Advertisement

Current Understanding of the Gut Microflora in Subjects with Nutrition-Associated Metabolic Disorder Such as Obesity and/or Diabetes: Is There Any Relevance with Oral Microflora?

Abstract

Purpose of Review

The oral cavity is one of the main gateways to the whole body and leads to the gastrointestinal tract. Both oral cavity and gastrointestinal tract have complex ecosystems of microorganisms called microbiota. Recent studies have shown that altered local microbiome in human, such as gut microflora, is associated with various systemic diseases. This review focuses on the association between the microbiota at local sites, such as gut and oral cavity, and the systemic diseases, especially nutrition-associated metabolic disorder, such as obesity and/or diabetes.

Recent Findings

The gut microbiota has a potential for regulation in host immune system and metabolisms, such as energy, glucose, and lipid, and is therefore an additional contributing environmental factor to the pathophysiology of obesity and diabetes as well as gut infectious inflammatory diseases. In addition, oral microorganisms play important roles as reservoirs for exacerbation of gut diseases, and altered oral microbial profiles causing periodontal diseases, which is one of common oral infectious diseases, has been also associated with several systemic diseases including diabetes.

Summary

It is necessary to consider that impaired oral microbiota, called oral dysbiosis, may affect the metabolic disorders leading to obesity and diabetes in addition to the gut inflammatory diseases via alteration of gut microflora. The relevance of oral microflora to gut dysbiosis leading to nutrition-associated metabolic disorder should be addressed as future investigations.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 99

This is the net price. Taxes to be calculated in checkout.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.

    Pascale A, Marchesi N, Marelli C, Coppola A, Luzi L, Govoni S, et al. Microbiota and metabolic diseases. Endocrine. 2018;61(3):357–71.

  2. 2.

    Le Bars P, Matamoros S, Montassier E, Le Vacon F, Potel G, Soueidan A, et al. The oral cavity microbiota: between health, oral disease, and cancers of the aerodigestive tract. Can J Microbiol. 2017;63(6):475–92.

  3. 3.

    Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 2016;14(8):e1002533.

  4. 4.

    •• Verma D, Garg PK, Dubey AK. Insights into the human oral microbiome. Arch Microbiol. 2018;200(4):525–40 This manuscript presents an insight of various associated aspects of the human oral microbiome and disbiotic oral microbiota.

  5. 5.

    Makki K, Deehan EC, Walter J, Backhed F. The impact of dietary fiber on gut microbiota in host health and disease. Cell Host Microbe. 2018;23(6):705–15.

  6. 6.

    Tap J, Mondot S, Levenez F, Pelletier E, Caron C, Furet JP, et al. Towards the human intestinal microbiota phylogenetic core. Environ Microbiol. 2009;11(10):2574–84.

  7. 7.

    Westfall S, Lomis N, Kahouli I, Dia SY, Singh SP, Prakash S. Microbiome, probiotics and neurodegenerative diseases: deciphering the gut brain axis. Cell Mol Life Sci. 2017;74(20):3769–87.

  8. 8.

    Nishijima S, Suda W, Oshima K, Kim SW, Hirose Y, Morita H, et al. The gut microbiome of healthy Japanese and its microbial and functional uniqueness. DNA Res. 2016;23(2):125–33.

  9. 9.

    Human Microbiome Project C. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486(7402):207–14.

  10. 10.

    Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59–65.

  11. 11.

    Salminen S, Bouley C, Boutron-Ruault MC, Cummings JH, Franck A, Gibson GR, et al. Functional food science and gastrointestinal physiology and function. Br J Nutr. 1998;80(Suppl 1):S147–71.

  12. 12.

    Rajilic-Stojanovic M, Smidt H, de Vos WM. Diversity of the human gastrointestinal tract microbiota revisited. Environ Microbiol. 2007;9(9):2125–36.

  13. 13.

    Schwarzer M, Makki K, Storelli G, Machuca-Gayet I, Srutkova D, Hermanova P, et al. Lactobacillus plantarum strain maintains growth of infant mice during chronic undernutrition. Science. 2016;351(6275):854–7.

  14. 14.

    Rescigno M. Intestinal microbiota and its effects on the immune system. Cell Microbiol. 2014;16(7):1004–13.

  15. 15.

    Backhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004;101(44):15718–23.

  16. 16.

    Schroeder BO, Backhed F. Signals from the gut microbiota to distant organs in physiology and disease. Nat Med. 2016;22(10):1079–89.

  17. 17.

    Schubert AM, Rogers MA, Ring C, Mogle J, Petrosino JP, Young VB, et al. Microbiome data distinguish patients with Clostridium difficile infection and non-C. difficile-associated diarrhea from healthy controls. MBio. 2014;5(3):e01021–14.

  18. 18.

    Sartor RB. Key questions to guide a better understanding of host-commensal microbiota interactions in intestinal inflammation. Mucosal Immunol. 2011;4(2):127–32.

  19. 19.

    Frank DN, Robertson CE, Hamm CM, Kpadeh Z, Zhang T, Chen H, et al. Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases. Inflamm Bowel Dis. 2011;17(1):179–84.

  20. 20.

    Mayer EA, Savidge T, Shulman RJ. Brain-gut microbiome interactions and functional bowel disorders. Gastroenterology. 2014;146(6):1500–12.

  21. 21.

    Grenham S, Clarke G, Cryan JF, Dinan TG. Brain-gut-microbe communication in health and disease. Front Physiol. 2011;2:94.

  22. 22.

    Marra F, Marra CA, Richardson K, Lynd LD, Kozyrskyj A, Patrick DM, et al. Antibiotic use in children is associated with increased risk of asthma. Pediatrics. 2009;123(3):1003–10.

  23. 23.

    Kalliomaki M, Collado MC, Salminen S, Isolauri E. Early differences in fecal microbiota composition in children may predict overweight. Am J Clin Nutr. 2008;87(3):534–8.

  24. 24.

    Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012;490(7418):55–60.

  25. 25.

    Karlsson FH, Tremaroli V, Nookaew I, Bergstrom G, Behre CJ, Fagerberg B, et al. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature. 2013;498(7452):99–103.

  26. 26.

    Pear SM, Williamson TH, Bettin KM, Gerding DN, Galgiani JN. Decrease in nosocomial Clostridium difficile-associated diarrhea by restricting clindamycin use. Ann Intern Med. 1994;120(4):272–7.

  27. 27.

    Chang JY, Antonopoulos DA, Kalra A, Tonelli A, Khalife WT, Schmidt TM, et al. Decreased diversity of the fecal Microbiome in recurrent Clostridium difficile-associated diarrhea. J Infect Dis. 2008;197(3):435–8.

  28. 28.

    Weingarden AR, Chen C, Bobr A, Yao D, Lu Y, Nelson VM, et al. Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection. Am J Physiol Gastrointest Liver Physiol. 2014;306(4):G310–9.

  29. 29.

    Sorg JA, Sonenshein AL. Bile salts and glycine as cogerminants for Clostridium difficile spores. J Bacteriol. 2008;190(7):2505–12.

  30. 30.

    Theriot CM, Koenigsknecht MJ, Carlson PE Jr, Hatton GE, Nelson AM, Li B, et al. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection. Nat Commun. 2014;5:3114.

  31. 31.

    Jernberg C, Lofmark S, Edlund C, Jansson JK. Long-term ecological impacts of antibiotic administration on the human intestinal microbiota. ISME J. 2007;1(1):56–66.

  32. 32.

    Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, et al. Host-gut microbiota metabolic interactions. Science. 2012;336(6086):1262–7.

  33. 33.

    Hernandez-Doria JD, Sperandio V. Nutrient and chemical sensing by intestinal pathogens. Microbes Infect. 2013;15(12):759–64.

  34. 34.

    den Besten G, van Eunen K, 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(9):2325–40.

  35. 35.

    Macfarlane S, Macfarlane GT. Regulation of short-chain fatty acid production. Proc Nutr Soc. 2003;62(1):67–72.

  36. 36.

    Fukuda S, Toh H, Hase K, Oshima K, Nakanishi Y, Yoshimura K, et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature. 2011;469(7331):543–7.

  37. 37.

    • Jacobson A, Lam L, Rajendram M, Tamburini F, Honeycutt J, Pham T, et al. A gut commensal-produced metabolite mediates colonization resistance to Salmonella infection. Cell Host Microbe. 2018;24(2):296–307 e7 This manuscript represents mechanism of colonization resistance of Salmonella infecction, via gut commensal-produced metabolite.

  38. 38.

    Wostmann BS, Larkin C, Moriarty A, Bruckner-Kardoss E. Dietary intake, energy metabolism, and excretory losses of adult male germfree Wistar rats. Lab Anim Sci. 1983;33(1):46–50.

  39. 39.

    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(7122):1027–31.

  40. 40.

    Jumpertz R, Le DS, Turnbaugh PJ, Trinidad C, Bogardus C, Gordon JI, et al. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am J Clin Nutr. 2011;94(1):58–65.

  41. 41.

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

  42. 42.

    Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, et al. A core gut microbiome in obese and lean twins. Nature. 2009;457(7228):480–4.

  43. 43.

    Rosenbaum M, Knight R, Leibel RL. The gut microbiota in human energy homeostasis and obesity. Trends Endocrinol Metab. 2015;26(9):493–501.

  44. 44.

    Bauer PV, Hamr SC, Duca FA. Regulation of energy balance by a gut-brain axis and involvement of the gut microbiota. Cell Mol Life Sci. 2016;73(4):737–55.

  45. 45.

    van de Wouw M, Schellekens H, Dinan TG, Cryan JF. Microbiota-gut-brain axis: modulator of host metabolism and appetite. J Nutr. 2017;147(5):727–45.

  46. 46.

    Bliss ES, Whiteside E. The gut-brain axis, the human gut microbiota and their integration in the development of obesity. Front Physiol. 2018;9:900.

  47. 47.

    Klingbeil E, de La Serre CB. Microbiota modulation by eating patterns and diet composition: impact on food intake. Am J Phys Regul Integr Comp Phys. 2018;315(6):R1254–R60.

  48. 48.

    Kaelberer MM, Buchanan KL, Klein ME, Barth BB, Montoya MM, Shen X, et al. A gut-brain neural circuit for nutrient sensory transduction. Science. 2018;361(6408):eaat5236.

  49. 49.

    Kocelak P, Zak-Golab A, Zahorska-Markiewicz B, Aptekorz M, Zientara M, Martirosian G, et al. Resting energy expenditure and gut microbiota in obese and normal weight subjects. Eur Rev Med Pharmacol Sci. 2013;17(20):2816–21.

  50. 50.

    Musso G, Gambino R, Cassader M. Obesity, diabetes, and gut microbiota: the hygiene hypothesis expanded? Diabetes Care. 2010;33(10):2277–84.

  51. 51.

    Tremaroli V, Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012;489(7415):242–9.

  52. 52.

    Duca FA, Lam TK. Gut microbiota, nutrient sensing and energy balance. Diabetes Obes Metab. 2014;16(Suppl 1):68–76.

  53. 53.

    Zhang X, Shen D, Fang Z, Jie Z, Qiu X, Zhang C, et al. Human gut microbiota changes reveal the progression of glucose intolerance. PLoS One. 2013;8(8):e71108.

  54. 54.

    Bouter KE, van Raalte DH, Groen AK, Nieuwdorp M. Role of the gut microbiome in the pathogenesis of obesity and obesity-related metabolic dysfunction. Gastroenterology. 2017;152(7):1671–8.

  55. 55.

    Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500(7464):541–6.

  56. 56.

    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. 2016;65(3):426–36.

  57. 57.

    Udayappan SD, Kovatcheva-Datchary P, Bakker GJ, Havik SR, Herrema H, Cani PD, et al. Intestinal Ralstonia pickettii augments glucose intolerance in obesity. PLoS One. 2017;12(11):e0181693.

  58. 58.

    Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci U S A. 2013;110(22):9066–71.

  59. 59.

    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. 2017;23(1):107–13.

  60. 60.

    Creely SJ, McTernan PG, Kusminski CM, Fisher f M, Da Silva NF, Khanolkar M, et al. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am J Physiol Endocrinol Metab. 2007;292(3):E740–7.

  61. 61.

    Gummesson A, Carlsson LM, Storlien LH, Backhed F, Lundin P, Lofgren L, et al. Intestinal permeability is associated with visceral adiposity in healthy women. Obesity (Silver Spring). 2011;19(11):2280–2.

  62. 62.

    Troseid M, Nestvold TK, Rudi K, Thoresen H, Nielsen EW, Lappegard KT. Plasma lipopolysaccharide is closely associated with glycemic control and abdominal obesity: evidence from bariatric surgery. Diabetes Care. 2013;36(11):3627–32.

  63. 63.

    Forslund K, Hildebrand F, Nielsen T, Falony G, Le Chatelier E, Sunagawa S, et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015;528(7581):262–6.

  64. 64.

    Kreznar JH, Keller MP, Traeger LL, Rabaglia ME, Schueler KL, Stapleton DS, et al. Host genotype and gut microbiome modulate insulin secretion and diet-induced metabolic phenotypes. Cell Rep. 2017;18(7):1739–50.

  65. 65.

    Vrieze A, Van Nood E, Holleman F, Salojarvi J, Kootte RS, Bartelsman JF, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143(4):913–6 e7.

  66. 66.

    Kang Y, Cai Y. Gut microbiota and obesity: implications for fecal microbiota transplantation therapy. Hormones (Athens). 2017;16(3):223–34.

  67. 67.

    Brunkwall L, Orho-Melander M. The gut microbiome as a target for prevention and treatment of hyperglycaemia in type 2 diabetes: from current human evidence to future possibilities. Diabetologia. 2017;60(6):943–51.

  68. 68.

    Ejtahed HS, Angoorani P, Hasani-Ranjbar S, Siadat SD, Ghasemi N, Larijani B, et al. Adaptation of human gut microbiota to bariatric surgeries in morbidly obese patients: a systematic review. Microb Pathog. 2018;116:13–21.

  69. 69.

    Park S, Bae JH. Probiotics for weight loss: a systematic review and meta-analysis. Nutr Res. 2015;35(7):566–75.

  70. 70.

    Kristensen NB, Bryrup T, Allin KH, Nielsen T, Hansen TH, Pedersen O. Alterations in fecal microbiota composition by probiotic supplementation in healthy adults: a systematic review of randomized controlled trials. Genome Med. 2016;8(1):52.

  71. 71.

    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(4):291–303.

  72. 72.

    McFarlin BK, Henning AL, Bowman EM, Gary MA, Carbajal KM. Oral spore-based probiotic supplementation was associated with reduced incidence of post-prandial dietary endotoxin, triglycerides, and disease risk biomarkers. World J Gastrointest Pathophysiol. 2017;8(3):117–26.

  73. 73.

    Meijnikman AS, Gerdes VE, Nieuwdorp M, Herrema H. Evaluating causality of gut microbiota in obesity and diabetes in humans. Endocr Rev. 2018;39(2):133–53.

  74. 74.

    • Zmora N, Zilberman-Schapira G, Suez J, Mor U, Dori-Bachash M, Bashiardes S, et al. Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features. Cell. 2018;174(6):1388–405 e21 This manuscript presents the role of inter-individual variations of gut microbiota on colonization efficacy of probiotics in human for the first time.

  75. 75.

    Lira-Junior R, Bostrom EA. Oral-gut connection: one step closer to an integrated view of the gastrointestinal tract? Mucosal Immunol. 2018;11(2):316–8.

  76. 76.

    Kilian M, Chapple IL, Hannig M, Marsh PD, Meuric V, Pedersen AM, et al. The oral microbiome—an update for oral healthcare professionals. Br Dent J. 2016;221(10):657–66.

  77. 77.

    Bik EM, Eckburg PB, Gill SR, Nelson KE, Purdom EA, Francois F, et al. Molecular analysis of the bacterial microbiota in the human stomach. Proc Natl Acad Sci U S A. 2006;103(3):732–7.

  78. 78.

    Blaser MJ. The microbiome revolution. J Clin Invest. 2014;124(10):4162–5.

  79. 79.

    Dewhirst FE, Chen T, Izard J, Paster BJ, Tanner AC, Yu WH, et al. The human oral microbiome. J Bacteriol. 2010;192(19):5002–17.

  80. 80.

    Poveda-Roda R, Jimenez Y, Carbonell E, Gavalda C, Margaix-Munoz MM, Sarrion-Perez G. Bacteremia originating in the oral cavity. A review. Med Oral Patol Oral Cir Bucal. 2008;13(6):E355–62.

  81. 81.

    Menon T, Gopalakrishnan SN, Balasubramanian R, Justin SR. Characterisation of the human oral microbiome in patients with coronary artery disease using next-generation sequencing of 16SrRNA amplicons. Indian J Med Microbiol. 2017;35(1):101–4.

  82. 82.

    Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D, et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med. 2015;21(8):895–905.

  83. 83.

    Said HS, Suda W, Nakagome S, Chinen H, Oshima K, Kim S, et al. Dysbiosis of salivary microbiota in inflammatory bowel disease and its association with oral immunological biomarkers. DNA Res. 2014;21(1):15–25.

  84. 84.

    Qin N, Yang F, Li A, Prifti E, Chen Y, Shao L, et al. Alterations of the human gut microbiome in liver cirrhosis. Nature. 2014;513(7516):59–64.

  85. 85.

    Kostic AD, Chun E, Robertson L, Glickman JN, Gallini CA, Michaud M, et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe. 2013;14(2):207–15.

  86. 86.

    Bashir A, Miskeen AY, Hazari YM, Asrafuzzaman S, Fazili KM. Fusobacterium nucleatum, inflammation, and immunity: the fire within human gut. Tumour Biol. 2016;37(3):2805–10.

  87. 87.

    Arimatsu K, Yamada H, Miyazawa H, Minagawa T, Nakajima M, Ryder MI, et al. Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota. Sci Rep. 2014;4:4828.

  88. 88.

    Kojima A, Nakano K, Wada K, Takahashi H, Katayama K, Yoneda M, et al. Infection of specific strains of Streptococcus mutans, oral bacteria, confers a risk of ulcerative colitis. Sci Rep. 2012;2:332.

  89. 89.

    Ayars GH, Altman LC, Fretwell MD. Effect of decreased salivation and pH on the adherence of Klebsiella species to human buccal epithelial cells. Infect Immun. 1982;38(1):179–82.

  90. 90.

    Barbosa FC, Mayer MP, Saba-Chujfi E, Cai S. Subgingival occurrence and antimicrobial susceptibility of enteric rods and pseudomonads from Brazilian periodontitis patients. Oral Microbiol Immunol. 2001;16(5):306–10.

  91. 91.

    Atarashi K, Suda W, Luo C, Kawaguchi T, Motoo I, Narushima S, et al. Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction and inflammation. Science. 2017;358(6361):359–65.

  92. 92.

    Souto R, Colombo AP. Detection of Helicobacter pylori by polymerase chain reaction in the subgingival biofilm and saliva of non-dyspeptic periodontal patients. J Periodontol. 2008;79(1):97–103.

  93. 93.

    Yoshizawa JM, Schafer CA, Schafer JJ, Farrell JJ, Paster BJ, Wong DT. Salivary biomarkers: toward future clinical and diagnostic utilities. Clin Microbiol Rev. 2013;26(4):781–91.

  94. 94.

    Mimee M, Citorik RJ, Lu TK. Microbiome therapeutics—advances and challenges. Adv Drug Deliv Rev. 2016;105(Pt A):44–54.

  95. 95.

    Strauss J, Kaplan GG, Beck PL, Rioux K, Panaccione R, Devinney R, et al. Invasive potential of gut mucosa-derived Fusobacterium nucleatum positively correlates with IBD status of the host. Inflamm Bowel Dis. 2011;17(9):lee1971–8.

Download references

Author information

Correspondence to Hiromichi Yumoto.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

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

This article is part of the Topical Collection on Oral Disease and Nutrition

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Yumoto, H., Uebanso, T., Shimohata, T. et al. Current Understanding of the Gut Microflora in Subjects with Nutrition-Associated Metabolic Disorder Such as Obesity and/or Diabetes: Is There Any Relevance with Oral Microflora?. Curr Oral Health Rep 6, 100–109 (2019). https://doi.org/10.1007/s40496-019-0221-7

Download citation

Keywords

  • Oral microflora
  • Gut microflora
  • Dysbiosis
  • Metabolic disorder
  • Obesity
  • Diabetes