title: Composition of the gut microbiota modulates the severity of malaria.
abstract: Plasmodium infections result in clinical presentations that range from asymptomatic to severe malaria, resulting in ∼1 million deaths annually. Despite this toll on humanity, the factors that determine disease severity remain poorly understood. Here, we show that the gut microbiota of mice influences the pathogenesis of malaria. Genetically similar mice from different commercial vendors, which exhibited differences in their gut bacterial community, had significant differences in parasite burden and mortality after infection with multiple Plasmodium species. Germfree mice that received cecal content transplants from "resistant" or "susceptible" mice had low and high parasite burdens, respectively, demonstrating the gut microbiota shaped the severity of malaria. Among differences in the gut flora were increased abundances of Lactobacillus and Bifidobacterium in resistant mice. Susceptible mice treated with antibiotics followed by yogurt made from these bacterial genera displayed a decreased parasite burden. Consistent with differences in parasite burden, resistant mice exhibited an elevated humoral immune response compared with susceptible mice. Collectively, these results identify the composition of the gut microbiota as a previously unidentified risk factor for severe malaria and modulation of the gut microbiota (e.g., probiotics) as a potential treatment to decrease parasite burden.
authors: Department of Microbiology, University of Tennessee, Knoxville, TN 37996;
authors: Nicolas F
authors: NF
authors: Villarino
authors: Department of Microbiology, University of Tennessee, Knoxville, TN 37996;
authors: Gary R
authors: GR
authors: LeCleir
authors: Department of Microbiology, University of Tennessee, Knoxville, TN 37996; Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40202;
authors: Joshua E
authors: JE
authors: Denny
authors: Department of Chemistry, University of Tennessee, Knoxville, TN 37996;
authors: Stephen P
authors: SP
authors: Dearth
authors: Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40202;
authors: Christopher L
authors: CL
authors: Harding
authors: Department of Microbiology, University of Tennessee, Knoxville, TN 37996;
authors: Sarah S
authors: SS
authors: Sloan
authors: Department of Microbiology, University of Tennessee, Knoxville, TN 37996;
authors: Jennifer L
authors: JL
authors: Gribble
authors: Department of Chemistry, University of Tennessee, Knoxville, TN 37996; Biological and Small Molecule Mass Spectrometry Core, University of Tennessee, Knoxville, TN 37996.
authors: Shawn R
authors: SR
authors: Campagna
authors: Department of Microbiology, University of Tennessee, Knoxville, TN 37996;
authors: Steven W
authors: SW
authors: Wilhelm
authors: Department of Microbiology, University of Tennessee, Knoxville, TN 37996; Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40202; nathan.schmidt@louisville.edu.
authors: Nathan W
authors: NW
authors: Schmidt
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001644:Bifidobacterium / Q000302:isolation & purification / Q000502:physiology; D000069196:Gastrointestinal Microbiome / Q000276:immunology / Q000502:physiology; D005856:Germ-Free Life; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D007778:Lactobacillus / Q000302:isolation & purification / Q000502:physiology; D008288:Malaria / Q000382:microbiology* / Q000469:parasitology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D059208:Parasite Load; D010967:Plasmodium yoelii; D019936:Probiotics / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents
keywords: Plasmodium; gut microbiome; severe malaria