Evidence map›Paper›PMID 41419476›Full record

ArticleNature communications2025

Distinct gastrointestinal microbial signatures predict parasite levels in controlled Plasmodium infections in both rhesus macaques and humans.

Andrew T Gustin, Courtney A Broedlow, Kevin Hager, Ernesto Coronado, Solomon Wangari, Naoto Iwayama, Chul Y Ahrens, William D Garrison, Kathryn A Guerriero, Kristina De Paris and 5 more

Registry-linked trialAbstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04072302 (A Two-part, Randomized, Double-blind, Placebo-controlled, Single-center Study to Evaluate the Safety and Causal Prophylactic Efficacy of KAF156 in a Controlled Human Malaria Challenge Model), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04072302 phase1completednot on this map

A Two-part, Randomized, Double-blind, Placebo-controlled, Single-center Study to Evaluate the Safety and Causal Prophylactic Efficacy of KAF156 in a Controlled Human Malaria Challenge Model

TypeinterventionalSponsorNovartis PharmaceuticalsRan2014 to 2017Enrolled86ConditionsMalariaArmsKAF156, Placebo
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Andrew T GustinDepartment of Immunology, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-8760-8320
Courtney A BroedlowWashington National Primate Research Center, University of Washington, Seattle, WA, USA.
Kevin HagerSeattle Malaria Clinical Trials Center, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-1398-8014
Ernesto CoronadoWashington National Primate Research Center, University of Washington, Seattle, WA, USA.
Solomon WangariWashington National Primate Research Center, University of Washington, Seattle, WA, USA.
Naoto IwayamaWashington National Primate Research Center, University of Washington, Seattle, WA, USA.
Chul Y AhrensWashington National Primate Research Center, University of Washington, Seattle, WA, USA.
William D GarrisonWashington National Primate Research Center, University of Washington, Seattle, WA, USA.
Kathryn A GuerrieroWashington National Primate Research Center, University of Washington, Seattle, WA, USA.
Kristina De ParisDepartment of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Berlin Londono-RenteriaDepartment of Tropical Medicine and Infectious Disease, Tulane University Celia Scott Weatherhead School of Public Health and Tropical Medicine, New Orleans, LA, USA.ORCID http://orcid.org/0000-0001-5956-5274
Michael GaleDepartment of Immunology, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-6332-7436
Nichole R KlattWashington National Primate Research Center, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-2968-5480
James G KublinSeattle Malaria Clinical Trials Center, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-1279-3741
Jennifer A ManuzakWashington National Primate Research Center, University of Washington, Seattle, WA, USA. jmanuzak@tulane.edu.ORCID http://orcid.org/0000-0002-0079-2306

Funding

Washington National Primate Research CenterP51OD010425 · OD · UNIVERSITY OF WASHINGTON · PI Mari Ostendorf · 2012 to 2026
$201.8M
Tulane NPRC SPF Sheltered Outdoor Enclosure ExpansionP51OD011104 · OD · TULANE UNIVERSITY OF LOUISIANA · PI L Lee HAMM · 2012 to 2026
$142.4M
Diseases of Public Health Importance Training GrantT32AI007509 · NIAID · UNIVERSITY OF WASHINGTON · PI LUND, JENNIFER M · 1997 to 2024
$6.3M
Impact of Malaria Co-Infection on HIV VaccinationK01OD024876 · OD · UNIVERSITY OF WASHINGTON · PI MANUZAK, JENNIFER · 2017 to 2019
$1.0M
NIAID NIH HHS T32 AI007509NIH HHS K01 OD024876NIH HHS P51 OD010425NIH HHS P51 OD011104U.S. Department of Health & Human Services | NIH | NIH Office of the Director (OD) K01OD024876
6 · The paper itself

Abstract

Functions of the gastrointestinal (GI) microbiome include maintenance of immune homeostasis and protection against infectious disease. Current assessments of the role of the GI microbiome in Plasmodium infection have been primarily conducted using mouse models and observational human cohorts. Here, we experimentally assessed associations between pre-infection GI microbiome composition and acute Plasmodium parasitemia using 16S rRNA sequencing and samples from rhesus macaques (RMs) and adult humans enrolled in a previously conducted controlled human malaria infection (CHMI) trial (NCT04072302) originally designed to test the efficacy of KAF156, a novel imidazolopiperazine class of antimalarial drugs. We identified distinct pre-infection 16S microbial signatures that were associated with increased risk for above median parasitemia in RMs infected with P. fragile and CHMI participants infected with P. falciparum. Further, we identified a Bifidobacterium feature set that accurately stratified parasitemia risk and could therefore serve as a foundation for a potential biomarker panel to aid prevention efforts in malaria endemic regions. Together, our findings demonstrate that pre-infection GI microbiome composition is indicative of risk for Plasmodium parasitemia, and our observation that the pre-infection microbiome-P. fragile dynamic in RMs mirrors the pre-infection microbiome-P. falciparum interaction in CHMI participants supports the future use of this model in pre-clinical investigations of novel microbiome-targeting approaches to reduce malaria burden.

Indexed as

Gastrointestinal MicrobiomeMalariaMalaria, FalciparumParasitemiaPlasmodium falciparumAdultAnimalsAntimalarialsFemaleHumansMacaca mulattaMaleRNA, Ribosomal, 16SAntimalarialsRNA, Ribosomal, 16S

Identifiers

PMID41419476
PMCPMC12808661

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.