{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T22:07:54Z","timestamp":1775340474698,"version":"3.50.1"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"The authors acknowledge the support of the Intramural Research Program of NIAID."},{"DOI":"10.13039\/100000060","name":"U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI130126"],"award-info":[{"award-number":["AI130126"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Visceral leishmaniasis (VL) is transmitted by <jats:italic>Leishmania<\/jats:italic>-infected sand fly bites and malnutrition is a known risk factor in human VL. Models using sand fly transmission or malnutrition promote parasite dissemination. By investigating features of <jats:italic>L. donovani<\/jats:italic>-<jats:italic>Lutzomyia longipalpis<\/jats:italic> transmission to malnourished mice, we show that a comparable IL1-\u03b2-driven acute inflammation is maintained in malnourished (MN-SF) and well-nourished (WN-SF) sand fly-infected mice. However, parasite dissemination was more pronounced in MN-SF that had a significantly higher acute (<jats:italic>P<\/jats:italic>\u2009\u2264\u20090.001) and chronic (<jats:italic>P<\/jats:italic>\u2009\u2264\u20090.0001) splenic parasite burden compared to WN-SF. Compared to WN-SF, MN-SF exhibited chronic clinical symptoms (<jats:italic>P<\/jats:italic>\u2009\u2264\u20090.0001), neutrophilia (<jats:italic>P<\/jats:italic>\u2009\u2264\u20090.001), lymphocytopenia (<jats:italic>P<\/jats:italic>\u2009\u2264\u20090.0001), increased heme oxygenase-1 (<jats:italic>P<\/jats:italic>\u2009\u2264\u20090.001) and IL17-A (<jats:italic>P<\/jats:italic>\u2009\u2264\u20090.0001) levels, dysregulation of liver enzymes, lymph node barrier dysfunction, and augmented dysbiosis, all associated with enhanced VL severity. Combining vector-transmission and malnutrition provides an improved model to study VL pathogenesis and host defense.<\/jats:p>","DOI":"10.1038\/s42003-025-08106-8","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T17:21:55Z","timestamp":1747156915000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Malnutrition exacerbates pathogenesis of Lutzomyia longipalpis sand fly-transmitted Leishmania donovani"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9027-0523","authenticated-orcid":false,"given":"Eva","family":"Iniguez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Doehl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5945-5040","authenticated-orcid":false,"given":"Pedro","family":"Cecilio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1606-559X","authenticated-orcid":false,"given":"Tiago Donatelli","family":"Serafim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1497-8128","authenticated-orcid":false,"given":"Caroline","family":"Percopo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yvonne","family":"Rangel-Gonzalez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5741-9668","authenticated-orcid":false,"given":"Somaditya","family":"Dey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elvia J.","family":"Osorio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Huffcutt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Roitman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Meneses","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9756-865X","authenticated-orcid":false,"given":"Mara","family":"Short","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5589-9450","authenticated-orcid":false,"given":"Jesus G.","family":"Valenzuela","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter C.","family":"Melby","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4304-636X","authenticated-orcid":false,"given":"Shaden","family":"Kamhawi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,13]]},"reference":[{"key":"8106_CR1","unstructured":"World Health Organization. WHO: Leishmaniasis Fact Sheet. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/leishmaniasis (2024)."},{"key":"8106_CR2","unstructured":"UNICEF. One third of children in the developing world are stunted by malnutrition. (2009)."},{"key":"8106_CR3","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/S0140-6736(86)91725-3","volume":"1","author":"R Badaro","year":"1986","unstructured":"Badaro, R., Carvalho, E. M., Rocha, H., Queiroz, A. C. & Jones, T. C. Leishmania donovani: an opportunistic microbe associated with progressive disease in three immunocompromised patients. Lancet 1, 647\u2013649 (1986).","journal-title":"Lancet"},{"key":"8106_CR4","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1093\/infdis\/156.6.1030","volume":"156","author":"BJ Cerf","year":"1987","unstructured":"Cerf, B. J. et al. Malnutrition as a risk factor for severe visceral leishmaniasis. J. Infect. Dis. 156, 1030\u20131033 (1987).","journal-title":"J. Infect. Dis."},{"key":"8106_CR5","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1017\/S0950268800051074","volume":"110","author":"C Dye","year":"1993","unstructured":"Dye, C., Vidor, E. & Dereure, J. Serological diagnosis of leishmaniasis: on detecting infection as well as disease. Epidemiol. Infect. 110, 647\u2013656 (1993).","journal-title":"Epidemiol. Infect."},{"key":"8106_CR6","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1093\/clinids\/8.3.447","volume":"8","author":"LH Harrison","year":"1986","unstructured":"Harrison, L. H., Naidu, T. G., Drew, J. S., de Alencar, J. E. & Pearson, R. D. Reciprocal relationships between undernutrition and the parasitic disease visceral leishmaniasis. Rev. Infect. Dis. 8, 447\u2013453 (1986).","journal-title":"Rev. Infect. Dis."},{"key":"8106_CR7","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1111\/j.1365-3024.2009.01117.x","volume":"31","author":"G Malafaia","year":"2009","unstructured":"Malafaia, G. Protein-energy malnutrition as a risk factor for visceral leishmaniasis: a review. Parasite Immunol. 31, 587\u2013596 (2009).","journal-title":"Parasite Immunol."},{"key":"8106_CR8","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1086\/381203","volume":"38","author":"S Collin","year":"2004","unstructured":"Collin, S. et al. Conflict and kala-azar: determinants of adverse outcomes of kala-azar among patients in southern Sudan. Clin. Infect. Dis. 38, 612\u2013619 (2004).","journal-title":"Clin. Infect. Dis."},{"key":"8106_CR9","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1128\/CMR.00119-16","volume":"30","author":"MK Ibrahim","year":"2017","unstructured":"Ibrahim, M. K., Zambruni, M., Melby, C. L. & Melby, P. C. Impact of childhood malnutrition on host defense and infection. Clin. Microbiol. Rev. 30, 919\u2013971 (2017).","journal-title":"Clin. Microbiol. Rev."},{"key":"8106_CR10","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1189\/jlb.0203064","volume":"74","author":"GM Anstead","year":"2003","unstructured":"Anstead, G. M., Chandrasekar, B., Zhang, Q. & Melby, P. C. Multinutrient undernutrition dysregulates the resident macrophage proinflammatory cytokine network, nuclear factor-kappaB activation, and nitric oxide production. J. Leukoc. Biol. 74, 982\u2013991 (2003).","journal-title":"J. Leukoc. Biol."},{"key":"8106_CR11","doi-asserted-by":"publisher","first-page":"4709","DOI":"10.1128\/IAI.69.8.4709-4718.2001","volume":"69","author":"GM Anstead","year":"2001","unstructured":"Anstead, G. M. et al. Malnutrition alters the innate immune response and increases early visceralization following Leishmania donovani infection. Infect. Immun. 69, 4709\u20134718 (2001).","journal-title":"Infect. Immun."},{"key":"8106_CR12","doi-asserted-by":"publisher","first-page":"e0011040","DOI":"10.1371\/journal.pntd.0011040","volume":"17","author":"EY Osorio","year":"2023","unstructured":"Osorio, E. Y. et al. Malnutrition-related parasite dissemination from the skin in visceral leishmaniasis is driven by PGE2-mediated amplification of CCR7-related trafficking of infected inflammatory monocytes. PLoS Negl. Trop. Dis. 17, e0011040 (2023).","journal-title":"PLoS Negl. Trop. Dis."},{"key":"8106_CR13","doi-asserted-by":"publisher","first-page":"e2329","DOI":"10.1371\/journal.pntd.0002329","volume":"7","author":"MK Ibrahim","year":"2013","unstructured":"Ibrahim, M. K. et al. The malnutrition-related increase in early visceralization of Leishmania donovani is associated with a reduced number of lymph node phagocytes and altered conduit system flow. PLoS Negl. Trop. Dis. 7, e2329 (2013).","journal-title":"PLoS Negl. Trop. Dis."},{"key":"8106_CR14","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.chom.2017.12.002","volume":"23","author":"R Dey","year":"2018","unstructured":"Dey, R. et al. Gut microbes egested during bites of infected sand flies augment severity of leishmaniasis via inflammasome-derived IL-1beta. Cell Host Microbe 23, 134\u2013143.e136 (2018).","journal-title":"Cell Host Microbe"},{"key":"8106_CR15","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1016\/j.pt.2021.07.003","volume":"37","author":"TD Serafim","year":"2021","unstructured":"Serafim, T. D. et al. Leishmaniasis: the act of transmission. Trends Parasitol. 37, 976\u2013987 (2021).","journal-title":"Trends Parasitol."},{"key":"8106_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108317","volume":"33","author":"T DeSouza-Vieira","year":"2020","unstructured":"DeSouza-Vieira, T. et al. Heme oxygenase-1 induction by blood-feeding arthropods controls skin inflammation and promotes disease tolerance. Cell Rep. 33, 108317 (2020).","journal-title":"Cell Rep."},{"key":"8106_CR17","first-page":"96","volume":"65","author":"KE O\u2019Connell","year":"2015","unstructured":"O\u2019Connell, K. E. et al. Practical murine hematopathology: a comparative review and implications for research. Comp. Med 65, 96\u2013113 (2015).","journal-title":"Comp. Med"},{"key":"8106_CR18","unstructured":"Charles River. BALB\/C Mouse Hematology. https:\/\/www.criver.com\/sites\/default\/files\/resources\/doc_a\/BALBcMouseClinicalPathologyData.pdf (2012)."},{"key":"8106_CR19","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.3389\/fimmu.2017.01620","volume":"8","author":"G Quintela-Carvalho","year":"2017","unstructured":"Quintela-Carvalho, G. et al. Heme drives oxidative stress-associated cell death in human neutrophils infected with leishmania infantum. Front. Immunol. 8, 1620 (2017).","journal-title":"Front. Immunol."},{"key":"8106_CR20","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1016\/j.pt.2006.09.004","volume":"22","author":"J Alvar","year":"2006","unstructured":"Alvar, J., Yactayo, S. & Bern, C. Leishmaniasis and poverty. Trends Parasitol. 22, 552\u2013557 (2006).","journal-title":"Trends Parasitol."},{"key":"8106_CR21","doi-asserted-by":"publisher","first-page":"e0005924","DOI":"10.1371\/journal.pntd.0005924","volume":"11","author":"GD Melo","year":"2017","unstructured":"Melo, G. D. et al. New insights into experimental visceral leishmaniasis: real-time in vivo imaging of Leishmania donovani virulence. PLoS Negl. Trop. Dis. 11, e0005924 (2017).","journal-title":"PLoS Negl. Trop. Dis."},{"key":"8106_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-09085-5","volume":"7","author":"GD Melo","year":"2017","unstructured":"Melo, G. D. et al. Unveiling cerebral Leishmaniasis: parasites and brain inflammation in Leishmania donovani infected mice. Sci. Rep. 7, 8454 (2017).","journal-title":"Sci. Rep."},{"key":"8106_CR23","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1186\/s12917-017-1174-5","volume":"13","author":"WL Macau","year":"2017","unstructured":"Macau, W. L. et al. Main lesions in the central nervous system of dogs due to Leishmania infantum infection. BMC Vet. Res. 13, 255 (2017).","journal-title":"BMC Vet. Res."},{"key":"8106_CR24","doi-asserted-by":"publisher","first-page":"e0188150","DOI":"10.1371\/journal.pone.0188150","volume":"12","author":"PO Staff","year":"2017","unstructured":"Staff, P. O. Correction: Occurrence of Leishmania infantum in the central nervous system of naturally infected dogs: parasite load, viability, co-infections and histological alterations. PLoS ONE 12, e0188150 (2017).","journal-title":"PLoS ONE"},{"key":"8106_CR25","doi-asserted-by":"publisher","first-page":"1752","DOI":"10.1093\/infdis\/jiw022","volume":"213","author":"H Aslan","year":"2016","unstructured":"Aslan, H. et al. New insights into the transmissibility of Leishmania infantum from dogs to sand flies: experimental vector-transmission reveals persistent parasite depots at bite sites.  J. Infect. Dis. 213, 1752\u20131761 (2016).","journal-title":"J. Infect. Dis."},{"key":"8106_CR26","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1093\/infdis\/jis932","volume":"207","author":"H Aslan","year":"2013","unstructured":"Aslan, H. et al. A new model of progressive visceral leishmaniasis in hamsters by natural transmission via bites of vector sand flies.  J. Infect. Dis. 207, 1328\u20131338 (2013).","journal-title":"J. Infect. Dis."},{"key":"8106_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00103-8","volume":"8","author":"JSP Doehl","year":"2017","unstructured":"Doehl, J. S. P. et al. Skin parasite landscape determines host infectiousness in visceral leishmaniasis. Nat. Commun. 8, 57 (2017).","journal-title":"Nat. Commun."},{"key":"8106_CR28","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1126\/science.1159194","volume":"321","author":"NC Peters","year":"2008","unstructured":"Peters, N. C. et al. In vivo imaging reveals an essential role for neutrophils in leishmaniasis transmitted by sand flies. Science 321, 970\u2013974 (2008).","journal-title":"Science"},{"key":"8106_CR29","doi-asserted-by":"publisher","first-page":"e1002536","DOI":"10.1371\/journal.ppat.1002536","volume":"8","author":"FL Ribeiro-Gomes","year":"2012","unstructured":"Ribeiro-Gomes, F. L., Peters, N. C., Debrabant, A. & Sacks, D. L. Efficient capture of infected neutrophils by dendritic cells in the skin inhibits the early anti-leishmania response. PLoS Pathog. 8, e1002536 (2012).","journal-title":"PLoS Pathog."},{"key":"8106_CR30","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1258\/td.2011.110058","volume":"41","author":"EA Khalil","year":"2011","unstructured":"Khalil, E. A. et al. Blindness following visceral leishmaniasis: a neglected post-kala-azar complication. Trop. Doct. 41, 139\u2013140 (2011).","journal-title":"Trop. Doct."},{"key":"8106_CR31","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-14-527","volume":"14","author":"RJ Maude","year":"2014","unstructured":"Maude, R. J. et al. Retinal changes in visceral leishmaniasis by retinal photography. BMC Infect. Dis. 14, 527 (2014).","journal-title":"BMC Infect. Dis."},{"key":"8106_CR32","doi-asserted-by":"publisher","first-page":"212","DOI":"10.3928\/1542-8877-20030501-10","volume":"34","author":"JA Montero","year":"2003","unstructured":"Montero, J. A., Ruiz-Moreno, J. M. & Sanchis, E. Intraretinal hemorrhage associated with leishmaniasis. Ophthalmic Surg. Lasers Imaging 34, 212\u2013214 (2003).","journal-title":"Ophthalmic Surg. Lasers Imaging"},{"key":"8106_CR33","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.846155","volume":"13","author":"GT Patterson","year":"2022","unstructured":"Patterson, G. T. et al. Pathologic inflammation in malnutrition is driven by proinflammatory intestinal microbiota, large intestine barrier dysfunction, and translocation of bacterial lipopolysaccharide. Front. Immunol. 13, 846155 (2022).","journal-title":"Front. Immunol."},{"key":"8106_CR34","doi-asserted-by":"publisher","unstructured":"Fasano, A. All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases. F1000Res 9, https:\/\/doi.org\/10.12688\/f1000research.20510.1 (2020).","DOI":"10.12688\/f1000research.20510.1"},{"key":"8106_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-34398-4","volume":"8","author":"HY Yoon","year":"2018","unstructured":"Yoon, H. Y. et al. Association between neutrophil-to-lymphocyte ratio and gut microbiota in a large population: a retrospective cross-sectional study. Sci. Rep. 8, 16031 (2018).","journal-title":"Sci. Rep."},{"key":"8106_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2019.102429","volume":"19","author":"JMG Ruiz de Morales","year":"2020","unstructured":"Ruiz de Morales, J. M. G. et al. Critical role of interleukin (IL)-17 in inflammatory and immune disorders: an updated review of the evidence focusing in controversies. Autoimmun. Rev. 19, 102429 (2020).","journal-title":"Autoimmun. Rev."},{"key":"8106_CR37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cimid.2024.102148","volume":"107","author":"A Duran-Galea","year":"2024","unstructured":"Duran-Galea, A. et al. Clinical importance of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and systemic immune-inflammation index in dogs with leishmaniasis. Comp. Immunol. Microbiol. Infect. Dis. 107, 102148 (2024).","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"8106_CR38","doi-asserted-by":"publisher","unstructured":"Almeida, V. et al. Hematological changes in dogs with visceral Leishmaniasis are associated with increased IFN-\u03b3 and TNF gene expression levels in the bone marrow. Microorganisms 9, https:\/\/doi.org\/10.3390\/microorganisms9081618 (2021).","DOI":"10.3390\/microorganisms9081618"},{"key":"8106_CR39","doi-asserted-by":"publisher","DOI":"10.1016\/j.cimid.2020.101431","volume":"69","author":"Z Babaloo","year":"2020","unstructured":"Babaloo, Z., Oskoei, M. R., Kohansal, M. H., Barac, A. & Ahmadpour, E. Serum profile of IL-1beta and IL-17 cytokines in patients with visceral leishmaniasis. Comp. Immunol. Microbiol. Infect. Dis. 69, 101431 (2020).","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"8106_CR40","doi-asserted-by":"publisher","first-page":"e0260022","DOI":"10.1371\/journal.pone.0260022","volume":"16","author":"HT Endale","year":"2021","unstructured":"Endale, H. T. et al. Assessment of liver function test and associated factors among visceral leishmaniasis patients attending university of gondar leishmaniasis research and treatment center, Northwest Ethiopia. PLoS ONE 16, e0260022 (2021).","journal-title":"PLoS ONE"},{"key":"8106_CR41","unstructured":"Hassan, Z. A., Idris. & Fadul, O. Impact of Visceral Leishmaniasis on Liver Function in Gadaref State-Sudan. Environmental Science, Medicine. https:\/\/api.semanticscholar.org\/CorpusID:33223506 (2016)."},{"key":"8106_CR42","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1016\/j.cgh.2008.04.033","volume":"6","author":"P Mathur","year":"2008","unstructured":"Mathur, P., Samantaray, J. C. & Samanta, P. High prevalence of functional liver derangement in visceral leishmaniasis at an Indian tertiary care center. Clin. Gastroenterol. Hepatol. 6, 1170\u20131172 (2008).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"8106_CR43","doi-asserted-by":"publisher","first-page":"135","DOI":"10.4103\/jgid.jgid_25_20","volume":"12","author":"O Salih","year":"2020","unstructured":"Salih, O. et al. Risk factors of inpatients mortality of visceral Leishmaniasis, Khartoum State, Sudan. J. Glob. Infect. Dis. 12, 135\u2013140 (2020).","journal-title":"J. Glob. Infect. Dis."},{"key":"8106_CR44","doi-asserted-by":"publisher","first-page":"3055","DOI":"10.2147\/IDR.S261698","volume":"13","author":"B Tesfanchal","year":"2020","unstructured":"Tesfanchal, B. et al. Alteration of clinical chemistry parameters among visceral Leishmaniasis patients in Western Tigrai, Ethiopia, 2018\/2019: a comparative cross-sectional study. Infect. Drug Resist. 13, 3055\u20133062 (2020).","journal-title":"Infect. Drug Resist."},{"key":"8106_CR45","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-15651-8","volume":"7","author":"MMC Abbehusen","year":"2017","unstructured":"Abbehusen, M. M. C. et al. Clinical and immunopathological findings during long term follow-up in Leishmania infantum experimentally infected dogs. Sci. Rep. 7, 15914 (2017).","journal-title":"Sci. Rep."},{"key":"8106_CR46","unstructured":"Lowe, D. et al. Alkaline Phosphatase. StatPearls Publishing LLC. (2023)."},{"key":"8106_CR47","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1038\/pr.2014.179","volume":"77","author":"AV Kane","year":"2015","unstructured":"Kane, A. V., Dinh, D. M. & Ward, H. D. Childhood malnutrition and the intestinal microbiome. Pediatr. Res. 77, 256\u2013262 (2015).","journal-title":"Pediatr. Res."},{"key":"8106_CR48","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/s41392-022-00974-4","volume":"7","author":"K Hou","year":"2022","unstructured":"Hou, K. et al. Microbiota in health and diseases. Signal Transduct. Target Ther. 7, 135 (2022).","journal-title":"Signal Transduct. Target Ther."},{"key":"8106_CR49","doi-asserted-by":"publisher","first-page":"14691","DOI":"10.1073\/pnas.1005963107","volume":"107","author":"C De Filippo","year":"2010","unstructured":"De Filippo, C. et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl Acad. Sci. USA 107, 14691\u201314696 (2010).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"8106_CR50","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1136\/gut.52.2.237","volume":"52","author":"P Seksik","year":"2003","unstructured":"Seksik, P. et al. Alterations of the dominant faecal bacterial groups in patients with Crohn\u2019s disease of the colon. Gut 52, 237\u2013242 (2003).","journal-title":"Gut"},{"key":"8106_CR51","doi-asserted-by":"publisher","first-page":"e5019","DOI":"10.1097\/MD.0000000000005019","volume":"95","author":"Y Zhou","year":"2016","unstructured":"Zhou, Y. et al. Increased Enterococcus faecalis infection is associated with clinically active Crohn disease. Medicine 95, e5019 (2016).","journal-title":"Medicine"},{"key":"8106_CR52","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1093\/ecco-jcc\/jjv147","volume":"9","author":"J Maukonen","year":"2015","unstructured":"Maukonen, J. et al. Altered fecal microbiota in paediatric inflammatory bowel disease. J. Crohns Colitis 9, 1088\u20131095 (2015).","journal-title":"J. Crohns Colitis"},{"key":"8106_CR53","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adh1469","volume":"15","author":"C Farias Amorim","year":"2023","unstructured":"Farias Amorim, C. et al. Multiomic profiling of cutaneous leishmaniasis infections reveals microbiota-driven mechanisms underlying disease severity. Sci. Transl. Med. 15, eadh1469 (2023).","journal-title":"Sci. Transl. Med."},{"key":"8106_CR54","doi-asserted-by":"publisher","unstructured":"Singh, T. P. et al. Regulatory T cells control Staphylococcus aureus and disease severity of cutaneous leishmaniasis. J. Exp. Med. 220, https:\/\/doi.org\/10.1084\/jem.20230558 (2023).","DOI":"10.1084\/jem.20230558"},{"key":"8106_CR55","unstructured":"The Jackson Laboratory. Body Weight Information for BALBc (000651) JAX\u00ae Mice Strain BALB\/cJ. https:\/\/www.jax.org\/jax-mice-and-services\/strain-data-sheet-pages\/body-weight-chart-000651#. (2025)."},{"key":"8106_CR56","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1038\/s41587-019-0252-6","volume":"37","author":"E Bolyen","year":"2019","unstructured":"Bolyen, E. et al. Author Correction: Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat. Biotechnol. 37, 1091 (2019).","journal-title":"Nat. Biotechnol."},{"key":"8106_CR57","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/nmeth.3869","volume":"13","author":"BJ Callahan","year":"2016","unstructured":"Callahan, B. J. et al. DADA2: high-resolution sample inference from Illumina amplicon data. Nat. Methods 13, 581\u2013583 (2016).","journal-title":"Nat. Methods"},{"key":"8106_CR58","doi-asserted-by":"publisher","first-page":"3059","DOI":"10.1093\/nar\/gkf436","volume":"30","author":"K Katoh","year":"2002","unstructured":"Katoh, K., Misawa, K., Kuma, K. & Miyata, T. MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform. Nucleic Acids Res. 30, 3059\u20133066 (2002).","journal-title":"Nucleic Acids Res."},{"key":"8106_CR59","doi-asserted-by":"publisher","first-page":"e9490","DOI":"10.1371\/journal.pone.0009490","volume":"5","author":"MN Price","year":"2010","unstructured":"Price, M. N., Dehal, P. S. & Arkin, A. P. FastTree 2\u2013approximately maximum-likelihood trees for large alignments. PLoS ONE 5, e9490 (2010).","journal-title":"PLoS ONE"},{"key":"8106_CR60","doi-asserted-by":"publisher","first-page":"e61217","DOI":"10.1371\/journal.pone.0061217","volume":"8","author":"PJ McMurdie","year":"2013","unstructured":"McMurdie, P. J. & Holmes, S. phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS ONE 8, e61217 (2013).","journal-title":"PLoS ONE"},{"key":"8106_CR61","doi-asserted-by":"crossref","unstructured":"Wickham, H. ggplot2: Elegant Graphics for Data Analysis (Springer-Verlag, 2016).","DOI":"10.1007\/978-3-319-24277-4_9"},{"key":"8106_CR62","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1093\/bioinformatics\/bty633","volume":"35","author":"E Paradis","year":"2019","unstructured":"Paradis, E. & Schliep, K. ape 5.0: an environment for modern phylogenetics and evolutionary analyses in R. Bioinformatics 35, 526\u2013528 (2019).","journal-title":"Bioinformatics"},{"key":"8106_CR63","unstructured":"Oksanen, J. S. G. et al. vegan: Community Ecology Package_. R package version 2.6-4. https:\/\/CRAN.R-project.org\/package=vegan (2022)."},{"key":"8106_CR64","doi-asserted-by":"publisher","unstructured":"Liu, C., Cui, Y., Li, X. & Yao, M. microeco: an R package for data mining in microbial community ecology. FEMS Microbiol. Ecol. 97, https:\/\/doi.org\/10.1093\/femsec\/fiaa255 (2021).","DOI":"10.1093\/femsec\/fiaa255"},{"key":"8106_CR65","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17041-7","volume":"11","author":"H Lin","year":"2020","unstructured":"Lin, H. & Peddada, S. D. Analysis of compositions of microbiomes with bias correction. Nat. Commun. 11, 3514 (2020).","journal-title":"Nat. Commun."},{"key":"8106_CR66","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32243-x","volume":"13","author":"H Lin","year":"2022","unstructured":"Lin, H., Eggesbo, M. & Peddada, S. D. Linear and nonlinear correlation estimators unveil undescribed taxa interactions in microbiome data. Nat. Commun. 13, 4946 (2022).","journal-title":"Nat. Commun."},{"key":"8106_CR67","unstructured":"Doehl, J. R scripts and raw data file required to reproduce the statistics report of the publication \u201cMalnutrition exacerbates pathogenesis of sand fly-transmitted Leishmania donovani\u201d. https:\/\/github.com\/joedoehl\/Malnutrition-exacerbates-pathogenesis-of-sand-fly-transmitted-Leishmania-donovani.git (2025)."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08106-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08106-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08106-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T18:05:12Z","timestamp":1747159512000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08106-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,13]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["8106"],"URL":"https:\/\/doi.org\/10.1038\/s42003-025-08106-8","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,13]]},"assertion":[{"value":"26 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"746"}}