Urinary Metabolic Profiling in Volunteers Undergoing Malaria Challenge in Gabon
The interaction of malaria parasites with their human host is extensively studied, yet only few studies reported how <i>P. falciparum</i> infection affects urinary metabolite profiles and how this is associated with immunity. We present a longitudinal study of the urinary metabolic profi...
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| Format: | Article |
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MDPI AG
2022-12-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/12/12/1224 |
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| author | Madeleine Eunice Betouke Ongwe Isabelle Kohler Mikhael D. Manurung Aswin Verhoeven Rico Derks Jacqueline J. Janse Yoanne D. Mouwenda Peter G. Kremsner Ayola A. Adegnika Bertrand Lell Bart Everts Oleg A. Mayboroda Maria Yazdanbakhsh |
| author_facet | Madeleine Eunice Betouke Ongwe Isabelle Kohler Mikhael D. Manurung Aswin Verhoeven Rico Derks Jacqueline J. Janse Yoanne D. Mouwenda Peter G. Kremsner Ayola A. Adegnika Bertrand Lell Bart Everts Oleg A. Mayboroda Maria Yazdanbakhsh |
| author_sort | Madeleine Eunice Betouke Ongwe |
| collection | DOAJ |
| description | The interaction of malaria parasites with their human host is extensively studied, yet only few studies reported how <i>P. falciparum</i> infection affects urinary metabolite profiles and how this is associated with immunity. We present a longitudinal study of the urinary metabolic profiles of twenty healthy Africans with lifelong exposure to malaria and five malaria-naïve Europeans, who were all challenged with direct venous inoculation of live <i>P. falciparum</i> sporozoïtes (PfSPZ) and followed up until they developed symptoms or became thick blood smear positive (TBS). Urine samples were collected before and at 2, 5, 9 and 11 days post challenge and were analysed. Upon infection, all Europeans became TBS positive, while Africans showed either a delay in time to parasitaemia or controlled infection. Our metabolic data showed that Europeans and Africans had distinct alterations in metabolite patterns, with changes mostly seen on days 5 and 9 post PfSPZ infection, and more prominently in Europeans. Within the African group, the levels of formate, urea, trimethylamine, threonine, choline, myo-inositol and acetate were significantly higher in TBS positive whereas the levels of pyruvate, 3-methylhistidine and dimethylglycine were significantly lower in individuals who remained TBS negative. Notably, before inoculation with PfSPZ, a group of metabolites including phenylacetylglutamine can potentially be used to predict parasitaemia control among Africans. Taken together, this study highlights the difference in urinary metabolic changes in response to malaria infection as a consequence of lifelong exposure to malaria and that change detectable before challenge might predict the control of parasitaemia in malaria-endemic areas. |
| first_indexed | 2024-03-09T16:06:37Z |
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| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T16:06:37Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-e55265ab675f4ebca1bc2efa4110b7b62023-11-24T16:37:50ZengMDPI AGMetabolites2218-19892022-12-011212122410.3390/metabo12121224Urinary Metabolic Profiling in Volunteers Undergoing Malaria Challenge in GabonMadeleine Eunice Betouke Ongwe0Isabelle Kohler1Mikhael D. Manurung2Aswin Verhoeven3Rico Derks4Jacqueline J. Janse5Yoanne D. Mouwenda6Peter G. Kremsner7Ayola A. Adegnika8Bertrand Lell9Bart Everts10Oleg A. Mayboroda11Maria Yazdanbakhsh12Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDivision of BioAnalytical Chemistry, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsDepartment of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsCenter for Proteomics and Metabolomics, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsCenter for Proteomics and Metabolomics, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsCentre de Recherches Médicales de Lambaréné, Lambaréné P.O. Box 242, GabonDepartment of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsCentre de Recherches Médicales de Lambaréné, Lambaréné P.O. Box 242, GabonDepartment of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsCenter for Proteomics and Metabolomics, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsThe interaction of malaria parasites with their human host is extensively studied, yet only few studies reported how <i>P. falciparum</i> infection affects urinary metabolite profiles and how this is associated with immunity. We present a longitudinal study of the urinary metabolic profiles of twenty healthy Africans with lifelong exposure to malaria and five malaria-naïve Europeans, who were all challenged with direct venous inoculation of live <i>P. falciparum</i> sporozoïtes (PfSPZ) and followed up until they developed symptoms or became thick blood smear positive (TBS). Urine samples were collected before and at 2, 5, 9 and 11 days post challenge and were analysed. Upon infection, all Europeans became TBS positive, while Africans showed either a delay in time to parasitaemia or controlled infection. Our metabolic data showed that Europeans and Africans had distinct alterations in metabolite patterns, with changes mostly seen on days 5 and 9 post PfSPZ infection, and more prominently in Europeans. Within the African group, the levels of formate, urea, trimethylamine, threonine, choline, myo-inositol and acetate were significantly higher in TBS positive whereas the levels of pyruvate, 3-methylhistidine and dimethylglycine were significantly lower in individuals who remained TBS negative. Notably, before inoculation with PfSPZ, a group of metabolites including phenylacetylglutamine can potentially be used to predict parasitaemia control among Africans. Taken together, this study highlights the difference in urinary metabolic changes in response to malaria infection as a consequence of lifelong exposure to malaria and that change detectable before challenge might predict the control of parasitaemia in malaria-endemic areas.https://www.mdpi.com/2218-1989/12/12/1224urinemetabolomics<i>Plasmodium falciparum</i> malarianuclear magnetic resonancehydrophilic interaction chromatography-mass spectrometryGabon |
| spellingShingle | Madeleine Eunice Betouke Ongwe Isabelle Kohler Mikhael D. Manurung Aswin Verhoeven Rico Derks Jacqueline J. Janse Yoanne D. Mouwenda Peter G. Kremsner Ayola A. Adegnika Bertrand Lell Bart Everts Oleg A. Mayboroda Maria Yazdanbakhsh Urinary Metabolic Profiling in Volunteers Undergoing Malaria Challenge in Gabon Metabolites urine metabolomics <i>Plasmodium falciparum</i> malaria nuclear magnetic resonance hydrophilic interaction chromatography-mass spectrometry Gabon |
| title | Urinary Metabolic Profiling in Volunteers Undergoing Malaria Challenge in Gabon |
| title_full | Urinary Metabolic Profiling in Volunteers Undergoing Malaria Challenge in Gabon |
| title_fullStr | Urinary Metabolic Profiling in Volunteers Undergoing Malaria Challenge in Gabon |
| title_full_unstemmed | Urinary Metabolic Profiling in Volunteers Undergoing Malaria Challenge in Gabon |
| title_short | Urinary Metabolic Profiling in Volunteers Undergoing Malaria Challenge in Gabon |
| title_sort | urinary metabolic profiling in volunteers undergoing malaria challenge in gabon |
| topic | urine metabolomics <i>Plasmodium falciparum</i> malaria nuclear magnetic resonance hydrophilic interaction chromatography-mass spectrometry Gabon |
| url | https://www.mdpi.com/2218-1989/12/12/1224 |
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