Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Clinical Research

Potential therapeutic applications of the gut microbiome in obesity: from brain function to body detoxification

Abstract

The prevalence of obesity is rising every year and associated comorbidities such as cardiovascular diseases are among the leading causes of death worldwide. The gut microbiota has recently emerged as a potential target for therapeutic applications to prevent and treat those comorbidities. In this review, we focus on three conditions related to obesity in which the use of gut microbiota modulators could have benefits; mood disorders, eating behaviors, and body detoxification of persistent organic pollutants (POPs). On one hand, modulation of gut-derived signals to the brain in a context of obesity is involved in the development of neuroinflammation and can subsequently alter behaviors. An altered gut microbiome could change these signals and alleviate their consequences. On the other hand, obesity is associated with an increased accumulation of lipophilic contaminants, such as POPs. Targeting the microbiota could help body detoxication by reducing bioavailability, enhancing degradation by bioremediation or their excretion through the enterohepatic circulation. Thus, a supplementation of prebiotics, probiotics, or synbiotics could represent a complementary strategy to current ones, such as medication and lifestyle modifications, to decrease depression, alter eating behaviors, and lower body burden of pollutants considering the actual obesity epidemic our society is facing.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Potential factors modulated by the gut microbiota and implicated in mood disorders and eating behaviors.
Fig. 2: Potential mechanisms by which changes in the gut microbiota can impact the (re)absorption and toxicity of POPs.

References

  1. 1.

    Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027–31.

    PubMed  Google Scholar 

  2. 2.

    Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013;341:1241214.

    PubMed  Google Scholar 

  3. 3.

    Sanchez M, Darimont C, Panahi S, Drapeau V, Marette A, Taylor VH, et al. Effects of a diet-based weight-reducing program with probiotic supplementation on satiety efficiency, eating behaviour traits, and psychosocial behaviours in obese individuals. Nutrients. 2017;9:284.

    PubMed Central  Google Scholar 

  4. 4.

    Zhang L, Nichols RG, Correll J, Murray IA, Tanaka N, Smith PB, et al. Persistent organic pollutants modify gut microbiota-host metabolic homeostasis in mice through aryl hydrocarbon receptor activation. Environ Health Perspect. 2015;123:679–88.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, et al. Expert consensus document: the International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017;14:491–502.

    PubMed  Google Scholar 

  6. 6.

    Anhe FF, Choi BSY, Dyck JRB, Schertzer JD, Marette A. Host-Microbe Interplay in the Cardiometabolic Benefits of Dietary Polyphenols. Trends Endocrinol Metab. 2019;30:384–95.

    CAS  PubMed  Google Scholar 

  7. 7.

    Masumoto S, Terao A, Yamamoto Y, Mukai T, Miura T, Shoji T. Non-absorbable apple procyanidins prevent obesity associated with gut microbial and metabolomic changes. Sci Rep. 2016;6:31208.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Selma MV, Gonzalez-Sarrias A, Salas-Salvado J, Andres-Lacueva C, Alasalvar C, Orem A, et al. The gut microbiota metabolism of pomegranate or walnut ellagitannins yields two urolithin-metabotypes that correlate with cardiometabolic risk biomarkers: comparison between normoweight, overweight-obesity and metabolic syndrome. Clin Nutr (Edinburgh, Scotland). 2018;37:897–905.

    CAS  Google Scholar 

  9. 9.

    Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11:506–14.

    PubMed  Google Scholar 

  10. 10.

    Le Barz M, Anhe FF, Varin TV, Desjardins Y, Levy E, Roy D, et al. Probiotics as complementary treatment for metabolic disorders. Diabetes Metab J. 2015;39:291–303.

    PubMed  PubMed Central  Google Scholar 

  11. 11.

    Chen Z, Guo L, Zhang Y, Walzem RL, Pendergast JS, Printz RL, et al. Incorporation of therapeutically modified bacteria into gut microbiota inhibits obesity. J Clin Invest. 2014;124:3391–406.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Markowiak P, Slizewska K. Effects of probiotics, prebiotics, and synbiotics on human health. Nutrients. 2017;9:1021.

    PubMed Central  Google Scholar 

  13. 13.

    Schneeberger M, Everard A, Gomez-Valades AG, Matamoros S, Ramirez S, Delzenne NM, et al. Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice. Sci Rep. 2015;5:16643.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Dao MC, Everard A, Aron-Wisnewsky J, Sokolovska N, Prifti E, Verger EO, et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut. 2015;65:426–36.

    PubMed  Google Scholar 

  15. 15.

    Chelakkot C, Choi Y, Kim DK, Park HT, Ghim J, Kwon Y, et al. Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions. Exper Mol Med. 2018;50:e450.

    CAS  Google Scholar 

  16. 16.

    Plovier H, Everard A, Druart C, Depommier C, Van Hul M, Geurts L, et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med. 2016;23:107–13.

    PubMed  Google Scholar 

  17. 17.

    Ashrafian F, Shahriary A, Behrouzi A, Moradi HR, Keshavarz Azizi Raftar S, Lari A, et al. Akkermansia muciniphila-Derived extracellular vesicles as a mucosal delivery vector for amelioration of obesity in Mice. Front Microbiol. 2019;10:2155.

    PubMed  PubMed Central  Google Scholar 

  18. 18.

    Cavallari JF, Fullerton MD, Duggan BM, Foley KP, Denou E, Smith BK, et al. Muramyl dipeptide-based postbiotics mitigate obesity-induced insulin resistance via IRF4. Cell Metabol. 2017;25:1063–74e3.

    CAS  Google Scholar 

  19. 19.

    Bailey C, Day C. Metformin: its botanical background. Pract Diabetes Int. 2004;21:115–7.

    Google Scholar 

  20. 20.

    Shin NR, Lee JC, Lee HY, Kim MS, Whon TW, Lee MS, et al. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut. 2014;63:727–35.

    CAS  PubMed  Google Scholar 

  21. 21.

    de la Cuesta-Zuluaga J, Mueller NT, Corrales-Agudelo V, Velasquez-Mejia EP, Carmona JA, Abad JM, et al. Metformin Is associated with higher relative abundance of mucin-degrading akkermansia muciniphila and several short-chain fatty acid-producing microbiota in the gut. Diab Care. 2017;40:54–62.

    Google Scholar 

  22. 22.

    Adeshirlarijaney A, Zou J, Tran H, Chassaing B, Gewirtz AT. Amelioration of metabolic syndrome by metformin associates with reduced indices of low-grade inflammation independently of the gut microbiota. Am J Physiol Endocrinol Metabol. 2019;317:E1121–E1130.

    CAS  Google Scholar 

  23. 23.

    Allegretti JR, Mullish BH, Kelly C, Fischer M. The evolution of the use of faecal microbiota transplantation and emerging therapeutic indications. Lancet. 2019;394:420–31.

    CAS  PubMed  Google Scholar 

  24. 24.

    Leshem A, Horesh N, Elinav E. Fecal microbial transplantation and its potential application in cardiometabolic syndrome. Front Immunol. 2019;10:1341.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Aron-Wisnewsky J, Clement K, Nieuwdorp M. Fecal microbiota transplantation: a future therapeutic option for obesity/diabetes? Curr Diab Rep. 2019;19:51.

    PubMed  Google Scholar 

  26. 26.

    Zhang Z, Mocanu V, Cai C, Dang J, Slater L, Deehan EC, et al. Impact of fecal microbiota transplantation on obesity and metabolic syndrome-a systematic review. Nutrients. 2019;11:2291.

    PubMed Central  Google Scholar 

  27. 27.

    Kootte RS, Levin E, Salojarvi J, Smits LP, Hartstra AV, Udayappan SD, et al. Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition. Cell Metabol. 2017;26:611–9e6.

    CAS  Google Scholar 

  28. 28.

    Gundling F, Roggenbrod S, Schleifer S, Sohn M, Schepp W. Patient perception and approval of faecal microbiota transplantation (FMT) as an alternative treatment option for obesity. Obes Sci Pract. 2019;5:68–74.

    CAS  PubMed  Google Scholar 

  29. 29.

    Cummings DE, Rubino F. Metabolic surgery for the treatment of type 2 diabetes in obese individuals. Diabetologia. 2018;61:257–64.

    PubMed  Google Scholar 

  30. 30.

    Anhe FF, Varin TV, Schertzer JD, Marette A. The gut microbiota as a mediator of metabolic benefits after bariatric surgery. Can J Diabetes. 2017;41:439–47.

    PubMed  Google Scholar 

  31. 31.

    Liu H, Hu C, Zhang X, Jia W. Role of gut microbiota, bile acids and their cross-talk in the effects of bariatric surgery on obesity and type 2 diabetes. J Diabetes Investig. 2018;9:13–20.

    PubMed  Google Scholar 

  32. 32.

    Aron-Wisnewsky J, Dore J, Clement K. The importance of the gut microbiota after bariatric surgery. Nat Rev Gastroenterol Hepatol. 2012;9:590–8.

    PubMed  Google Scholar 

  33. 33.

    van Greevenbroek MM, Schalkwijk CG, Stehouwer CD. Obesity-associated low-grade inflammation in type 2 diabetes mellitus: causes and consequences. Netherl J Med. 2013;71:174–87.

    Google Scholar 

  34. 34.

    Lizarbe B, Cherix A, Duarte JMN, Cardinaux JR, Gruetter R. High-fat diet consumption alters energy metabolism in the mouse hypothalamus. Int J Obes (2005). 2019;43:1295–304.

    CAS  Google Scholar 

  35. 35.

    Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, et al. Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest. 2012;122:153–62.

    CAS  PubMed  Google Scholar 

  36. 36.

    Waise TMZ, Toshinai K, Naznin F, NamKoong C, Md Moin AS, Sakoda H, et al. One-day high-fat diet induces inflammation in the nodose ganglion and hypothalamus of mice. Biochem Biophys Res Commun. 2015;464:1157–62.

    CAS  PubMed  Google Scholar 

  37. 37.

    Stranahan AM, Hao S, Dey A, Yu X, Baban B. Blood-brain barrier breakdown promotes macrophage infiltration and cognitive impairment in leptin receptor-deficient mice. J Cerebral Blood Flow Metabol. 2016;36:2108–21.

    CAS  Google Scholar 

  38. 38.

    Johnson PM, Kenny PJ. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci. 2010;13:635–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Valles-Colomer M, Falony G, Darzi Y, Tigchelaar EF, Wang J, Tito RY, et al. The neuroactive potential of the human gut microbiota in quality of life and depression. Nat Microbiol. 2019;4:623–32.

    CAS  PubMed  Google Scholar 

  40. 40.

    Lin P, Ding B, Feng C, Yin S, Zhang T, Qi X, et al. Prevotella and Klebsiella proportions in fecal microbial communities are potential characteristic parameters for patients with major depressive disorder. J Affect Disorders. 2017;207:300–4.

    PubMed  Google Scholar 

  41. 41.

    Hassan AM, Mancano G, Kashofer K, Frohlich EE, Matak A, Mayerhofer R, et al. High-fat diet induces depression-like behaviour in mice associated with changes in microbiome, neuropeptide Y, and brain metabolome. Nutr Neurosci. 2019;22:877–93.

    CAS  PubMed  Google Scholar 

  42. 42.

    Strandwitz P, Kim KH, Terekhova D, Liu JK, Sharma A, Levering J, et al. GABA-modulating bacteria of the human gut microbiota. Nat Microbiol. 2019;4:396–403.

    CAS  PubMed  Google Scholar 

  43. 43.

    Asano Y, Hiramoto T, Nishino R, Aiba Y, Kimura T, Yoshihara K, et al. Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice. Am J Physiol Gastroint Liver Physiol. 2012;303:G1288–95.

    CAS  Google Scholar 

  44. 44.

    Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161:264–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Dalile B, Van Oudenhove L, Vervliet B, Verbeke K. The role of short-chain fatty acids in microbiota-gut-brain communication. Nat Rev Gastroenterol Hepatol. 2019;16:461–78.

    PubMed  Google Scholar 

  46. 46.

    Frost G, Sleeth ML, Sahuri-Arisoylu M, Lizarbe B, Cerdan S, Brody L, et al. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat Commun. 2014;5:3611.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Arentsen T, Qian Y, Gkotzis S, Femenia T, Wang T, Udekwu K, et al. The bacterial peptidoglycan-sensing molecule Pglyrp2 modulates brain development and behavior. Mol Psych. 2017;22:257–66.

    CAS  Google Scholar 

  48. 48.

    Faith MS, Butryn M, Wadden TA, Fabricatore A, Nguyen AM, Heymsfield SB. Evidence for prospective associations among depression and obesity in population-based studies. Obes Rev. 2011;12:e438–53.

    CAS  PubMed  Google Scholar 

  49. 49.

    Zheng P, Zeng B, Zhou C, Liu M, Fang Z, Xu X, et al. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism. Mol Psych. 2016;21:786–96.

    CAS  Google Scholar 

  50. 50.

    Bruce-Keller AJ, Salbaum JM, Luo M, Et Blanchard, Taylor CM, Welsh DA, et al. Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity. Biol Psych. 2015;77:607–15.

    Google Scholar 

  51. 51.

    Jiang H, Ling Z, Zhang Y, Mao H, Ma Z, Yin Y, et al. Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun. 2015;48:186–94.

    PubMed  Google Scholar 

  52. 52.

    Aizawa E, Tsuji H, Asahara T, Takahashi T, Teraishi T, Yoshida S, et al. Possible association of Bifidobacterium and Lactobacillus in the gut microbiota of patients with major depressive disorder. J Affect Disorders. 2016;202:254–7.

    PubMed  Google Scholar 

  53. 53.

    Chen Z, Li J, Gui S, Zhou C, Chen J, Yang C, et al. Comparative metaproteomics analysis shows altered fecal microbiota signatures in patients with major depressive disorder. Neuroreport. 2018;29:417–25.

    CAS  PubMed  Google Scholar 

  54. 54.

    Kelly JR, Borre Y, C OB, Patterson E, El Aidy S, Deane J, et al. Transferring the blues: depression-associated gut microbiota induces neurobehavioural changes in the rat. J Psychiatric Res. 2016;82:109–18.

    Google Scholar 

  55. 55.

    Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008;57:1470–81.

    CAS  PubMed  Google Scholar 

  56. 56.

    Moloney GM, O’Leary OF, Salvo-Romero E, Desbonnet L, Shanahan F, Dinan TG, et al. Microbial regulation of hippocampal miRNA expression: Implications for transcription of kynurenine pathway enzymes. Behav Brain Res. 2017;334:50–4.

    CAS  PubMed  Google Scholar 

  57. 57.

    Soto M, Herzog C, Pacheco JA, Fujisaka S, Bullock K, Clish CB, et al. Gut microbiota modulate neurobehavior through changes in brain insulin sensitivity and metabolism. Mol Psych. 2018;23:2287–301.

    CAS  Google Scholar 

  58. 58.

    Gal Z, Huse RJ, Gonda X, Kumar S, Juhasz G, Bagdy G, et al. Anxiety and depression—the role of blood-brain barrier integrity. Neuropsychopharmacologia Hungarica: a Magyar Pszichofarmakologiai Egyesulet lapja = Off J Hungarian Assoc Psychopharmacol. 2019;21:19–25.

    Google Scholar 

  59. 59.

    Hargrave SL, Davidson TL, Zheng W, Kinzig KP. Western diets induce blood-brain barrier leakage and alter spatial strategies in rats. Behav Neurosci. 2016;130:123–35.

    CAS  PubMed  Google Scholar 

  60. 60.

    Davidson TL, Monnot A, Neal AU, Martin AA, Horton JJ, Zheng W. The effects of a high-energy diet on hippocampal-dependent discrimination performance and blood-brain barrier integrity differ for diet-induced obese and diet-resistant rats. Physiol Behav. 2012;107:26–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61.

    Braniste V, Al-Asmakh M, Kowal C, Anuar F, Abbaspour A, Toth M, et al. The gut microbiota influences blood-brain barrier permeability in mice. Sci Trans Med. 2014;6:263ra158.

    Google Scholar 

  62. 62.

    Alcock J, Maley CC, Aktipis CA. Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms. BioEssays. 2014;36:940–9.

    PubMed  PubMed Central  Google Scholar 

  63. 63.

    Duca FA, Swartz TD, Sakar Y, Covasa M. Increased oral detection, but decreased intestinal signaling for fats in mice lacking gut microbiota. PLoS ONE. 2012;7:e39748.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. 64.

    Swartz TD, Duca FA, de Wouters T, Sakar Y, Covasa M. Up-regulation of intestinal type 1 taste receptor 3 and sodium glucose luminal transporter-1 expression and increased sucrose intake in mice lacking gut microbiota. British J Nutr. 2012;107:621–30.

    CAS  Google Scholar 

  65. 65.

    Sclafani A, Ackroff K. Role of gut nutrient sensing in stimulating appetite and conditioning food preferences. Am J Physiol Reg Integr Comp Physiol. 2012;302:R1119–33.

    CAS  Google Scholar 

  66. 66.

    DiLeone RJ, Taylor JR, Picciotto MR. The drive to eat: comparisons and distinctions between mechanisms of food reward and drug addiction. Nat Neurosci. 2012;15:1330–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. 67.

    Wu C, Garamszegi SP, Xie X, Mash DC. Altered dopamine synaptic markers in postmortem brain of obese subjects. Front Human Neurosci. 2017;11:386.

    Google Scholar 

  68. 68.

    Delbes AS, Castel J, Denis RGP, Morel C, Quinones M, Everard A, et al. Prebiotics supplementation impact on the reinforcing and motivational aspect of feeding. Front Endocrinol. 2018;9:273.

    Google Scholar 

  69. 69.

    Nettleton JE, Klancic T, Schick A, Choo AC, Shearer J, Borgland SL, et al. Low-dose stevia (rebaudioside a) consumption perturbs gut microbiota and the mesolimbic dopamine reward system. Nutrients. 2019;11:1248.

    PubMed Central  Google Scholar 

  70. 70.

    Bernard A, Ancel D, Neyrinck AM, Dastugue A, Bindels LB, Delzenne NM, et al. A preventive prebiotic supplementation improves the sweet taste perception in diet-induced obese mice. Nutrients. 2019;11:549.

    PubMed Central  Google Scholar 

  71. 71.

    Alabduljader K, Cliffe M, Sartor F, Papini G, Cox WM, Kubis HP. Ecological momentary assessment of food perceptions and eating behavior using a novel phone application in adults with or without obesity. Eating Behav. 2018;30:35–41.

    Google Scholar 

  72. 72.

    Rezzi S, Ramadan Z, Martin FP, Fay LB, van Bladeren P, Lindon JC, et al. Human metabolic phenotypes link directly to specific dietary preferences in healthy individuals. J Proteome Res. 2007;6:4469–77.

    CAS  PubMed  Google Scholar 

  73. 73.

    Sanmiguel CP, Jacobs J, Gupta A, Ju T, Stains J, Coveleskie K, et al. Surgically induced changes in gut microbiome and hedonic eating as related to weight loss: preliminary findings in obese women undergoing bariatric surgery. Psychosomatic Med. 2017;79:880–7.

    Google Scholar 

  74. 74.

    Burokas A, Arboleya S, Moloney RD, Peterson VL, Murphy K, Clarke G, et al. Targeting the microbiota-gut-brain axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice. Biolog Psych. 2017;82:472–87.

    CAS  Google Scholar 

  75. 75.

    Vaghef-Mehrabany E, Ranjbar F, Asghari-Jafarabadi M, Hosseinpour-Arjmand S, Ebrahimi-Mameghani M. Calorie restriction in combination with prebiotic supplementation in obese women with depression: effects on metabolic and clinical response. Nutr Neurosci. 2019;8:1–15.

    Google Scholar 

  76. 76.

    Logan AC, Katzman M. Major depressive disorder: probiotics may be an adjuvant therapy. Med Hypoth. 2005;64:533–8.

    Google Scholar 

  77. 77.

    Dinan TG, Stanton C, Cryan JF. Psychobiotics: a novel class of psychotropic. Biolog Psych. 2013;74:720–6.

    CAS  Google Scholar 

  78. 78.

    Abildgaard A, Elfving B, Hokland M, Lund S, Wegener G. Probiotic treatment protects against the pro-depressant-like effect of high-fat diet in Flinders Sensitive Line rats. Brain, Behav Immun. 2017;65:33–42.

    CAS  Google Scholar 

  79. 79.

    Osadchiy V, Labus JS, Gupta A, Jacobs J, Ashe-McNalley C, Hsiao EY, et al. Correlation of tryptophan metabolites with connectivity of extended central reward network in healthy subjects. PLoS ONE. 2018;13:e0201772.

    PubMed  PubMed Central  Google Scholar 

  80. 80.

    Laurans L, Venteclef N, Haddad Y, Chajadine M, Alzaid F, Metghalchi S, et al. Genetic deficiency of indoleamine 2,3-dioxygenase promotes gut microbiota-mediated metabolic health. Nat Med. 2018;24:1113–20.

    CAS  PubMed  Google Scholar 

  81. 81.

    Jennis M, Cavanaugh CR, Leo GC, Mabus JR, Lenhard J, Hornby PJ. Microbiota-derived tryptophan indoles increase after gastric bypass surgery and reduce intestinal permeability in vitro and in vivo. Neurogastroenterol Motil. 2018;30:10.

    Google Scholar 

  82. 82.

    Tuomainen M, Lindstrom J, Lehtonen M, Auriola S, Pihlajamaki J, Peltonen M, et al. Associations of serum indolepropionic acid, a gut microbiota metabolite, with type 2 diabetes and low-grade inflammation in high-risk individuals. Nutr Diab. 2018;8:35.

    Google Scholar 

  83. 83.

    Saez-Lara MJ, Robles-Sanchez C, Ruiz-Ojeda FJ, Plaza-Diaz J, Gil A. Effects of probiotics and synbiotics on obesity, insulin resistance syndrome, type 2 diabetes and non-alcoholic fatty liver disease: a review of human clinical trials. Int J Mol Sci. 2016;17:928.

    PubMed Central  Google Scholar 

  84. 84.

    Koppel N, Maini Rekdal V, Balskus EP. Chemical transformation of xenobiotics by the human gut microbiota. Science. 2017;356:eaag2770.

    PubMed  Google Scholar 

  85. 85.

    Arrebola JP, Castano A, Esteban M, Bartolome M, Perez-Gomez B, Ramos JJ, et al. Differential contribution of animal and vegetable food items on persistent organic pollutant serum concentrations in Spanish adults. Data from BIOAMBIENT.ES project. Sci Total Environ. 2018;634:235–42.

    CAS  PubMed  Google Scholar 

  86. 86.

    Pestana D, Faria G, Sa C, Fernandes VC, Teixeira D, Norberto S, et al. Persistent organic pollutant levels in human visceral and subcutaneous adipose tissue in obese individuals–depot differences and dysmetabolism implications. Environ Res. 2014;133:170–7.

    CAS  PubMed  Google Scholar 

  87. 87.

    Lee DH, Porta M, Jacobs DR Jr., Vandenberg LN. Chlorinated persistent organic pollutants, obesity, and type 2 diabetes. Endocr Rev. 2014;35:557–601.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. 88.

    Ngwa EN, Kengne AP, Tiedeu-Atogho B, Mofo-Mato EP, Sobngwi E. Persistent organic pollutants as risk factors for type 2 diabetes. Diabetol Metab Syndr. 2015;7:41.

    PubMed  PubMed Central  Google Scholar 

  89. 89.

    Reaves DK, Ginsburg E, Bang JJ, Fleming JM. Persistent organic pollutants and obesity: are they potential mechanisms for breast cancer promotion? Endocr Relat Cancer. 2015;22:R69–86.

    CAS  PubMed  PubMed Central  Google Scholar 

  90. 90.

    Lim JE, Park SH, Jee SH, Park H. Body concentrations of persistent organic pollutants and prostate cancer: a meta-analysis. Environ Sci Pollut Res Int. 2015;22:11275–84.

    CAS  PubMed  Google Scholar 

  91. 91.

    Nadal A, Quesada I, Tuduri E, Nogueiras R, Alonso-Magdalena P. Endocrine-disrupting chemicals and the regulation of energy balance. Nat Rev Endocrinol. 2017;13:536–46.

    CAS  PubMed  Google Scholar 

  92. 92.

    Marushka L, Batal M, David W, Schwartz H, Ing A, Fediuk K, et al. Association between fish consumption, dietary omega-3 fatty acids and persistent organic pollutants intake, and type 2 diabetes in 18 First Nations in Ontario, Canada. Environ Res. 2017;156:725–37.

    CAS  PubMed  Google Scholar 

  93. 93.

    Lee YM, Kim KS, Kim SA, Hong NS, Lee SJ, Lee DH. Prospective associations between persistent organic pollutants and metabolic syndrome: a nested case-control study. Sci Total Environ. 2014;496:219–25.

    CAS  PubMed  Google Scholar 

  94. 94.

    Lee YM, Kim KS, Jacobs DR Jr., Lee DH. Persistent organic pollutants in adipose tissue should be considered in obesity research. Obes Rev. 2017;18:129–39.

    PubMed  Google Scholar 

  95. 95.

    Gauthier MS, Rabasa-Lhoret R, Prud’homme D, Karelis AD, Geng D, van Bavel B, et al. The metabolically healthy but obese phenotype is associated with lower plasma levels of persistent organic pollutants as compared to the metabolically abnormal obese phenotype. J Clin Endocrinol Metab. 2014;99:E1061–6.

    CAS  PubMed  Google Scholar 

  96. 96.

    Hue O, Marcotte J, Berrigan F, Simoneau M, Dore J, Marceau P, et al. Increased plasma levels of toxic pollutants accompanying weight loss induced by hypocaloric diet or by bariatric surgery. Obes Surgery. 2006;16:1145–54.

    Google Scholar 

  97. 97.

    Jansen A, Polder A, Muller MHB, Skjerve E, Aaseth J, Lyche JL. Increased levels of persistent organic pollutants in serum one year after a great weight loss in humans: are the levels exceeding health based guideline values? Sci Total Environ. 2018;622-623:1317–26.

    CAS  PubMed  Google Scholar 

  98. 98.

    Cheikh Rouhou M, Karelis AD, St-Pierre DH, Lamontagne L. Adverse effects of weight loss: are persistent organic pollutants a potential culprit? Diabetes Metab. 2016;42:215–23.

    CAS  PubMed  Google Scholar 

  99. 99.

    Pelletier C, Imbeault P, Tremblay A. Energy balance and pollution by organochlorines and polychlorinated biphenyls. Obes Rev. 2003;4:17–24.

    CAS  PubMed  Google Scholar 

  100. 100.

    Imbeault P, Tremblay A, Simoneau JA, Joanisse DR. Weight loss-induced rise in plasma pollutant is associated with reduced skeletal muscle oxidative capacity. Am J Physiol Endocrinol Metabol. 2002;282:E574–9.

    CAS  Google Scholar 

  101. 101.

    Pelletier C, Doucet E, Imbeault P, Tremblay A. Associations between weight loss-induced changes in plasma organochlorine concentrations, serum T3 concentration, and resting metabolic rate. Toxicol Sci. 2002;67:46–51.

    CAS  PubMed  Google Scholar 

  102. 102.

    Tremblay A, Pelletier C, Doucet E, Imbeault P. Thermogenesis and weight loss in obese individuals: a primary association with organochlorine pollution. Int J Obes Relat Metab Disord. 2004;28:936–9.

    CAS  PubMed  Google Scholar 

  103. 103.

    Vizcaino E, Grimalt JO, Fernandez-Somoano A, Tardon A. Transport of persistent organic pollutants across the human placenta. Environ Int. 2014;65:107–15.

    CAS  PubMed  Google Scholar 

  104. 104.

    Lee MH, Cho ER, Lim JE, Jee SH. Association between serum persistent organic pollutants and DNA methylation in Korean adults. Environ Res. 2017;158:333–41.

    CAS  PubMed  Google Scholar 

  105. 105.

    Rusiecki JA, Baccarelli A, Bollati V, Tarantini L, Moore LE, Bonefeld-Jorgensen EC. Global DNA hypomethylation is associated with high serum-persistent organic pollutants in Greenlandic Inuit. Environ Health Perspect. 2008;116:1547–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. 106.

    Acharya N, Gautam B, Subbiah S, Rogge MM, Anderson TA, Gao W. Polycyclic aromatic hydrocarbons in breast milk of obese vs normal women: Infant exposure and risk assessment. Sci Total Environ. 2019;668:658–67.

    CAS  PubMed  Google Scholar 

  107. 107.

    Iszatt N, Janssen S, Lenters V, Dahl C, Stigum H, Knight R, et al. Environmental toxicants in breast milk of Norwegian mothers and gut bacteria composition and metabolites in their infants at 1 month. Microbiome. 2019;7:34.

    PubMed  PubMed Central  Google Scholar 

  108. 108.

    Wang D, Yan J, Teng M, Yan S, Zhou Z, Zhu W. In utero and lactational exposure to BDE-47 promotes obesity development in mouse offspring fed a high-fat diet: impaired lipid metabolism and intestinal dysbiosis. Arch Toxicol. 2018;92:1847–60.

    CAS  PubMed  Google Scholar 

  109. 109.

    Chen L, Hu C, Lok-Shun Lai N, Zhang W, Hua J, Lam PKS, et al. Acute exposure to PBDEs at an environmentally realistic concentration causes abrupt changes in the gut microbiota and host health of zebrafish. Environ Pollut. 2018;240:17–26.

    CAS  PubMed  Google Scholar 

  110. 110.

    Petriello MC, Hoffman JB, Vsevolozhskaya O, Morris AJ, Hennig B. Dioxin-like PCB 126 increases intestinal inflammation and disrupts gut microbiota and metabolic homeostasis. Environ Pollut. 2018;242(Pt A):1022–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  111. 111.

    Zhan J, Liang Y, Liu D, Ma X, Li P, Zhai W, et al. Pectin reduces environmental pollutant-induced obesity in mice through regulating gut microbiota: a case study of p,p’-DDE. Environ Int. 2019;130:104861.

    CAS  PubMed  Google Scholar 

  112. 112.

    Hoffman JB, Flythe MD, Hennig B. Environmental pollutant-mediated disruption of gut microbial metabolism of the prebiotic inulin. Anaerobe. 2019;55:96–102.

    CAS  PubMed  Google Scholar 

  113. 113.

    Natividad JM, Agus A, Planchais J, Lamas B, Jarry AC, Martin R, et al. Impaired Aryl hydrocarbon receptor ligand production by the gut microbiota is a key factor in metabolic syndrome. Cell Metabol. 2018;28:737–49 e4.

    CAS  Google Scholar 

  114. 114.

    Petriello MC, Newsome BJ, Dziubla TD, Hilt JZ, Bhattacharyya D, Hennig B. Modulation of persistent organic pollutant toxicity through nutritional intervention: emerging opportunities in biomedicine and environmental remediation. Sci Total Environ. 2014;491-492:11–6.

    CAS  PubMed  Google Scholar 

  115. 115.

    Arguin H, Sanchez M, Bray GA, Lovejoy JC, Peters JC, Jandacek RJ, et al. Impact of adopting a vegan diet or an olestra supplementation on plasma organochlorine concentrations: results from two pilot studies. Br J Nutr. 2010;103:1433–41.

    CAS  PubMed  Google Scholar 

  116. 116.

    Girard C, Charette T, Leclerc M, Shapiro BJ, Amyot M. Cooking and co-ingested polyphenols reduce in vitro methylmercury bioaccessibility from fish and may alter exposure in humans. Sci Total Environ. 2018;616-617:863–74.

    CAS  PubMed  Google Scholar 

  117. 117.

    Ta CA, Zee JA, Desrosiers T, Marin J, Levallois P, Ayotte P, et al. Binding capacity of various fibre to pesticide residues under simulated gastrointestinal conditions. Food Chem Toxicol. 1999;37:1147–51.

    CAS  PubMed  Google Scholar 

  118. 118.

    Sera N, Morita K, Nagasoe M, Tokieda H, Kitaura T, Tokiwa H. Binding effect of polychlorinated compounds and environmental carcinogens on rice bran fiber. J Nutr Biochem. 2005;16:50–8.

    CAS  PubMed  Google Scholar 

  119. 119.

    Morita K, Tobiishi K. Increasing effect of nori on the fecal excretion of dioxin by rats. Biosci Biotechnol Biochem. 2002;66:2306–13.

    CAS  PubMed  Google Scholar 

  120. 120.

    Aislabie JM, Richards NK, Boul HL. Microbial degradation of DDT and its residues - a review. NZ J Agric Res. 2010;40:269–82.

    Google Scholar 

  121. 121.

    Murinova S, Dercova K, Dudasova H. Degradation of polychlorinated biphenyls (PCBs) by four bacterial isolates obtained from the PCB-contaminated soil and PCB-contaminated sediment. Int Biodet Biodegrad. 2014;91:52–9.

    CAS  Google Scholar 

  122. 122.

    De S, Ghosh S, Dutta SK. Congener specific polychlorinated biphenyl metabolism by human intestinal microbe Clostridium species: Comparison with human liver cell line-HepG2. Ind J Microbiol. 2006;46:199–207.

    CAS  Google Scholar 

  123. 123.

    Lee HS, Lee JC, Lee IK, Moon HB, Chang YS, Jacobs DR Jr., et al. Associations among organochlorine pesticides, Methanobacteriales, and obesity in Korean women. PLoS ONE. 2011;6:e27773.

    CAS  PubMed  PubMed Central  Google Scholar 

  124. 124.

    Jandacek RJ, Tso P. Enterohepatic circulation of organochlorine compounds: a site for nutritional intervention. J Nutr Biochem. 2007;18:163–7.

    CAS  PubMed  Google Scholar 

  125. 125.

    Fader KA, Nault R, Zhang C, Kumagai K, Harkema JR, Zacharewski TR. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-elicited effects on bile acid homeostasis: alterations in biosynthesis, enterohepatic circulation, and microbial metabolism. Sci Rep. 2017;7:5921.

    PubMed  PubMed Central  Google Scholar 

  126. 126.

    Wahlstrom A, Sayin SI, Marschall HU, Backhed F. Intestinal crosstalk between Bile Acids and microbiota and its impact on host metabolism. Cell Metabol. 2016;24:41–50.

    Google Scholar 

  127. 127.

    Degirolamo C, Rainaldi S, Bovenga F, Murzilli S, Moschetta A. Microbiota modification with probiotics induces hepatic bile acid synthesis via downregulation of the Fxr-Fgf15 axis in mice. Cell Rep. 2014;7:12–8.

    CAS  PubMed  Google Scholar 

  128. 128.

    Jeun J, Kim S, Cho SY, Jun HJ, Park HJ, Seo JG, et al. Hypocholesterolemic effects of Lactobacillus plantarum KCTC3928 by increased bile acid excretion in C57BL/6 mice. Nutrition. 2010;26:321–30.

    CAS  PubMed  Google Scholar 

  129. 129.

    Neves AL, Coelho J, Couto L, Leite-Moreira A, Roncon-Albuquerque R Jr. Metabolic endotoxemia: a molecular link between obesity and cardiovascular risk. J Mol Endocrinol. 2013;51:R51–64.

    CAS  PubMed  Google Scholar 

  130. 130.

    Anhe FF, Roy D, Pilon G, Dudonne S, Matamoros S, Varin TV, et al. A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice. Gut. 2015;64:872–83.

    CAS  PubMed  Google Scholar 

  131. 131.

    Skinner MK. Endocrine disruptors in 2015: epigenetic transgenerational inheritance. Nat Rev Endocrinol. 2016;12:68–70.

    CAS  PubMed  Google Scholar 

  132. 132.

    Krautkramer KA, Kreznar JH, Romano KA, Vivas EI, Barrett-Wilt GA, Rabaglia ME, et al. Diet-Microbiota interactions mediate global epigenetic programming in multiple host tissues. Mol Cell. 2016;64:982–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  133. 133.

    Vahamiko S, Laiho A, Lund R, Isolauri E, Salminen S, Laitinen K. The impact of probiotic supplementation during pregnancy on DNA methylation of obesity-related genes in mothers and their children. Eur J Nutr. 2018;58:367–77.

    PubMed  Google Scholar 

Download references

Acknowledgements

The research of A Tremblay is partly funded by the Canada Research Chair in Environment and Energy Balance. A. Marette’s research is funded by a CIHR/Pfizer research Chair in the pathogenesis of insulin resistance and cardiovascular diseases and by Sentinel North Program funded by the Canada First Research Excellence Fund. BSY Choi is funded by doctoral scholarships from Sentinel North and from CREATE-SMAART program funded by NSERC. L. Daoust is funded by the Jean-Paul-Houle fund from Université Laval.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Angelo Tremblay.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Choi, B.SY., Daoust, L., Pilon, G. et al. Potential therapeutic applications of the gut microbiome in obesity: from brain function to body detoxification. Int J Obes 44, 1818–1831 (2020). https://doi.org/10.1038/s41366-020-0618-3

Download citation

Search

Quick links