Journal of Gastrointestinal Infections

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VOLUME 5 , ISSUE 1 ( 2015 ) > List of Articles

REVIEW ARTICLE

Gut microbiome dysbiosis in metabolic disorders: implications for probiotics as prospective investigational new drugs

Baljinder Kaur, Praveen P. Balgir

Keywords : Dysbiosis, malnutrition, metagenome, microbiome, probiotic

Citation Information : Kaur B, Balgir PP. Gut microbiome dysbiosis in metabolic disorders: implications for probiotics as prospective investigational new drugs. J Gastrointest Infect 2015; 5 (1):5-12.

DOI: 10.5005/jp-jogi-5-1-5

License: CC BY-SA 4.0

Published Online: 01-06-2015

Copyright Statement:  Copyright © 2015; The Author(s).


Abstract

Gut microbiome has been analysed using metagenomics approach which combines the power of genomics, bioinformatics, and systems biology, providing new ways to access the microbial world. Gut microbiome evolves from the pre-birth exposure onwards in a child, as a result of its interaction with its environment; and is apparently influenced by various environmental factors all through the life, most important being diet and its composition. Metagenomic analysis of gut microbial communities of a malnourished and a healthy child revealed an abundance of enteric pathogens leading to intestinal inflammation and nutrient malabsorption. The change in diet from vegetarian to non-vegetarian also influences the composition and dynamics of the intestinal microbes. Gut microbiota have been observed to vary with age due to physiological changes in the gastrointestinal tract, modifications in lifestyle, nutritional behavior and weakened functionality of the host immune system. Studies in apparently healthy individuals and patients suffering from intestinal or metabolic disorders revealed differential microbiome compositions, proving that an imbalance of gut microflora leads to dysbiosis which is the major cause of metabolic disorders such as irritable bowel syndrome (IBS), obesity, diarrhea, etc. The investigational studies are trying to assess the relationship between intestinal microbiota dysbiosis and various metabolic diseases. Nutritional interventions in the form of probiotics and prebiotics as investigational new drugs (INDs) are being assessed for correcting dysbiosis in disease states. The current paper focuses on the recent knowledge and databases for the same with pointers to future investigations as the need of the hour studies.


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  1. Herbel SR, Vahjen W, Wieler LH, Guenther S. Timely approaches to identify probiotic species of the genus Lactobacillus. Gut Pathog. 2013;5:27.
  2. Palmer C, Bik EM, Digiulio DB, Relman DA, Brown PO. Development of the human infant intestinal microbiota. PLoS Biol. 2007;5:e177.
  3. Zoetendal EG, Rajilic-Stojanovic M, de Vos WM. High-throughput diversity and functionality analysis of the gastrointestinal tract microbiota. Gut. 2008;57:1605-15.
  4. O'Toole PW, Claesson MJ. Gut microbiota: Changes throughout the lifespan from infancy to elderly. Int Dairy J. 2010;20:281-91.
  5. Dethlefsen L, Huse S, Sogin ML, Relman DA. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol. 2008;6:e280.
  6. Raes J, Foerstner KU, Bork P. Get the most out of your metagenome: Computational analysis of environmental sequence data. Curr Opin Microbiol. 2007;10:490-8.
  7. Manichanh C. Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach. Gut. 2006; 55:205-11.
  8. Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermudez-Humaran LG, Gratadoux J-J, et al. Faecalibacterium prausnitzii is an antiinflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci USA. 2008;16731-6.
  9. Koenig J, Spor A, Scalfone N, Fricker A, Stombaugh J, Knight R, et al. Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci USA. 2011;108:4578-85.
  10. Emerson BC, Gillespie RG. Phylogenetic analysis of community assembly and structure over space and time. Trends Ecol Evol. 2008;23:619-30.
  11. Cavender-Bares J, Kozak KH, Fine PV, Kembel SW. The merging of community ecology and phylogenetic biology. Ecol Lett. 2009;12:693-715.
  12. Favier CF, Vaughan EE, De Vos WM, Akkermans AD. Molecular monitoring of succession of bacterial communities in human neonates. Appl Environ Microbiol. 2002;68:219-26.
  13. Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Trans Med 2009;1:6ra14-6ra14. doi: 10.1126/scitranslmed.3000322.
  14. David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2012;505:559-63.
  15. Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI. Human nutrition, the gut microbiome and the immune system. Nature 2011;474:327-36.
  16. Gupta SS, Mohammed MH, Ghosh TS, Kanungo S, Nair GB, Mande SS, et al. Metagenome of the gut of a malnourished child. Gut Pathog 2011;3:7.
  17. Lawley TD, Walker AW. Intestinal colonization resistance. Immunol. 2013;138:1-11.
  18. Morgan XC, Segata N, Huttenhower C. Biodiversity and functional genomics in the human microbiome. Trends Genet. 2012;29:51-58.
  19. He M, Miyajima F, Roberts P, Ellison L, Pickard DJ, Martin MJ, et al. Emergence and global spread of epidemic healthcare associated Clostridium difficile. Nat Genet. 2013;45:109-13.
  20. Clements ACA, Magalhes RJS, Tatem AJ, Paterson DL, Riley TV. Clostridium difficile PCR ribotype 027: assessing the risks of further worldwide spread. Lancet Infect Dis. 2010;10:395-404.
  21. Sekirov I, Russell SL, Antunes LCM, Finlay BB. Gut microbiota in health and disease. Physiol Rev. 2010;90:859-904.
  22. Borody TJ, Khoruts A. Fecal microbiota transplantation and emerging applications. Nat Rev Gastroenterol Hepatol. 2012;9:88-96.
  23. 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;464:59-65.
  24. Fraher MH, O'Toole PW, Quigley EMM. Techniques used to characterize the gut microbiota: a guide for the clinician. Nat Rev Gastroenterol Hepatol. 2012;9:312-22.
  25. Dave M, Higgins PD, Middha S, Rioux KP. The human gut microbiome: current knowledge, challenges, and future directions. Transl Res. 2012;160:246-57.
  26. Maurice CF, Haiser HJ, Turnbaugh PJ. Xenobiotics shape the physiology and gene expression of the active human gut microbiome. Cell. 2013;52:39-50.
  27. Turnbaugh PJ, RE Ley, Mahowald MA, Magrini V, Mardis ER, Gordon JI, et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027- 31.
  28. 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;457:480-4.
  29. Duncan SH, Lobley GE, Holtrop G, Ince J, Johnstone AM, Louis P, et al. Human colonic microbiota associated with diet, obesity and weight loss. Int J Obesity. 2008;32:1720-4.
  30. Schwiertz A, Tara D, Schafer K, Beijer S, Bos NA, Donus C et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity. 2010;18:190-5.
  31. Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci USA. 2007;104:13780-5.
  32. Kotlowski R, Bernstein CN, Sepehri S, Krause DO. High prevalence of Escherichia coli belonging to the B2+D phylogenetic group in inflammatory bowel disease. Gut. 2007; 56:669-75.
  33. Claesson MJ, Cusack S, O'Sullivan O, Greene-Diniz R, de Weerd H, Flannery E, et al. Composition, variability, and temporal stability of the intestinal microbiota of the elderly. PNAS. 2011;108:4586-91.
  34. Collado MC. Role of Probiotics in Health and Diseases. In: Lee, K.L. & Salminen, S. (eds) Handbook of Probiotics and Prebiotics. 2nd edn. John Wiley and Sons, 2009.
  35. Food and Agriculture Organization of the United States. Health and Nutritional Properties of Probiotics in Food Including Powdered Milk With Live Lactic Acid Bacteria. http://www.who. int/foodsafety/publications/fs_management/en/probiotics. pdf. 2001.
  36. Sonnenburg J, Fischbach M. Community health care: therapeutic opportunities in the human microbiome. Sci Transl Med. 2011; 3:78ps12. doi: 10.1126/scitranslmed.3001626
  37. O'Toole P, Cooney J. Probiotic bacteria influence the composition and function of the intestinal microbiota. Interdiscip Perspect Infect Dis. 2008;2008:175-85.
  38. Spinler J, Taweechotipatr M, Rognerud C, Ou C, Tumwasorn S, Versalovic J. Human derived probiotic Lactobacillus reuteri demonstrate antimicrobial activities targeting diverse enteric bacterial pathogens. Anaerobe. 2008;14:166-71.
  39. O'Shea E, Cotter P, Stanton C, Ross R, Hill C. Production of bioactive substances by intestinal bacteria as a basis for explaining probiotic mechanisms: bacteriocins and conjugated linoleic acid. Int J Food Microbiol. 2012;152:189-205.
  40. Collado M, Meriluoto J, Salminen S. Role of commercial probiotic strains against human pathogen adhesion to intestinal mucus. Lett Appl Microbiol. 2007;45:454-60.
  41. Lee B, Bak Y. Irritable bowel syndrome, gut microbiota and probiotics. J Neurogastroenterol Motil. 2011;17:252-66.
  42. Thomas C, Hong T, Van Pijkeren J, Hemarajata P, Trin D, Hu W et al. Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of Pka and Erk signaling. PLoS ONE. 2012;7:e31951. doi: 10.1371/journal.pone.0031951.
  43. Bron P, Van Baarlen P, Kleerebezem M. Emerging molecular insights into the interaction between probiotics and the host intestinal mucosa. Nat Rev Microbiol. 2011;10:66-78.
  44. Nobaek S, Johansson M, Molin G, Ahrne S, Jeppsson B. Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in patients with irritable bowel syndrome. Am J Gastroenterol. 2000;95:1231-8.
  45. Ki Cha B, Mun Jung S, Hwan Choi C, Song I, Woong Lee H, Joon Kim H, et al. The effect of a multispecies probiotic mixture on the symptoms and fecal microbiota in diarrhea-dominant irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. J Clin Gastroenterol. 2011;46:220-7.
  46. Cox M, Huang Y, Fujimura K, Liu J, McKean M, Boushey H. et al. Lactobacillus casei abundance is associated with profound shifts in the infant gut microbiome. PLoS One 2010;5: e8745. doi: 10.1371/journal.pone.0008745.
  47. Preidis G, Saulnier D, Blutt S, Mistretta T, Riehle K, Major A. et al. Probiotics stimulate enterocyte migration and microbial diversity in the neonatal mouse intestine. FASEB J. 2012;26: 1960-9.
  48. Hoffman FA. Development of Probiotics as Biologic Drugs. Clin Infect Dis. 2008;46:S125-S127.
  49. Lepay DA. Emerging issues in FDA's oversight of clinical research. Presented at the Food and Drug Administration Science Board Meeting, 16 November 2001.
  50. List developed by the California Dairy Research Foundation (January 2012) available at http://cdrf.org/home/checkoffinvestments/ usprobiotics/products-with probiotics/# commercial http://cdrf.org/home/checkoff-investments/usprobiotics/ products-with-probiotics/#commercial.
  51. Nagao F, Nakayama M, Muto T, Okumura K. Effects of a fermented milk drink containing Lactobacillus casei strain Shirota on the immune system in healthy human subjects. Biosci Biotechnol Biochem. 2000;64:2706-8.
  52. Sgouras D, Maragkoudakis P, Petraki K, Martinez-Gonzalez B, Eriotou E, Michopoulos S, Mentis 00C1. In vitro and in vivo inhibition of Helicobacter pylori by Lactobacillus casei strain Shirota. Appl Environ Microbiol. 2004;70:518-26.
  53. Lee JW, Kim EH, Yim IB, Joo HG. Immunomodulatory and antitumor effects in vivo by the cytoplasmic fraction of Lactobacillus casei and Bifidobacterium longum. J Vet Sci. 2004; 5:41-8.
  54. Bouvier M, Meance S, Bouley C, Berta JL, Grimaud JC. Effects of consumption of a milk fermented by the probiotic Bifidobacterium animalis DN-173 010 on colonic transit time in healthy humans. Biosci Microflora. 2001;20:43-8.
  55. Marteau P, Cuillerier E, Meance S, Gerhardt MF, Myara A, Bouvier M, et al. Bifidobacterium animalis, strain DN-173 010 shortens the colonic transit time in healthy women. A double-blind randomised controlled study. Aliment Pharmacol Ther. 2002;16:587-93.
  56. Nishida S, Ishikawa Y, Iino H. Effect of Bifidobacterium lactis DN- 173 010 on the Intestinal Transit Time, the Condition of Defecation and Intestinal Microflora: A Randomized, Double-blind, Placebocontrolled, Cross-over Study among Healthy Japanese Women. Pharmacometrics. 2008;74:99-106.
  57. Guyonnet D, Schlumberger A, Mhamdi L, Jakob S, Chassany O. Fermented milk containing Bifidobacterium lactis DN-173 010 improves gastrointestinal well-being and digestive symptoms in women reporting minor digestive symptoms: a randomized, double-blind, parallel, controlled study. Br J Nut. 2009;102:1654- 62.
  58. Doron S, Snydman DR, Gorbach SL. Lactobacillus GG: bacteriology and clinical applications. Gastroenterol Clin North Am. 2005;34:483-98.
  59. Kekkonen RA, Lummela N, Karjalainen H, Latvala S, Tynkkynen S, Jarvenpaa S et al. Probiotic intervention has strain-specific anti-inflammatory effects in healthy adults., World J Gastroenterol. 2008;14:2029-36.
  60. Lebeer S, Claesa I, Tytgata HLP, Verhoevena TLA, Mariena E, von Ossowski I et al. Functional analysis of the pili of Lactobacillus rhamnosus GG in relation to adhesion and immunomodulatory interactions with intestinal epithelial cells. Appl Environ Microbiol. 2012;78:185-93.
  61. Arunachalam K, Gill HS, Chandra RK. Enhancement of natural immune function by dietary consumption of Bifidobacterium lactis (HN019). Eur J Clin Nutr. 2000;54:263-7.
  62. Gill HS, Rutherfurd KJ, Cross ML. Dietary probiotic supplementation enhances natural killer cell activity in the elderly: an investigation of age-related immunological changes. J Clin Immunology. 2001;21:264-71.
  63. Ahmed M, Prasad J, Gill H, Stevenson L, Gopal P. Impact of consumption of different levels of Bifidobacterium lactis HN019 on the intestinal microflora of elderly human subjects. J Nutr Health Aging. 2007;11:26-31.
  64. Waller PA, Gopal PK, Leyer GJ, Ouwehand AC, Reifer C, Stewart ME, Miller LE. Dose-response effect of Bifidobacterium lactis HN019 on whole gut transit time and functional gastrointestinal symptoms in adults. Scand J Gastro. 2011;46:1057-64.
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