mechanisms involved in leptin sensitization in obesity. Biochem Pharmacol. 2024;223:116129. https://doi.org/10.1016/j.bcp.2024.116129
  37. Ringseis R, Gessner DK, Eder K. The Gut-Liver Axis in the Control of Energy Metabolism and Food Intake in Animals. Annu Rev Anim Biosci. 2020;8:295-319. https://doi.org/10.1146/annurev-animal-021419-083852
  38. Romaní-Pérez M, Bullich-Vilarrubias C, López-Almela I, Liébana-García R, Olivares M, Sanz Y. The Microbiota and the Gut-Brain Axis in Controlling Food Intake and Energy Homeostasis. Int J Mol Sci. 2021;22:5830. https://doi.org/10.3390/ijms22115830
  39. Dawson PA, Karpen SJ. Intestinal transport and metabolism of bile acids. J Lipid Res. 2015;56:1085-1099. https://doi.org/10.1194/jlr.R054114
  40. Lund ML, Egerod KL, Engelstoft MS, et al. Enterochromaffin 5-HT cells - A major target for GLP-1 and gut microbial metabolites. Mol Metab. 2018;11:70-83. https://doi.org/10.1016/j.molmet.2018.03.004
  41. Monteiro-Cardoso VF, Corlianò M, Singaraja RR. Bile Acids: A Communication Channel in the Gut-Brain Axis. Neuromolecular Med. 2021;23:99-117. https://doi.org/10.1007/s12017-020-08625-z
  42. Mertens KL, Kalsbeek A, Soeters MR, Eggink HM. Bile Acid Signaling Pathways from the Enterohepatic Circulation to the Central Nervous System. Front Neurosci. 2017;11:617. https://doi.org/10.3389/fnins.2017.00617
  43. Chiang JYL, Ferrell JM. Bile Acids as Metabolic Regulators and Nutrient Sensors. Annu Rev Nutr. 2019;39:175-200. https://doi.org/10.1146/annurev-nutr-082018-124344
  44. Fang S, Suh JM, Reilly SM, et al. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nat Med. 2015;21:159-165. https://doi.org/10.1038/nm.3760
  45. Sun L, Xie C, Wang G, et al. Gut microbiota and intestinal FXR mediate the clinical benefits of metformin. Nat Med. 2018;24:1919-1929. https://doi.org/10.1038/s41591-018-0222-4
  46. Tian P, O'Riordan KJ, Lee YK, et al. Towards a psychobiotic therapy for depression: Bifidobacterium breve CCFM1025 reverses chronic stress-induced depressive symptoms and gut microbial abnormalities in mice. Neurobiol Stress. 2020;12:100216. https://doi.org/10.1016/j.ynstr.2020.100216
  47. Reigstad CS, Salmonson CE, Rainey JF, et al. Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J. 2015;29:1395-1403. https://doi.org/10.1096/fj.14-259598
  48. Natividad JM, Agus A, Planchais J, et al. Impaired Aryl Hydrocarbon Receptor Ligand Production by the Gut Microbiota Is a Key Factor in Metabolic Syndrome. Cell Metab. 2018;28:737-749.e4. https://doi.org/10.1016/j.cmet.2018.07.001
  49. Laurans L, Venteclef N, Haddad Y, et al. Genetic deficiency of indoleamine 2,3-dioxygenase promotes gut microbiota-mediated metabolic health. Nat Med. 2018;24:1113-1120. https://doi.org/10.1038/s41591-018-0060-4
  50. Agudelo LZ, Ferreira DMS, Cervenka I, et al. Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation. Cell Metab. 2018;27:378-392.e5. https://doi.org/10.1016/j.cmet.2018.01.004
  51. Inotsuka R, Uchimura K, Yamatsu A, Kim M, Katakura Y. γ-Aminobutyric acid (GABA) activates neuronal cells by inducing the secretion of exosomes from intestinal cells. Food Funct. 2020;11:9285-9290. https://doi.org/10.1039/d0fo01184c
  52. Cabrera-Mulero A, Tinahones A, Bandera B, Moreno-Indias I, Macías-González M, Tinahones FJ. Keto microbiota: A powerful contributor to host disease recovery. Rev Endocr Metab Disord. 2019;20:415-425. https://doi.org/10.1007/s11154-019-09518-8
  53. Soty M, Gautier-Stein A, Rajas F, Mithieux G. Gut-Brain Glucose Signaling in Energy Homeostasis. Cell Metab. 2017;25:1231-1242. https://doi.org/10.1016/j.cmet.2017.04.032
  54. Hall KD, Guo J. Obesity Energetics: Body Weight Regulation and the Effects of Diet Composition. Gastroenterology. 2017;152:1718-1727.e3. https://doi.org/10.1053/j.gastro.2017.01.052
  55. Li Y, Schnabl K, Gabler SM, et al. Secretin-Activated Brown Fat Mediates Prandial Thermogenesis to Induce Satiation. Cell. 2018;175:1561-1574.e12. https://doi.org/10.1016/j.cell.2018.10.016
  56. Blachier F, Beaumont M, Portune KJ, et al. High-protein diets for weight management: Interactions with the intestinal microbiota and consequences for gut health. A position paper by the my new gut study group. Clin Nutr. 2019;38:1012-1022. https://doi.org/10.1016/j.clnu.2018.09.016
  57. Portune K, Beaumont M, Davila AM, Tomé D, Blachier F, Sanz Y. Gut microbiota role in dietary protein metabolism and health-related outcomes: The two sides of the coin. Trends in Food Science & Technology. 2016;57:213-232. https://doi.org/10.1016/j.tifs.2016.08.011
  58. Holsen LM, Hoge WS, Lennerz BS, et al. Diets Varying in Carbohydrate Content Differentially Alter Brain Activity in Homeostatic and Reward Regions in Adults. J Nutr. 2021;151:2465-2476. https://doi.org/10.1093/jn/nxab090
  59. Skytte MJ, Samkani A, Astrup A, et al. Effects of carbohydrate restriction on postprandial glucose metabolism, β-cell function, gut hormone secretion, and satiety in patients with Type 2 diabetes. Am J Physiol Endocrinol Metab. 2021;320:E7-E18. https://doi.org/10.1152/ajpendo.00165.2020
  60. Carneiro L, Geller S, Fioramonti X, et al. Evidence for hypothalamic ketone body sensing: impact on food intake and peripheral metabolic responses in mice. Am J Physiol Endocrinol Metab. 2016;310:E103-E115. https://doi.org/10.1152/ajpendo.00282.2015
  61. Wallenius V, Elias E, Elebring E, et al. Suppression of enteroendocrine cell glucagon-like peptide (GLP)-1 release by fat-induced small intestinal ketogenesis: a mechanism targeted by Roux-en-Y gastric bypass surgery but not by preoperative very-low-calorie diet. Gut. 2020;69:1423-1431. https://doi.org/10.1136/gutjnl-2019-319372
  62. Miyamoto J, Igarashi M, Watanabe K, et al. Gut microbiota confers host resistance to obesity by metabolizing dietary polyunsaturated fatty acids. Nat Commun. 2019;10:4007. https://doi.org/10.1038/s41467-019-11978-0