• SARI BEMA RAMDIKA Department of Nutrition Science, Faculty of Medicine, Diponegoro University, Semarang 50275, Indonesia
  • ENDANG MAHATI Department of Pharmacology and Therapy, Faculty of Medicine, Diponegoro University, Semarang 50275, Indonesia
  • ANANG MOHAMAD LEGOWO Department of Food Technology, Faculty of Animal and Agricultural Sciences, Diponegoro University, Semarang 50275, Indonesia
  • MUFLIHATUL MUNIROH Department of Physiology, Faculty of Medicine, Diponegoro University, Semarang 50275, Indonesia
  • YORA NINDITA Department of Pharmacology and Therapy, Faculty of Medicine, Diponegoro University, Semarang 50275, Indonesia
  • DIANA NUR AFIFAH Department of Nutrition Science, Faculty of Medicine, Diponegoro University, Semarang 50275, Indonesia


Objective: This study aims to determine the effect of fortified dadih with vitamin D3 on IL-6 expression level and the concentration of caecum SCFA in obese rats.

Methods: A total of 30 male Sprague Dawley rats were divided into five equal groups: healthy-control-(K-), obese-control-(K+), obese-intervention-(X1, X2, and X3). K(+), X1, X2, and X3 were in obesity conditions, which was induced by a high-fat sucrose diet (HFSD) and K(-) as a healthy-control-group. Furthermore, vitamin D3-fortified dadih at doses of 4 g/200 g-body-weight/d, dadih only at doses of 4 g/200 g-body-weight/d, and vitamin D3 only at 36 IU/200 g-body-weight/d was administered to X1, X2, and X3 groups, respectively.

Results: Treatment using fortified dadih with vitamin D3 showed significantly reduce weight gain (p<0.05) compare to K(+) and X2. In addition, X1 showed a decreased level of Interleukin-6 expression (p<0.05) than K(+), X2, and X3 groups but higher than K(-). Also, it showed the highest total SCFA, acetate, and propionate concentration (p<0.05). However, a moderately negative correlation was discovered between the pair of total SCFA and Interleukin-6 expression, acetate and Interleukin-6 expression, SCFA and body weight, propionate and body weight, butyrate and body weight. On the contrary, a strong positive correlation was observed between the pair of Interleukin-6 expression levels and body weight.

Conclusion: This study shows that fortified dadih with vitamin D3 from fermented foods improve the expression level of Interleukin-6 and increase the production of SCFA. Also, they improve intestinal homeostasis because of the increased SCFA production.

Keywords: Obesity, Dadih, Vitamin D3, IL-6, SCFA


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1. Schwartz MW, Seeley RJ, Zeltser LM, Drewnowski A, Ravussin E, Redman LM, et al. Obesity pathogenesis: an endocrine society scientific statement. Endocr Rev 2017;38:267–96.
2. Gu Z. Tailoring biomaterials for metabolic diseases. Adv Healthc Mater 2019;8:1–2.
3. Oussaada SM, Galen KA van, Cooiman MI, Kleinendorst L, Hazebroek EJ, Haelst MM van, et al. The pathogenesis of obesity. Metabolism 2019;92:26–36.
4. Gomez Hernandez A, Beneit N, Diaz Castroverde S, Escribano O. Differential role of adipose tissues in obesity and related metabolic and vascular complications. Int J Endocrinol 2016;2016:1–15.
5. Verboven K, Wouters K, Gaens K, Hansen D, Bijnen M, Wetzels S, et al. Abdominal subcutaneous and visceral adipocyte size, lipolysis and inflammation relate to insulin resistance in male obese humans. Sci Rep 2018;8:4677–85.
6. Chan PC, Hsieh PS. The role of adipocyte hypertrophy and hypoxia in the development of obesity-associated adipose tissue inflammation and insulin resistance. W: Gordeladze JO, red. Adiposity-Omics and Molecular Understanding. London: InTech; 2017. p. 127–41.
7. Venema K, Surono IS. Microbiota composition of dadih-a traditional fermented buffalo milk of West Sumatra. Lett Appl Microbiol 2019;68:234–40.
8. Mazloom K, Siddiqi I, Covasa M. Probiotics: how effective are they in the fight against obesity? Nutrients 2019;11:258–82.
9. Alipin K, Safitri R. The potential of indigenous lactic acid bacteria against Salmonella sp; 2016.
10. Hong SM, Chung EC, Kim CH. Anti-obesity effect of fermented whey beverage using lactic acid bacteria in diet-induced obese rats. Korean J Food Sci Anim Resour 2015;35:653–9.
11. Park SY, Cho SA, Lee MK, Lim SD. Effect of Lactobacillus plantarum FH185 on the reduction of adipocyte size and gut microbial changes in mice with diet-induced obesity. Korean J Food Sci Anim Resour 2015;35:171–8.
12. Tsai YT, Cheng PC, Pan TM. Anti-obesity effects of gut microbiota are associated with lactic acid bacteria. Appl Microbiol Biotechnol 2014;98:1–10.
13. Park DY, Ahn YT, Park SH, Huh CS, Yoo SR, Yu R, et al. Supplementation of Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 in diet-induced obese mice is associated with gut microbial changes and reduction in obesity. PLoS One 2013;8:108–35.
14. Azad MAK, Sarker M, Li T, Yin J. Probiotic species in the modulation of gut microbiota: an overview. Biomed Res Int 2018;2018:1–8.
15. Umu OCO, Rudi K, Diep DB. Modulation of the gut microbiota by prebiotic fibres and bacteriocins. Microb Ecol Health Dis 2017;28:1–12.
16. Baothman OA, Zamzami MA, Taher I, Abubaker J, Abu-Farha M. The role of gut microbiota in the development of obesity and diabetes. Lipids Health Dis 2016;15:108–16.
17. Lu Y, Fan C, Li P, Lu Y, 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;6:37589–602.
18. Wimalawansa SJ. Associations of vitamin D with insulin resistance, obesity, type 2 diabetes, and metabolic syndrome. J Steroid Biochem Mol Biol 2018;175:177–89.
19. Dimitrov V, White JH. Vitamin D signaling in intestinal innate immunity and homeostasis. Mol Cell Endocrinol 2017;453:68–78.
20. Clark A, Mach N. Role of vitamin D in the hygiene hypothesis: the interplay between vitamin D, vitamin D receptors, gut microbiota, and immune response. Front Immunol 2016;7:627–39.
21. Al-shahwan M, Gacem SA, Shamseddin S, Sammour M. Vitamin D impact on human health and its relation with several diseases. Int J Appl Pharm 2018;10:60.
22. Fish E, Beverstein G, Olson D, Reinhardt S, Garren M, Gould J. Vitamin D status of morbidly obese bariatric surgery patients. J Surg Res 2010;164:198–202.
23. Khandalavala BN, Hibma PP, Fang X. Prevalence and persistence of vitamin D deficiency in biliopancreatic diversion patients: a retrospective study. Obes Surg 2010;20:881–4.
24. Goldner WS, Stoner JA, Thompson J, Taylor K, Larson L, Erickson J, et al. Prevalence of vitamin D insufficiency and deficiency in morbidly obese patients: a comparison with non-obese controls. Obes Surg 2008;18:145–50.
25. Duggan C, Dieu Tapsoba J de, Mason C, Imayama I, Korde L, Wang CY, et al. Effect of vitamin D3 supplementation in combination with weight loss on inflammatory biomarkers in postmenopausal women: a randomized controlled trial. Cancer Prev Res 2015;8:628–35.
26. Shab Bidar S, Neyestani TR, Djazayery A, Eshraghian MR, Houshiarrad A, Gharavi A, et al. Regular consumption of vitamin D-fortified yogurt drink (doogh) improved endothelial biomarkers in subjects with type 2 diabetes: a randomized, double-blind clinical trial. BMC Med 2011;9:125–35.
27. Ranieri ML, Huck JR, Sonnen M, Barbano DM, Boor KJ. High temperature, short-time pasteurization temperatures inversely affect bacterial numbers during refrigerated storage of pasteurized fluid milk. J Dairy Sci 2009;92:4823–32.
28. Huazano Garcia AGM. Metabolism of short-chain fatty acids in the colon and faeces of mice after supplementation of diets with agave fructans. W: Valenzuela Baez R. red. Lipid Metabolism; 2013.
29. Cuesta Zuluaga J de la, Mueller N, Alvarez Quintero R, Velasquez Mejia E, Sierra J, Corrales Agudelo V, et al. Higher fecal short-chain fatty acid levels are associated with gut microbiome dysbiosis, obesity, hypertension and cardiometabolic disease risk factors. Nutrients 2018;11:51–67.
30. Rosas Villegas A, Sanchez Tapia M, Avila Nava A, Ramírez V, Tovar A, Torres N. Differential effect of sucrose and fructose in combination with a high-fat diet on intestinal microbiota and kidney oxidative stress. Nutrients 2017;9:393–406.
31. Fan Y, Futawaka K, Koyama R, Fukuda Y, Hayashi M, Imamoto M, et al. Vitamin D3/VDR resists diet-induced obesity by modulating UCP3 expression in muscles. J Biomed Sci 2016;23:56.
32. Lee E, Jung SR, Lee SY, Lee NK, Paik HD, Lim SI. Lactobacillus plantarum strain Ln4 attenuates diet-induced obesity, insulin resistance, and changes in hepatic mRNA levels associated with glucose and lipid metabolism. Nutrients 2018;10:643–58.
33. Rontoyanni V, Avila J, Kaul S, Wong R, Veeranki S. Association between obesity and serum 25(OH)D concentrations in older mexican adults. Nutrients 2017;9:97.
34. Zakharova I, Klimov L, Kuryaninova V, Nikitina I, Malyavskaya S, Dolbnya S, et al. Vitamin D insufficiency in overweight and obese children and adolescents. Front Endocrinol 2019;10:103–16.
35. Hamid Mehmood ZTN, Papandreou D. An updated mini-review of vitamin d and obesity: adipogenesis and inflammation state. Open Access Maced J Med Sci 2016;4:526–32.
36. Dura Trave T, Gallinas Victoriano F, Chueca Guindulain MJ, Berrade Zubiri S, Urretavizcaya Martinez M, Ahmed Mohamed L. Assessment of vitamin D status and parathyroid hormone during a combined intervention for the treatment of childhood obesity. Nutr Diabetes 2019;9:18–26.
37. Fabersani E, Abeijon Mukdsi MC, Ross R, Medina R, Gonzalez S, Gauffin Cano P. Specific strains of lactic acid bacteria differentially modulate the profile of adipokines in vitro. Front Immunol 2017;8:266–81.
38. Ellulu MS, Patimah I, Khazaai H, Rahmat A, Abed Y. Obesity and inflammation: the linking mechanism and the complications. Arch Med Sci 2017;4:851–63.
39. Xu G, Jiang J, Wang M, Li L, Su J, Ren X. Lactic acid reduces LPS-Induced TNF-? and IL-6 mRNA levels through decreasing IKB? phosphorylation. J Integr Agric 2013;12:1073–8.
40. Karimi G, Sabran MR, Jamaluddin R, Parvaneh K, Mohtarrudin N, Ahmad Z, et al. The anti-obesity effects of Lactobacillus casei strain shirota versus orlistat on high fat diet-induced obese rats. Food Nutr Res 2015;59:29273–82.
41. Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol 2014;21:319–29.
42. Wöbke TK, Sorg BL, Steinhilber D. Vitamin D in inflammatory diseases. Front Physiol 2014;5:244–64.
43. Mousa A, Misso M, Teede H, Scragg R, Courten B de. Effect of vitamin D supplementation on inflammation: protocol for a systematic review. Br Med J Open 2016;6:e010804–9.
44. Cortez M, Carmo LS, Rogero MM, Borelli P, Fock RA. A high-fat diet increases IL-1, IL-6, and TNF-? production by increasing NF-?B and attenuating PPAR-? expression in bone marrow mesenchymal stem cells. Inflammation 2013;36:379–86.
45. Besten G den, Eunen K van, Groen AK, Venema K, Reijngoud DJ, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res 2013;54:2325–40.
46. Abdul Rahim MBH, Chilloux J, Martinez Gili L, Neves AL, Myridakis A, Gooderham N, et al. Diet-induced metabolic changes of the human gut microbiome: importance of short-chain fatty acids, methylamines and indoles. Acta Diabetol 2019;56:493–500.
47. Soldavini J, Kaunitz JD. Pathobiology and potential therapeutic value of intestinal short-chain fatty acids in gut inflammation and obesity. Dig Dis Sci 2013;58:2756–66.
48. Gabriel FC, Fantuzzi G. The association of short-chain fatty acids and leptin metabolism: a systematic review. Nutr Res 2019;72:18–35.
49. Kim KN, Yao Y, Ju SY. Short-chain fatty acids and fecal microbiota abundance in humans with obesity: a systematic review and meta-analysis. Nutrients 2019;11:2512–26.
50. Li M, Esch BCAM van, Henricks PAJ, Folkerts G, Garssen J. The anti-inflammatory effects of short-chain fatty acids on lipopolysaccharide-or tumor necrosis factor ?-stimulated endothelial cells via activation of GPR41/43 and inhibition of HDACs. Front Pharmacol 2018;9:533–45.
51. McLoughlin RF, Berthon BS, Jensen ME, Baines KJ, Wood LG. Short-chain fatty acids, prebiotics, synbiotics, and systemic inflammation: a systematic review and meta-analysis. Am J Clin Nutr 2017;106:930–45.
52. Chambers ES, Preston T, Frost G, Morrison DJ. Role of gut microbiota-generated short-chain fatty acids in metabolic and cardiovascular health. Curr Nutr Rep 2018;7:198–206.
53. 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;5:3611–22.
54. Perry RJ, Peng L, Barry NA, Cline GW, Zhang D, Cardone RL, et al. Acetate mediates a microbiome–brain–?-cell axis to promote metabolic syndrome. Nature 2016;534:213–7.
55. Sindhu S, Thomas R, Shihab P, Sriraman D, Behbehani K, Ahmad R. Obesity is a positive modulator of IL-6R and IL-6 expression in the subcutaneous adipose tissue: significance for metabolic inflammation. PLoS One 2015;10:e0133494–511.
56. Makki K, Froguel P, Wolowczuk I. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflammation 2013;2013:1–12.
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How to Cite
RAMDIKA, S. B., E. MAHATI, A. M. LEGOWO, M. MUNIROH, Y. NINDITA, and D. N. AFIFAH. “FORTIFIED DADIH (FERMENTED BUFFALO MILK) WITH VITAMIN D3 IMPROVES INTERLEUKIN-6 AND CAECUM SHORT CHAIN FATTY ACIDS ON DIET-INDUCED OBESE RAT”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 12, no. 11, Nov. 2020, pp. 100-5, doi:10.22159/ijpps.2020v12i11.39209.
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