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Stool microbiota composition is associated with the prospective risk of Plasmodium falciparum infection.

ABSTRACT: BACKGROUND:In humans it is unknown if the composition of the gut microbiota alters the risk of Plasmodium falciparum infection or the risk of developing febrile malaria once P. falciparum infection is established. Here we collected stool samples from a cohort composed of 195 Malian children and adults just prior to an intense P. falciparum transmission season. We assayed these samples using massively parallel sequencing of the 16S ribosomal RNA gene to identify the composition of the gut bacterial communities in these individuals. During the ensuing 6-month P. falciparum transmission season we examined the relationship between the stool microbiota composition of individuals in this cohort and their prospective risk of both P. falciparum infection and febrile malaria. RESULTS:Consistent with prior studies, stool microbial diversity in the present cohort increased with age, although the overall microbiota profile was distinct from cohorts in other regions of Africa, Asia and North America. Age-adjusted Cox regression analysis revealed a significant association between microbiota composition and the prospective risk of P. falciparum infection; however, no relationship was observed between microbiota composition and the risk of developing febrile malaria once P. falciparum infection was established. CONCLUSIONS:These findings underscore the diversity of gut microbiota across geographic regions, and suggest that strategic modulation of gut microbiota composition could decrease the risk of P. falciparum infection in malaria-endemic areas, potentially as an adjunct to partially effective malaria vaccines.

SUBMITTER: Yooseph S

PROVIDER: S-EPMC4546150 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Stool microbiota composition is associated with the prospective risk of Plasmodium falciparum infection.

Yooseph Shibu S Kirkness Ewen F EF Tran Tuan M TM Harkins Derek M DM Jones Marcus B MB Torralba Manolito G MG O'Connell Elise E Nutman Thomas B TB Doumbo Safiatou S Doumbo Ogobara K OK Traore Boubacar B Crompton Peter D PD Nelson Karen E KE

BMC genomics 20150822

<h4>Background</h4>In humans it is unknown if the composition of the gut microbiota alters the risk of Plasmodium falciparum infection or the risk of developing febrile malaria once P. falciparum infection is established. Here we collected stool samples from a cohort composed of 195 Malian children and adults just prior to an intense P. falciparum transmission season. We assayed these samples using massively parallel sequencing of the 16S ribosomal RNA gene to identify the composition of the gut ...[more]

PMID: 26296559

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Project description:Cellular responses to Plasmodium falciparum parasites, in particular interferon-gamma (IFN?) production, play an important role in anti-malarial immunity. However, clinical immunity to malaria develops slowly amongst naturally exposed populations, the dynamics of cellular responses in relation to exposure are difficult to study and data about the persistence of such responses are controversial. Here we assess the longevity and composition of cellular immune responses following experimental malaria infection in human volunteers. We conducted a longitudinal study of cellular immunological responses to sporozoites (PfSpz) and asexual blood-stage (PfRBC) malaria parasites in naïve human volunteers undergoing single (n?=?5) or multiple (n?=?10) experimental P. falciparum infections under highly controlled conditions. IFN? and interleukin-2 (IL-2) responses following in vitro re-stimulation were measured by flow-cytometry prior to, during and more than one year post infection. We show that cellular responses to both PfSpz and PfRBC are induced and remain almost undiminished up to 14 months after even a single malaria episode. Remarkably, not only 'adaptive' but also 'innate' lymphocyte subsets contribute to the increased IFN? response, including ??T cells, ??T cells and NK cells. Furthermore, results from depletion and autologous recombination experiments of lymphocyte subsets suggest that immunological memory for PfRBC is carried within both the ??T cells and ??T compartments. Indeed, the majority of cytokine producing T lymphocytes express an CD45RO(+) CD62L(-) effector memory (EM) phenotype both early and late post infection. Finally, we demonstrate that malaria infection induces and maintains polyfunctional (IFN?(+)IL-2(+)) EM responses against both PfRBC and PfSpz, previously found to be associated with protection. These data demonstrate that cellular responses can be readily induced and are long-lived following infection with P. falciparum, with a persisting contribution by not only adaptive but also (semi-)innate lymphocyte subsets. The implications hereof are positive for malaria vaccine development, but focus attention on those factors potentially inhibiting such responses in the field.

Dataset Information

Stool microbiota composition is associated with the prospective risk of Plasmodium falciparum infection.

Publications

Stool microbiota composition is associated with the prospective risk of Plasmodium falciparum infection.

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