Effects of probiotics, prebiotics or synbiotics on jawbone in obese-insulin resistant rats

  • Sathima Eaimworawuthikul
  • Wannipa Tunapong
  • Titikorn Chunchai
  • Sakawdaurn Yasom
  • Keerati Wanchai
  • Panan Suntornsaratoon
  • Narattaphol Charoenphandhu
  • Parameth Thiennimitr
  • Nipon Chattipakorn
  • Siriporn C. Chattipakorn
Original Contribution



Chronic high-fat diet (HFD) consumption results in gut dysbiosis, systemic inflammation, obese-insulin resistance, and osteoporosis of the jawbones. The probiotics, prebiotics or synbiotics alleviated gut dysbiosis and the metabolic disturbance in HFD-induced obesity. However, the effects on jawbone properties have not been investigated. This study aimed to investigate the effects of probiotic Lactobacillus paracasei HII01, prebiotic xylooligosaccharide (XOS), and synbiotics on the jawbone properties along with metabolic parameters, gut and systemic inflammation in HFD-fed rats.


Forty-eight male Wistar rats were fed with either a HFD or normal diet for 12 weeks. Rats in each group were subdivided into four subgroups to be treated with either vehicle, probiotics, prebiotics, or synbiotics for the additional 12 weeks. Blood samples, gut, bone marrows, and jawbones were collected to determine metabolic parameters, inflammation, and bone properties.


The HFD-fed rats developed obese-insulin resistance, as indicated by increased body weight, dyslipidemia and decreased insulin sensitivity. Serum lipopolysaccharide levels and interleukin-6 mRNA expression in the ileum and bone marrows were elevated. Altered bone metabolism and the impaired jawbone properties were evident as indicated by decreased bone mineral density with increased trabecular separation. Reduced ultimate load and stiffness were observed in HFD-fed rats. Treatments with probiotics, prebiotics or synbiotics in HFD-fed rats improved metabolic parameters and reduced inflammation. However, no alterations in jawbone properties were found in all treatments.


The osteoporosis of the jawbone occurred in obese-insulin resistance, and treatments with probiotics, prebiotics and synbiotics were not sufficient to improve the jawbone properties.


Lactobacillus paracasei HII01 Xylooligosaccharide Synbiotics Obesity Insulin resistance Jawbone 



This work was supported by Thailand Research Fund (TRF) Grants: TRF-Senior Research Scholar RTA6080003 (to SCC), RTA6080007 (to N. Charoenphandhu), IRN60W0001 (to N. Charoenphandhu) and MRG 6180187 (to PT); a CMU 50th Anniversary grant by Chiang Mai University (PHD/014/2557 SE&SCC); a NSTDA Research Chair Grant from the National Science and Technology Development Agency Thailand (N. Chattipakorn) and a Chiang Mai University Center of Excellence Award (N. Chattipakorn).

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.


  1. 1.
    Correction NM, Wang H, Lozano R, Davis A, Liang X, Zhou M, Vollset SE, Ozgoren AA, Abdalla S, Abd-Allah F (2015) Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013. Lancet 385(9963):117–171CrossRefGoogle Scholar
  2. 2.
    Potikanond S, Rattanachote P, Pintana H, Suntornsaratoon P, Charoenphandhu N, Chattipakorn N, Chattipakorn S (2016) Obesity does not aggravate osteoporosis or osteoblastic insulin resistance in orchiectomized rats. J Endocrinol 228(2):85–95CrossRefGoogle Scholar
  3. 3.
    Pramojanee SN, Phimphilai M, Kumphune S, Chattipakorn N, Chattipakorn SC (2013) Decreased jaw bone density and osteoblastic insulin signaling in a model of obesity. J Dent Res 92(6):560–565CrossRefGoogle Scholar
  4. 4.
    Khamaisi M, Regev E, Yarom N, Avni B, Leitersdorf E, Raz I, Elad S (2007) Possible association between diabetes and bisphosphonate-related jaw osteonecrosis. J Clin Endocrinol Metab 92:1172–1175CrossRefGoogle Scholar
  5. 5.
    Wessel JH, Dodson TB, Zavras AI (2008) Zoledronate, smoking, and obesity are strong risk factors for osteonecrosis of the jaw: a case-control study. J Oral Maxillofac Surg 66:625–631CrossRefGoogle Scholar
  6. 6.
    Eaimworawuthikul S, Thiennimitr P, Chattipakorn N, Chattipakorn SC (2017) Diet-induced obesity, gut microbiota and bone, including alveolar bone loss. Arch Oral Biol 78:65–81CrossRefGoogle Scholar
  7. 7.
    Blasco-Baque V, Serino M, Vergnes JN, Riant E, Loubieres P, Arnal JF, Gourdy P, Sixou M, Burcelin R, Kemoun P (2012) High-fat diet induces periodontitis in mice through lipopolysaccharides (LPS) receptor signaling: protective action of estrogens. PLoS One 7(11):e48220CrossRefGoogle Scholar
  8. 8.
    Li Y, Lu Z, Zhang X, Yu H, Kirkwood KL, Lopes-Virella MF, Huang Y (2015) Metabolic syndrome exacerbates inflammation and bone loss in periodontitis. J Dent Res 94(2):362–370CrossRefGoogle Scholar
  9. 9.
    Benites BD, Gilli SC, Saad ST (2014) Obesity and inflammation and the effect on the hematopoietic system. Rev Bras Hematol Hemoter 36(2):147–151CrossRefGoogle Scholar
  10. 10.
    Luo Y, Chen GL, Hannemann N, Ipseiz N, Kronke G, Bauerle T, Munos L, Wirtz S, Schett G, Bozec A (2015) Microbiota from obese mice regulate hematopoietic stem cell differentiation by altering the bone niche. Cell Metab 22(5):886–894CrossRefGoogle Scholar
  11. 11.
    da Silva SV, Renovato-Martins M, Ribeiro-Pereira C, Citelli M, Barja-Fidalgo C (2016) Obesity modifies bone marrow microenvironment and directs bone marrow mesenchymal cells to adipogenesis. Obesity (Silver Spring Md) 24(12):2522–2532CrossRefGoogle Scholar
  12. 12.
    Ejtahed HS, Soroush AR, Angoorani P, Larijani B, Hasani-Ranjbar S (2016) Gut microbiota as a target in the pathogenesis of metabolic disorders: a new approach to novel therapeutic agents. Horm Metab Res 48(06):349–358CrossRefGoogle Scholar
  13. 13.
    Gérard P (2016) Gut microbiota and obesity. Cell Mol Life Sci 73(1):147–162CrossRefGoogle Scholar
  14. 14.
    Ojeda P, Bobe A, Dolan K, Leone V, Martinez K (2016) Nutritional modulation of gut microbiota—the impact on metabolic disease pathophysiology. J Nutr Biochem 28:191–200CrossRefGoogle Scholar
  15. 15.
    de La Serre CB, Ellis CL, Lee J, Hartman AL, Rutledge JC, Raybould HE (2010) Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation. Am J Physiol Gastrointest Liver Physiol 299(2):G440–G448CrossRefGoogle Scholar
  16. 16.
    Kim KA, Gu W, Lee IA, Joh EH, Kim DH (2012) High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PLoS One 7(10):e47713CrossRefGoogle Scholar
  17. 17.
    Shin NR, Whon TW, Bae JW (2015) Proteobacteria: microbial signature of dysbiosis in gut microbiota. Trends Biotechnol 33(9):496–503CrossRefGoogle Scholar
  18. 18.
    Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmee E, Cousin B, Sulpice T, Chamontin B, Ferrieres J, Tanti JF, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R (2007) Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56(7):1761–1772CrossRefGoogle Scholar
  19. 19.
    Sjogren K, Engdahl C, Henning P, Lerner UH, Tremaroli V, Lagerquist MK, Backhed F, Ohlsson C (2012) The gut microbiota regulates bone mass in mice. J Bone Miner Res 27(6):1357–1367CrossRefGoogle Scholar
  20. 20.
    Flint HJ, Scott KP, Louis P, Duncan SH (2012) The role of the gut microbiota in nutrition and health. Nat Rev Gastroenterol Hepatol 9(10):577–589CrossRefGoogle Scholar
  21. 21.
    Tunapong W, Apaijai N, Yasom S, Tanajak P, Wanchai K, Chunchai T, Kerdphoo S, Eaimworawuthikul S, Thiennimitr P, Pongchaidecha A, Lungkaphin A, Pratchayasakul W, Chattipakorn SC, Chattipakorn N (2017) Chronic treatment with prebiotics, probiotics and synbiotics attenuated cardiac dysfunction by improving cardiac mitochondrial dysfunction in male obese insulin-resistant rats. Eur J Nutr. CrossRefPubMedGoogle Scholar
  22. 22.
    Chunchai T, Thunapong W, Yasom S, Wanchai K, Eaimworawuthikul S, Metzler G, Lungkaphin A, Pongchaidecha A, Sirilun S, Chaiyasut C, Pratchayasakul W, Thiennimitr P, Chattipakorn N, Chattipakorn SC (2018) Decreased microglial activation through gut-brain axis by prebiotics, probiotics, or synbiotics effectively restored cognitive function in obese-insulin resistant rats. J Neuroinflamm 15(1):11CrossRefGoogle Scholar
  23. 23.
    Suntornsaratoon P, Krishnamra N, Charoenphandhu N (2015) Positive long-term outcomes from presuckling calcium supplementation in lactating rats and the offspring. Am J Physiol Endocrinol Metab 308(11):E1010–E1022CrossRefGoogle Scholar
  24. 24.
    Haffner SM, Miettinen H, Stern MP (1997) The homeostasis model in the San Antonio heart study. Diabetes Care 20(7):1087–1092CrossRefGoogle Scholar
  25. 25.
    Peinnequin A, Mouret C, Birot O, Alonso A, Mathieu J, Clarencon D, Agay D, Chancerelle Y, Multon E (2004) Rat pro-inflammatory cytokine and cytokine related mRNA quantification by real-time polymerase chain reaction using SYBR green. BMC Immunol 5(1):3CrossRefGoogle Scholar
  26. 26.
    Abbassy MA, Watari I, Soma K (2010) The effect of diabetes mellitus on rat mandibular bone formation and microarchitecture. Eur J Oral Sci 118(4):364–369CrossRefGoogle Scholar
  27. 27.
    Jiang GZ, Matsumoto H, Hori M, Gunji A, Hakozaki K, Akimoto Y, Fujii A (2008) Correlation among geometric, densitometric, and mechanical properties in mandible and femur of osteoporotic rats. J Bone Miner Metab 26(2):130–137CrossRefGoogle Scholar
  28. 28.
    Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG (2010) Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol 8(6):e1000412CrossRefGoogle Scholar
  29. 29.
    Vasikaran S, Cooper C, Eastell R, Griesmacher A, Morris HA, Trenti T, Kanis JA (2011) International osteoporosis foundation and international federation of clinical chemistry and laboratory medicine position on bone marker standards in osteoporosis. Clin Chem Lab Med 49(8):1271–1274CrossRefGoogle Scholar
  30. 30.
    Devkota S, Wang Y, Musch MW, Leone V, Fehlner-Peach H, Nadimpalli A, Antonopoulos DA, Jabri B, Chang EB (2012) Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10−/− mice. Nature 487(7405):104–108CrossRefGoogle Scholar
  31. 31.
    Martinez-Medina M, Denizot J, Dreux N, Robin F, Billard E, Bonnet R, Darfeuille-Michaud A, Barnich N (2014) Western diet induces dysbiosis with increased E coli in CEABAC10 mice, alters host barrier function favouring AIEC colonisation. Gut 63(1):116–124CrossRefGoogle Scholar
  32. 32.
    Li Z, Summanen PH, Komoriya T, Finegold SM (2015) In vitro study of the prebiotic xylooligosaccharide (XOS) on the growth of Bifidobacterium spp. and Lactobacillus spp. Int J Food Sci Nutr 66(8):919–922CrossRefGoogle Scholar
  33. 33.
    Nagpal R, Kaur A (2011) Synbiotic effect of various prebiotics on in vitro activities of probiotic lactobacilli. Ecol Food Nutr 50(1):63–68CrossRefGoogle Scholar
  34. 34.
    Scholz-Ahrens KE, Adolphi B, Rochat F, Barclay DV, de Vrese M, Açil Y, Schrezenmeir J (2016) Effects of probiotics, prebiotics, and synbiotics on mineral metabolism in ovariectomized rats—impact of bacterial mass, intestinal absorptive area and reduction of bone turn-over. NFS J 3:41–50CrossRefGoogle Scholar
  35. 35.
    Kekkonen RA, Lummela N, Karjalainen H, Latvala S, Tynkkynen S, Järvenpää S, Kautiainen H, Julkunen I, Vapaatalo H, Korpela R (2008) Probiotic intervention has strain-specific anti-inflammatory effects in healthy adults. World J Gastroenterol 14(13):2029–2036CrossRefGoogle Scholar
  36. 36.
    Maekawa T, Hajishengallis G (2014) Topical treatment with probiotic Lactobacillus brevis CD2 inhibits experimental periodontal inflammation and bone loss. J Periodontal Res 49(6):785–791CrossRefGoogle Scholar
  37. 37.
    Ohlsson C, Engdahl C, Fak F, Andersson A, Windahl SH, Farman HH, Moverare-Skrtic S, Islander U, Sjogren K (2014) Probiotics protect mice from ovariectomy-induced cortical bone loss. PLoS One 9(3):e92368CrossRefGoogle Scholar
  38. 38.
    Peerajan S, Chaiyasut C, Sirilun S, Chaiyasut K, Kesika P, Sivamaruthi BS (2016) Enrichment of nutritional value of Phyllanthus emblica fruit juice using the probiotic bacterium, Lactobacillus paracasei HII01 mediated fermentation. Food Sci Technol (Campinas) 36:116–123CrossRefGoogle Scholar
  39. 39.
    Whisner CM, Castillo LF (2017) Prebiotics, bone and mineral metabolism. Calcif Tissue Int 102(4):443–479CrossRefGoogle Scholar
  40. 40.
    Gatej SM, Marino V, Bright R, Fitzsimmons TR, Gully N, Zilm P, Gibson RJ, Edwards S, Bartold PM (2018) Probiotic Lactobacillus rhamnosus GG prevents alveolar bone loss in a mouse model of experimental periodontitis. J Clin Periodontol 45(2):204–212CrossRefGoogle Scholar
  41. 41.
    Ricoldi MST, Furlaneto FAC, Oliveira LFF, Teixeira GC, Pischiotini JP, Moreira ALG, Ervolino E, de Oliveira MN, Bogsan CSB, Salvador SL, Messora MR (2017) Effects of the probiotic Bifidobacterium animalis subsp. lactis on the non-surgical treatment of periodontitis. A histomorphometric, microtomographic and immunohistochemical study in rats. PLoS One 12(6):e0179946CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Sathima Eaimworawuthikul
    • 1
    • 2
    • 3
  • Wannipa Tunapong
    • 3
  • Titikorn Chunchai
    • 3
  • Sakawdaurn Yasom
    • 4
  • Keerati Wanchai
    • 3
  • Panan Suntornsaratoon
    • 5
    • 6
  • Narattaphol Charoenphandhu
    • 5
    • 6
    • 7
  • Parameth Thiennimitr
    • 4
  • Nipon Chattipakorn
    • 3
  • Siriporn C. Chattipakorn
    • 2
    • 3
    • 8
  1. 1.Department of Orthodontics and Pediatric Dentistry, Faculty of DentistryChiang Mai UniversityChiang MaiThailand
  2. 2.Department of Oral Biology and Diagnostic Sciences, Faculty of DentistryChiang Mai UniversityChiang MaiThailand
  3. 3.Center of Excellence in Cardiac Electrophysiology Research, Faculty of MedicineChiang Mai UniversityChiang MaiThailand
  4. 4.Department of Microbiology, Faculty of MedicineChiang Mai UniversityChiang MaiThailand
  5. 5.Center of Calcium and Bone Research (COCAB), Faculty of ScienceMahidol UniversityBangkokThailand
  6. 6.Department of Physiology, Faculty of ScienceMahidol UniversityBangkokThailand
  7. 7.Institute of Molecular BiosciencesMahidol UniversityNakhon PathomThailand
  8. 8.Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of MedicineChiang Mai UniversityChiang MaiThailand

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