Malaria has consistently remained on the list of top causes of morbidity and mortality especially in sub-Saharan Africa, for decades. Its clinical presentation is heterogeneous with asymptomatic, mild and severe phenotypes. That clinical presentation is partly determined by host immune responses which, themselves, are subject to altering by several factors. In recent years, research has increasingly reported the gut microbiota as one of such factors. On the other hand, Soil Transmitted Helminths (STHs) have been shown to affect both the immune responses to malaria and the gut microbiota (GM) composition. The latter can also be shaped by genetics, geographic location, age, nutrition and other factors. However, to our knowledge, there in not a single study about malaria and the GM in Rwanda. Thus, our project comprised two studies and was aimed at investigating malaria-GM relationships, considering multiple counfounding factors, in Rwanda. The first study was conducted in 3 malaria-endemic provinces of Rwanda: East, South and West. The terms ‘West’ and ‘Western’ province were used intercheangably to represent a geographic region of the Republic of Rwanda. We explored associations between malaria and the gut microbiota across the three geographic regions, considering host’s nutritional habits, STH coinfections and age. We used questionnaire-derived qualitative data for demographic analysis while malaria and soil-transmitted helminth diagnosis was assessed by microscopy. The gut microbial composition was analyzed based on bacterial 16S rRNA gene amplicon sequencing. We observed that preschool children had a significantly lower microbiota diversity compared to both school children and adults. Unlike age, infection status (uninfected, malaria alone, soil-transmitted helminth alone or coinfection) was not significantly associated with the gut microbiota. Moreover, using Bray-Curtis distances, we found a significantly differential gut microbial beta diversity in the West province compared to the other provinces. This geographic difference was not explained by any change in energy intake, protein, lipids, or carbohydrates consumption but was likely due to lower dietary fibre intake in the West compared to the South and the East (results’ chapter 1). The second study was conducted in the central plateau of Rwanda to compare the gut microbiota profiles of malaria patients with different clinical presentations (severe, mild, asymptomatic and uninfected). Results (chapter 2) showed significantly lower alpha diversity in severe malaria patients compared to other malaria severity groups across all measured metrics. Furthermore, beta diversity analysis using Bray Curtis distance showed that severe malaria samples were significantly different and formed a unique cluster visualized by PCoA compared to other groups. In the same direction, ANCOM-BC differential analysis at genus level revealed that genera Suterella and Veillonella were depleted in asymptomatic and mild samples respectively, while both Lactobacillus and Bacteroides were among the top 6 genera depleted in both groups compared to severe malaria group. In summary, our research project analyzed malaria-gut microbiota relationships by age, geographic location, parasitic infection and/or coinfection status and malaria severity in Rwanda. We reported significant differences in the gut microbiota composition of participants by age, geographic location – with possible connection to low-fibre food intake, and most importantly by malaria severity. Interestingly, we have not found significant links between gut microbiota composition and the presence or absence of parasitic infection. Further studies are recommended to unravel malaria-GM interactions towards discovering novel interventions to defeat severe malaria.
Mutoni, J. d. (2025). Relationships between malaria, helminth infections and the gut microbiota composition in Rwanda. https://hdl.handle.net/2078.5/245082