{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:19:13Z","timestamp":1783523953097,"version":"3.55.0"},"reference-count":86,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T00:00:00Z","timestamp":1650931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1132975"],"award-info":[{"award-number":["1132975"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["SRI40200003"],"award-info":[{"award-number":["SRI40200003"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Diabetes is recognised as the world\u2019s fastest growing chronic condition globally. Helminth infections have been shown to be associated with a lower prevalence of type 2 diabetes (T2D), in part due to their ability to induce a type 2 immune response. Therefore, to understand the molecular mechanisms that underlie the development of T2D-induced insulin resistance, we treated mice fed on normal or diabetes-promoting diets with excretory\/secretory products (ES) from the gastrointestinal helminth Nippostrongylus brasiliensis. We demonstrated that treatment with crude ES products from adult worms (AES) or infective third-stage larvae (L3ES) from N. brasiliensis improved glucose tolerance and attenuated body weight gain in mice fed on a high glycaemic index diet. N. brasiliensis ES administration to mice was associated with a type 2 immune response measured by increased eosinophils and IL-5 in peripheral tissues but not IL-4, and with a decrease in the level of IL-6 in adipose tissue and corresponding increase in IL-6 levels in the liver. Moreover, treatment with AES or L3ES was associated with significant changes in the community composition of the gut microbiota at the phylum and order levels. These data highlight a role for N. brasiliensis ES in modulating the immune response associated with T2D, and suggest that N. brasiliensis ES contain molecules with therapeutic potential for treating metabolic syndrome and T2D.<\/jats:p>","DOI":"10.3390\/biom12050637","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T11:45:55Z","timestamp":1650973555000},"page":"637","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Administration of Hookworm Excretory\/Secretory Proteins Improves Glucose Tolerance in a Mouse Model of Type 2 Diabetes"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0294-5385","authenticated-orcid":false,"given":"Zainab","family":"Khudhair","sequence":"first","affiliation":[{"name":"Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafid","family":"Alhallaf","sequence":"additional","affiliation":[{"name":"Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia"},{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9337-9616","authenticated-orcid":false,"given":"Ramon M.","family":"Eichenberger","sequence":"additional","affiliation":[{"name":"Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia"},{"name":"Institute of Parasitology, Vetsuisse Faculty, University of Zurich, CH-8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0788-6513","authenticated-orcid":false,"given":"Matt","family":"Field","sequence":"additional","affiliation":[{"name":"Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia"},{"name":"John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutz","family":"Krause","sequence":"additional","affiliation":[{"name":"Microba Life Sciences, Brisbane, QLD 4000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1443-7233","authenticated-orcid":false,"given":"Javier","family":"Sotillo","sequence":"additional","affiliation":[{"name":"Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia"},{"name":"Parasitology Reference and Research Laboratory, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0896-8441","authenticated-orcid":false,"given":"Alex","family":"Loukas","sequence":"additional","affiliation":[{"name":"Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,26]]},"reference":[{"key":"ref_1","unstructured":"Suvi Karuranga, J.d.R.F., Huang, Y., and Malanda, B. (2017). IDF Diabetes Atlas, International Diabetes Federation. [8th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.jaci.2016.07.007","article-title":"Regulation of the host immune system by helminth parasites","volume":"138","author":"Maizels","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1146\/annurev-immunol-032713-120218","article-title":"Immunity to helminths: Resistance, regulation, and susceptibility to gastrointestinal nematodes","volume":"33","author":"Grencis","year":"2015","journal-title":"Annu. Rev. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zakeri, A., Hansen, E.P., Andersen, S.D., Williams, A.R., and Nejsum, P. (2018). Immunomodulation by Helminths: Intracellular Pathways and Extracellular Vesicles. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02349"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Logan, J., Manda, S.S., Choi, Y.J., Field, M., Eichenberger, R.M., Mulvenna, J., Nagaraj, S.H., Fujiwara, R.T., Gazzinelli-Guimaraes, P., and Bueno, L. (2018). Comprehensive analysis of human hookworm secreted proteins using a proteogenomic approach. bioRxiv.","DOI":"10.1101\/406843"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1128\/CMR.05040-11","article-title":"Helminth infections and host immune regulation","volume":"25","author":"McSorley","year":"2012","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.molbiopara.2009.04.008","article-title":"Helminth immunoregulation: The role of parasite secreted proteins in modulating host immunity","volume":"167","author":"Hewitson","year":"2009","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1128\/IAI.00563-12","article-title":"Hookworm excretory\/secretory products induce interleukin-4 (IL-4) + IL-10 + CD4 + T cell responses and suppress pathology in a mouse model of colitis","volume":"81","author":"Ferreira","year":"2013","journal-title":"Infect. Immun."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ferreira, I.B., Pickering, D.A., Troy, S., Croese, J., Loukas, A., and Navarro, S. (2017). Suppression of inflammation and tissue damage by a hookworm recombinant protein in experimental colitis. Clin. Transl. Immunol., 6.","DOI":"10.1038\/cti.2017.42"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Sotillo, J., Ferreira, I., Potriquet, J., Laha, T., Navarro, S., Loukas, A., and Mulvenna, J. (2017). Changes in protein expression after treatment with Ancylostoma caninum excretory\/secretory products in a mouse model of colitis. Sci. Rep., 7.","DOI":"10.1038\/srep41883"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wangchuk, P., Shepherd, C., Constantinoiu, C., Ryan, R.Y.M., Kouremenos, K.A., Becker, L., Jones, L., Buitrago, G., Giacomin, P., and Wilson, D. (2019). Hookworm-Derived Metabolites Suppress Pathology in a Mouse Model of Colitis and Inhibit Secretion of Key Inflammatory Cytokines in Primary Human Leukocytes. Infect. Immun., 87.","DOI":"10.1128\/IAI.00851-18"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Navarro, S., Pickering, D.A., Ferreira, I.B., Jones, L., Ryan, S., Troy, S., Leech, A., Hotez, P.J., Zhan, B., and Laha, T. (2016). Hookworm recombinant protein promotes regulatory T cell responses that suppress experimental asthma. Sci. Transl. Med., 8.","DOI":"10.1126\/scitranslmed.aaf8807"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1002\/eji.200636553","article-title":"Impairment of dendritic cell function by excretory-secretory products: A potential mechanism for nematode-induced immunosuppression","volume":"37","author":"Segura","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1084\/jem.20101074","article-title":"Helminth secretions induce de novo T cell Foxp3 expression and regulatory function through the TGF-beta pathway","volume":"207","author":"Grainger","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1002\/eji.200425167","article-title":"Selective maturation of dendritic cells by Nippostrongylus brasiliensis-secreted proteins drives Th2 immune responses","volume":"34","author":"Balic","year":"2004","journal-title":"Eur. J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Eichenberger, R.M., Ryan, S., Jones, L., Buitrago, G., Polster, R., Montes de Oca, M., Zuvelek, J., Giacomin, P.R., Dent, L.A., and Engwerda, C.R. (2018). Hookworm Secreted Extracellular Vesicles Interact with Host Cells and Prevent Inducible Colitis in Mice. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00850"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1164\/rccm.200601-054OC","article-title":"Helminth-derived products inhibit the development of allergic responses in mice","volume":"175","author":"Wohlleben","year":"2007","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7380","DOI":"10.1128\/IAI.69.12.7380-7386.2001","article-title":"Nippocystatin, a cysteine protease inhibitor from Nippostrongylus brasiliensis, inhibits antigen processing and modulates antigen-specific immune response","volume":"69","author":"Dainichi","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1111\/imm.12049","article-title":"Modulation of dendritic cell function and immune response by cysteine protease inhibitor from murine nematode parasite Heligmosomoides polygyrus","volume":"138","author":"Sun","year":"2013","journal-title":"Immunology"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Lund, M.E., O\u2019Brien, B.A., Hutchinson, A.T., Robinson, M.W., Simpson, A.M., Dalton, J.P., and Donnelly, S. (2014). Secreted proteins from the helminth Fasciola hepatica inhibit the initiation of autoreactive T cell responses and prevent diabetes in the NOD mouse. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0086289"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zaccone, P., Burton, O.T., Gibbs, S., Miller, N., Jones, F.M., Dunne, D.W., and Cooke, A. (2010). Immune modulation by Schistosoma mansoni antigens in NOD mice: Effects on both innate and adaptive immune systems. J. Biomed. Biotechnol., 2010.","DOI":"10.1155\/2010\/795210"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1096\/fj.14-266239","article-title":"Chronic helminth infection and helminth-derived egg antigens promote adipose tissue M2 macrophages and improve insulin sensitivity in obese mice","volume":"29","author":"Hussaarts","year":"2015","journal-title":"FASEB J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1038\/nm.2962","article-title":"Immunomodulatory glycan LNFPIII alleviates hepatosteatosis and insulin resistance through direct and indirect control of metabolic pathways","volume":"18","author":"Bhargava","year":"2012","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1096\/fj.15-277822","article-title":"The helminth T2 RNase omega1 promotes metabolic homeostasis in an IL-33- and group 2 innate lymphoid cell-dependent mechanism","volume":"30","author":"Hams","year":"2016","journal-title":"FASEB J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1530\/JME-17-0112","article-title":"Helminth antigens counteract a rapid high-fat diet-induced decrease in adipose tissue eosinophils","volume":"59","author":"Kusters","year":"2017","journal-title":"J. Mol. Endocrinol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Tang, C.L., Yu, X.H., Li, Y., Zhang, R.H., Xie, J., and Liu, Z.M. (2019). Schistosoma japonicum Soluble Egg Antigen Protects Against Type 2 Diabetes in Lepr (db\/db) Mice by Enhancing Regulatory T Cells and Th2 Cytokines. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01471"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1159\/000448401","article-title":"Filarial Infection or Antigen Administration Improves Glucose Tolerance in Diet-Induced Obese Mice","volume":"8","author":"Berbudi","year":"2016","journal-title":"J. Innate Immun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.immuni.2015.09.012","article-title":"The Intestinal Microbiota Contributes to the Ability of Helminths to Modulate Allergic Inflammation","volume":"43","author":"Zaiss","year":"2015","journal-title":"Immunity"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1126\/science.aaf3229","article-title":"Helminth infection promotes colonization resistance via type 2 immunity","volume":"352","author":"Ramanan","year":"2016","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.phrs.2018.04.008","article-title":"Helminth infection in mice improves insulin sensitivity via modulation of gut microbiota and fatty acid metabolism","volume":"132","author":"Pace","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Shimokawa, C., Obi, S., Shibata, M., Olia, A., Imai, T., Suzue, K., and Hisaeda, H. (2019). Suppression of Obesity by an Intestinal Helminth through Interactions with Intestinal Microbiota. Infect. Immun., 87.","DOI":"10.1128\/IAI.00042-19"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ben-Amram, H., Bashi, T., Werbner, N., Neuman, H., Fridkin, M., Blank, M., Shoenfeld, Y., and Koren, O. (2017). Tuftsin-Phosphorylcholine Maintains Normal Gut Microbiota in Collagen Induced Arthritic Mice. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.01222"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Doonan, J., Tarafdar, A., Pineda, M.A., Lumb, F.E., Crowe, J., Khan, A.M., Hoskisson, P.A., Harnett, M.M., and Harnett, W. (2019). The parasitic worm product ES-62 normalises the gut microbiota bone marrow axis in inflammatory arthritis. Nat. Commun., 10.","DOI":"10.1038\/s41467-019-09361-0"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Neuman, H., Mor, H., Bashi, T., Givol, O., Watad, A., Shemer, A., Volkov, A., Barshack, I., Fridkin, M., and Blank, M. (2019). Helminth-Based Product and the Microbiome of Mice with Lupus. mSystems, 4.","DOI":"10.1128\/mSystems.00160-18"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/j.ijpara.2007.04.006","article-title":"Impaired resistance in early secondary Nippostrongylus brasiliensis infections in mice with defective eosinophilopoeisis","volume":"37","author":"Knott","year":"2007","journal-title":"Int. J. Parasitol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.1074\/mcp.M114.038950","article-title":"Secreted Proteomes of Different Developmental Stages of the Gastrointestinal Nematode Nippostrongylus brasiliensis","volume":"13","author":"Sotillo","year":"2014","journal-title":"Mol. Cell Proteom."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Khudhair, Z., Alhallaf, R., Eichenberger, R.M., Whan, J., Kupz, A., Field, M., Krause, L., Wilson, D.T., Daly, N.L., and Giacomin, P. (2020). Gastrointestinal Helminth Infection Improves Insulin Sensitivity, Decreases Systemic Inflammation, and Alters the Composition of Gut Microbiota in Distinct Mouse Models of Type 2 Diabetes. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.606530"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Thang, M.W.C., Chua, X.Y., Price, G., Gorse, D., and Field, M.A. (2019). MetaDEGalaxy: Galaxy workflow for differential abundance analysis of 16s metagenomic data. F1000Research, 8.","DOI":"10.12688\/f1000research.18866.1"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nmeth.f.303","article-title":"QIIME allows analysis of high-throughput community sequencing data","volume":"7","author":"Caporaso","year":"2010","journal-title":"Nat. Methods"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1093\/bioinformatics\/btr381","article-title":"UCHIME improves sensitivity and speed of chimera detection","volume":"27","author":"Edgar","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5069","DOI":"10.1128\/AEM.03006-05","article-title":"Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB","volume":"72","author":"DeSantis","year":"2006","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1093\/bioinformatics\/btq461","article-title":"Search and clustering orders of magnitude faster than BLAST","volume":"26","author":"Edgar","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"McDonald, D., Clemente, J.C., Kuczynski, J., Rideout, J.R., Stombaugh, J., Wendel, D., Wilke, A., Huse, S., Hufnagle, J., and Meyer, F. (2012). The Biological Observation Matrix (BIOM) format or: How I learned to stop worrying and love the ome-ome. Gigascience, 1.","DOI":"10.1186\/2047-217X-1-7"},{"key":"ref_46","first-page":"235","article-title":"Phyloseq: A bioconductor package for handling and analysis of high-throughput phylogenetic sequence data","volume":"2012","author":"McMurdie","year":"2012","journal-title":"Pac. Symp. Biocomput."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1093\/bioinformatics\/btw725","article-title":"Calypso: A user-friendly web-server for mining and visualizing microbiome-environment interactions","volume":"33","author":"Zakrzewski","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1242\/bio.016790","article-title":"Development of a diet-induced murine model of diabetes featuring cardinal metabolic and pathophysiological abnormalities of type 2 diabetes","volume":"5","author":"Morris","year":"2016","journal-title":"Biol. Open"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2952","DOI":"10.1182\/blood.V79.11.2952.bloodjournal79112952","article-title":"Interleukin-5 selectively enhances the chemotactic response of eosinophils obtained from normal but not eosinophilic subjects","volume":"79","author":"Sehmi","year":"1992","journal-title":"Blood"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.4049\/jimmunol.143.7.2311","article-title":"IL-5-dependent conversion of normodense human eosinophils to the hypodense phenotype uses 3T3 fibroblasts for enhanced viability, accelerated hypodensity, and sustained antibody-dependent cytotoxicity","volume":"143","author":"Rothenberg","year":"1989","journal-title":"J. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1084\/jem.167.1.43","article-title":"Purified interleukin 5 supports the terminal differentiation and proliferation of murine eosinophilic precursors","volume":"167","author":"Yamaguchi","year":"1988","journal-title":"J. Exp. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1159\/000237717","article-title":"Protective roles of eosinophils in Nippostrongylus brasiliensis infection","volume":"114","author":"Shin","year":"1997","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1084\/jem.20121964","article-title":"Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages","volume":"210","author":"Molofsky","year":"2013","journal-title":"J. Exp. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1126\/science.1201475","article-title":"Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis","volume":"332","author":"Wu","year":"2011","journal-title":"Science"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Tran, G.T., Wilcox, P.L., Dent, L.A., Robinson, C.M., Carter, N., Verma, N.D., Hall, B.M., and Hodgkinson, S.J. (2017). Interleukin-5 Mediates Parasite-Induced Protection against Experimental Autoimmune Encephalomyelitis: Association with Induction of Antigen-Specific CD4(+)CD25(+) T Regulatory Cells. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01453"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"703","DOI":"10.4049\/jimmunol.1501820","article-title":"Helminth Products Protect against Autoimmunity via Innate Type 2 Cytokines IL-5 and IL-33, which Promote Eosinophilia","volume":"196","author":"Finlay","year":"2016","journal-title":"J. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1615\/CritRevEukaryotGeneExpr.2017019712","article-title":"Role of Interleukin-6 in Development of Insulin Resistance and Type 2 Diabetes Mellitus","volume":"27","author":"Rehman","year":"2017","journal-title":"Crit. Rev. Eukaryot. Gene Expr."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1126\/science.1160794","article-title":"A stress signaling pathway in adipose tissue regulates hepatic insulin resistance","volume":"322","author":"Sabio","year":"2008","journal-title":"Science"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1038\/nrm1489","article-title":"Liver regeneration: From myth to mechanism","volume":"5","author":"Taub","year":"2004","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1007\/s00125-010-1865-y","article-title":"Interleukin-6-deficient mice develop hepatic inflammation and systemic insulin resistance","volume":"53","author":"Matthews","year":"2010","journal-title":"Diabetologia"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.cmet.2010.06.011","article-title":"Interleukin-6 signaling in liver-parenchymal cells suppresses hepatic inflammation and improves systemic insulin action","volume":"12","author":"Wunderlich","year":"2010","journal-title":"Cell Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1046\/j.1365-2567.2002.01501.x","article-title":"Interleukin-6 promotes the production of interleukin-4 and interleukin-5 by interleukin-2-dependent and -independent mechanisms in freshly isolated human T cells","volume":"107","author":"Heijink","year":"2002","journal-title":"Immunology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4761","DOI":"10.4049\/jimmunol.174.8.4761","article-title":"IL-6 increases primed cell expansion and survival","volume":"174","author":"Rochman","year":"2005","journal-title":"J. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1084\/jem.20062027","article-title":"Eosinophil-derived neurotoxin acts as an alarmin to activate the TLR2-MyD88 signal pathway in dendritic cells and enhances Th2 immune responses","volume":"205","author":"Yang","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/j.1440-1711.2005.01303.x","article-title":"Secretory products from infective forms of Nippostrongylus brasiliensis induce a rapid allergic airway inflammatory response","volume":"83","author":"Marsland","year":"2005","journal-title":"Immunol. Cell Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1128\/IAI.00053-13","article-title":"Parasitic nematode-induced modulation of body weight and associated metabolic dysfunction in mouse models of obesity","volume":"81","author":"Yang","year":"2013","journal-title":"Infect. Immun."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Nirmalkar, K., Murugesan, S., Pizano-Zarate, M.L., Villalobos-Flores, L.E., Garcia-Gonzalez, C., Morales-Hernandez, R.M., Nunez-Hernandez, J.A., Hernandez-Quiroz, F., Romero-Figueroa, M.D.S., and Hernandez-Guerrero, C. (2018). Gut Microbiota and Endothelial Dysfunction Markers in Obese Mexican Children and Adolescents. Nutrients, 10.","DOI":"10.3390\/nu10122009"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"108","DOI":"10.15436\/2376-0949.15.031","article-title":"Composition, Diversity and Abundance of Gut Microbiome in Prediabetes and Type 2 Diabetes","volume":"2","author":"Lambeth","year":"2015","journal-title":"J. Diabetes Obes."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Di Luccia, B., Crescenzo, R., Mazzoli, A., Cigliano, L., Venditti, P., Walser, J.C., Widmer, A., Baccigalupi, L., Ricca, E., and Iossa, S. (2015). Rescue of Fructose-Induced Metabolic Syndrome by Antibiotics or Faecal Transplantation in a Rat Model of Obesity. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0134893"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4175","DOI":"10.1128\/AEM.00380-09","article-title":"Diet-induced metabolic improvements in a hamster model of hypercholesterolemia are strongly linked to alterations of the gut microbiota","volume":"75","author":"Martinez","year":"2009","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Hou, Y.P., He, Q.Q., Ouyang, H.M., Peng, H.S., Wang, Q., Li, J., Lv, X.F., Zheng, Y.N., Li, S.C., and Liu, H.L. (2017). Human Gut Microbiota Associated with Obesity in Chinese Children and Adolescents. BioMed Res. Int., 2017.","DOI":"10.1155\/2017\/7585989"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Zhang, X., Shen, D., Fang, Z., Jie, Z., Qiu, X., Zhang, C., Chen, Y., and Ji, L. (2013). Human gut microbiota changes reveal the progression of glucose intolerance. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071108"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"10454","DOI":"10.18632\/aging.102469","article-title":"Abnormal gut microbiota composition contributes to the development of type 2 diabetes mellitus in db\/db mice","volume":"11","author":"Yu","year":"2019","journal-title":"Aging"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Kim, J., Choi, J.H., Oh, T., Ahn, B., and Unno, T. (2020). Codium fragile Ameliorates High-Fat Diet-Induced Metabolism by Modulating the Gut Microbiota in Mice. Nutrients, 12.","DOI":"10.3390\/nu12061848"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Fujio-Vejar, S., Vasquez, Y., Morales, P., Magne, F., Vera-Wolf, P., Ugalde, J.A., Navarrete, P., and Gotteland, M. (2017). The Gut Microbiota of Healthy Chilean Subjects Reveals a High Abundance of the Phylum Verrucomicrobia. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.01221"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1099\/ijs.0.02873-0","article-title":"Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium","volume":"54","author":"Derrien","year":"2004","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Tailford, L.E., Crost, E.H., Kavanaugh, D., and Juge, N. (2015). Mucin glycan foraging in the human gut microbiome. Front. Genet., 6.","DOI":"10.3389\/fgene.2015.00081"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/1574-6941.12228","article-title":"A gut microbiota-targeted dietary intervention for amelioration of chronic inflammation underlying metabolic syndrome","volume":"87","author":"Xiao","year":"2014","journal-title":"FEMS Microbiol. Ecol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/ismej.2009.112","article-title":"Interactions between gut microbiota, host genetics and diet relevant to development of metabolic syndromes in mice","volume":"4","author":"Zhang","year":"2010","journal-title":"ISME J."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Brandt, A., Hernandez-Arriaga, A., Kehm, R., Sanchez, V., Jin, C.J., Nier, A., Baumann, A., Camarinha-Silva, A., and Bergheim, I. (2019). Metformin attenuates the onset of non-alcoholic fatty liver disease and affects intestinal microbiota and barrier in small intestine. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-43228-0"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Larsen, N., Vogensen, F.K., van den Berg, F.W., Nielsen, D.S., Andreasen, A.S., Pedersen, B.K., Al-Soud, W.A., Sorensen, S.J., Hansen, L.H., and Jakobsen, M. (2010). Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009085"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3465","DOI":"10.1111\/1462-2920.13826","article-title":"Comparative genomics of the DNA damage-inducible network in the Patescibacteria","volume":"19","author":"Barbe","year":"2017","journal-title":"Environ. Microbiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1080\/10408398.2014.934438","article-title":"Gut microbiota and probiotics: Focus on diabetes mellitus","volume":"57","author":"Ribeiro","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1093\/nutrit\/nux062","article-title":"Interindividual variability in gut microbiota and host response to dietary interventions","volume":"75","author":"Healey","year":"2017","journal-title":"Nutr. Rev."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Rinninella, E., Raoul, P., Cintoni, M., Franceschi, F., Miggiano, G.A.D., Gasbarrini, A., and Mele, M.C. (2019). What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases. Microorganisms, 7.","DOI":"10.3390\/microorganisms7010014"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/5\/637\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:01:20Z","timestamp":1760137280000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/5\/637"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,26]]},"references-count":86,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["biom12050637"],"URL":"https:\/\/doi.org\/10.3390\/biom12050637","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,26]]}}}