Advertisement

Current HIV/AIDS Reports

, Volume 16, Issue 3, pp 204–213 | Cite as

HIV and the Gut Microbiota: Composition, Consequences, and Avenues for Amelioration

  • Ivan Vujkovic-CvijinEmail author
  • Ma SomsoukEmail author
HIV Pathogenesis and Treatment (AL Landay and NS Utay, Section Editors)
Part of the following topical collections:
  1. Topical Collection on HIV Pathogenesis and Treatment

Abstract

Purpose of Review

We discuss recent advances in understanding of gut bacterial microbiota composition in HIV-infected subjects and comment on controversies. We discuss the putative effects of microbiota shifts on systemic inflammation and HIV disease progression and potential mechanisms, as well as ongoing strategies being developed to modulate the gut microbiota in humans for amelioration of infectious and inflammatory diseases.

Recent Findings

Lifestyle and behavioral factors relevant to HIV infection studies have independent effects on the microbiota. Microbial metabolism of immunomodulatory compounds and direct immune stimulation by translocation of microbes are putative mechanisms contributing to HIV disease. Fecal microbiota transplantation, microbial enzyme inhibition, phage therapy, and rationally selected probiotic cocktails have emerged as promising strategies for microbiota modulation.

Summary

Numerous surveys of the HIV gut microbiota matched for lifestyle factors suggest consistent shifts in gut microbiota composition among HIV-infected subjects. Evidence exists for a complex pathogenic role of the gut microbiota in HIV disease progression, warranting further study.

Keywords

Gut microbiota Fecal transplant Engraftment HIV Inflammation 

Notes

Acknowledgements

I.V.C. received support from the Cancer Research Institute Irvington Postdoctoral Fellowship Award.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts 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.

References

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

  1. 1.
    Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 2009;139(3):485–98.Google Scholar
  2. 2.
    Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science. 2011;331(6015):337–41.Google Scholar
  3. 3.
    Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science. 2012;336(6086):1268–73.Google Scholar
  4. 4.
    Kamada N, Seo SU, Chen GY, Nunez G. Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol. 2013;13(5):321–35.Google Scholar
  5. 5.
    Deeks SG, Tracy R, Douek DC. Systemic effects of inflammation on health during chronic HIV infection. Immunity. 2013;39(4):633–45.Google Scholar
  6. 6.
    Kuller LH, Tracy R, Belloso W, De Wit S, Drummond F, Lane HC, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 2008;5(10):e203.Google Scholar
  7. 7.
    Kalayjian RC, Machekano RN, Rizk N, Robbins GK, Gandhi RT, Rodriguez BA, et al. Pretreatment levels of soluble cellular receptors and interleukin-6 are associated with HIV disease progression in subjects treated with highly active antiretroviral therapy. J Infect Dis. 2010;201(12):1796–805.Google Scholar
  8. 8.
    Deeks SG, Kitchen CMR, Liu L, Guo H, Gascon R, Narváez AB, et al. Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load. Blood. 2004;104(4):942–7.Google Scholar
  9. 9.
    Giorgi JV, Hultin LE, McKeating JA, Johnson TD, Owens B, Jacobson LP, et al. Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. J Infect Dis. 1999;179(4):859–70.Google Scholar
  10. 10.
    Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006;12(12):1365–71.Google Scholar
  11. 11.
    Lohse N, Hansen A-BE, Pedersen G, Kronborg G, Gerstoft J, Sørensen HT, et al. Survival of persons with and without HIV infection in Denmark, 1995--2005. Ann Intern Med. 2007;146(2):87–95.Google Scholar
  12. 12.
    Neuhaus J, Jacobs DR Jr, Baker JV, Calmy A, Duprez D, La Rosa A, et al. Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection. J Infect Dis. 2010;201(12):1788–95.Google Scholar
  13. 13.
    Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368(17):1575–84.Google Scholar
  14. 14.
    Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013;19(5):576–85.Google Scholar
  15. 15.
    Alejos B, Hernando V, Lopez-Aldeguer J, Segura F, Oteo JA, Rubio R, et al. Overall and cause-specific mortality in HIV-positive subjects compared to the general population. J Int AIDS Soc. 2014;17(4 Suppl 3):19711.Google Scholar
  16. 16.
    Serrano-Villar S, Sainz T, Lee SA, Hunt PW, Sinclair E, Shacklett BL, et al. HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality. PLoS Pathog. 2014;10(5):e1004078.Google Scholar
  17. 17.
    Hunt PW, Sinclair E, Rodriguez B, Shive C, Clagett B, Funderburg N, et al. Gut epithelial barrier dysfunction and innate immune activation predict mortality in treated HIV infection. J Infect Dis. 2014;210:1228–38.Google Scholar
  18. 18.
    Hatano H, Jain V, Hunt PW, Lee TH, Sinclair E, Do TD, et al. Cell-based measures of viral persistence are associated with immune activation and programmed cell death protein 1 (PD-1)-expressing CD4+ T cells. J Infect Dis. 2013;208(1):50–6.Google Scholar
  19. 19.
    Li Q, Duan L, Estes JD, Ma ZM, Rourke T, Wang Y, et al. Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells. Nature. 2005;434(7037):1148–52.Google Scholar
  20. 20.
    Brenchley JM, Paiardini M, Knox KS, Asher AI, Cervasi B, Asher TE, et al. Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood. 2008;112(7):2826–35.Google Scholar
  21. 21.
    Favre D, Lederer S, Kanwar B, Ma ZM, Proll S, Kasakow Z, et al. Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection. PLoS Pathog. 2009;5(2):e1000295.Google Scholar
  22. 22.
    Kok A, Hocqueloux L, Hocini H, Carriere M, Lefrou L, Guguin A, et al. Early initiation of combined antiretroviral therapy preserves immune function in the gut of HIV-infected patients. Mucosal Immunol. 2015;8(1):127–40.Google Scholar
  23. 23.
    Eyerich K, Dimartino V, Cavani A. IL-17 and IL-22 in immunity: driving protection and pathology. Eur J Immunol. 2017;47(4):607–14.Google Scholar
  24. 24.
    Chevalier MF, Petitjean G, Dunyach-Remy C, Didier C, Girard PM, Manea ME, et al. The Th17/Treg ratio, IL-1RA and sCD14 levels in primary HIV infection predict the T-cell activation set point in the absence of systemic microbial translocation. PLoS Pathog. 2013;9(6):e1003453.Google Scholar
  25. 25.
    Ryan ES, Micci L, Fromentin R, Paganini S, McGary CS, Easley K, et al. Loss of function of intestinal IL-17 and IL-22 producing cells contributes to inflammation and viral persistence in SIV-infected rhesus macaques. PLoS Pathog. 2016;12(2):e1005412.Google Scholar
  26. 26.
    Marchetti G, Tincati C, Silvestri G. Microbial translocation in the pathogenesis of HIV infection and AIDS. Clin Microbiol Rev. 2013;26(1):2–18.Google Scholar
  27. 27.
    Shacklett BL, Anton PA. HIV infection and gut mucosal immune function: updates on pathogenesis with implications for management and intervention. Curr Infect Dis Rep. 2010;12(1):19–27.Google Scholar
  28. 28.
    Chitre AS, Kattah MG, Rosli YY, Pao M, Deswal M, Deeks SG, et al. A20 upregulation during treated HIV disease is associated with intestinal epithelial cell recovery and function. PLoS Pathog. 2018;14(3):e1006806.Google Scholar
  29. 29.
    Estes JD, Harris LD, Klatt NR, Tabb B, Pittaluga S, Paiardini M, et al. Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections. PLoS Pathog. 2010;6(8):e1001052.Google Scholar
  30. 30.
    Somsouk M, Estes JD, Deleage C, Dunham RM, Albright R, Inadomi JM, et al. Gut epithelial barrier and systemic inflammation during chronic HIV infection. AIDS. 2015;29(1):43–51.Google Scholar
  31. 31.
    Klatt NR, Estes JD, Sun X, Ortiz AM, Barber JS, Harris LD, et al. Loss of mucosal CD103+ DCs and IL-17+ and IL-22+ lymphocytes is associated with mucosal damage in SIV infection. Mucosal Immunol. 2012;5(6):646–57.Google Scholar
  32. 32.
    Zaragoza MM, Sankaran-Walters S, Canfield DR, Hung JK, Martinez E, Ouellette AJ, et al. Persistence of gut mucosal innate immune defenses by enteric alpha-defensin expression in the simian immunodeficiency virus model of AIDS. J Immunol. 2011;186(3):1589–97.Google Scholar
  33. 33.
    Allers K, Fehr M, Conrad K, Epple HJ, Schurmann D, Geelhaar-Karsch A, et al. Macrophages accumulate in the gut mucosa of untreated HIV-infected patients. J Infect Dis. 2014;209(5):739–48.Google Scholar
  34. 34.
    Salzman NH, Hung K, Haribhai D, Chu H, Karlsson-Sjoberg J, Amir E, et al. Enteric defensins are essential regulators of intestinal microbial ecology. Nat Immunol. 2010;11(1):76–83.Google Scholar
  35. 35.
    Kumar P, Monin L, Castillo P, Elsegeiny W, Horne W, Eddens T, et al. Intestinal Interleukin-17 receptor signaling mediates reciprocal control of the gut microbiota and autoimmune inflammation. Immunity. 2016;44(3):659–71.Google Scholar
  36. 36.
    Garrett WS, Lord GM, Punit S, Lugo-Villarino G, Mazmanian SK, Ito S, et al. Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell. 2007;131(1):33–45.Google Scholar
  37. 37.
    Garrett WS, Gallini CA, Yatsunenko T, Michaud M, DuBois A, Delaney ML, et al. Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. Cell Host Microbe. 2010;8(3):292–300.Google Scholar
  38. 38.
    Armstrong AJS, Shaffer M, Nusbacher NM, Griesmer C, Fiorillo S, Schneider JM, et al. An exploration of Prevotella-rich microbiomes in HIV and men who have sex with men. Microbiome. 2018;6(1):198.Google Scholar
  39. 39.
    Dillon SM, Lee EJ, Kotter CV, Austin GL, Dong Z, Hecht DK, et al. An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia. Mucosal Immunol. 2014;7(4):983–94.Google Scholar
  40. 40.
    Dinh DM, Volpe GE, Duffalo C, Bhalchandra S, Tai AK, Kane AV, et al. Intestinal microbiota, microbial translocation, and systemic inflammation in chronic HIV infection. J Infect Dis. 2015;211(1):19–27.Google Scholar
  41. 41.
    Lu W, Feng Y, Jing F, Han Y, Lyu N, Liu F, et al. Association between gut microbiota and CD4 recovery in HIV-1 infected patients. Front Microbiol. 2018;9:1451.Google Scholar
  42. 42.
    Lozupone CA, Li M, Campbell TB, Flores SC, Linderman D, Gebert MJ, et al. Alterations in the gut microbiota associated with HIV-1 infection. Cell Host Microbe. 2013;14(3):329–39.Google Scholar
  43. 43.
    Ling Z, Jin C, Xie T, Cheng Y, Li L, Wu N. Alterations in the fecal microbiota of patients with HIV-1 infection: an observational study in a Chinese population. Sci Rep. 2016;6:30673.Google Scholar
  44. 44.
    Lee SC, Chua LL, Yap SH, Khang TF, Leng CY, Raja Azwa RI, et al. Enrichment of gut-derived fusobacterium is associated with suboptimal immune recovery in HIV-infected individuals. Sci Rep. 2018;8(1):14277.Google Scholar
  45. 45.
    Monaco CL, Gootenberg DB, Zhao G, Handley SA, Ghebremichael MS, Lim ES, et al. Altered virome and bacterial microbiome in human immunodeficiency virus-associated acquired immunodeficiency syndrome. Cell Host Microbe. 2016;19(3):311–22.Google Scholar
  46. 46.
    McHardy IH, Li X, Tong M, Ruegger P, Jacobs J, Borneman J, et al. HIV infection is associated with compositional and functional shifts in the rectal mucosal microbiota. Microbiome. 2013;1(1):26.Google Scholar
  47. 47.
    Mutlu EA, Keshavarzian A, Losurdo J, Swanson G, Siewe B, Forsyth C, et al. A compositional look at the human gastrointestinal microbiome and immune activation parameters in HIV infected subjects. PLoS Pathog. 2014;10(2):e1003829.Google Scholar
  48. 48.
    •• Noguera-Julian M, Rocafort M, Guillen Y, Rivera J, Casadella M, Nowak P, et al. Gut microbiota linked to sexual preference and HIV infection. EBioMedicine. 2016;5:135–46. This paper (along with Kelley et al.) demonstrated microbiota differences between MSM and non-MSM, highlighting the importance of matching subject groups by sexual orientation. Google Scholar
  49. 49.
    Nowak P, Troseid M, Avershina E, Barqasho B, Neogi U, Holm K, et al. Gut microbiota diversity predicts immune status in HIV-1 infection. AIDS. 2015;29(18):2409–18.Google Scholar
  50. 50.
    Vujkovic-Cvijin I, Dunham RM, Iwai S, Maher MC, Albright RG, Broadhurst MJ, et al. Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism. Sci Transl Med. 2013;5(193):193ra91.Google Scholar
  51. 51.
    • Vazquez-Castellanos JF, Serrano-Villar S, Latorre A, Artacho A, Ferrus ML, Madrid N, et al. Altered metabolism of gut microbiota contributes to chronic immune activation in HIV-infected individuals. Mucosal Immunol. 2015;8(4):760–72. This paper investigated stool metabolite profiles of HIV-infected and uninfected subjects, finding that kynurenine pathway enzymatic products were enriched in stool of HIV-infected subjects. Google Scholar
  52. 52.
    San-Juan-Vergara H, Zurek E, Ajami NJ, Mogollon C, Pena M, Portnoy I, et al. A Lachnospiraceae-dominated bacterial signature in the fecal microbiota of HIV-infected individuals from Colombia, South America. Sci Rep. 2018;8(1):4479.Google Scholar
  53. 53.
    Yu G, Fadrosh D, Ma B, Ravel J, Goedert JJ. Anal microbiota profiles in HIV-positive and HIV-negative MSM. AIDS. 2014;28(5):753–60.Google Scholar
  54. 54.
    Zhou Y, Ou Z, Tang X, Zhou Y, Xu H, Wang X, et al. Alterations in the gut microbiota of patients with acquired immune deficiency syndrome. J Cell Mol Med. 2018;22(4):2263–71.Google Scholar
  55. 55.
    Dubourg G, Lagier JC, Hüe S, et al. Gut microbiota associated with HIV infection is significantly enriched in bacteria tolerant to oxygen. BMJ Open Gastroenterol. 2016;3(1):e000080.  https://doi.org/10.1136/bmjgast-2016-000080.
  56. 56.
    Sun Y, Ma Y, Lin P, et al. Fecal bacterial microbiome diversity in chronic HIV-infected patients in China. Emerg Microbes Infect. 2016;5(4):e31.  https://doi.org/10.1038/emi.2016.25.
  57. 57.
    Vesterbacka J, Rivera J, Noyan K, et al. Richer gut microbiota with distinct metabolic profile in HIV infected Elite Controllers. Sci Rep. 2017;7(1):6269.  https://doi.org/10.1038/s41598-017-06675-1.
  58. 58.
    Hoel H, Hove-Skovsgaard M, Hov JR, Gaardbo JC, Holm K, Kummen M, et al. Impact of HIV and type 2 diabetes on gut microbiota diversity, tryptophan catabolism and endothelial dysfunction. Sci Rep. 2018;8(1):6725.Google Scholar
  59. 59.
    Winter SE, Winter MG, Xavier MN, Thiennimitr P, Poon V, Keestra AM, et al. Host-derived nitrate boosts growth of E. coli in the inflamed gut. Science. 2013;339(6120):708–11.Google Scholar
  60. 60.
    Winter SE, Thiennimitr P, Winter MG, Butler BP, Huseby DL, Crawford RW, et al. Gut inflammation provides a respiratory electron acceptor for Salmonella. Nature. 2010;467(7314):426–9.Google Scholar
  61. 61.
    Deleage C, Schuetz A, Alvord WG, Johnston L, Hao XP, Morcock DR, et al. Impact of early cART in the gut during acute HIV infection. JCI Insight. 2016;1(10).Google Scholar
  62. 62.
    Mahjoub-Messai F, Bidet P, Caro V, Diancourt L, Biran V, Aujard Y, et al. Escherichia coli isolates causing bacteremia via gut translocation and urinary tract infection in young infants exhibit different virulence genotypes. J Infect Dis. 2011;203(12):1844–9.Google Scholar
  63. 63.
    O'Boyle CJ, MacFie J, Mitchell CJ, Johnstone D, Sagar PM, Sedman PC. Microbiology of bacterial translocation in humans. Gut. 1998;42(1):29–35.Google Scholar
  64. 64.
    Steffen EK, Berg RD, Deitch EA. Comparison of translocation rates of various indigenous bacteria from the gastrointestinal tract to the mesenteric lymph node. J Infect Dis. 1988;157(5):1032–8.Google Scholar
  65. 65.
    Ortiz AM, Flynn JK, DiNapoli SR, Vujkovic-Cvijin I, Starke CE, Lai SH, et al. Experimental microbial dysbiosis does not promote disease progression in SIV-infected macaques. Nat Med. 2018;24(9):1313–6.Google Scholar
  66. 66.
    Amato KR, Yeoman CJ, Cerda G, Schmitt CA, Cramer JD, Miller ME, et al. Variable responses of human and non-human primate gut microbiomes to a Western diet. Microbiome. 2015;3:53.Google Scholar
  67. 67.
    McKenna P, Hoffmann C, Minkah N, Aye PP, Lackner A, Liu Z, et al. The macaque gut microbiome in health, lentiviral infection, and chronic enterocolitis. PLoS Pathog. 2008;4(2):e20.Google Scholar
  68. 68.
    Nagpal R, Wang S, Solberg Woods LC, Seshie O, Chung ST, Shively CA, et al. Comparative microbiome signatures and short-chain fatty acids in mouse, rat, non-human primate, and human feces. Front Microbiol. 2018;9:2897.Google Scholar
  69. 69.
    Glavan TW, Gaulke CA, Santos Rocha C, Sankaran-Walters S, Hirao LA, Raffatellu M, et al. Gut immune dysfunction through impaired innate pattern recognition receptor expression and gut microbiota dysbiosis in chronic SIV infection. Mucosal Immunol. 2016;9(3):677–88.Google Scholar
  70. 70.
    Klase Z, Ortiz A, Deleage C, Mudd JC, Quinones M, Schwartzman E, et al. Dysbiotic bacteria translocate in progressive SIV infection. Mucosal Immunol. 2015;8(5):1009–20.Google Scholar
  71. 71.
    Vujkovic-Cvijin I, Swainson LA, Chu SN, Ortiz AM, Santee CA, Petriello A, et al. Gut-resident Lactobacillus abundance associates with IDO1 inhibition and Th17 dynamics in SIV-infected macaques. Cell Rep. 2015;13(8):1589–97.Google Scholar
  72. 72.
    Chen L, Wilson JE, Koenigsknecht MJ, Chou WC, Montgomery SA, Truax AD, et al. NLRP12 attenuates colon inflammation by maintaining colonic microbial diversity and promoting protective commensal bacterial growth. Nat Immunol. 2017;18(5):541–51.Google Scholar
  73. 73.
    Truax AD, Chen L, Tam JW, Cheng N, Guo H, Koblansky AA, et al. The inhibitory innate immune sensor NLRP12 maintains a threshold against obesity by regulating gut microbiota homeostasis. Cell Host Microbe. 2018;24(3):364–78 e6.Google Scholar
  74. 74.
    Desvignes L, Ernst JD. Interferon-gamma-responsive nonhematopoietic cells regulate the immune response to Mycobacterium tuberculosis. Immunity. 2009;31(6):974–85.Google Scholar
  75. 75.
    Favre D, Mold J, Hunt PW, Kanwar B, Loke P, Seu L, et al. Tryptophan catabolism by indoleamine 2,3-dioxygenase 1 alters the balance of TH17 to regulatory T cells in HIV disease. Sci Transl Med. 2010;2(32):32ra6.Google Scholar
  76. 76.
    Routy JP, Mehraj V, Vyboh K, Cao W, Kema I, Jenabian MA. Clinical relevance of kynurenine pathway in HIV/AIDS: an immune checkpoint at the crossroads of metabolism and inflammation. AIDS Rev. 2015;17(2):96–106.Google Scholar
  77. 77.
    Serrano-Villar S, Rojo D, Martinez-Martinez M, Deusch S, Vazquez-Castellanos JF, Sainz T, et al. HIV infection results in metabolic alterations in the gut microbiota different from those induced by other diseases. Sci Rep. 2016;6:26192.Google Scholar
  78. 78.
    Lamas B, Richard ML, Leducq V, Pham H-P, Michel M-L, Da Costa G, et al. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat Med. 2016;22(6):598–605.Google Scholar
  79. 79.
    Zelante T, Iannitti RG, Cunha C, De Luca A, Giovannini G, Pieraccini G, et al. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity. 2013;39(2):372–85.Google Scholar
  80. 80.
    Rothhammer V, Mascanfroni ID, Bunse L, Takenaka MC, Kenison JE, Mayo L, et al. Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat Med. 2016;22(6):586–97.Google Scholar
  81. 81.
    Atarashi K, Tanoue T, Oshima K, Suda W, Nagano Y, Nishikawa H, et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature. 2013;500(7461):232–6.Google Scholar
  82. 82.
    • Desai MS, Seekatz AM, Koropatkin NM, Kamada N, Hickey CA, Wolter M, et al. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell. 2016;167(5):1339–53. e21. This study demonstrated the importance of dietary fiber fermentation by the gut microbiota (which produces short-chain fatty acids) in preventing gut mucosal inflammation. Google Scholar
  83. 83.
    • Rivera-Chavez F, Zhang LF, Faber F, Lopez CA, Byndloss MX, Olsan EE, et al. Depletion of butyrate-producing Clostridia from the gut microbiota drives an aerobic luminal expansion of Salmonella. Cell Host Microbe. 2016;19(4):443–54. This study found that loss of SCFA-producing microbes creates a niche for Enterobacteriaceae and facilitates their promotion of inflammation. Google Scholar
  84. 84.
    Singh SB, Lin HC. Hydrogen sulfide in physiology and diseases of the digestive tract. Microorganisms. 2015;3(4):866–89.Google Scholar
  85. 85.
    Ijssennagger N, van der Meer R, van Mil SWC. Sulfide as a mucus barrier-breaker in inflammatory bowel disease? Trends Mol Med. 2016;22(3):190–9.Google Scholar
  86. 86.
    Guo FF, Yu TC, Hong J, Fang JY. Emerging roles of hydrogen sulfide in inflammatory and neoplastic colonic diseases. Front Physiol. 2016;7:156.Google Scholar
  87. 87.
    Hunt PW. Th17, gut, and HIV: therapeutic implications. Curr Opin HIV AIDS. 2010;5:189–93.Google Scholar
  88. 88.
    •• Kelley CF, Kraft CS, de Man TJ, Duphare C, Lee HW, Yang J, et al. The rectal mucosa and condomless receptive anal intercourse in HIV-negative MSM: implications for HIV transmission and prevention. Mucosal Immunol. 2017;10(4):996–1007. This study concurrently supported the aforementioned conclusion of Noguera-Julian et al. Google Scholar
  89. 89.
    McFarland LV, Elmer GW, Surawicz CM. Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile disease. Am J Gastroenterol. 2002;97(7):1769–75.Google Scholar
  90. 90.
    van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368(5):407–15.Google Scholar
  91. 91.
    Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis. 2011;53(10):994–1002.Google Scholar
  92. 92.
    Brandt LJ, Aroniadis OC, Mellow M, Kanatzar A, Kelly C, Park T, et al. Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012;107(7):1079–87.Google Scholar
  93. 93.
    Ihunnah C, Kelly C, Hohmann E, Brandt LJ, Khoruts A, Stollman N, et al. Fecal microbiota transplantation (FMT) for treatment of Clostridium difficile infection (CDI) in immunocompromised patients. Am J Gastroenterol. 2013;1745628(ACG Abstract).Google Scholar
  94. 94.
    Elopre L, Rodriguez M. Fecal microbiota therapy for recurrent Clostridium difficile infection in HIV-infected persons. Ann Intern Med. 2013;158(10):779–80.Google Scholar
  95. 95.
    Vujkovic-Cvijin I, Rutishauser RL, Pao M, Hunt PW, Lynch SV, McCune JM, et al. Limited engraftment of donor microbiome via one-time fecal microbial transplantation in treated HIV-infected individuals. Gut Microbes. 2017;8(5):440–50.Google Scholar
  96. 96.
    • Costello SP, Hughes PA, Waters O, Bryant RV, Vincent AD, Blatchford P, et al. Effect of fecal microbiota transplantation on 8-week remission in patients with ulcerative colitis: a randomized clinical trial. JAMA. 2019;321(2):156–64. This study found that multi-dose anaerobically-prepared healthy donor stool in the context of fecal microbiota transplant effectively induced remission of ulcerative colitis in a subset of subjects. Google Scholar
  97. 97.
    Rossen NG, Fuentes S, van der Spek MJ, Tijssen JG, Hartman JH, Duflou A, et al. Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis. Gastroenterology. 2015;149(1):110–8 e4.Google Scholar
  98. 98.
    Moayyedi P, Surette MG, Kim PT, Libertucci J, Wolfe M, Onischi C, et al. Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology. 2015;149(1):102–9 e6.Google Scholar
  99. 99.
    Rothschild D, Weissbrod O, Barkan E, Kurilshikov A, Korem T, Zeevi D, et al. Environment dominates over host genetics in shaping human gut microbiota. Nature. 2018;555(7695):210–5.Google Scholar
  100. 100.
    David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559–63.Google Scholar
  101. 101.
    Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334(6052):105–8.Google Scholar
  102. 102.
    Duncan SH, Belenguer A, Holtrop G, Johnstone AM, Flint HJ, Lobley GE. Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces. Appl Environ Microbiol. 2007;73(4):1073–8.Google Scholar
  103. 103.
    Kim MS, Hwang SS, Park EJ, Bae JW. Strict vegetarian diet improves the risk factors associated with metabolic diseases by modulating gut microbiota and reducing intestinal inflammation. Environ Microbiol Rep. 2013;5(5):765–75.Google Scholar
  104. 104.
    • Wang Z, Roberts AB, Buffa JA, Levison BS, Zhu W, Org E, et al. Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis. Cell. 2015;163(7):1585–95. This study demonstrated efficacy of targeting microbial enzymes with small molecules to block pathogenic functions of the microbiota, a novel strategy to alter human health by modulating the microbiota. Google Scholar
  105. 105.
    Stein JH, Hsue PY. Inflammation, immune activation, and CVD risk in individuals with HIV infection. JAMA. 2012;308(4):405–6.Google Scholar
  106. 106.
    Missailidis C, Neogi U, Stenvinkel P, Troseid M, Nowak P, Bergman P. The microbial metabolite trimethylamine-N-oxide in association with inflammation and microbial dysregulation in three HIV cohorts at various disease stages. AIDS. 2018;32(12):1589–98.Google Scholar
  107. 107.
    • Zhu W, Winter MG, Byndloss MX, Spiga L, Duerkop BA, Hughes ER, et al. Precision editing of the gut microbiota ameliorates colitis. Nature. 2018;553(7687):208–11. This study demonstrated efficacy of targeting fundamental microbial metabolic pathways with small molecules to specifically delete pro-inflammatory Enterobacteriaceae from the microbiota. Google Scholar
  108. 108.
    Kutter E, De Vos D, Gvasalia G, Alavidze Z, Gogokhia L, Kuhl S, et al. Phage therapy in clinical practice: treatment of human infections. Curr Pharm Biotechnol. 2010;11(1):69–86.Google Scholar
  109. 109.
    Sulakvelidze A, Alavidze Z, Morris JG Jr. Bacteriophage therapy. Antimicrob Agents Chemother. 2001;45(3):649–59.Google Scholar
  110. 110.
    Atterbury RJ. Bacteriophage biocontrol in animals and meat products. Microb Biotechnol. 2009;2(6):601–12.Google Scholar
  111. 111.
    Miller RW, Skinner EJ, Sulakvelidze A, Mathis GF, Hofacre CL. Bacteriophage therapy for control of necrotic enteritis of broiler chickens experimentally infected with Clostridium perfringens. Avian Dis. 2010;54(1):33–40.Google Scholar
  112. 112.
    de Melo AG, Levesque S, Moineau S. Phages as friends and enemies in food processing. Curr Opin Biotechnol. 2018;49:185–90.Google Scholar
  113. 113.
    Buttimer C, McAuliffe O, Ross RP, Hill C, O'Mahony J, Coffey A. Bacteriophages and bacterial plant diseases. Front Microbiol. 2017;8:34.Google Scholar
  114. 114.
    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.Google Scholar
  115. 115.
    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.Google Scholar
  116. 116.
    Hempel S, Newberry SJ, Maher AR, Wang Z, Miles JN, Shanman R, et al. Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. JAMA. 2012;307(18):1959–69.Google Scholar
  117. 117.
    Ford AC, Quigley EM, Lacy BE, Lembo AJ, Saito YA, Schiller LR, et al. Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis. Am J Gastroenterol. 2014;109(10):1547–61 quiz 6, 62.Google Scholar
  118. 118.
    • Buffie CG, Bucci V, Stein RR, Mckenney PT, Ling L, Gobourne A, et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature. 2015;517(7533):205–8. This study identified gut bacteria that were anti-correlated with a pro-inflammatory gut bacterium ( C. difficile ), and demonstrated that anti-correlates were competitors and could be used to eliminate the pro-inflammatory bacterium in the context of exogenous supplementation. Google Scholar
  119. 119.
    Seres Therapeutics announces initiation of SER-287 Phase 2B ECO-RESET Clinical Study for Ulcerative Colitis [press release]. Seres Therapeutics, Inc.2019.Google Scholar
  120. 120.
    Nature paper by team at RIKEN and Vedanta shows efficacy of candidate in autoimmune diseases [press release]. Vedanta Biosciences, Inc.2013.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Metaorganism Immunity Section, National Institute of Allergy & Infectious DiseaseNational Institutes of HealthBethesdaUSA
  2. 2.Division of GastroenterologyUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations