Impact of prebiotics, probiotics, and gut derived metabolites on host immunity
Abstract
Increasing evidence indicates that gut microorganisms impact multiple aspects of the innate and adaptive mucosal immune system. Current research focuses on the potential of prebiotics (non-digestible fibres that nourish beneficial bacteria) and probiotics (beneficial live bacteria) to promote health, prevent disease, and for use as a treatment strategy for a variety of immune-mediated conditions. The immune modulatory effects of probiotics and prebiotics are strain- or structure-specific and vary with disease state, age, and sex. Prebiotics and live beneficial bacteria, including their metabolic products or soluble mediators, have the ability to affect the composition of the intestinal microbiota. As well, they influence the integrity and functions of intestinal epithelial cells and antigen presenting cells, including dendritic cells and macrophages, by both direct and indirect mechanisms of action.
Statement of novelty: This review serves to highlight select advances related to the impact of prebiotics, probiotics, and gut microbe-derived metabolites on host immune function.
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REFERENCES
Abrahamsson T.R., Jakobsson H.E., Andersson A.F., Bjorksten B., Engstrand L., and Jenmalm M.C.2014. Low gut microbiota diversity in early infancy precedes asthma at school age. Clin. Exp. Allergy. 44(6):842–850.
Alam A., Leoni G., Wentworth C.C., Kwal J.M., Wu H., Ardita C.S., Swanson P.A., Lambeth J.D., Jones R.M., Nusrat A., and Neish A.S.2014. Redox signaling regulates commensal-mediated mucosal homeostasis and restitution and requires formyl peptide receptor 1. Mucosal Immunol.7(3):645–655.
Arpaia N., Campbell C., Fan X., Dikiy S., van der Veeken J., deRoos P., Liu H., Cross J.R., Pfeffer K., Coffer P.J., and Rudensky A.Y.2013. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 504(7480):451–455.
Audy J., Mathieu O., Belvis J., and Tompkins T.A.2012. Transcriptomic response of immune signalling pathways in intestinal epithelial cells exposed to lipopolysaccharides, Gram-negative bacteria or potentially probiotic microbes. Benef. Microbes. 3(4):273–286.
Autran C.A., Schoterman M.H., Jantscher-Krenn E., Kamerling J.P., and Bode L.2016. Sialylated galacto-oligosaccharides and 2-fucosyllactose reduce necrotising enterocolitis in neonatal rats. Br. J. Nutr.116(2):294–299.
Ayres J.S.2016. Cooperative microbial tolerance behaviors in host-microbiota mutualism. Cell. 165(6):1323–1331.
Bai A.P., Ouyang Q., Zhang W., Wang C.H., and Li S.F.2004. Probiotics inhibit TNF-alpha-induced interleukin-8 secretion of HT29 cells. World J. Gastroenterol.10(3):455–457.
Baumler A.J. and Sperandio V.2016. Interactions between the microbiota and pathogenic bacteria in the gut. Nature. 535(7610):85–93.
Bermudez-Brito M., Munoz-Quezada S., Gomez-Llorente C., Romero F., and Gil A.2014. Lactobacillus rhamnosus and its cell-free culture supernatant differentially modulate inflammatory biomarkers in Escherichia coli-challenged human dendritic cells. Br. J. Nutr.111(10):1727–1737.
Bode L. and Jantscher-Krenn E.2012. Structure-function relationships of human milk oligosaccharides. Adv. Nutr.3(3):383S–391S.
Braat H., van den Brande J., van Tol E., Hommes D., Peppelenbosch M., and van Deventer S.2004. Lactobacillus rhamnosus induces peripheral hyporesponsiveness in stimulated CD4+ T cells via modulation of dendritic cell function. Am. J. Clin. Nutr.80(6):1618–1625.
Buck B.L., Azcarate-Peril M.A., and Klaenhammer T.R.2009. Role of autoinducer-2 on the adhesion ability of Lactobacillus acidophilus. J. Appl. Microbiol.107(1):269–279.
Candela M., Perna F., Carnevali P., Vitali B., Ciati R., Gionchetti P., Rizzello F., Campieri M., and Brigidi P.2008. Interaction of probiotic Lactobacillus and Bifidobacterium strains with human intestinal epithelial cells: Adhesion properties, competition against enteropathogens and modulation of IL-8 production. Int. J. Food Microbiol.125(3):286–292.
Capitan-Canadas F., Ortega-Gonzalez M., Guadix E., Zarzuelo A., Suarez M.D., de Medina F.S., and Martinez-Augustin O.2014. Prebiotic oligosaccharides directly modulate proinflammatory cytokine production in monocytes via activation of TLR4. Mol. Nutr. Food Res.58(5):1098–1110.
Charbonneau M.R., O’Donnell D., Blanton L.V., Totten S.M., Davis J.C., Barratt M.J., Cheng J., Guruge J., Talcott M., Bain J.R., Muehlbauer M.J., Ilkayeva O., Wu C., Struckmeyer T., Barile D., Mangani C., Jorgensen J., Fan Y.M., Maleta K., Dewey K.G., Ashorn P., Newgard C.B., Lebrilla C., Mills D.A., and Gordon J.I.2016. Sialylated milk oligosaccharides promote microbiota-dependent growth in models of infant undernutrition. Cell. 164(5):859–871.
Christoffersen T.E., Hult L.T., Kuczkowska K., Moe K.M., Skeie S., Lea T., and Kleiveland C.R.2014. In vitro comparison of the effects of probiotic, commensal and pathogenic strains on macrophage polarization. Probiotics Antimicrob. Proteins. 6(1):1–10.
Claes I.J., Schoofs G., Regulski K., Courtin P., Chapot-Chartier M.P., Rolain T., Hols P., von Ossowski I., Reunanen J., de Vos W.M., Palva A., Vanderleyden J., De Keersmaecker S.C., and Lebeer S.2012. Genetic and biochemical characterization of the cell wall hydrolase activity of the major secreted protein of Lactobacillus rhamnosus GG. PLoS ONE. 7(2):e31588.
Clarke S.T., Green-Johnson J.M., Brooks S.P., Ramdath D.D., Bercik P., Avila C., Inglis G.D., Green J., Yanke L.J., Selinger L.B., and Kalmokoff M.2016. β2-1 Fructan supplementation alters host immune responses in a manner consistent with increased exposure to microbial components: Results from a double-blinded, randomised, cross-over study in healthy adults. Br. J. Nutr.115(10):1748–1759.
Correa-Oliveira R., Fachi J.L., Vieira A., Sato F.T., and Vinolo M.A.2016. Regulation of immune cell function by short-chain fatty acids. Clin. Transl. Immunol.5(4):e73.
Coyte K.Z., Schluter J., and Foster K.R.2015. The ecology of the microbiome: Networks, competition, and stability. Science. 350(6261):663–666.
David L.A., Maurice C.F., Carmody R.N., Gootenberg D.B., Button J.E., Wolfe B.E., Ling A.V., Devlin A.S., Varma Y., Fischbach M.A., Biddinger S.B., Dutton R.J., and Turnbaugh P.J.2014. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 505(7484):559–563.
Demont A., Hacini-Rachinel F., Doucet-Ladeveze R., Ngom-Bru C., Mercenier A., Prioult G., and Blanchard C.2016. Live and heat-treated probiotics differently modulate IL10 mRNA stabilization and microRNA expression. J. Allergy Clin. Immunol.137(4):1264-7.e1–1264-7.e10.
Esser C., Rannug A., and Stockinger B.2009. The aryl hydrocarbon receptor in immunity. Trends Immunol.30(9):447–454.
Eun C.S., Han D.S., Lee S.H., Jeon Y.C., Sohn J.H., Kim Y.S., and Lee J.2007. [Probiotics may reduce inflammation by enhancing peroxisome proliferator activated receptor gamma activation in HT-29 cells]. Korean J. Gastroenterol.49(3):139–146.
Ewaschuk J., Endersby R., Thiel D., Diaz H., Backer J., Ma M., Churchill T., and Madsen K.2007. Probiotic bacteria prevent hepatic damage and maintain colonic barrier function in a mouse model of sepsis. Hepatology. 46(3):841–850.
Faith J.J., Guruge J.L., Charbonneau M., Subramanian S., Seedorf H., Goodman A.L., Clemente J.C., Knight R., Heath A.C., Leibel R.L., Rosenbaum M., and Gordon J.I.2013. The long-term stability of the human gut microbiota. Science. 341(6141):1237439.
Falony G., Joossens M., Vieira-Silva S., Wang J., Darzi Y., Faust K., Kurilshikov A., Bonder M.J., Valles-Colomer M., Vandeputte D., Tito R.Y., Chaffron S., Rymenans L., Verspecht C., DeSutter L., Lima-Mendez G., D’Hoe K., Jonckheere K., Homola D., Garcia R., Tigchelaar E.F., Eeckhaudt L., Fu J., Henckaerts L., Zhernakova A., Wijmenga C., and Raes J.2016. Population-level analysis of gut microbiome variation. Science. 352(6285):560–564.
Fischbach M.A. and Segre J.A.2016. Signaling in host-associated microbial communities. Cell. 164(6):1288–1300.
Fischer K., Hoffmann P., Voelkl S., Meidenbauer N., Ammer J., Edinger M., Gottfried E., Schwarz S., Rothe G., Hoves S., Renner K., Timischl B., Mackensen A., Kunz-Schughart L., Andreesen R., Krause S.W., and Kreutz M.2007. Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood. 109(9):3812–3819.
Fong F.L., Kirjavainen P.V., and El-Nezami H.2016. Immunomodulation of Lactobacillus rhamnosus GG (LGG)-derived soluble factors on antigen-presenting cells of healthy blood donors. Sci. Rep.6:22845.
Freedman S.B., Williamson-Urquhart S., Schuh S., Sherman P.M., Farion K.J., Gouin S., Willan A.R., Goeree R., Johnson D.W., Black K., Schnadower D., and Gorelick M.H., andPediatric Emergency Research Canada Gastroenteritis Study Group. 2014. Impact of emergency department probiotic treatment of pediatric gastroenteritis: Study protocol for the PROGUT (Probiotic Regimen for Outpatient Gastroenteritis Utility of Treatment) randomized controlled trial. Trials. 15:170.
Fujiya M., Musch M.W., Nakagawa Y., Hu S., Alverdy J., Kohgo Y., Schneewind O., Jabri B., and Chang E.B.2007. The Bacillus subtilis quorum-sensing molecule CSF contributes to intestinal homeostasis via OCTN2, a host cell membrane transporter. Cell Host Microbe. 1(4):299–308.
Fusunyan R.D., Quinn J.J., Fujimoto M., MacDermott R.P., and Sanderson I.R.1999. Butyrate switches the pattern of chemokine secretion by intestinal epithelial cells through histone acetylation. Mol. Med.5(9):631–640.
Ganguli K., Meng D., Rautava S., Lu L., Walker W.A., and Nanthakumar N.2013. Probiotics prevent necrotizing enterocolitis by modulating enterocyte genes that regulate innate immune-mediated inflammation. Am. J. Physiol. Gastrointest. Liver Physiol.304(2):G132–G141.
Gareau M.G., Wine E., Reardon C., and Sherman P.M.2010. Probiotics prevent death caused by Citrobacter rodentium infection in neonatal mice. J. Infect. Dis.201(1):81–91.
Garrote G.L., Abraham A.G., and Rumbo M.2015. Is lactate an undervalued functional component of fermented food products?Front. Microbiol.6:629.
Geijtenbeek T.B. and Gringhuis S.I.2009. Signalling through C-type lectin receptors: Shaping immune responses. Nat. Rev. Immunol.9(7):465–479.
Ghadimi D., Helwig U., Schrezenmeir J., Heller K.J., and de Vrese M.2012. Epigenetic imprinting by commensal probiotics inhibits the IL-23/IL-17 axis in an in vitro model of the intestinal mucosal immune system. J. Leukoc. Biol.92(4):895–911.
Giahi L., Aumueller E., Elmadfa I., and Haslberger A.G.2012. Regulation of TLR4, p38 MAPkinase, IκB and miRNAs by inactivated strains of lactobacilli in human dendritic cells. Benef. Microbes. 3(2):91–98.
Gilbert J.A., Quinn R.A., Debelius J., Xu Z.Z., Morton J., Garg N., Jansson J.K., Dorrestein P.C., and Knight R.2016. Microbiome-wide association studies link dynamic microbial consortia to disease. Nature. 535(7610):94–103.
Ginsburg I.2002. Role of lipoteichoic acid in infection and inflammation. Lancet Infect. Dis.2(3):171–179.
Habil N., Al-Murrani W., Beal J., and Foey A.D.2011. Probiotic bacterial strains differentially modulate macrophage cytokine production in a strain-dependent and cell subset-specific manner. Benef. Microbes. 2(4):283–293.
Hallam M.C. and Reimer R.A.2014. Postnatal prebiotic fiber intake in offspring exposed to gestational protein restriction has sex-specific effects on insulin resistance and intestinal permeability in rats. J. Nutr.144(10):1556–1563.
Hancock R.E., Nijnik A., and Philpott D.J.2012. Modulating immunity as a therapy for bacterial infections. Nat. Rev. Microbiol.10(4):243–254.
Harb H., van Tol E.A., Heine H., Braaksma M., Gross G., Overkamp K., Hennen M., Alrifai M., Conrad M.L., Renz H., and Garn H.2013. Neonatal supplementation of processed supernatant from Lactobacillus rhamnosus GG improves allergic airway inflammation in mice later in life. Clin. Exp. Allergy. 43(3):353–364.
Hardy H., Harris J., Lyon E., Beal J., and Foey A.D.2013. Probiotics, prebiotics and immunomodulation of gut mucosal defences: Homeostasis and immunopathology. Nutrients. 5(6):1869–1912.
Hayes C.L., Natividad J.M., Jury J., Martin R., Langella P., and Verdu E.F.2014. Efficacy of Bifidobacterium breve NCC2950 against DSS-induced colitis is dependent on bacterial preparation and timing of administration. Benef. Microbes. 5(1):79–88.
He C., Shan Y., and Song W.2015. Targeting gut microbiota as a possible therapy for diabetes. Nutr. Res.35(5):361–367.
Hemarajata P. and Versalovic J.2013. Effects of probiotics on gut microbiota: Mechanisms of intestinal immunomodulation and neuromodulation. Therap. Adv. Gastroenterol.6(1):39–51.
Hemarajata P., Gao C., Pflughoeft K.J., Thomas C.M., Saulnier D.M., Spinler J.K., and Versalovic J.2013. Lactobacillus reuteri-specific immunoregulatory gene rsiR modulates histamine production and immunomodulation by Lactobacillus reuteri. J. Bacteriol.195(24):5567–5576.
Hill C., Guarner F., Reid G., Gibson G.R., Merenstein D.J., Pot B., Morelli L., Canani R.B., Flint H.J., Salminen S., Calder P.C., and Sanders M.E.2014. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat. Rev. Gastroenterol. Hepatol.11(8):506–514.
Ho N.K., Hawley S.P., Ossa J.C., Mathieu O., Tompkins T.A., Johnson-Henry K.C., and Sherman P.M.2013. Immune signalling responses in intestinal epithelial cells exposed to pathogenic Escherichia coli and lactic acid-producing probiotics. Benef. Microbes. 4(2):195–209.
Honda K. and Littman D.R.2016. The microbiota in adaptive immune homeostasis and disease. Nature. 535(7610):75–84.
Hormannsperger G., von Schillde M.A., and Haller D.2013. Lactocepin as a protective microbial structure in the context of IBD. Gut Microbes. 4(2):152–157.
Hubbard T.D., Murray I.A., Bisson W.H., Lahoti T.S., Gowda K., Amin S.G., Patterson A.D., and Perdew G.H.2015. Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles. Sci. Rep.5:12689.
Imaoka A. and Umesaki Y.2009. Rationale for using of Bifidobacterium probiotic strains-fermented milk against colitis based on animal experiments and clinical trials. Probiotics Antimicrob. Proteins. 1(1):8–14.
Iraporda C., Errea A., Romanin D.E., Cayet D., Pereyra E., Pignataro O., Sirard J.C., Garrote G.L., Abraham A.G., and Rumbo M.2015. Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells. Immunobiology. 220(10):1161–1169.
Iraporda C., Romanin D.E., Rumbo M., Garrote G.L., and Abrahama A.G.2014. The role of lactate on the immunomodulatory properties of the nonbacterial fraction of kefir. Food Res. Int.62:247–253.
Isidro R.A., Bonilla F.J., Pagan H., Cruz M.L., Lopez P., Godoy L., Hernandez S., Loucil-Alicea R.Y., Rivera-Amill V., Yamamura Y., Isidro A.A., and Appleyard C.B.2014. The probiotic mixture VSL#3 alters the morphology and secretion profile of both polarized and unpolarized human macrophages in a polarization-dependent manner. J. Clin. Cell. Immunol.5(3):1000227.
Iyer C., Kosters A., Sethi G., Kunnumakkara A.B., Aggarwal B.B., and Versalovic J.2008. Probiotic Lactobacillus reuteri promotes TNF-induced apoptosis in human myeloid leukemia-derived cells by modulation of NF-kappaB and MAPK signaling. Cell. Microbiol.10(7):1442–1452.
Johnson-Henry K.C., Abrahamsson T.R., Wu R.Y., and Sherman P.M.2016. Probiotics, prebiotics, and synbiotics for the prevention of necrotizing enterocolitis. Adv. Nutr.7(5):928–937.
Johnson-Henry K.C., Nadjafi M., Avitzur Y., Mitchell D.J., Ngan B.Y., Galindo-Mata E., Jones N.L., and Sherman P.M.2005. Amelioration of the effects of Citrobacter rodentium infection in mice by pretreatment with probiotics. J. Infect. Dis.191(12):2106–2117.
Johnson-Henry K.C., Pinnell L.J., Waskow A.M., Irrazabal T., Martin A., Hausner M., and Sherman P.M.2014. Short-chain fructo-oligosaccharide and inulin modulate inflammatory responses and microbial communities in Caco2-bbe cells and in a mouse model of intestinal injury. J. Nutr.144(11):1725–1733.
Kabat A.M., Srinivasan N., and Maloy K.J.2014. Modulation of immune development and function by intestinal microbiota. Trends Immunol.35(11):507–517.
Kim H., Jung B.J., Jung J.H., Kim J.Y., Chung S.K., and Chung D.K.2012. Lactobacillus plantarum lipoteichoic acid alleviates TNF-α-induced inflammation in the HT-29 intestinal epithelial cell line. Mol. Cells. 33(5):479–486.
Kim H.G., Lee S.Y., Kim N.R., Ko M.Y., Lee J.M., Yi T.H., Chung S.K., and Chung D.K.2008. Inhibitory effects of Lactobacillus plantarum lipoteichoic acid (LTA) on Staphylococcus aureus LTA-induced tumor necrosis factor-alpha production. J. Microbiol. Biotechnol.18(6):1191–1196.
Kim J.Y., Kim H., Jung B.J., Kim N.R., Park J.E., and Chung D.K.2013a. Lipoteichoic acid isolated from Lactobacillus plantarum suppresses LPS-mediated atherosclerotic plaque inflammation. Mol. Cells. 35(2):115–124.
Kim M., Qie Y., Park J., and Kim C.H.2016. Gut microbial metabolites fuel host antibody responses. Cell Host Microbe. 20(2):202–214.
Kim M.H., Kang S.G., Park J.H., Yanagisawa M., and Kim C.H.2013b. Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice. Gastroenterology. 145(2):396–406.e10.
Kim S.O., Sheikh H.I., Ha S.D., Martins A., and Reid G.2006. G-CSF-mediated inhibition of JNK is a key mechanism for Lactobacillus rhamnosus-induced suppression of TNF production in macrophages. Cell. Microbiol.8(12):1958–1971.
Ko J.S., Yang H.R., Chang J.Y., and Seo J.K.2007. Lactobacillus plantarum inhibits epithelial barrier dysfunction and interleukin-8 secretion induced by tumor necrosis factor-alpha. World J. Gastroenterol.13(13):1962–1965.
Konieczna P., Groeger D., Ziegler M., Frei R., Ferstl R., Shanahan F., Quigley E.M., Kiely B., Akdis C.A., and O’Mahony L.2012. Bifidobacterium infantis 35624 administration induces Foxp3 T regulatory cells in human peripheral blood: Potential role for myeloid and plasmacytoid dendritic cells. Gut. 61(3):354–366.
Konieczna P., Schiavi E., Ziegler M., Groeger D., Healy S., Grant R., and O’Mahony L.2015. Human dendritic cell DC-SIGN and TLR-2 mediate complementary immune regulatory activities in response to Lactobacillus rhamnosus JB-1. PLoS ONE. 10(3):e0120261.
Konstantinov S.R., Smidt H., de Vos W.M., Bruijns S.C., Singh S.K., Valence F., Molle D., Lortal S., Altermann E., Klaenhammer T.R., and van Kooyk Y.2008. S layer protein A of Lactobacillus acidophilus NCFM regulates immature dendritic cell and T cell functions. Proc. Natl. Acad. Sci. USA. 105(49):19474–19479.
Kovacs-Nolan J., Kanatani H., Nakamura A., Ibuki M., and Mine Y.2013. β-1,4-mannobiose stimulates innate immune responses and induces TLR4-dependent activation of mouse macrophages but reduces severity of inflammation during endotoxemia in mice. J. Nutr.143(3):384–391.
Kristensen N.B., Bryrup T., Allin K.H., Nielsen T., Hansen T.H., and Pedersen O.2016. Alterations in fecal microbiota composition by probiotic supplementation in healthy adults: A systematic review of randomized controlled trials. Genome Med.8(1):52.
Kumar A., Wu H., Collier-Hyams L.S., Hansen J.M., Li T., Yamoah K., Pan Z.Q., Jones D.P., and Neish A.S.2007. Commensal bacteria modulate cullin-dependent signaling via generation of reactive oxygen species. EMBO J.26(21):4457–4466.
Latham T., Mackay L., Sproul D., Karim M., Culley J., Harrison D.J., Hayward L., Langridge-Smith P., Gilbert N., and Ramsahoye B.H.2012. Lactate, a product of glycolytic metabolism, inhibits histone deacetylase activity and promotes changes in gene expression. Nucleic Acids Res.40(11):4794–4803.
Lathrop S.K., Bloom S.M., Rao S.M., Nutsch K., Lio C.W., Santacruz N., Peterson D.A., Stappenbeck T.S., and Hsieh C.S.2011. Peripheral education of the immune system by colonic commensal microbiota. Nature. 478(7368):250–254.
Le D.T., Uram J.N., Wang H., Bartlett B.R., Kemberling H., Eyring A.D., Skora A.D., Luber B.S., Azad N.S., Laheru D., Biedrzycki B., Donehower R.C., Zaheer A., Fisher G.A., Crocenzi T.S., Lee J.J., Duffy S.M., Goldberg R.M., delaChapelle A., Koshiji M., Bhaijee F., Huebner T., Hruban R.H., Wood L.D., Cuka N., Pardoll D.M., Papadopoulos N., Kinzler K.W., Zhou S., Cornish T.C., Taube J.M., Anders R.A., Eshleman J.R., Vogelstein B., and Diaz L.A. Jr.2015. PD-1 blockade in tumors with mismatch-repair deficiency. N. Engl. J. Med.372(26):2509–2520.
Lebeer S., Claes I.J., and Vanderleyden J.2012. Anti-inflammatory potential of probiotics: Lipoteichoic acid makes a difference. Trends Microbiol.20(1):5–10.
Lebeer S., Vanderleyden J., and De Keersmaecker S.C.2010. Host interactions of probiotic bacterial surface molecules: Comparison with commensals and pathogens. Nat. Rev. Microbiol.8(3):171–184.
Lehmann S., Hiller J., van Bergenhenegouwen J., Knippels L.M., Garssen J., and Traidl-Hoffmann C.2015. In vitro evidence for immune-modulatory properties of non-digestible oligosaccharides: Direct effect on human monocyte derived dendritic cells. PLoS ONE. 10(7):e0132304.
Lin P.W., Myers L.E., Ray L., Song S.C., Nasr T.R., Berardinelli A.J., Kundu K., Murthy N., Hansen J.M., and Neish A.S.2009. Lactobacillus rhamnosus blocks inflammatory signaling in vivo via reactive oxygen species generation. Free Radic. Biol. Med.47(8):1205–1211.
Lin Q., Mathieu O., Tompkins T.A., Buckley N.D., and Green-Johnson J.M.2016. Modulation of the TNFα-induced gene expression profile of intestinal epithelial cells by soy fermented with lactic acid bacteria. J. Funct. Foods. 23:400–411.
Liu S., da Cunha A.P., Rezende R.M., Cialic R., Wei Z., Bry L., Comstock L.E., Gandhi R., and Weiner H.L.2016. The host shapes the gut microbiota via fecal microRNA. Cell Host Microbe. 19(1):32–43.
Lomax A.R., Cheung L.V., Noakes P.S., Miles E.A., and Calder P.C.2015. Inulin-type β2-1 fructans have some effect on the antibody response to seasonal influenza vaccination in healthy middle-aged humans. Front. Immunol.6:490.
Lomax A.R., Cheung L.V., Tuohy K.M., Noakes P.S., Miles E.A., and Calder P.C.2012. β2-1 Fructans have a bifidogenic effect in healthy middle-aged human subjects but do not alter immune responses examined in the absence of an in vivo immune challenge: Results from a randomised controlled trial. Br. J. Nutr.108(10):1818–1828.
Ma D., Forsythe P., and Bienenstock J.2004. Live Lactobacillus rhamnosus [corrected] is essential for the inhibitory effect on tumor necrosis factor alpha-induced interleukin-8 expression. Infect. Immun.72(9):5308–5314.
Macpherson C., Audy J., Mathieu O., and Tompkins T.A.2014. Multistrain probiotic modulation of intestinal epithelial cells’ immune response to a double-stranded RNA ligand, poly(i·c). Appl. Environ. Microbiol.80(5):1692–1700.
Marchesi J.R., Adams D.H., Fava F., Hermes G.D., Hirschfield G.M., Hold G., Quraishi M.N., Kinross J., Smidt H., Tuohy K.M., Thomas L.V., Zoetendal E.G., and Hart A.2016. The gut microbiota and host health: A new clinical frontier. Gut. 65(2):330–339.
Martinez F.O. and Gordon S.2014. The M1 and M2 paradigm of macrophage activation: Time for reassessment. F1000Prime Rep.6:13.
Martinez-Nunez R.T., Louafi F., Friedmann P.S., and Sanchez-Elsner T.2009. MicroRNA-155 modulates the pathogen binding ability of dendritic cells (DCs) by down-regulation of DC-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN). J. Biol. Chem.284(24):16334–16342.
Maslowski K.M., Vieira A.T., Ng A., Kranich J., Sierro F., Yu D., Schilter H.C., Rolph M.S., Mackay F., Artis D., Xavier R.J., Teixeira M.M., and Mackay C.R.2009. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 461(7268):1282–1286.
McCracken V.J., Chun T., Baldeon M.E., Ahrne S., Molin G., Mackie R.I., and Gaskins H.R.2002. TNF-alpha sensitizes HT-29 colonic epithelial cells to intestinal lactobacilli. Exp. Biol. Med. (Maywood). 227(8):665–670.
Mechoud M.A., Mateos M.V., de Valdez G.F., Villena J., Salvador G.A., and Rodriguez A.V.2012. Lactobacillus reuteri CRL1098 soluble factors modulate tumor necrosis factor alpha production in peripheral blood mononuclear cells: Involvement of lipid rafts. Int. Immunopharmacol.14(4):446–453.
Medellin-Pena M.J., Wang H., Johnson R., Anand S., and Griffiths M.W.2007. Probiotics affect virulence-related gene expression in Escherichia coli O157:H7. Appl. Environ. Microbiol.73(13):4259–4267.
Menard S., Candalh C., Bambou J.C., Terpend K., Cerf-Bensussan N., and Heyman M.2004. Lactic acid bacteria secrete metabolites retaining anti-inflammatory properties after intestinal transport. Gut. 53(6):821–828.
Miettinen M., Lehtonen A., Julkunen I., and Matikainen S.2000. Lactobacilli and Streptococci activate NF-kappa B and STAT signaling pathways in human macrophages. J. Immunol.164(7):3733–3740.
Migeotte I., Communi D., and Parmentier M.2006. Formyl peptide receptors: A promiscuous subfamily of G protein-coupled receptors controlling immune responses. Cytokine Growth Factor Rev.17(6):501–519.
Monaco C.L., Gootenberg D.B., Zhao G., Handley S.A., Ghebremichael M.S., Lim E.S., Lankowski A., Baldridge M.T., Wilen C.B., Flagg M., Norman J.M., Keller B.C., Luevano J.M., Wang D., Boum Y., Martin J.N., Hunt P.W., Bangsberg D.R., Siedner M.J., Kwon D.S., and Virgin H.W.2016. Altered virome and bacterial microbiome in human immunodeficiency virus-associated acquired immunodeficiency syndrome. Cell Host Microbe. 19(3):311–322.
Murata K., Tomosada Y., Villena J., Chiba E., Shimazu T., Aso H., Iwabuchi N., Xiao J.Z., Saito T., and Kitazawa H.2014. Bifidobacterium breve MCC-117 induces tolerance in porcine intestinal epithelial cells: Study of the mechanisms involved in the immunoregulatory effect. Biosci. Microbiota Food Health. 33(1):1–10.
Murofushi Y., Villena J., Morie K., Kanmani P., Tohno M., Shimazu T., Aso H., Suda Y., Hashiguchi K., Saito T., and Kitazawa H.2015. The toll-like receptor family protein RP105/MD1 complex is involved in the immunoregulatory effect of exopolysaccharides from Lactobacillus plantarum N14. Mol. Immunol.64(1):63–75.
Musilova S., Rada V., Vlkova E., and Bunesova V.2014. Beneficial effects of human milk oligosaccharides on gut microbiota. Benef. Microbes. 5(3):273–283.
Nandakumar N.S., Pugazhendhi S., Madhu Mohan K., Jayakanthan K., and Ramakrishna B.S.2009. Effect of Vibrio cholerae on chemokine gene expression in HT29 cells and its modulation by Lactobacillus GG. Scand. J. Immunol.69(3):181–187.
Neish A.S., Gewirtz A.T., Zeng H., Young A.N., Hobert M.E., Karmali V., Rao A.S., and Madara J.L.2000. Prokaryotic regulation of epithelial responses by inhibition of IkappaB-alpha ubiquitination. Science. 289(5484):1560–1563.
Noakes R. and Mellick N.2013. Immunohistochemical studies of the kynurenine pathway in morphea. Int. J. Tryptophan Res.6:97–102.
O’Callaghan J., Butto L.F., MacSharry J., Nally K., and O’Toole P.W.2012. Influence of adhesion and bacteriocin production by Lactobacillus salivarius on the intestinal epithelial cell transcriptional response. Appl. Environ. Microbiol.78(15):5196–5203.
O’Flaherty S. and Klaenhammer T.R.2012. Influence of exposure time on gene expression by human intestinal epithelial cells exposed to Lactobacillus acidophilus. Appl. Environ. Microbiol.78(14):5028–5032.
O’Hara A.M., O’Regan P., Fanning A., O’Mahony C., Macsharry J., Lyons A., Bienenstock J., OMahony L., and Shanahan F.2006. Functional modulation of human intestinal epithelial cell responses by Bifidobacterium infantis and Lactobacillus salivarius. Immunology. 118(2):202–215.
O’Mahony L., O’Callaghan L., McCarthy J., Shilling D., Scully P., Sibartie S., Kavanagh E., Kirwan W.O., Redmond H.P., Collins J.K., and Shanahan F.2006. Differential cytokine response from dendritic cells to commensal and pathogenic bacteria in different lymphoid compartments in humans. Am. J. Physiol. Gastrointest. Liver Physiol.290(4):G839–G845.
Ortega-Gonzalez M., Ocon B., Romero-Calvo I., Anzola A., Guadix E., Zarzuelo A., Suarez M.D., Sanchez de Medina F., and Martinez-Augustin O.2014. Nondigestible oligosaccharides exert nonprebiotic effects on intestinal epithelial cells enhancing the immune response via activation of TLR4-NFκB. Mol. Nutr. Food Res.58(2):384–393.
Patten D.A., Leivers S., Chadha M.J., Maqsood M., Humphreys P.N., Laws A.P., and Collett A.2014. The structure and immunomodulatory activity on intestinal epithelial cells of the EPSs isolated from Lactobacillus helveticus sp. Rosyjski and Lactobacillus acidophilus sp. 5e2. Carbohydr. Res.384:119–127.
Pearce E.J. and Everts B.2015. Dendritic cell metabolism. Nat. Rev. Immunol.15(1):18–29.
Petersen C. and Round J.L.2014. Defining dysbiosis and its influence on host immunity and disease. Cell. Microbiol.16(7):1024–1033.
Peterson L.W. and Artis D.2014. Intestinal epithelial cells: Regulators of barrier function and immune homeostasis. Nat. Rev. Immunol.14(3):141–153.
Rachmilewitz D., Katakura K., Karmeli F., Hayashi T., Reinus C., Rudensky B., Akira S., Takeda K., Lee J., Takabayashi K., and Raz E.2004. Toll-like receptor 9 signaling mediates the anti-inflammatory effects of probiotics in murine experimental colitis. Gastroenterology. 126(2):520–528.
Riedel C.U., Foata F., Philippe D., Adolfsson O., Eikmanns B.J., and Blum S.2006. Anti-inflammatory effects of bifidobacteria by inhibition of LPS-induced NF-kappaB activation. World J. Gastroenterol.12(23):3729–3735.
Roberfroid M.2007. Prebiotics: The concept revisited. J. Nutr.137(3 Suppl 2):830S–837S.
Rolig A.S., Parthasarathy R., Burns A.R., Bohannan B.J., and Guillemin K.2015. Individual members of the microbiota disproportionately modulate host innate immune responses. Cell Host Microbe. 18(5):613–620.
Ruiz L., Hevia A., Bernardo D., Margolles A., and Sanchez B.2014. Extracellular molecular effectors mediating probiotic attributes. FEMS Microbiol. Lett.359(1):1–11.
Sanders M.E., Guarner F., Guerrant R., Holt P.R., Quigley E.M., Sartor R.B., Sherman P.M., and Mayer E.A.2013. An update on the use and investigation of probiotics in health and disease. Gut. 62(5):787–796.
Schroder N.W., Morath S., Alexander C., Hamann L., Hartung T., Zahringer U., Gobel U.B., Weber J.R., and Schumann R.R.2003. Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via Toll-like receptor (TLR)-2, lipopolysaccharide-binding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved. J. Biol. Chem.278(18):15587–15594.
Seth A., Yan F., Polk D.B., and Rao R.K.2008. Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC- and MAP kinase-dependent mechanism. Am. J. Physiol. Gastrointest. Liver Physiol.294(4):G1060–G1069.
Shastri P., McCarville J., Kalmokoff M., Brooks S.P., and Green-Johnson J.M.2015. Sex differences in gut fermentation and immune parameters in rats fed an oligofructose-supplemented diet. Biol. Sex Differ.6:13.
Sivan A., Corrales L., Hubert N., Williams J.B., Aquino-Michaels K., Earley Z.M., Benyamin F.W., Lei Y.M., Jabri B., Alegre M.L., Chang E.B., and Gajewski T.F.2015. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 350(6264):1084–1089.
Smith P.M., Howitt M.R., Panikov N., Michaud M., Gallini C.A., Bohlooly Y.M., Glickman J.N., and Garrett W.S.2013. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 341(6145):569–573.
Smits H.H., Engering A., van der Kleij D., de Jong E.C., Schipper K., van Capel T.M., Zaat B.A., Yazdanbakhsh M., Wierenga E.A., van Kooyk Y., and Kapsenberg M.L.2005. Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J. Allergy Clin. Immunol.115(6):1260–1267.
Sonnenburg E.D., Smits S.A., Tikhonov M., Higginbottom S.K., Wingreen N.S., and Sonnenburg J.L.2016. Diet-induced extinctions in the gut microbiota compound over generations. Nature. 529(7585):212–215.
Sonnenburg J.L. and Backhed F.2016. Diet-microbiota interactions as moderators of human metabolism. Nature. 535(7610):56–64.
Tan J., McKenzie C., Vuillermin P.J., Goverse G., Vinuesa C.G., Mebius R.E., Macia L., and Mackay C.R.2016. Dietary fiber and bacterial SCFA enhance oral tolerance and protect against food allergy through diverse cellular pathways. Cell Rep.15(12):2809–2824.
Tao Y., Nomura M., Kitabatake N., and Tani F.2007. Mouse CD40-transfected cell lines cannot exhibit the binding and RANTES-stimulating activity of exogenous heat shock protein 70. Mol. Immunol.44(6):1262–1273.
Thaiss C.A., Zmora N., Levy M., and Elinav E.2016. The microbiome and innate immunity. Nature. 535(7610):65–74.
Thomas C.M., Hong T., van Pijkeren J.P., Hemarajata P., Trinh D.V., Hu W., Britton R.A., Kalkum M., and Versalovic J.2012. Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signaling. PLoS ONE. 7(2):e31951.
Thorburn A.N., McKenzie C.I., Shen S., Stanley D., Macia L., Mason L.J., Roberts L.K., Wong C.H., Shim R., Robert R., Chevalier N., Tan J.K., Marino E., Moore R.J., Wong L., McConville M.J., Tull D.L., Wood L.G., Murphy V.E., Mattes J., Gibson P.G., and Mackay C.R.2015. Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites. Nat. Commun.6:7320.
Tien M.T., Girardin S.E., Regnault B., Le Bourhis L., Dillies M.A., Coppee J.Y., Bourdet-Sicard R., Sansonetti P.J., and Pedron T.2006. Anti-inflammatory effect of Lactobacillus casei on Shigella-infected human intestinal epithelial cells. J. Immunol.176(2):1228–1237.
Tomosada Y., Villena J., Murata K., Chiba E., Shimazu T., Aso H., Iwabuchi N., Xiao J.Z., Saito T., and Kitazawa H.2013. Immunoregulatory effect of bifidobacteria strains in porcine intestinal epithelial cells through modulation of ubiquitin-editing enzyme A20 expression. PLoS ONE. 8(3):e59259.
Trompette A., Gollwitzer E.S., Yadava K., Sichelstiel A.K., Sprenger N., Ngom-Bru C., Blanchard C., Junt T., Nicod L.P., Harris N.L., and Marsland B.J.2014. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat. Med.20(2):159–166.
Tulini F.L., Hymery N., Choiset Y., Chobert J.-M., Haertlé T., De Martinis E.C.P., and Le Blay G.2015. Milk fermented with the probiotic candidate Lactobacillus paracasei FT700 induces differentiation of monocytes toward macrophages in vitro. J. Funct. Foods. 15:533–540.
Underwood M.A., Gaerlan S., De Leoz M.L., Dimapasoc L., Kalanetra K.M., Lemay D.G., German J.B., Mills D.A., and Lebrilla C.B.2015. Human milk oligosaccharides in premature infants: Absorption, excretion, and influence on the intestinal microbiota. Pediatr. Res.78(6):670–677.
Valladares R., Bojilova L., Potts A.H., Cameron E., Gardner C., Lorca G., and Gonzalez C.F.2013. Lactobacillus johnsonii inhibits indoleamine 2,3-dioxygenase and alters tryptophan metabolite levels in BioBreeding rats. FASEB J.27(4):1711–1720.
van Baarlen P., Wells J.M., and Kleerebezem M.2013. Regulation of intestinal homeostasis and immunity with probiotic lactobacilli. Trends Immunol.34(5):208–215.
Vatanen T., Kostic A.D., d’Hennezel E., Siljander H., Franzosa E.A., Yassour M., Kolde R., Vlamakis H., Arthur T.D., Hamalainen A.M., Peet A., Tillmann V., Uibo R., Mokurov S., Dorshakova N., Ilonen J., Virtanen S.M., Szabo S.J., Porter J.A., Lahdesmaki H., Huttenhower C., Gevers D., Cullen T.W., Knip M., Group D.S., and Xavier R.J.2016. Variation in microbiome LPS immunogenicity contributes to autoimmunity in humans. Cell. 165(6):1551.
Villena J., Suzuki R., Fujie H., Chiba E., Takahashi T., Tomosada Y., Shimazu T., Aso H., Ohwada S., Suda Y., Ikegami S., Itoh H., Alvarez S., Saito T., and Kitazawa H.2012. Immunobiotic Lactobacillus jensenii modulates the Toll-like receptor 4-induced inflammatory response via negative regulation in porcine antigen-presenting cells. Clin. Vaccine Immunol.19(7):1038–1053.
Vogel C.F., Khan E.M., Leung P.S., Gershwin M.E., Chang W.L., Wu D., Haarmann-Stemmann T., Hoffmann A., and Denison M.S.2014. Cross-talk between aryl hydrocarbon receptor and the inflammatory response: A role for nuclear factor-κB. J. Biol. Chem.289(3):1866–1875.
Vogt L., Meyer D., Pullens G., Faas M., Smelt M., Venema K., Ramasamy U., Schols H.A., and De Vos P.2015a. Immunological properties of inulin-type fructans. Crit. Rev. Food Sci. Nutr.55(3):414–436.
Vogt L.M., Meyer D., Pullens G., Faas M.M., Venema K., Ramasamy U., Schols H.A., and de Vos P.2014. Toll-like receptor 2 activation by β2→1-fructans protects barrier function of T84 human intestinal epithelial cells in a chain length-dependent manner. J. Nutr.144(7):1002–1008.
Vogt S.L., Pena-Diaz J., and Finlay B.B.2015b. Chemical communication in the gut: Effects of microbiota-generated metabolites on gastrointestinal bacterial pathogens. Anaerobe. 34:106–115.
Voltan S., Martines D., Elli M., Brun P., Longo S., Porzionato A., Macchi V., D’Inca R., Scarpa M., Palu G., Sturniolo G.C., Morelli L., and Castagliuolo I.2008. Lactobacillus crispatus M247-derived H2O2 acts as a signal transducing molecule activating peroxisome proliferator activated receptor-gamma in the intestinal mucosa. Gastroenterology. 135(4):1216–1227.
von Schillde M.A., Hormannsperger G., Weiher M., Alpert C.A., Hahne H., Bauerl C., van Huynegem K., Steidler L., Hrncir T., Perez-Martinez G., Kuster B., and Haller D.2012. Lactocepin secreted by Lactobacillus exerts anti-inflammatory effects by selectively degrading proinflammatory chemokines. Cell Host Microbe. 11(4):387–396.
Vong L., Pinnell L.J., Maattanen P., Yeung C.W., Lurz E., and Sherman P.M.2015. Selective enrichment of commensal gut bacteria protects against Citrobacter rodentium-induced colitis. Am. J. Physiol. Gastrointest. Liver Physiol.309(3):G181–G192.
Wagar L.E., Champagne C.P., Buckley N.D., Raymond Y., and Green-Johnson J.M.2009. Immunomodulatory properties of fermented soy and dairy milks prepared with lactic acid bacteria. J. Food Sci.74(8):M423–M430.
Wang L., Cao H., Liu L., Wang B., Walker W.A., Acra S.A., and Yan F.2014. Activation of epidermal growth factor receptor mediates mucin production stimulated by p40, a Lactobacillus rhamnosus GG-derived protein. J. Biol. Chem.289(29):20234–20244.
Wang Y., Liu L., Moore D.J., Shen X., Peek R.M., Acra S.A., Li H., Ren X., Polk D.B., and Yan F.2016. An LGG-derived protein promotes IgA production through upregulation of APRIL expression in intestinal epithelial cells. Mucosal Immunol.
Wentworth C.C., Alam A., Jones R.M., Nusrat A., and Neish A.S.2011. Enteric commensal bacteria induce extracellular signal-regulated kinase pathway signaling via formyl peptide receptor-dependent redox modulation of dual specific phosphatase 3. J. Biol. Chem.286(44):38448–38455.
Wheeler M.L., Limon J.J., Bar A.S., Leal C.A., Gargus M., Tang J., Brown J., Funari V.A., Wang H.L., Crother T.R., Arditi M., Underhill D.M., and Iliev I.D.2016. Immunological consequences of intestinal fungal dysbiosis. Cell Host Microbe. 19(6):865–873.
Wikoff W.R., Anfora A.T., Liu J., Schultz P.G., Lesley S.A., Peters E.C., and Siuzdak G.2009. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc. Natl. Acad. Sci. USA. 106(10):3698–3703.
Wu G.D., Compher C., Chen E.Z., Smith S.A., Shah R.D., Bittinger K., Chehoud C., Albenberg L.G., Nessel L., Gilroy E., Star J., Weljie A.M., Flint H.J., Metz D.C., Bennett M.J., Li H., Bushman F.D., and Lewis J.D.2016. Comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production. Gut. 65(1):63–72.
Yan F., Cao H., Cover T.L., Whitehead R., Washington M.K., and Polk D.B.2007. Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth. Gastroenterology. 132(2):562–575.
Yan F., Liu L., Dempsey P.J., Tsai Y.H., Raines E.W., Wilson C.L., Cao H., Cao Z., Liu L., and Polk D.B.2013. A Lactobacillus rhamnosus GG-derived soluble protein, p40, stimulates ligand release from intestinal epithelial cells to transactivate epidermal growth factor receptor. J. Biol. Chem.288(42):30742–30751.
Zelante T., Iannitti R.G., Cunha C., De Luca A., Giovannini G., Pieraccini G., Zecchi R., D’Angelo C., Massi-Benedetti C., Fallarino F., Carvalho A., Puccetti P., and Romani L.2013. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity. 39(2):372–385.
Zenhom M., Hyder A., de Vrese M., Heller K.J., Roeder T., and Schrezenmeir J.2011. Prebiotic oligosaccharides reduce proinflammatory cytokines in intestinal Caco-2 cells via activation of PPARγ and peptidoglycan recognition protein 3. J. Nutr.141(5):971–977.
Zhang C., Derrien M., Levenez F., Brazeilles R., Ballal S.A., Kim J., Degivry M.C., Quere G., Garault P., van Hylckama Vlieg J.E., Garrett W.S., Dore J., and Veiga P.2016. Ecological robustness of the gut microbiota in response to ingestion of transient food-borne microbes. ISME J.10(9):2235–2245.
Zhou W., Yuan Y., Li J., Yuan W.M., Huang L.G., and Zheng S.W.2015. Effect of Bifidobacterium on the mRNA expression levels of TRAF6, GSK-3beta, and microRNA-146a in LPS-stimulated rat intestinal epithelial cells. Genet. Mol. Res.14(3):10050–10056.
Zou W., Wolchok J.D., and Chen L.2016. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations. Sci. Transl. Med.8(328):328rv4.
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LymphoSign Journal
Volume 4 • Number 1 • March 2017
Pages: 1 - 24
History
Received: 12 October 2016
Accepted: 12 December 2016
Accepted manuscript online: 22 December 2016
Version of record online: 22 December 2016
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© 2017.
Authors
Competing Interests
Research efforts of the authors are supported by Lallemand Health Solutions (Montreal, Quebec, Canada) and PMS has received honoraria from Abbott Nutrition, Mead Johnson Nutritionals, and Nestlé Nutrition.
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Richard Y.Wu, Michael P.Jeffrey, Kathene C.Johnson-Henry, Julia M.Green-Johnson, and Philip M.Sherman. 2017. Impact of prebiotics, probiotics, and gut derived metabolites on host immunity. LymphoSign Journal.
4(1): 1-24. https://doi.org/10.14785/lymphosign-2016-0012
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