Capsaicin has an anti-obesity effect through alterations in gut microbiota populations and short-chain fatty acid concentrations

  • Yuanwei Wang
  • Cheng Tang
  • Yong Tang
  • Haiyan Yin
  • Xiong Liu
Keywords: anti-obesity; capsaicin; gut; microbiota; short-chain fatty acids; food intake


Objective: The present study investigated whether CAP exerted its anti-obesity effect through changes in the composition of gut microbiota and SCFAs, and whether the TRPV1 contributes to CAP’s effects against obesity in HFD-fed mice.

Design: C57BL/6J (TRPV1+/+) and B6.129X1-Trpv1tm1Jul/J (TRPV1-/-) mice were respectively divided into three groups (n = 6),that is SLD, HFD-fed, and CAP (2 mg/kg, po) +HFD fed and were administered respective treatment for 12 weeks.

Results: We observed significantly lower weight gain and food intake, triglyceride, cholesterol, glucose, and insulin levels in HFD+CAP-fed TRPV1knockout (KO) mice compared to the HFD-fed KO mice, though this effect was more obvious in wild-type (WT) mice. CAP increased the numbers of Akkermansia, Prevotella, Bacteroides, Odoribacter, Allobaculum, Coprococcus, and S24-7, and reduced the numbers of Desulfovibrio, Escherichia, Helicobacter, and Sutterella in the HFD+CAP-fed WT and KO mice compared with HFD-fed WT and KO mice. CAP increased the relative abundances of SCFAs producing the bacterial species, which increased intestinal acetate and propionate concentrations, which were beneficial in prevention and treatment of obesity.

Conclusions: Results from our study indicate that the reduced food intake and anti-obesity effect of CAP had been observed regardless of TRPV1 channel activation, and which is mediated by changes in the gut microbiota populations and SCFAs concentrations.


Download data is not yet available.


  1. NCD-RisC. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet 2016; 387(10026): 1377–96. doi: 10.1016/S0140-6736(16)30054-X

  2. Benaiges D, Pedro-Botet J, Flores-Le Roux JA, Climent E, Goday A. Past, present and future of pharmacotherapy for obesity. Clin Invest Arteriosclerosis 2017; 29(6): 256–64. doi: 10.1016/j.arteri.2017.06.002

  3. Barte JC, ter Bogt NC, Bogers RP, Teixeira PJ, Blissmer B, Mori TA, et al. Maintenance of weight loss after lifestyle interventions for overweight and obesity, a systematic review. Obes Rev 2010; 11(12): 899–906. doi: 10.1111/j.1467-789X.2010.00740.x

  4. Azzini E, Giacometti J, Russo GL. Antiobesity effects of anthocyanins in preclinical and clinical studies. Oxid Med Cell Longev 2017; 2017: 2740364. doi: 10.1155/2017/2740364

  5. Zhang LL, Yan Liu D, Ma LQ, Luo ZD, Cao TB, Zhong J, et al. Activation of transient receptor potential vanilloid type-1 channel prevents adipogenesis and obesity. Circ Res 2007; 100(7): 1063–70. doi: 10.1161/01.RES.0000262653.84850.8b

  6. Chen J, Li L, Li Y, Liang X, Sun Q, Yu H, et al. Activation of TRPV1 channel by dietary capsaicin improves visceral fat remodeling through connexin 43-mediated Ca2+ influx. Cardiovasc Diabetol 2015; 14: 22. doi: 10.1186/s12933-015-0183-6

  7. Li X, Guo J, Ji K, Zhang P. Bamboo shoot fiber prevents obesity in mice by modulating the gut microbiota. Sci Rep 2016; 6: 32953. doi: 10.1038/srep32953

  8. Wang J, Jia H. Metagenome-wide association studies: fine-mining the microbiome. Nature Rev Microbiol 2016; 14(8): 508–22. doi: 10.1038/nrmicro.2016.83

  9. Chambers ES, Viardot A, Psichas A, Morrison DJ, Murphy KG, Zac-Varghese SE, et al. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut 2015; 64(11): 1744–54. doi: 10.1136/gutjnl-2014-307913

  10. Canfora EE, van der Beek CM, Jocken JWE, Goossens GH, Holst JJ, Olde Damink SWM, et al. Colonic infusions of short-chain fatty acid mixtures promote energy metabolism in overweight/obese men: a randomized crossover trial. Sci Rep 2017; 7(1): 2360. doi: 10.1038/s41598-017-02546-x

  11. Lu Y, Fan C, Li P, Chang X, Qi K. Short chain fatty acids prevent high-fat-diet-induced obesity in mice by regulating G protein-coupled receptors and gut microbiota. Sci Rep 2016; 6: 37589. doi: 10.1038/srep37589

  12. Baboota RK, Murtaza N, Jagtap S, Singh DP, Karmase A, Kaur J, et al. Capsaicin-induced transcriptional changes in hypothalamus and alterations in gut microbial count in high fat diet fed mice. J Nutr Biochem 2014; 25(9): 893–902. doi: 10.1016/j.jnutbio.2014.04.004

  13. Shen W, Shen M, Zhao X, Zhu H, Yang Y, Lu S, et al. Anti-obesity effect of capsaicin in mice fed with high-fat diet is associated with an increase in population of the gut bacterium Akkermansia muciniphila. Front Microbiol 2017; 8: 272. doi: 10.3389/fmicb.2017.00272

  14. Kang C, Wang B, Kaliannan K, Wang X, Lang H, Hui S, et al. Gut microbiota mediates the protective effects of dietary capsaicin against chronic low-grade inflammation and associated obesity induced by high-fat diet. mBio 2017; 8(3): pii: e00470-17. doi: 10.1128/mBio.00470-17

  15. Nonogaki K, Kaji T. The acute anorexic effect of liraglutide, a GLP-1 receptor agonist, does not require functional leptin receptor, serotonin, and hypothalamic POMC and CART activities in mice. Diab Res Clin Pract 2016; 120: 186–9. doi: 10.1016/j.diabres.2016.08.009

  16. Loh K, Zhang L, Brandon A, Wang Q, Begg D, Qi Y, et al. Insulin controls food intake and energy balance via NPY neurons. Molec Metab 2017; 6(6): 574–84. doi: 10.1016/j.molmet.2017.03.013

  17. Hassan AM, Jain P, Mayerhofer R, Frohlich EE, Farzi A, Reichmann F, et al. Visceral hyperalgesia caused by peptide YY deletion and Y2 receptor antagonism. Sci Rep 2017; 7: 40968. doi: 10.1038/srep40968

  18. Zynat J, Guo Y, Lu Y, Lin D. The improvement of hyperglycemia after RYGB surgery in diabetic rats is related to elevated hypothalamus GLP-1 receptor expression. Int J Endocrinol 2016; 2016: 5308347. doi: 10.1155/2016/5308347

  19. Pettersson US, Walden TB, Carlsson PO, Jansson L, Phillipson M. Female mice are protected against high-fat diet induced metabolic syndrome and increase the regulatory T cell population in adipose tissue. PLoS One 2012; 7(9): e46057. doi: 10.1371/journal.pone.0046057

  20. Giles DA, Moreno-Fernandez ME, Stankiewicz TE, Graspeuntner S, Cappelletti M, Wu D, et al. Thermoneutral housing exacerbates nonalcoholic fatty liver disease in mice and allows for sex-independent disease modeling. Nat Med 2017; 23(7): 829–38. doi: 10.1038/nm.4346

  21. Rohm B, Riedel A, Ley JP, Widder S, Krammer GE, Somoza V. Capsaicin, nonivamide and trans-pellitorine decrease free fatty acid uptake without TRPV1 activation and increase acetyl-coenzyme a synthetase activity in Caco-2 cells. Food Func 2015; 6(1): 173–85. doi: 10.1039/c4fo00435c

  22. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature 2006; 444(7122): 1022–3. doi: 10.1038/4441022a

  23. 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(6): 872–83. doi: 10.1136/gutjnl-2014-307142

  24. Roopchand DE, Carmody RN, Kuhn P, Moskal K, Rojas-Silva P, Turnbaugh PJ, et al. Dietary polyphenols promote growth of the gut bacterium Akkermansia muciniphila and attenuate high-fat diet-induced metabolic syndrome. Diabetes 2015; 64(8): 2847–58. doi: 10.2337/db14-1916

  25. van Dorsten FA, Peters S, Gross G, Gomez-Roldan V, Klinkenberg M, de Vos RC, et al. Gut microbial metabolism of polyphenols from black tea and red wine/grape juice is source-specific and colon-region dependent. J Agric Food Chem 2012; 60(45): 11331–42. doi: 10.1021/jf303165w

  26. Kovatcheva-Datchary P, Nilsson A, Akrami R, Lee YS, De Vadder F, Arora T, et al. Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of Prevotella. Cell Metabolism 2015; 22(6): 971–82. doi: 10.1016/j.cmet.2015.10.001

  27. Brahe LK, Le Chatelier E, Prifti E, Pons N, Kennedy S, Hansen T, et al. Specific gut microbiota features and metabolic markers in postmenopausal women with obesity. Nutr Diab 2015; 5: e159. doi: 10.1038/nutd.2015.9

  28. Etxeberria U, Hijona E, Aguirre L, Milagro FI, Bujanda L, Rimando AM, et al. Pterostilbene-induced changes in gut microbiota composition in relation to obesity. Molec Nutri Food Res 2017; 61(1): 1500906. doi: 10.1002/Mnfr.201500906

  29. Herrmann E, Young W, Rosendale D, Reichert-Grimm V, Riedel CU, Conrad R, et al. RNA-based stable isotope probing suggestsAllobaculum spp. as particularly active glucose assimilators in a complex murine microbiota cultured in vitro. BioMed Res Int 2017; 2017: 1829685. doi: 10.1155/2017/1829685

  30. Van Hul M, Geurts L, Plovier H, Druart C, Everard A, Stahlman M, et al. Reduced obesity, diabetes and steatosis upon cinnamon and grape pomace are associated with changes in gut microbiota and markers of gut barrier. Am J Physiol Endocrinol Metab 2018; 314(4): E334–52. doi: 10.1152/ajpendo.00107.2017

  31. Everard A, Lazarevic V, Gaia N, Johansson M, Stahlman M, Backhed F, et al. Microbiome of prebiotic-treated mice reveals novel targets involved in host response during obesity. ISME J. 2014; 8(10): 2116–30. doi: 10.1038/ismej.2014.45

  32. Ravussin Y, Koren O, Spor A, LeDuc C, Gutman R, Stombaugh J, et al. Responses of gut microbiota to diet composition and weight loss in lean and obese mice. Obesity (Silver Spring) 2012; 20(4): 738–47. doi: 10.1038/oby.2011.111

  33. Cani PD, Amar J, Iglesias MA, Knauf C, Poggi M, Bastelica D, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007; 56(7): 1761–72. doi: 10.2337/db06-1491

  34. Cox AJ, West NP, Cripps AW. Obesity, inflammation, and the gut microbiota. Lancet Diab Endocrinol 2015; 3(3): 207–15. doi: 10.1016/S2213-8587(14)70134-2

  35. Figliuolo VR, dos Santos LM, Abalo A, Nanini H, Santos A, Brittes NM, et al. Sulfate-reducing bacteria stimulate gut immune responses and contribute to inflammation in experimental colitis. Life Sci 2017; 189: 29–38. doi: 10.1016/j.lfs.2017.09.014

  36. Hiippala K, Kainulainen V, Kalliomaki M, Arkkila P, Satokari R. Mucosal Prevalence and interactions with the epithelium indicate commensalism of Sutterella spp. Front Microbiol 2016; 7: 1706. doi: 10.3389/fmicb.2016.01706

  37. Rowan F, Docherty NG, Murphy M, Murphy B, Coffey JC, O’Connell PR. Desulfovibrio bacterial species are increased in ulcerative colitis. Dis Colon Rectum 2010; 53(11): 1530–6. doi: 10.1007/DCR.0b013e3181f1e620

  38. Shin NR, Whon TW, Bae JW. Proteobacteria: microbial signature of dysbiosis in gut microbiota. Trends Biotechnol 2015; 33(9): 496–503. doi: 10.1016/j.tibtech.2015.06.011

  39. Xu MY, Liu L, Yuan BS, Yin J, Lu QB. Association of obesity with Helicobacter pylori infection: a retrospective study. World J Gastroenterol 2017; 23(15): 2750–6. doi: 10.3748/wjg.v23.i15.2750

  40. Murugesan S, Nirmalkar K, Hoyo-Vadillo C, Garcia-Espitia M, Ramirez-Sanchez D, Garcia-Mena J. Gut microbiome production of short-chain fatty acids and obesity in children. Eur J Clin Microbiol Infect Dis 2018; 37(4): 621–5. doi: 10.1007/s10096-017-3143-0

  41. Weitkunat K, Stuhlmann C, Postel A, Rumberger S, Fankhanel M, Woting A, et al. Short-chain fatty acids and inulin, but not guar gum, prevent diet-induced obesity and insulin resistance through differential mechanisms in mice. Sci Rep 2017; 7(1): 6109. doi: 10.1038/s41598-017-06447-x

  42. Murphy EF, Cotter PD, Healy S, Marques TM, O’Sullivan O, Fouhy F, et al. Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut 2010; 59(12): 1635–42. doi: 10.1136/gut.2010.215665

  43. Lin HV, Frassetto A, Kowalik EJ, Jr., Nawrocki AR, Lu MM, Kosinski JR, et al. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One 2012; 7(4): e35240. doi: 10.1371/journal.pone.0035240

  44. Brown AJ, Goldsworthy SM, Barnes AA, Eilert MM, Tcheang L, Daniels D, et al. The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem 2003; 278(13): 11312–19. doi: 10.1074/jbc.M211609200

  45. Nilsson NE, Kotarsky K, Owman C, Olde B. Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids. Biochem Biophys Res Commun 2003; 303(4): 1047–52. doi: 10.1016/s0006-291x(03)00488-1

  46. Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK, et al. 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 2008; 105(43): 16767–72. doi: 10.1073/pnas.0808567105

  47. Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 2012; 61(2): 364–71. doi: 10.2337/db11-1019

  48. Psichas A, Sleeth ML, Murphy KG, Brooks L, Bewick GA, Hanyaloglu AC, et al. The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Int J Obes (Lond) 2015; 39(3): 424–9. doi: 10.1038/ijo.2014.153

  49. NamKoong C, Kim MS, Jang BT, Lee YH, Cho YM, Choi HJ. Central administration of GLP-1 and GIP decreases feeding in mice. Biochem Biophys Res Commun 2017; 490(2): 247–52. doi: 10.1016/j.bbrc.2017.06.031

  50. Reiner DJ, Mietlicki-Baase EG, McGrath LE, Zimmer DJ, Bence KK, Sousa GL, et al. Astrocytes regulate GLP-1 receptor-mediated effects on energy balance. J Neurosc 2016; 36(12): 3531–40. doi: 10.1523/JNEUROSCI.3579-15.2016

  51. Zhou J, Martin RJ, Raggio AM, Shen L, McCutcheon K, Keenan MJ. The importance of GLP-1 and PYY in resistant starch’s effect on body fat in mice. Molec Nutr Food Res 2015; 59(5): 1000–3. doi: 10.1002/mnfr.201400904

  52. van Avesaat M, Troost FJ, Westerterp-Plantenga MS, Helyes Z, Le Roux CW, Dekker J, et al. Capsaicin-induced satiety is associated with gastrointestinal distress but not with the release of satiety hormones. Am J Clin Nutr 2016; 103(2): 305–13. doi: 10.3945/ajcn.115.123414

  53. Hill JW. Gene expression and the control of food intake by hypothalamic POMC/CART neurons. Open Neuroendocrinol J 2010; 3: 21–7.

  54. Krashes MJ, Shah BP, Koda S, Lowell BB. Rapid versus delayed stimulation of feeding by the endogenously released AgRP neuron mediators GABA, NPY, and AgRP. Cell Metab 2013; 18(4): 588–95. doi: 10.1016/j.cmet.2013.09.009

How to Cite
Wang Y, Tang C, Tang Y, Yin H, Liu X. Capsaicin has an anti-obesity effect through alterations in gut microbiota populations and short-chain fatty acid concentrations. fnr [Internet]. 2020Feb.19 [cited 2020Mar.28];64. Available from:
Original Articles