Fig 1.
Gut bacteria associated with human malaria.
To date 5 peer-reviewed studies have been published on the impact of the gut microbiota in Plasmodium infection in humans. A cohort of children in Kalifabougou, Mali was used for 2 prospective studies (Yilmaz and colleagues (2014) [18] and Yooseph and colleagues (2015) [28]). Additionally, 3 case-control studies investigated association of gut microbiota at the time of Plasmodium infection (Huwe and colleagues (2019) [32] and Easton and colleagues (2020) [33]) and SMA (Mandal and colleagues (2021) [6]). Prospective and case-control studies have their own advantages and disadvantages. Bacteria associated with the clinical outcome is shown. Pf: P. falciparum, neg: negative, pos: positive. Figure was created with BioRender.com.
Fig 2.
Gut bacteria associated with nonhuman model of malaria.
Top 2 panels show baseline gut bacteria differentially abundant in mice either susceptible or resistant to P. yoelii 17XNL hyperparasitemia and P. chabaudi AS pregnancy outcomes. Fecal pellets are collected at baseline prior to Plasmodium infection to determine the gut microbiota composition. Bottom 2 panels show the shift in gut microbiota composition during Plasmodium infection in mice and monkeys. In nonlethal infection models, fecal pellet microbiota composition at peak parasitemia is compared to before Plasmodium infection. Bacteria that are significantly increased (up arrow) or decreased (down arrow) are shown. P. yoelii 17XL causes lethal infection due to hyperparasitemia while P. berghei ANKA causes mortality due to experimental cerebral malaria. Gut fecal samples are collected before mortality and compared to baseline gut microbiota. Changes in bacteria population at phylum, family, and genus level are shown. Figure was created with BioRender.com.
Fig 3.
Gut microbiota intervention strategy and possible immunological mechanism of action against severity to malaria.
Agents that can modulate gut microbiota composition or deplete gut bacteria that can influence gut or systemic immunity are shown. Dotted arrow indicates the potential interactions which need further validation. Color of arrows connect gut microbiota modifying agents and their impact on respective immune cells. Role of different immune populations to inhibit or exacerbate various stage and types of malaria are connected. Although, the exact mechanism on how gut microbiota impacts severe malaria is unknown, this figure provides a plausible connection between gut microbiota and malaria severity. Figure was created with BioRender.com.