Journal of Gastrointestinal Infections

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VOLUME 8 , ISSUE 1 ( December, 2018 ) > List of Articles

REVIEW ARTICLE

Gut Microbiota and Human Health with Special Reference to Autoimmunity

Sujit Bharti, Pratibha Gavel, Gopal Nath

Keywords : Autoimmunity, Dysbiosis, Gut microbiome, Inflammatory bowel disease, Obesity

Citation Information : Bharti S, Gavel P, Nath G. Gut Microbiota and Human Health with Special Reference to Autoimmunity. J Gastrointest Infect 2018; 8 (1):32-38.

DOI: 10.5005/jp-journals-10068-0018

License: CC BY-NC 4.0

Published Online: 01-12-2018

Copyright Statement:  Copyright © 2018; The Author(s).


Abstract

Human body is basically composed of human and microbial cells. The microbial cells outnumber the human cells by 10 fold. These microbes are an integral part of human body residing on mucosal and skin surfaces. In this way, we have got two genomes. The gastrointestinal tract is the most significant niche for majority of the microbiota. Gut is considered as a huge fermenter producing a variety of metabolites/products affecting human health. Such products may be beneficial or harmful. Apart from different metabolic products, the microbes are speculated to be the trainers of the immune cells. Therefore, a particular time-point of colonization by specific type of microbes decides the fate of immunity, whether protective or detrimental. Dysbiosis may lead to a variety of metabolic, autoimmune and infectious diseases. In this review, we have focused on the issue of gut microbiota and its possible role in causation of different types of diseases, e.g., autoimmunity, asthma, obesity, etc. Further, we have looked into what can be done to modify this genome in favor of good health with change in diet, antibiotics, probiotics, bacteriophages, exercise, Ayurvedic Panch Karma-like practices, etc.


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  1. Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 2006 Feb;124(4):837-848.
  2. Helander HF, Fändriks L. Surface area of the digestive tractrevisited. Scand J Gastroenterol 2014 Jun;49(6):681-689.
  3. Patra VK, Byrne SN, Wolf P. The skin microbiome: is it affected by UV-induced immune suppression? Front Microbiol 2016 Aug;7:1235.
  4. Zhang YJ, Li S, Gan RY, Zhou T, Xu DP, Li HB. Impacts of gut bacteria on human health and diseases. Int J Mol Sci 2015 Apr;16(4):7493-7519.
  5. Bhargava P, Mowry EM. Gut microbiome and multiple sclerosis. Curr Neurol Neurosci Rep 2014 Oct;14(10):492.
  6. ESNM. Gut microbiota and early life. Vienna: ESNM; 2017. [cited 2017 Sep]. Available from: http://www.gutmicrobiotaforhealth. com/wpcontent/uploads/2017/09/GMFH_BEST_ OF_GUT_MICROBIOTA_EARLY_LIFE.pdf.
  7. Lozupone CA, Stombaugh J, Gonzalez A, Ackermann G, Wendel D, Vázquez-Baeza Y, Jansson JK, Gordon JI, Knight R. Meta-analyses of studies of the human microbiota. Genome Res 2013 Oct;23(10):1704-1714.
  8. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010 Mar;464(7285):59-65.
  9. Gordon JI, Dewey KG, Mills DA, Medzhitov RM. The human gut microbiota and undernutrition. Sci Transl Med 2012 Jun;4(137):137ps12.
  10. Mesquita DN, Barbieri MA, Goldani HA, Cardoso VC, Goldani MZ, Kac G, Silva AA, Bettiol H. Cesarean section is associated with increased peripheral and central adiposity in young adulthood: cohort study. PLoS One 2013 Jun;8(6):e66827.
  11. Gibbs BG, Forste R. Socioeconomic status, infant feeding practices and early childhood obesity. Pediatr Obes 2014 Apr;9(2):135-146.
  12. Cho I, Yamanishi S, Cox L, Methé BA, Zavadil J, Li K, Gao Z, Mahana D, Raju K, Teitler I, et al. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature 2012 Aug;488(7413):621-626.
  13. Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, Guiot Y, Derrien M, Muccioli GG, Delzenne NM, et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci U S A 2013 May;110(22):9066-9071.
  14. Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, Griffin NW, Lombard V, Henrissat B, Bain JR, et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 2013 Sep;341(6150):1241214.
  15. Smith MI, Yatsunenko T, Manary MJ, Trehan I, Mkakosya R, Cheng J, Kau AL, Rich SS, Concannon P, Mychaleckyj JC, et al. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science 2013 Feb;339(6119):548-554.
  16. Trehan I, Goldbach HS, LaGrone LN, Meuli GJ, Wang RJ, Maleta KM, Manary MJ. Antibiotics as part of the management of severe acute malnutrition. N Engl J Med 2013 Jan;368(5): 425-435.
  17. Hansen CH, Nielsen DS, Kverka M, Zakostelska Z, Klimesova K, Hudcovic T, Tlaskalova-Hogenova H, Hansen AK. Patterns of early gut colonization shape future immune responses of the host. PLoS One 2012 Mar;7(3):e34043.
  18. Cerutti A, Chen K, Chorny A. Immunoglobulin responses at the mucosal interface. Annu Rev Immunol 2011 Apr;29: 273-293.
  19. Olszak T, An D, Zeissig S, Vera MP, Richter J, Franke A, Glickman JN, Siebert R, Baron RM, Kasper DL, et al. Microbial exposure during early life has persistent effects on natural killer T cell function. Science 2012 Apr;336(6080):489-493.
  20. Schmidt AM, Lu W, Sindhava VJ, Huang Y, Burkhardt JK, Yang E, Riese MJ, Maltzman JS, Jordan MS, Kambayashi T. Regulatory T cells require TCR signaling for their suppressive function. J Immunol 2015 May;194(9):4362-4370.
  21. Russell SL, Gold MJ, Willing BP, Thorson L, McNagny KM, Finlay BB. Perinatal antibiotic treatment affects murine microbiota, immune responses and allergic asthma. Gut Microbes 2013 Mar;4(2):158-164.
  22. Hill DA, Siracusa MC, Abt MC, Kim BS, Kobuley D, Kubo M, Kambayashi T, Larosa DF, Renner ED, Orange JS, et al. Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation. Nat Med 2012 Mar;18(4):538-546.
  23. Cahenzli J, Koller Y, Wyss M, Geuking MB, McCoy KD. Intestinal microbial diversity during early-life colonization shapes long-term IgE levels. Cell Host Microbe 2013 Nov;14(5): 559-570.
  24. Hepworth MR, Fung TC, Masur SH, Kelsen JR, McConnell FM, Dubrot J, Withers DR, Hugues S, Farrar MA, Reith W, et al. Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4+ T cells. Science 2015 May;348(6238):1031-1035.
  25. Round JL, Mazmanian SK. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci U S A 2010 Jul;107(27): 12204-12209.
  26. Geuking MB, Cahenzli J, Lawson MA, Ng DC, Slack E, Hapfelmeier S, McCoy KD, Macpherson AJ. Intestinal bacterial colonization induces mutualistic regulatory T cell responses. Immunity 2011 May;34(5):794-806.
  27. Weiss JM, Bilate AM, Gobert M, Ding Y, Curotto LMA, Parkhurst CN, Xiong H, Dolpady J, Frey AB, Ruocco MG, et al. Neuropilin 1 is expressed on thymus-derived natural regulatory T cells, but not mucosa-generated induced Foxp3+ T reg cells. J Exp Med 2012 Sep;209(10):1723-1742.
  28. Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, Cheng G, Yamasaki S, Saito T, Ohba Y, et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 2011 Jan;331(6015):337-341.
  29. Ohnmacht C, Park JH, Cording S, Wing JB, Atarashi K, Obata Y, Gaboriau-Routhiau V, Marques R, Dulauroy S, Fedoseeva M, et al. Mucosal immunology. The microbiota regulates type 2 immunity through RORƒÁt+ T cells. Science 2015 Aug;349(6251):989-993.
  30. Sefik E, Geva-Zatorsky N, Oh S, Konnikova L, Zemmour D, McGuire AM, Burzyn D, Ortiz-Lopez A, Lobera M, Yang J, et al. Individual intestinal symbionts induce a distinct population of RORƒÁ+ regulatory T cells. Science 2015 Aug;349(6251):993-997.
  31. Yang BH, Hagemann S, Mamareli P, Lauer U, Hoffmann U, Beckstette M, Fohse L, Prinz I, Pezoldt J, Suerbaum S, et al. Foxp3(+) T cells expressing RORƒÁt represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation. Mucosal Immunol 2016 Mar;9(2):444-457.
  32. Lathrop SK, Bloom SM, Rao SM, Nutsch K, Lio CW, Santacruz N, Peterson DA, Stappenbeck TS, Hsieh CS. Peripheral education of the immune system by colonic commensal microbiota. Nature 2011 Sep;478(7368):250-254.
  33. Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 2005 Nov;6(11):1123-1132.
  34. Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Hood L, Zhu Z, Tian Q, Dong C. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 2005 Nov;6(11):1133-1141.
  35. Shabgah AG, Fattahi E, Shahneh FZ. Interleukin-17 in human inflammatory diseases. Post.py Dermatol Alergol 2014 Aug;31(4):256-261.
  36. Tesmer LA, Lundy SK, Sarkar S, Fox DA. Th17 cells in human disease. Immunol Rev 2008 Jun;223:87-113.
  37. Zenobia C, Hajishengallis G. Basic biology and role of interleukin- 17 in immunity and inflammation. Periodontol 2000 2015 Oct;69(1):142-159.
  38. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA, Cua DJ. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 2005 Jan;201(2):233-240.
  39. Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem 2003 Jan;278(3):1910-1914.
  40. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006 May;441(7090):235-238.
  41. Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B. TGF beta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 2006 Feb;24(2):179-189.
  42. St Leger AJ, Desai JV, Drummond A, Kugadas A, Almaghrabi F, Silver P, Raychaudhuri K, Gadjeva M, Iwakura Y, Lionakis MS, et al. An ocular commensal protects against corneal infection by driving an interleukin-17 response from mucosal ƒÁƒÂ t cells. Immunity 2017 Jul;47(1):148-158.
  43. Wu HJ, Wu E. The role of gut microbiota in immune homeostasis and autoimmunity. Gut Microbes 2012 Jan-Feb;3(1):4-14.
  44. Manfredo Vieira S, Hiltensperger M, Kumar V, Zegarra-Ruiz D, Dehner C, Khan N, Costa FR, Tiniakou E, Greiling T, Ruff W, et al. Translocation of a gut pathobiont drives autoimmunity in mice and humans. Science 2018 Mar;359(6380):1156-1161.
  45. Devkota S, Wang Y, Musch MW, Leone V, Fehlner-Peach H, Nadimpalli A, Antonopoulos DA, Jabri B, Chang EB. Dietaryfat- induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice. Nature 2012 Jul;487(7405):104-108.
  46. Small CL, Reid-Yu SA, McPhee JB, Coombes BK. Persistent infection with Crohn's disease-associated adherent-invasive Escherichia coli leads to chronic inflammation and intestinal fibrosis. Nat Commun 2013;4:1957.
  47. Scharschmidt TC, Vasquez KS, Truong HA, Gearty SV, Pauli ML, Nosbaum A, Gratz IK, Otto M, Moon JJ, Liese J5, et al. A wave of regulatory T cells into neonatal skin mediates tolerance to commensal microbes. Immunity 2015 Nov;43(5): 1011-1021.
  48. Frank DN, Robertson CE, Hamm CM, Kpadeh Z, Zhang T, Chen H, Zhu W, Sartor RB, Boedeker EC, Harpaz N, et al. Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases. Inflamm Bowel Dis 2011 Jan;17(1):179-184.
  49. Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C, Rostron T, Cerundolo V, Pamer EG, Abramson SB, et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife 2013 Nov;2:e01202.
  50. Gevers D, Kugathasan S, Denson LA, Vazquez-Baeza Y, Van Treuren W, Ren B, Schwager E, Knights D, Song SJ, Yassour M, et al. The treatment-naive microbiome in new-onset Crohn's disease. Cell Host Microbe 2014 Mar;15(3):382-392.
  51. Lodes MJ, Cong Y, Elson CO, Mohamath R, Landers CJ, Targan SR, Fort M, Hershberg RM. Bacterial flagellin is a dominant antigen in Crohn disease. J Clin Invest 2004 May;113(9): 1296-1306.
  52. Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature 2011 Jun;474(7351): 307-317.
  53. Aujnarain A, Mack DR, Benchimol EI. The role of the environment in the development of pediatric inflammatory bowel disease. Curr Gastroenterol Rep 2013 Jun;15(6):326.
  54. Bramhall M, Florez-Vargas O, Stevens R, Brass A, Cruickshank S. Quality of methods reporting in animal models of colitis. Inflamm Bowel Dis 2015 Jun;21(6):1248-1259.
  55. Kennedy RJ, Hoper M, Deodhar K, Erwin PJ, Kirk SJ, Gardiner KR. Interleukin 10-deficient colitis: new similarities to human inflammatory bowel disease. Br J Surg 2000 Oct;87(10): 1346-1351.
  56. Lin PW, Stoll BJ. Necrotising enterocolitis. Lancet 2006 Oct;368(9543):1271-1283.
  57. Obladen M. Necrotizing enterocolitis.150 years of fruitless search for the cause. Neonatology 2009 Apr;96(4):203-210.
  58. Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med 2011 Jan;364(3):255-264.
  59. Markel TA, Crisostomo PR, Wairiuko GM, Pitcher J, Tsai BM, Meldrum DR. Cytokines in necrotizing enterocolitis. Shock 2006 Apr;25(4):329-337.
  60. Sharma R, Tepas JJ 3rd, Hudak ML, Mollitt DL, Wludyka PS, Teng RJ, Premachandra BR. Neonatal gut barrier and multiple organ failure: role of endotoxin and proinflammatory cytokines in sepsis and necrotizing enterocolitis. J Pediatr Surg 2007 Mar;42(3):454-461.
  61. Maheshwari A, Schelonka RL, Dimmitt RA, Carlo WA, Munoz-Hernandez B, Das A, McDonald SA, Thorsen P, Skogstrand K, Hougaard DM, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Cytokines associated with necrotizing enterocolitis in extremely-low-birth-weight infants. Pediatr Res 2014 Jul;76(1):100-108.
  62. Bergmann KR, Liu SX, Tian R, Kushnir A, Turner JR, Li HL, Chou PM, Weber CR, De Plaen IG. Bifidobacteria stabilize claudins at tight junctions and prevent intestinal barrier dysfunction in mouse necrotizing enterocolitis. Am J Pathol 2013 May;182(5):1595-1606.
  63. Jakaitis BM, Denning PW. Commensal and probiotic bacteria may prevent NEC by maturing intestinal host defenses. Pathophysiology 2014 Feb;21(1):47-54.
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