Abstract
Purpose of Review
Thriving microbiome research for the past few years is providing new insights into biological mechanisms guiding human health and/or disease states. In this review, we will highlight the recent literature providing further evidence for the central role that the microbiota plays in association with the human host.
Recent Findings
The host microbiota, both bacteria and fungi, with their collective genome (metagenome) and metabolites (metabolome) play a key role in health and disease states. We now have enough evidence that there are strong relationships and multidirectional interactions between the human host and the commensal bacterial, fungal, and viral inhabitants.
Summary
Microbiome research has been at the forefront of research as a potential future target for precision medicine with the development of novel diagnostic assays and treatment approaches. Ongoing investigations are still unraveling the mechanisms by which such organisms contribute to health and disease.
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References
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
Chen Y, Zhao Y, Cheng Q, Wu D, Liu H. The Role of Intestinal Microbiota in Acute Graft- versus-Host Disease. Journal of immunology research. 2015;2015:145859.
Manzo VE, Bhatt AS. The human microbiome in hematopoiesis and hematologic disorders. Blood. 2015;126(3):311–8.
Arthur JC, Jobin C. The struggle within: microbial influences on colorectal cancer. Inflammatory bowel diseases. 2011;17(1):396–409.
Breban M. Gut microbiota and inflammatory joint diseases. Joint, bone, spine: revue du rhumatisme. 2016.
Doycheva I, Leise MD, Watt KD. The Intestinal Microbiome and the Liver Transplant Recipient: What We Know and What We Need to Know. Transplantation. 2016;100(1):61–8.
Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013;155(7):1451–63.
Jangi S, Gandhi R, Cox LM, Li N, von Glehn F, Yan R, et al. Alterations of the human gut microbiome in multiple sclerosis. Nature communications. 2016;7:12015.
Nallu A, Sharma S, Ramezani A, Muralidharan J, Raj D. Gut microbiome in chronic kidney disease: challenges and opportunities. Transl Res. 2016.
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.
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.
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. Scientific reports. 2016;6:26192.
Stefka AT, Feehley T, Tripathi P, Qiu J, McCoy K, Mazmanian SK, et al. Commensal bacteria protect against food allergen sensitization. Proceedings of the National Academy of Sciences of the United States of America. 2014;111(36):13145–50.
Suhr MJ, Banjara N, Hallen-Adams HE. Sequence-based methods for detecting and evaluating the human gut mycobiome. Letters in applied microbiology. 2016;62(3):209–15.
Zilberman-Schapira G, Zmora N, Itav S, Bashiardes S, Elinav H, Elinav E. The gut microbiome in human immunodeficiency virus infection. BMC medicine. 2016;14(1):83.
Vieira AT, Fukumori C, Ferreira CM. New insights into therapeutic strategies for gut microbiota modulation in inflammatory diseases. Clinical & translational immunology. 2016;5(6):e87.
Levy M, Blacher E, Elinav E. Microbiome, metabolites and host immunity. Current opinion in microbiology. 2016;35:8–15.
•• Ghannoum MA, Jurevic RJ, Mukherjee PK, Cui F, Sikaroodi M, Naqvi A, et al. Characterization of the oral fungal microbiome (mycobiome) in healthy individuals. PLoS pathogens. 2010;6(1):e1000713. The authors used next generation sequencing approaches to characterize the oral fungal mycobiome in healthy individuals.
Findley K, Oh J, Yang J, Conlan S, Deming C, Meyer JA, et al. Topographic diversity of fungal and bacterial communities in human skin. Nature. 2013;498(7454):367–70.
Iliev ID, Funari VA, Taylor KD, Nguyen Q, Reyes CN, Strom SP, et al. Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science (New York). 2012;336(6086):1314–7.
Mukherjee PK, Sendid B, Hoarau G, Colombel JF, Poulain D, Ghannoum MA. Mycobiota in gastrointestinal diseases. Nature reviews Gastroenterology & hepatology. 2015;12(2):77–87.
Ostaff MJ, Stange EF, Wehkamp J. Antimicrobial peptides and gut microbiota in homeostasis and pathology. EMBO molecular medicine. 2013;5(10):1465–83.
Singh B, Qin N, Reid G. Microbiome Regulation of Autoimmune, Gut and Liver Associated Diseases. Inflammation & allergy drug targets. 2015;14(2):84–93.
Suhr MJ, Hallen-Adams HE. The human gut mycobiome: pitfalls and potentials--a mycologist's perspective. Mycologia. 2015;107(6):1057–73.
•• Mukherjee PK, Chandra J, Retuerto M, Sikaroodi M, Brown RE, Jurevic R, et al. Oral mycobiome analysis of HIV-infected patients: identification of Pichia as an antagonist of opportunistic fungi. PLoS pathogens. 2014;10(3):e1003996. The authors identified an interaction amongst members of the oral fungal community through the secretion of a product that could also serve as a potential novel antifungal agent.
Brown RE, Ghannoum MA, Mukherjee PK, Gillevet PM, Sikaroodi M. Quorum-sensing dysbiotic shifts in the HIV-infected oral metabiome. PloS one. 2015;10(4):e0123880.
Lu H, Wu Z, Xu W, Yang J, Chen Y, Li L. Intestinal microbiota was assessed in cirrhotic patients with hepatitis B virus infection. Intestinal microbiota of HBV cirrhotic patients. Microbial ecology. 2011;61(3):693–703.
Chen Y, Chen Z, Guo R, Chen N, Lu H, Huang S, et al. Correlation between gastrointestinal fungi and varying degrees of chronic hepatitis B virus infection. Diagnostic microbiology and infectious disease. 2011;70(4):492–8.
Dollive S, Chen YY, Grunberg S, Bittinger K, Hoffmann C, Vandivier L, et al. Fungi of the murine gut: episodic variation and proliferation during antibiotic treatment. PloS one. 2013;8(8):e71806.
Kelly CR, Khoruts A, Staley C, Sadowsky MJ, Abd M, Alani M, et al. Effect of Fecal Microbiota Transplantation on Recurrence in Multiply Recurrent Clostridium difficile Infection: A Randomized Trial. Annals of internal medicine. 2016;165(9):609–16.
Rohlke F, Surawicz CM, Stollman N. Fecal flora reconstitution for recurrent Clostridium difficile infection: results and methodology. Journal of clinical gastroenterology. 2010;44(8):567–70.
Young VB. Therapeutic manipulation of the microbiota: past, present, and considerations for the future. Clin Microbiol Infect. 2016.
Jin Y, Wu Y, Zeng Z, Jin C, Wu S, Wang Y, et al. From the Cover: Exposure to Oral Antibiotics Induces Gut Microbiota Dysbiosis Associated with Lipid Metabolism Dysfunction and Low-Grade Inflammation in Mice. Toxicological sciences: an official journal of the Society of Toxicology. 2016;154(1):140–52.
Wang WL, Xu SY, Ren ZG, Tao L, Jiang JW, Zheng SS. Application of metagenomics in the human gut microbiome. World journal of gastroenterology. 2015;21(3):803–14.
Imhann F, Vich Vila A, Bonder MJ, Fu J, Gevers D, Visschedijk MC, et al. Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease. Gut. 2016.
•• Hoarau G, Mukherjee PK, Gower-Rousseau C, Hager C, Chandra J, Retuerto MA, et al. Bacteriome and Mycobiome Interactions Underscore Microbial Dysbiosis in Familial Crohn's Disease. mBio. 2016;7(5). The authors identify specific inter-kingdom correlations between bacteria and fungi in the gut microbiota using in vitro biofilms in Crohn’s Disease.
Ghannoum M. Cooperative Evolutionary Strategy between the Bacteriome and Mycobiome. mBio. 2016;7(6).
Zwolinska-Wcislo M, Brzozowski T, Budak A, Kwiecien S, Sliwowski Z, Drozdowicz D, et al. Effect of Candida colonization on human ulcerative colitis and the healing of inflammatory changes of the colon in the experimental model of colitis ulcerosa. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society. 2009;60(1):107–18.
Samuel S, Loftus Jr EV, Sandborn WJ. The effects of itraconazole on inflammatory bowel disease activity in patients treated for histoplasmosis. Alimentary pharmacology & therapeutics. 2010;32(9):1207–9.
Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(31):11070–5.
Furet JP, Kong LC, Tap J, Poitou C, Basdevant A, Bouillot JL, et al. Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: links with metabolic and low- grade inflammation markers. Diabetes. 2010;59(12):3049–57.
Schwiertz A, Taras D, Schafer K, Beijer S, Bos NA, Donus C, et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring, Md). 2010;18(1):190–5.
Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science (New York). 2011;334(6052):105–8.
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.
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. Proceedings of the National Academy of Sciences of the United States of America. 2004;101(44):15718–23.
Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science (New York). 2013;341(6150):1241214.
Tilg H, Cani PD, Mayer EA. Gut microbiome and liver diseases. Gut. 2016.
Burcelin R, Cani PD, Knauf C. Glucagon-like peptide-1 and energy homeostasis. The Journal of nutrition. 2007;137(11 Suppl):2534s–8s.
Cani PD, Delzenne NM. Gut microflora as a target for energy and metabolic homeostasis. Current opinion in clinical nutrition and metabolic care. 2007;10(6):729–34.
Delzenne NM, Cani PD, Neyrinck AM. Modulation of glucagon-like peptide 1 and energy metabolism by inulin and oligofructose: experimental data. The Journal of nutrition. 2007;137(11 Suppl):2547s–51s.
Pospisilik JA, Knauf C, Joza N, Benit P, Orthofer M, Cani PD, et al. Targeted deletion of AIF decreases mitochondrial oxidative phosphorylation and protects from obesity and diabetes. Cell. 2007;131(3):476–91.
Stenman LK, Lehtinen MJ, Meland N, Christensen JE, Yeung N, Saarinen MT, et al. Probiotic With or Without Fiber Controls Body Fat Mass, Associated With Serum Zonulin, in Overweight and Obese Adults-Randomized Controlled Trial. EBioMedicine. 2016.
Malik A, Sharma D, Zhu Q, Karki R, Guy CS, Vogel P, et al. IL-33 regulates the IgA- microbiota axis to restrain IL-1alpha-dependent colitis and tumorigenesis. J Clin Invest. 2016.
Wang X, Yang Y, Huycke MM. Microbiome-driven carcinogenesis in colorectal cancer: models and mechanisms. Free Radic Biol Med. 2016.
Coleman OI, Nunes T. Role of the Microbiota in Colorectal Cancer: Updates on Microbial Associations and Therapeutic Implications. BioResearch open access. 2016;5(1):279–88.
Yamamura K, Baba Y, Nakagawa S, Mima K, Miyake K, Nakamura K, et al. Human Microbiome Fusobacterium Nucleatum in Esophageal Cancer Tissue Is Associated with Prognosis. Clin Cancer Res. 2016.
Michaud DS, Izard J, Wilhelm-Benartzi CS, You DH, Grote VA, Tjonneland A, et al. Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study. Gut. 2013;62(12):1764–70.
Fan X, Alekseyenko AV, Wu J, Peters BA, Jacobs EJ, Gapstur SM, et al. Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study. Gut. 2016.
Florez AB, Sierra M, Ruas-Madiedo P, Mayo B. Susceptibility of lactic acid bacteria, bifidobacteria and other bacteria of intestinal origin to chemotherapeutic agents. International journal of antimicrobial agents. 2016;48(5):547–50.
Viaud S, Saccheri F, Mignot G, Yamazaki T, Daillere R, Hannani D, et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science (New York). 2013;342(6161):971–6.
Iida N, Dzutsev A, Stewart CA, Smith L, Bouladoux N, Weingarten RA, et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science (New York). 2013;342(6161):967–70.
Kwa M, Plottel CS, Blaser MJ, Adams S. The Intestinal Microbiome and Estrogen Receptor-Positive Female Breast Cancer. J Natl Cancer Inst. 2016;108(8).
Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science (New York). 2015;350(6264):1084–9.
Kawamoto S, Tran TH, Maruya M, Suzuki K, Doi Y, Tsutsui Y, et al. The inhibitory receptor PD-1 regulates IgA selection and bacterial composition in the gut. Science (New York). 2012;336(6080):485–9.
Botticelli A, Zizzari I, Mazzuca F, Ascierto PA, Putignani L, Marchetti L, et al. Cross-talk between microbiota and immune fitness to steer and control response to anti PD-1/PDL-1 treatment. Oncotarget. 2016.
Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science (New York). 2012;336(6086):1268–73.
Atarashi K, Tanoue T, Ando M, Kamada N, Nagano Y, Narushima S, et al. Th17 Cell Induction by Adhesion of Microbes to Intestinal Epithelial Cells. Cell. 2015;163(2):367–80.
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 (New York). 2011;331(6015):337–41.
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.
Jones L, Ho WQ, Ying S, Ramakrishna L, Srinivasan KG, Yurieva M, et al. A subpopulation of high IL-21-producing CD4(+) T cells in Peyer's Patches is induced by the microbiota and regulates germinal centers. Scientific reports. 2016;6:30784.
Kawamoto S, Maruya M, Kato LM, Suda W, Atarashi K, Doi Y, et al. Foxp3(+) T cells regulate immunoglobulin a selection and facilitate diversification of bacterial species responsible for immune homeostasis. Immunity. 2014;41(1):152–65.
Nishio J, Baba M, Atarashi K, Tanoue T, Negishi H, Yanai H, et al. Requirement of full TCR repertoire for regulatory T cells to maintain intestinal homeostasis. Proceedings of the National Academy of Sciences of the United States of America. 2015;112(41):12770–5.
Ochi T, Feng Y, Kitamoto S, Nagao-Kitamoto H, Kuffa P, Atarashi K, et al. Diet-dependent, microbiota-independent regulation of IL-10-producing lamina propria macrophages in the small intestine. Scientific reports. 2016;6:27634.
Ohnmacht C, Park JH, Cording S, Wing JB, Atarashi K, Obata Y, et al. MUCOSAL IMMUNOLOGY. The microbiota regulates type 2 immunity through RORgammat(+) T cells. Science (New York). 2015;349(6251):989–93.
Penack O, Holler E, van den Brink MR. Graft-versus-host disease: regulation by microbe- associated molecules and innate immune receptors. Blood. 2010;115(10):1865–72.
Shlomchik WD. Graft-versus-host disease. Nature reviews Immunology. 2007;7(5):340–52.
Eriguchi Y, Nakamura K, Hashimoto D, Shimoda S, Shimono N, Akashi K, et al. Decreased secretion of Paneth cell alpha-defensins in graft-versus-host disease. Transplant infectious disease: an official journal of the Transplantation Society. 2015;17(5):702–6.
Levine JE, Huber E, Hammer ST, Harris AC, Greenson JK, Braun TM, et al. Low Paneth cell numbers at onset of gastrointestinal graft-versus-host disease identify patients at high risk for nonrelapse mortality. Blood. 2013;122(8):1505–9.
Schroeder BO, Ehmann D, Precht JC, Castillo PA, Kuchler R, Berger J, et al. Paneth cell alpha-defensin 6 (HD-6) is an antimicrobial peptide. Mucosal immunology. 2015;8(3):661–71.
Ferrara JL, Harris AC, Greenson JK, Braun TM, Holler E, Teshima T, et al. Regenerating islet-derived 3-alpha is a biomarker of gastrointestinal graft-versus-host disease. Blood. 2011;118(25):6702–8.
Buckner CD, Clift RA, Sanders JE, Meyers JD, Counts GW, Farewell VT, et al. Protective environment for marrow transplant recipients: a prospective study. Annals of internal medicine. 1978;89(6):893–901.
Storb R, Prentice RL, Buckner CD, Clift RA, Appelbaum F, Deeg J, et al. Graft-versus-host disease and survival in patients with aplastic anemia treated by marrow grafts from HLA- identical siblings. Beneficial effect of a protective environment. The New England journal of medicine. 1983;308(6):302–7.
Vossen JM, Heidt PJ, van den Berg H, Gerritsen EJ, Hermans J, Dooren LJ. Prevention of infection and graft-versus-host disease by suppression of intestinal microflora in children treated with allogeneic bone marrow transplantation. European journal of clinical microbiology & infectious diseases: official publication of the European Society of Clinical Microbiology. 1990;9(1):14–23.
Beelen DW, Haralambie E, Brandt H, Linzenmeier G, Muller KD, Quabeck K, et al. Evidence that sustained growth suppression of intestinal anaerobic bacteria reduces the risk of acute graft-versus-host disease after sibling marrow transplantation. Blood. 1992;80(10):2668–76.
Beelen DW, Elmaagacli A, Muller KD, Hirche H, Schaefer UW. Influence of intestinal bacterial decontamination using metronidazole and ciprofloxacin or ciprofloxacin alone on the development of acute graft-versus-host disease after marrow transplantation in patients with hematologic malignancies: final results and long-term follow-up of an open-label prospective randomized trial. Blood. 1999;93(10):3267–75.
Vossen JM, Guiot HF, Lankester AC, Vossen AC, Bredius RG, Wolterbeek R, et al. Complete suppression of the gut microbiome prevents acute graft-versus-host disease following allogeneic bone marrow transplantation. PloS one. 2014;9(9):e105706.
Taur Y, Jenq RR, Perales MA, Littmann ER, Morjaria S, Ling L, et al. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood. 2014;124(7):1174–82.
Taur Y, Xavier JB, Lipuma L, Ubeda C, Goldberg J, Gobourne A, et al. Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2012;55(7):905–14.
Jenq RR, Ubeda C, Taur Y, Menezes CC, Khanin R, Dudakov JA, et al. Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. The Journal of experimental medicine. 2012;209(5):903–11.
Holler E, Butzhammer P, Schmid K, Hundsrucker C, Koestler J, Peter K, et al. Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease. Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation. 2014;20(5):640–5.
Weber D, Oefner PJ, Hiergeist A, Koestler J, Gessner A, Weber M, et al. Low urinary indoxyl sulfate levels early after transplantation reflect a disrupted microbiome and are associated with poor outcome. Blood. 2015;126(14):1723–8.
Collins MD, Lawson PA, Willems A, Cordoba JJ, Fernandez-Garayzabal J, Garcia P, et al. The phylogeny of the genus Clostridium: proposal of five new genera and eleven new species combinations. International journal of systematic bacteriology. 1994;44(4):812–26.
Mathewson ND, Jenq R, Mathew AV, Koenigsknecht M, Hanash A, Toubai T, et al. Gut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft- versus-host disease. Nature immunology. 2016;17(5):505–13.
Jenq RR, Taur Y, Devlin SM, Ponce DM, Goldberg JD, Ahr KF, et al. Intestinal Blautia Is Associated with Reduced Death from Graft-versus-Host Disease. Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation. 2015;21(8):1373–83.
Eriguchi Y, Takashima S, Oka H, Shimoji S, Nakamura K, Uryu H, et al. Graft-versus-host disease disrupts intestinal microbial ecology by inhibiting Paneth cell production of alpha- defensins. Blood. 2012;120(1):223–31.
Gerbitz A, Schultz M, Wilke A, Linde HJ, Scholmerich J, Andreesen R, et al. Probiotic effects on experimental graft-versus-host disease: let them eat yogurt. Blood. 2004;103(11):4365–7.
van der Velden WJ, Netea MG, de Haan AF, Huls GA, Donnelly JP, Blijlevens NM. Role of the mycobiome in human acute graft-versus-host disease. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2013;19(2):329–32.
Pamer EG, Taur Y, Jenq R, van den Brink MRM. Impact of the Intestinal Microbiota on Infections and Survival Following Hematopoietic Stem Cell Transplantation. Blood. 2014;124(21):SCI-48-SCI.
Marr KA, Seidel K, Slavin MA, Bowden RA, Schoch HG, Flowers ME, et al. Prolonged fluconazole prophylaxis is associated with persistent protection against candidiasis-related death in allogeneic marrow transplant recipients: long-term follow-up of a randomized, placebo- controlled trial. Blood. 2000;96(6):2055–61.
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El-Jurdi, N., de Lima, M., Lazarus, H. et al. Microbiome: Its Impact Is Being Revealed!. Curr Clin Micro Rpt 4, 78–87 (2017). https://doi.org/10.1007/s40588-017-0063-9
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DOI: https://doi.org/10.1007/s40588-017-0063-9