The Impact of the Microbiome on Immunity to Vaccination in Humans

Sanne E de Jong, Axel Olin, Bali Pulendran, Sanne E de Jong, Axel Olin, Bali Pulendran

Abstract

Vaccines are the most effective means available for preventing infectious diseases. However, vaccine-induced immune responses are highly variable between individuals and between populations in different regions of the world. Understanding the basis of this variation is, thus, of fundamental importance to human health. Although the factors that are associated with intra- and inter-population variation in vaccine responses are manifold, emerging evidence points to a key role for the gut microbiome in controlling immune responses to vaccination. Much of this evidence comes from studies in mice, and causal evidence for the impact of the microbiome on human immunity is sparse. However, recent studies on vaccination in subjects treated with broad-spectrum antibiotics have provided causal evidence and mechanistic insights into how the microbiota controls immune responses in humans.

Keywords: human immunology; microbiome; systems vaccinology; vaccines.

Copyright © 2020 Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
The Microbiota Exerts Local and Global Immune Influence Through a Variety of Mechanisms (A) The microbiota can influence host responses locally at the site, such as the airways, skin, and intestines, or act at a distance and exert profound influences systemically in, for example, lymph nodes, bone marrow, or the circulation. (B) The microbiota can influence immune reactions in distal locations in several ways. Model 1 depicts systemic translocation of bacterial products such as LPS from mucosal sites. Model 2 depicts a “domino effect” mechanism, where signals from the microbiota are delivered to cells in the vicinity, which then circulate throughout the body and relay this information. Model 3 describes the effects of microbiota on distant locations via secretion of microbiota-derived metabolites. HSCs, hematopoietic stem cells. PAMPs, pathogen-associated molecular patterns.
Figure 2
Figure 2
Antibiotics Impair the Vaccine Response in Healthy Adults (A) Outline of the study by Hagan et al. 11 subjects were treated with antibiotics for 5 days and vaccinated with the trivalent influenza vaccine on the fourth day. These were then compared with 11 vaccinated controls untreated with antibiotics. Fecal and blood samples were collected at regular intervals. (B) Results from the study by Hagan et al. Administration of antibiotics led to reduced microbial diversity and abundance and a consequential reduction in secondary bile acids. This in turn led to increased inflammation and a diminished vaccine response. TIV, trivalent influenza vaccine; LCA, litocholic acid.
Figure 3
Figure 3
Unique Environmental Factors and Biological Changes in the Very Young and the Very Old that Can Be Detrimental to Vaccine Efficacy Newborn children and elderly people undergo physiological changes and are exposed to environmental stimuli that can be detrimental to their immune system. Simultaneously, they often experience decreased microbial diversity. These factors interplay to make them less responsive to vaccination.

References

    1. Abt M.C., Osborne L.C., Monticelli L.A., Doering T.A., Alenghat T., Sonnenberg G.F., Paley M.A., Antenus M., Williams K.L., Erikson J., et al. Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity. 2012;37:158–170.
    1. Al Nabhani Z., Dulauroy S., Marques R., Cousu C., Al Bounny S., Déjardin F., Sparwasser T., Bérard M., Cerf-Bensussan N., Eberl G. A weaning reaction to microbiota is required for resistance to immunopathologies in the adult. Immunity. 2019;50:1276–1288.e5.
    1. An D., Oh S.F., Olszak T., Neves J.F., Avci F.Y., Erturk-Hasdemir D., Lu X., Zeissig S., Blumberg R.S., Kasper D.L. Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal natural killer T cells. Cell. 2014;156:123–133.
    1. Armah G.E., Sow S.O., Breiman R.F., Dallas M.J., Tapia M.D., Feikin D.R., Binka F.N., Steele A.D., Laserson K.F., Ansah N.A., et al. Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in sub-Saharan Africa: a randomised, double-blind, placebo-controlled trial. Lancet. 2010;376:606–614.
    1. Arunachalam P.S., Charles T.P., Joag V., Bollimpelli V.S., Scott M.K.D., Wimmers F., Burton S.L., Labranche C.C., Petitdemange C., Gangadhara S., et al. T cell-inducing vaccine durably prevents mucosal SHIV infection even with lower neutralizing antibody titers. Nat. Med. 2020;26:932–940.
    1. Atarashi K., Tanoue T., Ando M., Kamada N., Nagano Y., Narushima S., Suda W., Imaoka A., Setoyama H., Nagamori T., et al. Th17 cell induction by adhesion of microbes to intestinal epithelial cells. Cell. 2015;163:367–380.
    1. Bakke D., Sun J. Ancient nuclear receptor VDR With new functions: microbiome and inflammation. Inflamm. Bowel Dis. 2018;24:1149–1154.
    1. Belkaid Y., Hand T.W. Role of the microbiota in immunity and inflammation. Cell. 2014;157:121–141.
    1. Belkaid Y., Harrison O.J. Homeostatic immunity and the microbiota. Immunity. 2017;46:562–576.
    1. Carabotti M., Scirocco A., Maselli M.A., Severi C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann. Gastroenterol. 2015;28:203–209.
    1. Clarke E., Desselberger U. Correlates of protection against human rotavirus disease and the factors influencing protection in low-income settings. Mucosal Immunol. 2015;8:1–17.
    1. Clarke T.B., Davis K.M., Lysenko E.S., Zhou A.Y., Yu Y., Weiser J.N. Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity. Nat. Med. 2010;16:228–231.
    1. Cram J.A., Fiore-Gartland A.J., Srinivasan S., Karuna S., Pantaleo G., Tomaras G.D., Fredricks D.N., Kublin J.G. Human gut microbiota is associated with HIV-reactive immunoglobulin at baseline and following HIV vaccination. PLoS One. 2019;14:e0225622.
    1. Dickson R.P., Erb-Downward J.R., Martinez F.J., Huffnagle G.B. The microbiome and the respiratory tract. Annu. Rev. Physiol. 2016;78:481–504.
    1. Duraisingham S.S., Rouphael N., Cavanagh M.M., Nakaya H.I., Goronzy J.J., Pulendran B. Systems biology of vaccination in the elderly. Curr. Top. Microbiol. Immunol. 2013;363:117–142.
    1. Fine P.E. Variation in protection by BCG: implications of and for heterologous immunity. Lancet. 1995;346:1339–1345.
    1. Ganeshan K., Chawla A. Metabolic regulation of immune responses. Annu. Rev. Immunol. 2014;32:609–634.
    1. Gopalakrishnan V., Spencer C.N., Nezi L., Reuben A., Andrews M.C., Karpinets T.V., Prieto P.A., Vicente D., Hoffman K., Wei S.C., et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359:97–103.
    1. Grassly N.C., Praharaj I., Babji S., Kaliappan S.P., Giri S., Venugopal S., Parker E.P., Abraham A., Muliyil J., Doss S., et al. The effect of azithromycin on the immunogenicity of oral poliovirus vaccine: a double-blind randomised placebo-controlled trial in seronegative Indian infants. Lancet Infect. Dis. 2016;16:905–914.
    1. Greenberg H.B., Estes M.K. Rotaviruses: from pathogenesis to vaccination. Gastroenterology. 2009;136:1939–1951.
    1. Guo C., Xie S., Chi Z., Zhang J., Liu Y., Zhang L., Zheng M., Zhang X., Xia D., Ke Y., et al. Bile acids control inflammation and metabolic disorder through inhibition of NLRP3 inflammasome. Immunity. 2016;45:802–816.
    1. Hagan T., Cortese M., Rouphael N., Boudreau C., Linde C., Maddur M.S., Das J., Wang H., Guthmiller J., Zheng N.Y., et al. Antibiotics-driven gut microbiome perturbation alters immunity to vaccines in humans. Cell. 2019;178:1313–1328.e13.
    1. Hall J.A., Bouladoux N., Sun C.M., Wohlfert E.A., Blank R.B., Zhu Q., Grigg M.E., Berzofsky J.A., Belkaid Y. Commensal DNA limits regulatory T cell conversion and is a natural adjuvant of intestinal immune responses. Immunity. 2008;29:637–649.
    1. Hang S., Paik D., Yao L., Kim E., Trinath J., Lu J., Ha S., Nelson B.N., Kelly S.P., Wu L., et al. Bile acid metabolites control TH17 and Treg cell differentiation. Nature. 2019;576:143–148.
    1. Hanlon P., Hanlon L., Marsh V., Byass P., Shenton F., Hassan-King M., Jobe O., Sillah H., Hayes R., M'Boge B.H. Trial of an attenuated bovine rotavirus vaccine (RIT 4237) in Gambian infants. Lancet. 1987;1:1342–1345.
    1. Harris V.C., Armah G., Fuentes S., Korpela K.E., Parashar U., Victor J.C., Tate J., de Weerth C., Giaquinto C., Wiersinga W.J., et al. Significant correlation between the infant gut microbiome and rotavirus vaccine response in Rural Ghana. J. Infect. Dis. 2017;215:34–41.
    1. Harris V., Ali A., Fuentes S., Korpela K., Kazi M., Tate J., Parashar U., Wiersinga W.J., Giaquinto C., de Weerth C., de Vos W.M. Rotavirus vaccine response correlates with the infant gut microbiota composition in Pakistan. Gut Microbes. 2018;9:93–101.
    1. Harris V.C., Haak B.W., Handley S.A., Jiang B., Velasquez D.E., Hykes B.L., Jr., Droit L., Berbers G.A.M., Kemper E.M., van Leeuwen E.M.M., et al. Effect of antibiotic-mediated microbiome modulation on rotavirus vaccine immunogenicity: A human, randomized-control proof-of-Concept Trial. Cell Host Microbe. 2018;24:197–207.e4.
    1. Hotamisligil G.S. Inflammation and metabolic disorders. Nature. 2006;444:860–867.
    1. Huda M.N., Ahmad S.M., Alam M.J., Khanam A., Kalanetra K.M., Taft D.H., Raqib R., Underwood M.A., Mills D.A., Stephensen C.B. Bifidobacterium abundance in early infancy and vaccine response at 2 years of age. Pediatrics. 2019;143:e20181489.
    1. Huda M.N., Lewis Z., Kalanetra K.M., Rashid M., Ahmad S.M., Raqib R., Qadri F., Underwood M.A., Mills D.A., Stephensen C.B. Stool microbiota and vaccine responses of infants. Pediatrics. 2014;134:e362–e372.
    1. Hur Y.G., Gorak-Stolinska P., Lalor M.K., Mvula H., Floyd S., Raynes J., Ben-Smith A., Fitchett J.R., Flanagan K.L., Burl S., et al. Factors affecting immunogenicity of BCG in infants, a study in Malawi, The Gambia and the UK. BMC Infect. Dis. 2014;14:184.
    1. Ichinohe T., Pang I.K., Kumamoto Y., Peaper D.R., Ho J.H., Murray T.S., Iwasaki A. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc. Natl. Acad. Sci. USA. 2011;108:5354–5359.
    1. Isolauri E., Joensuu J., Suomalainen H., Luomala M., Vesikari T. Improved immunogenicity of oral D x RRV reassortant rotavirus vaccine by Lactobacillus casei GG. Vaccine. 1995;13:310–312.
    1. Jiang W., Wang X., Zeng B., Liu L., Tardivel A., Wei H., Han J., MacDonald H.R., Tschopp J., Tian Z., Zhou R. Recognition of gut microbiota by NOD2 is essential for the homeostasis of intestinal intraepithelial lymphocytes. J. Exp. Med. 2013;210:2465–2476.
    1. Kandasamy S., Chattha K.S., Vlasova A.N., Rajashekara G., Saif L.J. Lactobacilli and bifidobacteria enhance mucosal B cell responses and differentially modulate systemic antibody responses to an oral human rotavirus vaccine in a neonatal gnotobiotic pig disease model. Gut Microbes. 2014;5:639–651.
    1. Kim D., Kim Y.G., Seo S.U., Kim D.J., Kamada N., Prescott D., Chamaillard M., Philpott D.J., Rosenstiel P., Inohara N., Núñez G. Nod2-mediated recognition of the microbiota is critical for mucosal adjuvant activity of cholera toxin. Nat. Med. 2016;22:524–530.
    1. Kim M., Qie Y., Park J., Kim C.H. Gut microbial metabolites fuel host antibody responses. Cell Host Microbe. 2016;20:202–214.
    1. Kobayashi T., Voisin B., Kim D.Y., Kennedy E.A., Jo J.H., Shih H.Y., Truong A., Doebel T., Sakamoto K., Cui C.Y., et al. Homeostatic control of sebaceous glands by innate lymphoid cells regulates commensal bacteria equilibrium. Cell. 2019;176:982–997.e16.
    1. Kollmann T.R., Kampmann B., Mazmanian S.K., Marchant A., Levy O. Protecting the newborn and young infant from infectious diseases: lessons from immune ontogeny. Immunity. 2017;46:350–363.
    1. Kostic A.D., Xavier R.J., Gevers D. The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology. 2014;146:1489–1499.
    1. Kundu P., Blacher E., Elinav E., Pettersson S. Our gut microbiome: the evolving inner self. Cell. 2017;171:1481–1493.
    1. Laborel-Preneron E., Bianchi P., Boralevi F., Lehours P., Fraysse F., Morice-Picard F., Sugai M., Sato'o Y., Badiou C., Lina G., et al. Effects of the Staphylococcus aureus and Staphylococcus epidermidis secretomes isolated from the skin microbiota of atopic children on CD4+ T cell activation. PLoS One. 2015;10:e0141067.
    1. Levy M., Kolodziejczyk A.A., Thaiss C.A., Elinav E. Dysbiosis and the immune system. Nat. Rev. Immunol. 2017;17:219–232.
    1. Li F., Hao X., Chen Y., Bai L., Gao X., Lian Z., Wei H., Sun R., Tian Z. The microbiota maintain homeostasis of liver-resident γδT-17 cells in a lipid antigen/CD1d-dependent manner. Nat. Commun. 2017;7:13839.
    1. Li S., Sullivan N.L., Rouphael N., Yu T., Banton S., Maddur M.S., McCausland M., Chiu C., Canniff J., Dubey S., et al. Metabolic phenotypes of response to vaccination in humans. Cell. 2017;169:862–877.e17.
    1. Li Y., Innocentin S., Withers D.R., Roberts N.A., Gallagher A.R., Grigorieva E.F., Wilhelm C., Veldhoen M. Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation. Cell. 2011;147:629–640.
    1. Lynn M.A., Tumes D.J., Choo J.M., Sribnaia A., Blake S.J., Leong L.E.X., Young G.P., Marshall H.S., Wesselingh S.L., Rogers G.B., Lynn D.J. Early-life antibiotic-driven dysbiosis leads to dysregulated vaccine immune responses in mice. Cell Host Microbe. 2018;23:653–660.e5.
    1. Macia L., Tan J., Vieira A.T., Leach K., Stanley D., Luong S., Maruya M., Ian McKenzie C., Hijikata A., Wong C., et al. Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. Nat. Commun. 2015;6:6734.
    1. Macpherson A.J., Uhr T. Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science. 2004;303:1662–1665.
    1. Madhi S.A., Cunliffe N.A., Steele D., Witte D., Kirsten M., Louw C., Ngwira B., Victor J.C., Gillard P.H., Cheuvart B.B., et al. Effect of human rotavirus vaccine on severe diarrhea in African infants. N. Engl. J. Med. 2010;362:289–298.
    1. Matsuda F., Chowdhury M.I., Saha A., Asahara T., Nomoto K., Tarique A.A., Ahmed T., Nishibuchi M., Cravioto A., Qadri F. Evaluation of a probiotics, Bifidobacterium breve BBG-01, for enhancement of immunogenicity of an oral inactivated cholera vaccine and safety: a randomized, double-blind, placebo-controlled trial in Bangladeshi children under 5 years of age. Vaccine. 2011;29:1855–1858.
    1. Mazmanian S.K., Liu C.H., Tzianabos A.O., Kasper D.L. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell. 2005;122:107–118.
    1. Mitre E., Susi A., Kropp L.E., Schwartz D.J., Gorman G.H., Nylund C.M. Association Between use of acid-suppressive medications and antibiotics during infancy and allergic diseases in early childhood. JAMA Pediatr. 2018;172:e180315.
    1. Muyanja E., Ssemaganda A., Ngauv P., Cubas R., Perrin H., Srinivasan D., Canderan G., Lawson B., Kopycinski J., Graham A.S., et al. Immune activation alters cellular and humoral responses to yellow fever 17D vaccine. J. Clin. Invest. 2014;124:3147–3158.
    1. Naik S., Bouladoux N., Wilhelm C., Molloy M.J., Salcedo R., Kastenmuller W., Deming C., Quinones M., Koo L., Conlan S., et al. Compartmentalized control of skin immunity by resident commensals. Science. 2012;337:1115–1119.
    1. Nakaya H.I., Hagan T., Duraisingham S.S., Lee E.K., Kwissa M., Rouphael N., Frasca D., Gersten M., Mehta A.K., Gaujoux R., et al. Systems analysis of immunity to influenza vaccination across multiple years and in diverse populations reveals shared molecular signatures. Immunity. 2015;43:1186–1198.
    1. Nicholson J.K., Holmes E., Kinross J., Burcelin R., Gibson G., Jia W., Pettersson S. Host-gut microbiota metabolic interactions. Science. 2012;336:1262–1267.
    1. Norton E.B., Lawson L.B., Freytag L.C., Clements J.D. Characterization of a mutant Escherichia coli heat-labile toxin, LT(R192G/L211A), as a safe and effective oral adjuvant. Clin. Vaccine Immunol. 2011;18:546–551.
    1. Oh J.Z., Ravindran R., Chassaing B., Carvalho F.A., Maddur M.S., Bower M., Hakimpour P., Gill K.P., Nakaya H.I., Yarovinsky F., et al. TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination. Immunity. 2014;41:478–492.
    1. Olin A., Henckel E., Chen Y., Lakshmikanth T., Pou C., Mikes J., Gustafsson A., Bernhardsson A.K., Zhang C., Bohlin K., Brodin P. Stereotypic immune system development in newborn children. Cell. 2018;174:1277–1292.e14.
    1. Parker E.P.K., Praharaj I., Zekavati A., Lazarus R.P., Giri S., Operario D.J., Liu J., Houpt E., Iturriza-Gómara M., Kampmann B., et al. Influence of the intestinal microbiota on the immunogenicity of oral rotavirus vaccine given to infants in south India. Vaccine. 2018;36:264–272.
    1. Patel M., Pedreira C., De Oliveira L.H., Tate J., Orozco M., Mercado J., Gonzalez A., Malespin O., Amador J.J., Umaña J., et al. Association between pentavalent rotavirus vaccine and severe rotavirus diarrhea among children in Nicaragua. JAMA. 2009;301:2243–2251.
    1. Patrick D.M., Sbihi H., Dai D.L.Y., Al Mamun A., Rasali D., Rose C., Marra F., Boutin R.C.T., Petersen C., Stiemsma L.T., et al. Decreasing antibiotic use, the gut microbiota, and asthma incidence in children: evidence from population-based and prospective cohort studies. Lancet Respir. Med. 2020:30052–30057. doi: 10.1016/S2213-2600.
    1. Pfeiffer J.K., Virgin H.W. Viral immunity. Transkingdom control of viral infection and immunity in the mammalian intestine. Science. 2016;351:aad5872.
    1. Praharaj I., John S.M., Bandyopadhyay R., Kang G. Probiotics, antibiotics and the immune responses to vaccines. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2015;370:20140144.
    1. Praharaj I., Parker E.P.K., Giri S., Allen D.J., Silas S., Revathi R., Kaliappan S.P., John J., Prasad J.H., Kampmann B., et al. Influence of nonpolio enteroviruses and the bacterial gut microbiota on oral poliovirus vaccine response: a study from South India. J. Infect. Dis. 2019;219:1178–1186.
    1. Pulendran B. Learning immunology from the yellow fever vaccine: innate immunity to systems vaccinology. Nat. Rev. Immunol. 2009;9:741–747.
    1. Pulendran B. Systems vaccinology: probing humanity's diverse immune systems with vaccines. Proc. Natl. Acad. Sci. USA. 2014;111:12300–12306.
    1. Qadri F., Bhuiyan T.R., Sack D.A., Svennerholm A.M. Immune responses and protection in children in developing countries induced by oral vaccines. Vaccine. 2013;31:452–460.
    1. Querec T.D., Akondy R.S., Lee E.K., Cao W., Nakaya H.I., Teuwen D., Pirani A., Gernert K., Deng J., Marzolf B., et al. Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat. Immunol. 2009;10:116–125.
    1. Rampelli S., Candela M., Turroni S., Biagi E., Collino S., Franceschi C., O'Toole P.W., Brigidi P. Functional metagenomic profiling of intestinal microbiome in extreme ageing. Aging (Albany, NY) 2013;5:902–912.
    1. Ridlon J.M., Kang D.J., Hylemon P.B., Bajaj J.S. Bile acids and the gut microbiome. Curr. Opin. Gastroenterol. 2014;30:332–338.
    1. Robinson C.M., Pfeiffer J.K. Viruses and the microbiota. Annu. Rev. Virol. 2014;1:55–69.
    1. Routy B., Le Chatelier E., Derosa L., Duong C.P.M., Alou M.T., Daillère R., Fluckiger A., Messaoudene M., Rauber C., Roberti M.P., et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359:91–97.
    1. San-Cristobal R., Navas-Carretero S., Martínez-González M.Á., Ordovas J.M., Martínez J.A. Contribution of macronutrients to obesity: implications for precision nutrition. Nat. Rev. Endocrinol. 2020;16:305–320.
    1. Sandler N.G., Douek D.C. Microbial translocation in HIV infection: causes, consequences and treatment opportunities. Nat. Rev. Microbiol. 2012;10:655–666.
    1. Santos Rocha C., Hirao L.A., Weber M.G., Méndez-Lagares G., Chang W.L.W., Jiang G., Deere J.D., Sparger E.E., Roberts J., Barry P.A., et al. Subclinical Cytomegalovirus infection is associated with altered host immunity, gut microbiota, and vaccine responses. J. Virol. 2018;92 e00167-18.
    1. Scher J.U., Sczesnak A., Longman R.S., Segata N., Ubeda C., Bielski C., Rostron T., Cerundolo V., Pamer E.G., Abramson S.B., et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. eLife. 2013;2:e01202.
    1. Shi C., Jia T., Mendez-Ferrer S., Hohl T.M., Serbina N.V., Lipuma L., Leiner I., Li M.O., Frenette P.S., Pamer E.G. Bone marrow mesenchymal stem and progenitor cells induce monocyte emigration in response to circulating toll-like receptor ligands. Immunity. 2011;34:590–601.
    1. Shi Z., Zou J., Zhang Z., Zhao X., Noriega J., Zhang B., Zhao C., Ingle H., Bittinger K., Mattei L.M., et al. Segmented filamentous bacteria prevent and cure rotavirus infection. Cell. 2019;179:644–658.e13.
    1. Sissoko M.S., Healy S.A., Katile A., Omaswa F., Zaidi I., Gabriel E.E., Kamate B., Samake Y., Guindo M.A., Dolo A., et al. Safety and efficacy of PfSPZ Vaccine against Plasmodium falciparum via direct venous inoculation in healthy malaria-exposed adults in Mali: a randomised, double-blind phase 1 trial. Lancet Infect. Dis. 2017;17:498–509.
    1. Skabytska Y., Wölbing F., Günther C., Köberle M., Kaesler S., Chen K.M., Guenova E., Demircioglu D., Kempf W.E., Volz T., et al. Cutaneous innate immune sensing of Toll-like receptor 2–6 ligands suppresses T cell immunity by inducing myeloid-derived suppressor cells. Immunity. 2014;41:762–775.
    1. Soh S.E., Ong D.Q., Gerez I., Zhang X., Chollate P., Shek L.P., Lee B.W., Aw M. Effect of probiotic supplementation in the first 6 months of life on specific antibody responses to infant hepatitis B vaccination. Vaccine. 2010;28:2577–2579.
    1. Sonnenburg J.L., Bäckhed F. Diet-microbiota interactions as moderators of human metabolism. Nature. 2016;535:56–64.
    1. Stacy A., Belkaid Y. Microbial guardians of skin health. Science. 2019;363:227–228.
    1. Staudinger J.L., Goodwin B., Jones S.A., Hawkins-Brown D., MacKenzie K.I., LaTour A., Liu Y., Klaassen C.D., Brown K.K., Reinhard J., et al. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc. Natl. Acad. Sci. USA. 2001;98:3369–3374.
    1. Stelekati E., Wherry E.J. Chronic bystander infections and immunity to unrelated antigens. Cell Host Microbe. 2012;12:458–469.
    1. Tate J.E., Burton A.H., Boschi-Pinto C., Steele A.D., Duque J., Parashar U.D., WHO-coordinated Global Rotavirus Surveillance Network 2008 Estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis. Lancet Infect. Dis. 2012;12:136–141.
    1. Thevaranjan N., Puchta A., Schulz C., Naidoo A., Szamosi J.C., Verschoor C.P., Loukov D., Schenck L.P., Jury J., Foley K.P., et al. Age-associated microbial dysbiosis promotes intestinal permeability, systemic inflammation, and macrophage dysfunction. Cell Host Microbe. 2017;21:455–466.e4.
    1. Trama A.M., Moody M.A., Alam S.M., Jaeger F.H., Lockwood B., Parks R., Lloyd K.E., Stolarchuk C., Scearce R., Foulger A., et al. HIV-1 envelope gp41 antibodies can originate from terminal ileum B cells that share cross-reactivity with commensal bacteria. Cell Host Microbe. 2014;16:215–226.
    1. Uchimura Y., Fuhrer T., Li H., Lawson M.A., Zimmermann M., Yilmaz B., Zindel J., Ronchi F., Sorribas M., Hapfelmeier S., et al. Antibodies set boundaries limiting microbial metabolite penetration and the resultant mammalian host response. Immunity. 2018;49:545–559.e5.
    1. Uchiyama R., Chassaing B., Zhang B., Gewirtz A.T. Antibiotic treatment suppresses rotavirus infection and enhances specific humoral immunity. J. Infect. Dis. 2014;210:171–182.
    1. Williams W.B., Han Q., Haynes B.F. Cross-reactivity of HIV vaccine responses and the microbiome. Curr. Opin. HIV AIDS. 2018;13:9–14.
    1. World Health Organization Draft landscape of COVID-19 candidate vaccines. 2020.
    1. Zaman K., Dang D.A., Victor J.C., Shin S., Yunus M., Dallas M.J., Podder G., Vu D.T., Le T.P., Luby S.P., et al. Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in Asia: a randomised, double-blind, placebo-controlled trial. Lancet. 2010;376:615–623.
    1. Zeng M.Y., Cisalpino D., Varadarajan S., Hellman J., Warren H.S., Cascalho M., Inohara N., Núñez G. Gut microbiota-induced immunoglobulin G controls systemic infection by symbiotic bacteria and pathogens. Immunity. 2016;44:647–658.
    1. Zhao Y., Wang Z. Gut microbiome and cardiovascular disease. Curr. Opin. Cardiol. 2020;35:207–218.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi