Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Oct 12;19(10):e1011665.
doi: 10.1371/journal.ppat.1011665. eCollection 2023 Oct.

Mechanistic insights into the interaction between the host gut microbiome and malaria

Rabindra K Mandal  1 , Nathan W Schmidt  1
Affiliations
Review

Mechanistic insights into the interaction between the host gut microbiome and malaria

Rabindra K Mandal et al. PLoS Pathog. .

Abstract

Malaria is a devastating infectious disease and significant global health burden caused by the bite of a Plasmodium-infected female Anopheles mosquito. Gut microbiota was recently discovered as a risk factor of severe malaria. This review entails the recent advances on the impact of gut microbiota composition on malaria severity and consequence of malaria infection on gut microbiota in mammalian hosts. Additionally, this review provides mechanistic insight into interactions that might occur between gut microbiota and host immunity which in turn can modulate malaria severity. Finally, approaches to modulate gut microbiota composition are discussed. We anticipate this review will facilitate novel hypotheses to move the malaria-gut microbiome field forward.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
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
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
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.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. World Health Organization. World Malaria Report 2021 (World Health Organization). 2021.
    1. Jagannathan P, Kakuru A. Malaria in 2022: Increasing challenges, cautious optimism. Nat Commun. 2022;13(1):2678. doi: 10.1038/s41467-022-30133-w - DOI - PMC - PubMed
    1. Zekar L, Sharman T. Plasmodium falciparum malaria. 2020. - PubMed
    1. Ashley EA, Pyae Phyo A, Woodrow CJ. Malaria Lancet. 2018;391(10130):1608–21. Epub 2018/04/11. doi: 10.1016/s0140-6736(18)30324-6 . - DOI - PubMed
    1. White NJ, Pukrittayakamee S, Hien TT, Faiz MA, Mokuolu OA, Dondorp AM. Malaria Lancet. 2014;383(9918):723–35. Epub 2013/08/21. doi: 10.1016/s0140-6736(13)60024-0 . - DOI - PubMed