The low efficacy of human rotavirus (HRV) vaccines in low- and middle-income countries (LMIC) remains a major challenge for global health. Protein-calorie malnutrition (kwashiorkor) affects the gut microbiota and compromises immune development, leading to environmental enteropathy, vaccine failures, and increased susceptibility to enteric diseases in young children. Relationship between diet and reduced vaccine efficacy in developing countries is not well established; therefore, we investigated the interconnections between the host-microbiota-nutrition-HRV vaccine using HRV-vaccinated, human infant faecal microbiota (HIFM)-transplanted neonatal gnotobiotic pigs fed with a protein deficient or sufficient diet. The microbiota from faecal, intestinal (duodenum, ileum, jejunum, and colon), and systemic tissue (liver, spleen, and mesenteric lymph node [MLN]) samples was analysed before and after HRV challenge using MiSeq 16S rRNA sequencing. Overall, microbiota from deficient fed HIFM pigs displayed, compared to the sufficient group, significantly higher Shannon index, especially in the faeces and lower intestines; higher level of Proteus and Enterococcus, and lower level of Bifidobacterium, Clostridium, and Streptococcus in the three types of samples collected (P<0.05); and higher unique operational taxonomic units (OTUs), especially in the systemic tissues. Further, the multivariate analysis between microbiota and immunologic data showed that 38 OTUs at the genus level correlated (r2≤0.5 or ≥-0.5; P<0.05) with at least one host immune response parameter (regulatory [Tregs and transforming growth factor-β], effectors [interferon (IFN)-γ+ CD4+ and CD8+ T cells, IFN-γ and interleukin (IL)-12], and inflammatory [tumour necrosis factor-α, IL-17 and IL-22]) and with opposite trends between diet groups. Differences described above were increased after HRV challenge. We demonstrated that a protein deficient diet affects the composition of the gut microbiota and those changes may further correlate with immune responses induced by HRV and perturbed by the deficient diet. Thus, our findings suggest that the reduced efficacy of HRV vaccine observed in Gn pig model is in part attributed to the altered microbiota composition.
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Alexander, C. and Rietschel, E.T., 2001. Bacterial lipopolysaccharides and innate immunity. Journal of Endotoxin Research 7: 167-202.
'Bacterial lipopolysaccharides and innate immunity ' () 7 Journal of Endotoxin Research : 167 -202.
Angel, J., Franco, M.A. and Greenberg, H.B., 2012. Rotavirus immune responses and correlates of protection. Current Opinion in Virology 2: 419-425. https://doi.org/10.1016/j.coviro.2012.05.003
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., Levine, M.M., Lewis, K., Coia, M.L., Attah-Poku, M., Ojwando, J., Rivers, S.B., Victor, J.C., Nyambane, G., Hodgson, A., Schodel, F., Ciarlet, M. and Neuzil, K.M., 2010. 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. The Lancet 376: 606-614. https://doi.org/10.1016/s0140-6736(10)60889-6
Arrieta, M.C., Walter, J. and Finlay, B.B., 2016. Human microbiota-associated mice: a model with challenges. Cell Host & Microbe 19: 575-578. https://doi.org/10.1016/j.chom.2016.04.014
Azevedo, M.S.P., Yuan, L., Pouly, S., Gonzales, A.M., Jeong, K.I., Nguyen, T.V. and Saif, L.J., 2006. Cytokine responses in gnotobiotic pigs after infection with virulent or attenuated human rotavirus. Journal of Virology 80: 372-382. https://doi.org/10.1128/jvi.80.1.372-382.2006
Belkaid, Y. and Hand, T.W., 2014. Role of the microbiota in immunity and inflammation. Cell 157: 121-141. https://doi.org/10.1016/j.cell.2014.03.011
Biasucci, G., Benenati, B., Morelli, L., Bessi, E. and Boehm, G.N., 2008. Cesarean delivery may affect the early biodiversity of intestinal bacteria. Journal of Nutrition 138: 1796S-1800S. https://doi.org/10.1093/jn/138.9.1796S
Caporaso, J.G., Kuczynski, J., Stombaugh, J., Bittinger, K., Bushman, F.D., Costello, E.K., Fierer, N., Pena, A.G., Goodrich, J.K., Gordon, J.I., Huttley, G.A., Kelley, S.T., Knights, D., Koenig, J.E., Ley, R.E., Lozupone, C.A., McDonald, D., Muegge, B.D., Pirrung, M., Reeder, J., Sevinsky, J.R., Turnbaugh, P.J., Walters, W.A., Widmann, J., Yatsunenko, T., Zaneveld, J. and Knight, R., 2010. QIIME allows analysis of high-throughput community sequencing data. Nature Methods 7: 335-336. https://doi.org/10.1038/nmeth.f.303
Chattha, K.S., Vlasova, A.N., Kandasamy, S., Rajashekara, G. and Saif, L.J., 2013. Divergent immunomodulating effects of probiotics on T cell responses to oral attenuated human rotavirus vaccine and virulent human rotavirus infection in a neonatal gnotobiotic piglet disease model. Journal of Immunology 191: 2446-2456. https://doi.org/10.4049/jimmunol.1300678
Chen, M.-Y., Kirkwood, C.D., Bines, J., Cowley, D., Pavlic, D., Lee, K.J., Orsini, F., Watts, E., Barnes, G. and Danchin, M., 2017. Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand. Human Vaccines and Immunotherapeutics 13: 1126-1135. https://doi.org/10.1080/21645515.2016.1274474
Chilengi, R., Simuyandi, M., Beach, L., Mwila, K., Becker-Dreps, S., Emperador, D.M., Velasquez, D.E., Bosomprah, S. and Jiang, B., 2016. Association of maternal immunity with rotavirus vaccine immunogenicity in Zambian infants. PLoS ONE 11: e0150100. https://doi.org/10.1371/journal.pone.0150100
d’Hennezel, E., Abubucker, S., Murphy, L.O. and Cullen, T.W., 2017. Total lipopolysaccharide from the human gut microbiome silences toll-like receptor signaling. mSystems 2: e00046-00017.
'Total lipopolysaccharide from the human gut microbiome silences toll-like receptor signaling ' () 2 mSystems : e00046 -00017.
De Filippo, C., Cavalieri, D., Di Paola, M., Ramazzotti, M., Poullet, J.B., Massart, S., Collini, S., Pieraccini, G. and Lionetti, P., 2010. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proceedings of the National Academy of Sciences of the USA 107: 14691-14696. https://doi.org/10.1073/pnas.1005963107
Dehner, C., Fine, R. and Kriegel, M.A., 2019. The microbiome in systemic autoimmune disease: mechanistic insights from recent studies. Current Opinion in Rheumatology 31: 201-207. https://doi.org/10.1097/bor.0000000000000574
Dennehy, P.H., 2008. Rotavirus vaccines: an overview. Clinical Microbiology Reviews 21: 198-208. https://doi.org/10.1128/CMR.00029-07
Desselberger, U., 2017. Differences of rotavirus vaccine effectiveness by country: likely causes and contributing factors. Pathogens 6: 65. https://doi.org/10.3390/pathogens6040065
Fischer, D.D., Kandasamy, S., Paim, F.C., Langel, S.N., Alhamo, M.A., Shao, L., Chepngeno, J., Miyazaki, A., Huang, H.-C., Kumar, A., Rajashekara, G., Saif, L.J. and Vlasova, A.N., 2017. Protein malnutrition alters tryptophan and angiotensin-converting enzyme 2 homeostasis and adaptive immune responses in human rotavirus-infected gnotobiotic pigs with human infant fecal microbiota transplant. Clinical and Vaccine Immunology 24: e00172-00117. https://doi.org/10.1128/CVI.00172-17
Forbes, J.D., Van Domselaar, G. and Bernstein, C.N., 2016. The gut microbiota in immune-mediated inflammatory diseases. Frontiers in Microbiology 7: 1081-1081. https://doi.org/10.3389/fmicb.2016.01081
Garrett, W.S., Gallini, C.A., Yatsunenko, T., Michaud, M., DuBois, A., Delaney, M.L., Punit, S., Karlsson, M., Bry, L., Glickman, J.N., Gordon, J.I., Onderdonk, A.B. and Glimcher, L.H., 2010. Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. Cell Host and Microbe 8: 292-300. https://doi.org/10.1016/j.chom.2010.08.004
Gilmartin, A.A. and Petri Jr, W.A., 2015. Exploring the role of environmental enteropathy in malnutrition, infant development and oral vaccine response. Philosophical transactions of the Royal Society of London. Series B, Biological Sciences 370: 20140143. https://doi.org/10.1098/rstb.2014.0143
Glass, R.I., Parashar, U., Patel, M., Gentsch, J. and Jiang, B., 2014. Rotavirus vaccines: successes and challenges. Journal of Infection 68, Suppl. 1: S9-18. https://doi.org/10.1016/j.jinf.2013.09.010
Gough, E.K., Stephens, D.A., Moodie, E.E., Prendergast, A.J., Stoltzfus, R.J., Humphrey, J.H. and Manges, A.R., 2015. Linear growth faltering in infants is associated with Acidaminococcus sp. and community-level changes in the gut microbiota. Microbiome 3: 24. https://doi.org/10.1186/s40168-015-0089-2
Gray, J., 2011. Rotavirus vaccines: safety, efficacy and public health impact. Journal of Internal Medicine 270: 206-214. https://doi.org/10.1111/j.1365-2796.2011.02409.x
Groome, M.J., Moon, S.S., Velasquez, D., Jones, S., Koen, A., Van Niekerk, N., Jiang, B., Parashar, U.D. and Madhi, S.A., 2014. Effect of breastfeeding on immunogenicity of oral live-attenuated human rotavirus vaccine: a randomized trial in HIV-uninfected infants in Soweto, South Africa. Bulletin of the World Health Organization 92: 238-245. https://doi.org/10.2471/blt.13.128066
Guerrant, R.L., Oriá, R.B., Moore, S.R., Oriá, M.O.B. and Lima, A.A.M., 2008. Malnutrition as an enteric infectious disease with long-term effects on child development. Nutrition Reviews 66: 487-505. https://doi.org/10.1111/j.1753-4887.2008.00082.x
Harris, V., Ali, A., Fuentes, S., Korpela, K., Kazi, M., Tate, J., Parashar, U., Wiersinga, W.J., Giaquinto, C., De Weerth, C. and de Vos, W.M., 2018. Rotavirus vaccine response correlates with the infant gut microbiota composition in Pakistan. Gut Microbes 9: 93-101. https://doi.org/10.1080/19490976.2017.1376162
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., Lewis, K.D.C. and De Vos, W.M., 2017. Significant correlation between the infant gut microbiome and rotavirus vaccine response in rural Ghana. Journal of Infectious Diseases 215: 34-41. https://doi.org/10.1093/infdis/jiw518
Huang, H.C., Vlasova, A.N., Kumar, A., Kandasamy, S., Fischer, D.D., Deblais, L., Paim, F.C., Langel, S.N., Alhamo, M.A., Rauf, A., Shao, L., Saif, L.J. and Rajashekara, G., 2018. Effect of antibiotic, probiotic, and human rotavirus infection on colonisation dynamics of defined commensal microbiota in a gnotobiotic pig model. Beneficial Microbes 9: 71-86. https://doi.org/10.3920/bm2016.0225
Huda, M.N., Lewis, Z., Kalanetra, K.M., Rashid, M., Ahmad, S.M., Raqib, R., Qadri, F., Underwood, M.A., Mills, D.A. and Stephensen, C.B., 2014. Stool microbiota and vaccine responses of infants. Pediatrics 134: e362-e372. https://doi.org/10.1542/peds.2013-3937
Istrate, C., Hagbom, M., Vikström, E., Magnusson, K.-E. and Svensson, L., 2014. Rotavirus infection increases intestinal motility but not permeability at the onset of diarrhea. Journal of Virology 88: 3161. https://doi.org/10.1128/JVI.02927-13
Iturriza-Gómara, M. and Cunliffe, N.A., 2017. The gut microbiome as possible key to understanding and improving rotavirus vaccine performance in high-disease burden settings. Journal of Infectious Diseases 215: 8-10. https://doi.org/10.1093/infdis/jiw521
Kanareykina, S.K., Misautova, A.A., Zlatkina, A.R. and Levina, E.N., 1987. Proteus dysbioses in patients with ulcerative colitis. Nahrung 31: 557-561.
'Proteus dysbioses in patients with ulcerative colitis ' () 31 Nahrung : 557 -561.
Kers, J.G., Velkers, F.C., Fischer, E.A.J., Hermes, G.D.A., Stegeman, J.A. and Smidt, H., 2018. Host and environmental factors affecting the intestinal microbiota in chickens. Frontiers in Microbiology 9: 235-235. https://doi.org/10.3389/fmicb.2018.00235
Kim, Y.-G., 2017. Microbiota influences vaccine and mucosal adjuvant efficacy. Immune Network 17: 20-24. https://doi.org/10.4110/in.2017.17.1.20
Kumar, A., Vlasova, A.N., Deblais, L., Huang, H.-C., Wijeratne, A., Kandasamy, S., Fischer, D.D., Langel, S.N., Paim, F.C., Alhamo, M.A., Shao, L., Saif, L.J. and Rajashekara, G., 2018. Impact of nutrition and rotavirus infection on the infant gut microbiota in a humanized pig model. BMC Gastroenterology 18: 93. https://doi.org/10.1186/s12876-018-0810-2
Kuss, S.K., Best, G.T., Etheredge, C.A., Pruijssers, A.J., Frierson, J.M., Hooper, L.V., Dermody, T.S. and Pfeiffer, J.K., 2011. Intestinal microbiota promote enteric virus replication and systemic pathogenesis. Science 334: 249-252. https://doi.org/10.1126/science.1211057
Lamberti, L.M., Ashraf, S., Walker, C.L.F. and Black, R.E., 2016. A systematic review of the effect of rotavirus vaccination on diarrhea outcomes among children younger than 5 years. Pediatric Infectious Disease Journal 35: 992-998. https://doi.org/10.1097/inf.0000000000001232
Marchesi, J.R., Adams, D.H., Fava, F., Hermes, G.D.A., 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: 330-339. https://doi.org/10.1136/gutjnl-2015-309990
Marteau, P., Flourie, B., Pochart, P., Chastang, C., Desjeux, J.-F. and Rambaud, J.-C., 2007. Effect of the microbial lactase (EC 3.2.1.23) activity in yoghurt on the intestinal absorption of lactose: an in vivo study in lactase-deficient humans. British Journal of Nutrition 64: 71-79. https://doi.org/10.1079/BJN19900010
Meurens, F., Summerfield, A., Nauwynck, H., Saif, L. and Gerdts, V., 2012. The pig: a model for human infectious diseases. Trends in Microbiology 20: 50-57. https://doi.org/10.1016/j.tim.2011.11.002
Meyer, R.C., Bohl, E.H. and Kohler, E.M., 1964. Procurement and maintenance of germ-free swine for microbiological investigations. Applied Microbiology 12: 295-300.
'Procurement and maintenance of germ-free swine for microbiological investigations ' () 12 Applied Microbiology : 295 -300.
Milani, C., Duranti, S., Bottacini, F., Casey, E., Turroni, F., Mahony, J., Belzer, C., Delgado Palacio, S., Arboleya Montes, S., Mancabelli, L., Lugli, G.A., Rodriguez, J.M., Bode, L., De Vos, W., Gueimonde, M., Margolles, A., Van Sinderen, D. and Ventura, M., 2017. The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota. Microbiology and Molecular Biology Reviews 81: e00036-00017.
'The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota ' () 81 Microbiology and Molecular Biology Reviews : e00036 -00017.
Miyazaki, A., Kandasamy, S., Michael, H., Langel, S.N., Paim, F.C., Chepngeno, J., Alhamo, M.A., Fischer, D.D., Huang, H.-C., Srivastava, V., Kathayat, D., Deblais, L., Rajashekara, G., Saif, L.J. and Vlasova, A.N., 2018. Protein deficiency reduces efficacy of oral attenuated human rotavirus vaccine in a human infant fecal microbiota transplanted gnotobiotic pig model. Vaccine 36: 6270-6281. https://doi.org/10.1016/j.vaccine.2018.09.008
Monedero, V., Buesa, J. and Rodríguez-Díaz, J., 2018. The interactions between host glycobiology, bacterial microbiota, and viruses in the gut. Viruses 10: 96. https://doi.org/10.3390/v10020096
Moore, T.A., Hanson, C.K. and Anderson-Berry, A., 2011. Colonization of the gastrointestinal tract in neonates: a review. Infant, Child, and Adolescent Nutrition 3: 291-295. https://doi.org/10.1177/1941406411421629
Muszer, M., Noszczyńska, M., Kasperkiewicz, K. and Skurnik, M., 2015. Human microbiome: when a friend becomes an enemy. Archivum Immunologiae et Therapiae Experimentalis 63: 287-298. https://doi.org/10.1007/s00005-015-0332-3
Mwape, I., Bosomprah, S., Mwaba, J., Mwila-Kazimbaya, K., Laban, N.M., Chisenga, C.C., Sijumbila, G., Simuyandi, M. and Chilengi, R., 2017. Immunogenicity of rotavirus vaccine (Rotarix™) in infants with environmental enteric dysfunction. PLoS ONE 12: e0187761. https://doi.org/10.1371/journal.pone.0187761
Mwila, K., Chilengi, R., Simuyandi, M., Permar, S.R. and Becker-Dreps, S., 2017. Contribution of maternal immunity to decreased rotavirus vaccine performance in low- and middle-income countries. Clinical and Vaccine Immunology 24: e00405-00416. https://doi.org/10.1128/CVI.00405-16
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., John, J., Kang, G. and Grassly, N.C., 2018. Influence of the intestinal microbiota on the immunogenicity of oral rotavirus vaccine given to infants in south India. Vaccine 36: 264-272. https://doi.org/10.1016/j.vaccine.2017.11.031
Parker, E.P.K., Ramani, S., Lopman, B.A., Church, J.A., Iturriza-Gómara, M., Prendergast, A.J. and Grassly, N.C., 2017. Causes of impaired oral vaccine efficacy in developing countries. Future Microbiology 13: 97-118. https://doi.org/10.2217/fmb-2017-0128
Ramig, R.F., 2004. Pathogenesis of intestinal and systemic rotavirus infection. Journal of Virology 78: 10213. https://doi.org/10.1128/JVI.78.19.10213-10220.2004
Rooks, M.G. and Garrett, W.S., 2016. Gut microbiota, metabolites and host immunity. Nature Reviews Immunology 16: 341. https://doi.org/10.1038/nri.2016.42
Saavedra, J.M., Bauman, N.A., Perman, J.A., Yolken, R.H., Saavedra, J.M., Bauman, N.A. and Oung, I., 1994. Feeding of Bifidobacterium bifidum and Streptococcus thermophilus to infants in hospital for prevention of diarrhoea and shedding of rotavirus. The Lancet 344: 1046-1049. https://doi.org/10.1016/S0140-6736(94)91708-6
Shin, N.R., Whon, T.W. and Bae, J.W., 2015. Proteobacteria: microbial signature of dysbiosis in gut microbiota. Trends in Biotechnology 33: 496-503. https://doi.org/10.1016/j.tibtech.2015.06.011
Sindhu, K.N.C., Cunliffe, N., Peak, M., Turner, M., Darby, A., Grassly, N., Gordon, M., Dube, Q., Babji, S., Praharaj, I., Verghese, V., Iturriza-Gómara, M. and Kang, G., 2017. Impact of maternal antibodies and infant gut microbiota on the immunogenicity of rotavirus vaccines in African, Indian and European infants: protocol for a prospective cohort study. BMJ Open 7: e016577. https://doi.org/10.1136/bmjopen-2017-016577
Su, L., Shen, L., Clayburgh, D.R., Nalle, S.C., Sullivan, E.A., Meddings, J.B., Abraham, C. and Turner, J.R., 2009. Targeted epithelial tight junction dysfunction causes immune activation and contributes to development of experimental colitis. Gastroenterology 136: 551-563. https://doi.org/10.1053/j.gastro.2008.10.081
Tate, J.E., Burton, A.H., Boschi-Pinto, C. and Parashar, U.D., 2016. Global, regional, and national estimates of rotavirus mortality in children <5 years of age, 2000-2013. Clinical Infectious Diseases 62, Suppl. 2: S96-S105. https://doi.org/10.1093/cid/civ1013
The, H.C., Florez de Sessions, P., Jie, S., Pham Thanh, D., Thompson, C.N., Nguyen Ngoc Minh, C., Chu, C.W., Tran, T.-A., Thomson, N.R., Thwaites, G.E., Rabaa, M.A., Hibberd, M. and Baker, S., 2018. Assessing gut microbiota perturbations during the early phase of infectious diarrhea in Vietnamese children. Gut Microbes 9: 38-54. https://doi.org/10.1080/19490976.2017.1361093
Twitchell, E.L., Tin, C., Wen, K., Zhang, H., Becker-Dreps, S., Azcarate-Peril, M.A., Vilchez, S., Li, G., Ramesh, A., Weiss, M., Lei, S., Bui, T., Yang, X., Schultz-Cherry, S. and Yuan, L., 2016. Modeling human enteric dysbiosis and rotavirus immunity in gnotobiotic pigs. Gut Pathogens 8: 51. https://doi.org/10.1186/s13099-016-0136-y
Uchiyama, R., Chassaing, B., Zhang, B. and Gewirtz, A.T., 2014. Antibiotic treatment suppresses rotavirus infection and enhances specific humoral immunity. Journal of Infectious Diseases 210: 171-182. https://doi.org/10.1093/infdis/jiu037
Valdez, Y., Brown, E.M. and Finlay, B.B., 2014. Influence of the microbiota on vaccine effectiveness. Trends in Immunology 35: 526-537. https://doi.org/10.1016/j.it.2014.07.003
Vatanen, T., Kostic, A.D., d’Hennezel, E., Siljander, H., Franzosa, E.A., Yassour, M., Kolde, R., Vlamakis, H., Arthur, T.D., Hämäläinen, A.-M., Peet, A., Tillmann, V., Uibo, R., Mokurov, S., Dorshakova, N., Ilonen, J., Virtanen, S.M., Szabo, S.J., Porter, J.A., Lähdesmäki, H., Huttenhower, C., Gevers, D., Cullen, T.W., Knip, M. and Xavier, R.J., 2016. Variation in microbiome LPS immunogenicity contributes to autoimmunity in humans. Cell 165: 842-853. https://doi.org/10.1016/j.cell.2016.04.007
Velasquez, D.E., Parashar, U. and Jiang, B., 2018. Decreased performance of live attenuated, oral rotavirus vaccines in low-income settings: causes and contributing factors. Expert Review of Vaccines 17: 145-161. https://doi.org/10.1080/14760584.2018.1418665
Vlasova, A.N., Paim, F.C., Kandasamy, S., Alhamo, M.A., Fischer, D.D., Langel, S.N., Deblais, L., Kumar, A., Chepngeno, J., Shao, L., Huang, H.-C., Candelero-Rueda, R.A., Rajashekara, G. and Saif, L.J., 2017. Protein malnutrition modifies innate immunity and gene expression by intestinal epithelial cells and human rotavirus infection in neonatal gnotobiotic pigs. mSphere 2: e00046-00017. https://doi.org/10.1128/mSphere.00046-17
Wallace, T.C., Guarner, F., Madsen, K., Cabana, M.D., Gibson, G., Hentges, E. and Sanders, M.E., 2011. Human gut microbiota and its relationship to health and disease. Nutrition Reviews 69: 392-403. https://doi.org/10.1111/j.1753-4887.2011.00402.x
Wang, M. and Donovan, S.M., 2015. Human microbiota-associated swine: current progress and future opportunities. ILAR Journal 56: 63-73. https://doi.org/10.1093/ilar/ilv006
Wu, H.J. and Wu, E., 2012. The role of gut microbiota in immune homeostasis and autoimmunity. Gut Microbes 3: 4-14. https://doi.org/10.4161/gmic.19320
Yatsunenko, T., Rey, F.E., Manary, M.J., Trehan, I., Dominguez-Bello, M.G., Contreras, M., Magris, M., Hidalgo, G., Baldassano, R.N., Anokhin, A.P., Heath, A.C., Warner, B., Reeder, J., Kuczynski, J., Caporaso, J.G., Lozupone, C.A., Lauber, C., Clemente, J.C., Knights, D., Knight, R. and Gordon, J.I., 2012. Human gut microbiome viewed across age and geography. Nature 486: 222. https://doi.org/10.1038/nature11053
Yuan, L., Ward, L.A., Rosen, B.I., To, T.L. and Saif, L.J., 1996. Systematic and intestinal antibody-secreting cell responses and correlates of protective immunity to human rotavirus in a gnotobiotic pig model of disease. Journal of Virology 70: 3075.
'Systematic and intestinal antibody-secreting cell responses and correlates of protective immunity to human rotavirus in a gnotobiotic pig model of disease ' () 70 Journal of Virology : 3075.
Yuan, L., Wen, K., Azevedo, M.S.P., Gonzalez, A.M., Zhang, W. and Saif, L.J., 2008. Virus-specific intestinal IFN-gamma producing T cell responses induced by human rotavirus infection and vaccines are correlated with protection against rotavirus diarrhea in gnotobiotic pigs. Vaccine 26: 3322-3331. https://doi.org/10.1016/j.vaccine.2008.03.085
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., Le, H.T., Coia, M.L., Lewis, K., Rivers, S.B., Sack, D.A., Schodel, F., Steele, A.D., Neuzil, K.M. and Ciarlet, M., 2010. Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in Asia: a randomised, double-blind, placebo-controlled trial. The Lancet 376: 615-623. https://doi.org/10.1016/s0140-6736(10)60755-6
Zhang, H., Wang, H., Shepherd, M., Wen, K., Li, G., Yang, X., Kocher, J., Giri-Rachman, E., Dickerman, A., Settlage, R. and Yuan, L., 2014. Probiotics and virulent human rotavirus modulate the transplanted human gut microbiota in gnotobiotic pigs. Gut Pathogens 6: 39-39. https://doi.org/10.1186/s13099-014-0039-8
Zijlstra, R.T., Donovan, S.M., Odle, J., Gelberg, H.B., Petschow, B.W. and Gaskins, H.R., 1997. Protein-energy malnutrition delays small-intestinal recovery in neonatal pigs infected with rotavirus. Journal of Nutrition 127: 1118-1127. https://doi.org/10.1093/jn/127.6.1118
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The low efficacy of human rotavirus (HRV) vaccines in low- and middle-income countries (LMIC) remains a major challenge for global health. Protein-calorie malnutrition (kwashiorkor) affects the gut microbiota and compromises immune development, leading to environmental enteropathy, vaccine failures, and increased susceptibility to enteric diseases in young children. Relationship between diet and reduced vaccine efficacy in developing countries is not well established; therefore, we investigated the interconnections between the host-microbiota-nutrition-HRV vaccine using HRV-vaccinated, human infant faecal microbiota (HIFM)-transplanted neonatal gnotobiotic pigs fed with a protein deficient or sufficient diet. The microbiota from faecal, intestinal (duodenum, ileum, jejunum, and colon), and systemic tissue (liver, spleen, and mesenteric lymph node [MLN]) samples was analysed before and after HRV challenge using MiSeq 16S rRNA sequencing. Overall, microbiota from deficient fed HIFM pigs displayed, compared to the sufficient group, significantly higher Shannon index, especially in the faeces and lower intestines; higher level of Proteus and Enterococcus, and lower level of Bifidobacterium, Clostridium, and Streptococcus in the three types of samples collected (P<0.05); and higher unique operational taxonomic units (OTUs), especially in the systemic tissues. Further, the multivariate analysis between microbiota and immunologic data showed that 38 OTUs at the genus level correlated (r2≤0.5 or ≥-0.5; P<0.05) with at least one host immune response parameter (regulatory [Tregs and transforming growth factor-β], effectors [interferon (IFN)-γ+ CD4+ and CD8+ T cells, IFN-γ and interleukin (IL)-12], and inflammatory [tumour necrosis factor-α, IL-17 and IL-22]) and with opposite trends between diet groups. Differences described above were increased after HRV challenge. We demonstrated that a protein deficient diet affects the composition of the gut microbiota and those changes may further correlate with immune responses induced by HRV and perturbed by the deficient diet. Thus, our findings suggest that the reduced efficacy of HRV vaccine observed in Gn pig model is in part attributed to the altered microbiota composition.
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