Dynamic modulation of spleen germinal center reactions by gut bacteria during Plasmodium infection

Abstract

Highlights d Human gut bacteria composition correlates with severity of malaria d Gut bacteria dynamically modulate spleen GC reactions to systemic infection d Modulating gut bacteria can halt escalating parasitemia d Antibiotic-induced changes in gut bacteria can boost anti-Plasmodium host immunity

High-risk microbial signatures are associated with severe parasitemia in controlledPlasmodiuminfections of both humans and rhesus macaques

“…Here, we observed that baseline GI microbiota composition in humans was strongly associated with the potential for severe P. falciparum infection. Our findings are in agreement with observational studies using incident detection in human children in malaria endemic areas 19,20 and previous murine studies 21–23 , both of which have suggested a link between GI microbiome composition and risk for severe malaria infection. Importantly, our work extends these observations to adult humans and highlights Bifidobacterium as a defining microbial feature in limiting risk for severe P. falciparum parasitemia.…”

“…Downstream analyses indicated that key GI microbes, including Bifidobacterium longum, Bifidobacterium adolescentis , and Akkermansia muciniphila were detected less frequently and at lower abundances in participants that were more likely to develop severe parasitemia. Our findings extend previous observations made in the murine model 21-23 , as well as observational studies using incident detection in human children living in malaria endemic areas 19,20 , both of which suggested a link between GI microbiome composition and the risk of developing severe malaria infection. Importantly, our work extends these observations to adult humans and highlights Bifidobacterium as a defining microbial feature in determining risk for severe P. falciparum parasitemia.…”

“…Interestingly, several lines of evidence indicate that GI microbiome community structure may be linked with protection against severe Plasmodium infection. For example, recent work conducted among Ugandan children demonstrated significant differences in alpha-diversity measures of fecal bacterial composition, including Shannon index and community evenness (Pielou) between participants with severe malaria anemia and participants with asymptomatic P. falciparum infection or healthy controls, which suggests a link between intestinal microbial community structure and the severity of Plasmodium infection 19 . Additionally, a study conducted among children in Mali demonstrated that participants with higher stool abundances of Bifidobacterium and Streptococcus species had a statistically significant delay in time to P. falciparum infection, as compared to participants with greater abundances in Ruminococcaceae and Lachnospiraceae , suggesting an association between 3 specific GI microbiome composition and decreased prospective risk for Plasmodium acquisition 20 .…”

Mouse Models for Unravelling Immunology of Blood Stage Malaria

“…Studies in humans and mice have shown that gut microbiota is associated with the level of malarial disease in those living in malaria-endemic areas [68][69][70]. This has also been shown in mice [9,71], specifically with respect to modulating germinal center reactions [71], even within the spleen [72]. This is relevant in the selection of mouse vendor given clear evidence that the severity of erythrocytic Plasmodium infection in genetically similar mice obtained from different vendors was significantly altered in response owing to the differences in gut microbiome [9].…”

Parasite co-infection: an ecological, molecular and experimental perspective

“…This is true of malaria, where the gut microbiota influences disease severity caused by, and the immune response to, the parasite (e.g. [93][94][95]). A further particularly relevant example concerns trypanosome infections in the tsetse fly, where tsetse endosymbionts can have significant impact on the vectorial capacity of the arthropod [96].…”