Gut microbiota influences Plasmodium falciparum malaria susceptibility

Abstract

Background: The gut microbiota has recently been associated with malaria susceptibility/resistance in animal models and humans. This study aimed to assess its influence on malaria attack and Plasmodium parasitemia in children living in a malaria-endemic area of Mali.

Methods: Healthy children were enrolled in a 16-month cohort study in Bandiagara. Their gut bacteria and fungi community structures were characterized via 16S and ITS metabarcoding at enrolment. Clinicians monitored malaria attacks. Asymptomatic Plasmodium carriage was assessed by real-time polymerase chain reaction.

Results: Of the 300 children, 107 (36 %) had at least one malaria attack, and 82 (27 %) had at least one episode of asymptomatic Plasmodium parasitemia. The gut bacterial community structure, but not the fungal community, was associated with susceptibility/resistance to both malaria attacks and asymptomatic P. falciparum parasitemia. Higher gut bacteria richness was independently associated with susceptibility to both asymptomatic parasitemia episodes and malaria attacks. 17 bacteria, and 7 fungi were associated with susceptibility to malaria attacks, and 8 bacteria, and 3 fungi were associated with resistance. 15 bacteria and 13 fungi were associated with susceptibility to asymptomatic Plasmodium parasitemia episodes, and 19 bacteria and 3 fungi were associated with resistance.

Conclusion: Further studies are needed to confirm these findings, which point the way to strategies aimed at reducing the risk of malaria by modulating gut microbiota components in at-risk populations.

Keywords: 16S metagenomics; Children; Gut microbiota; ITS metagenomics; Malaria; Mali; Parasitemia; Plasmodium falciparum; malaria attack.

Fig. 1

Relative frequency (A) and abundance (B) of the major gut bacterial phyla, and relative frequency (C) and abundance (D) of the major gut fungal phyla, characterised via 16S or ITS metabarcoding.

Fig. 2

Distribution of the relative frequency A), and abundance B) of gut fungi phyla metabarcoding reads according to age. (Figures inside the bars are the mean abundance and number of the phylum for each group).

Fig. 3

Gut bacterial community structure and malaria risk. Principal Coordinates Analysis (PCoA) of the gut bacterial community a) in children who experienced (yellow dots), or did not experience (blue dots), at least one malaria attack within 16 months of follow-up (Permanova test, p = 0.0054); b) in children who developed (green dots), or did not develop (pink dots), at least one asymptomatic Plasmodium parasitaemia episode within 16 months of follow-up (Permanova test, p = 0.012).

Fig. 4

Richness and diversity indices of the gut bacterial community in children who experienced or did not experience at least one malaria attack within 16 months of follow-up. Scatter dot plot and Box-Whisker's graph shows Median, Min and Max of children who experienced at least one malaria attack (green) compared to control (blue) A) for chao-1 index (p = 0.036); B) for Shannon index (p = 0.141); C) for OTU Richness (p = 0.001); D) for Simpson index (p = 0.799).

Fig. 5

Richness and diversity indices of gut bacterial community of children who developed or did not develop at least one asymptomatic Plasmodium parasitaemia episode within 16 months of follow-up. Median and range of chao-1 index (p = 0.049) a); of Shannon index (p = 0.957) b); for OTU richness (p = 0.02) c) and Simpson index (p = 0.395) d) of children who developed at least one asymptomatic Plasmodium parasitaemia episode (light blue) compared to control (pink) for Scatter dot plot, Box and Whiskers graph.

Fig. 6

Linear size effect discriminant analysis (LDA LEfSe) of the gut bacterial community structure at, A) Order, B) Family, C) Genus and D) species levels, between children who did (green), or did not (red), experienced at least one malaria attack within 16 months of follow-up. Horizontal bars represent the effect size for each taxon. The length of the bar represents the log10 transformed LDA score, indicated by vertical dotted lines.

Fig. 7

Linear size effect discriminant analysis (LDA LEfSe) between of bacterial gut microbiota of children who developed (green) or did not develop (red bars) at least one asymptomatic Plasmodium parasitaemia episode within 16 months of follow-up at the level of taxonomic classes of the bacterial community structure at, A) Phyla, B) Order, C) Class, D) Family, E) genus, and F) species levels. Horizontal bars represent the effect size for each taxon. The length of the bar represents the log10 transformed LDA score, indicated by vertical dotted lines.

Fig. 8

Gut fungal community and malaria risk. Principal Coordinates Analysis (PCoA) of the gut fungal community structure a) in children who experienced at least one malaria attack (crimson dots) or those who did not (blue dots) (PERMANOVA test, p = 0.27); b) in children who developed at least one episode of Plasmodium parasitaemia (red dots) or did not (green dots) (PERMANOVA test, p = 0.76).

Fig. 9

Linear size effect discriminant analysis (LDA LEfSe) of the fungal community structure at B) family, C) genus, and D) species levels, between children who experienced (green), or did not experience (red), at least one malaria attack within 16 months of follow-up. For A) Order children who experienced at least one malaria attack within 16 months of follow-up (red) were significant. Horizontal bars represent the effect size for each taxon. The length of the bar represents the log10 transformed LDA score, indicated by vertical dotted lines.

Fig. 10

Linear size effect discriminant analysis (LDA LEfSe) of the fungi community structure at, C) Family and E) species levels, between children who developed (green), or did not develop (red), at least one asymptomatic Plasmodium parasitaemia episode within 16 months of follow-up. Fungi community structure at A) Order, B) Class and D) genus were significant in children who developed (red) at least one asymptomatic Plasmodium parasitaemia episode within 16 months of follow-up. Horizontal bars represent the effect size for each taxon. The length of the bar represents the log10 transformed LDA score, indicated by vertical dotted lines.