Abstract
Cerebral malaria (CM) is the most severe form of malaria with the highest mortality rate and can result in life-long neurological deficits and ongoing comorbidities. Factors contributing to severity of infection and development of CM are not fully elucidated. Recent studies have indicated a key role of the gut microbiome in a range of health conditions that affect the brain, but limited microbiome research has been conducted in the context of malaria. To address this knowledge gap, the impact of CM on the gut microbiome was investigated in mice. C57BL/6J mice were infected with Plasmodium berghei ANKA (PbA) parasites and compared to non-infected controls. Microbial DNA from faecal pellets collected daily for 6-days post-infection were extracted, and microbiome comparisons conducted using 16S rRNA profiling. We identified significant differences in the composition of bacterial communities between the infected and the non-infected groups, including a higher abundance of the genera Akkermansia, Alistipes and Alloprevotella in PbA-infected mice. Furthermore, intestinal samples were collected post-cull for morphological analysis. We determined that the caecal weight was significantly lower, and the small intestine was significantly longer in PbA-infected mice than in the non-infected controls. We concluded that changes in microbial community composition were primarily driven by the infection protocol and, to a lesser extent, by the time of infection. Our findings pave the way for a new area of research and novel intervention strategies to modulate the severity of cerebral malaria disease.
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Funding
This work was supported by an Australian Postgraduate Award to SAK at La Trobe University. ELH-Y is the recipient of an NHMRC Ideas Grant (APP2003848). TdK-W is the recipient of an NHMRC Senior Research Fellowship (1136300). SAK has been supported by a Defence Science Institute’s Research Higher Degree Student Grant.
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Sarah A Knowler: data analysis, investigation, writing—original draft. Anya Shindler: supervision, writing—review and editing. Jennifer L Wood: supervision, writing—review and editing. Colleen J Thomas: supervision, writing—review and editing. Asha Lakkavaram: Animal husbandry, experimental infections and faecal collection. Ashley E Franks: conceptualisation, tissue collection, supervision, writing—review and editing. Tania F de Koning-Ward: conceptualisation, tissue collection, writing—review and editing. Elisa L Hill-Yardin: conceptualisation, tissue collection, writing—review and editing. Teresa G Carvalho: conceptualisation, tissue collection, writing—review and editing.
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The experiment was performed in strict accordance with the recommendations of the National Health and Medical Research Council Australian ‘Code of practice for the care and use of animals for scientific purposes.’ The protocols were approved by the Deakin University Animal Welfare Committee (approval number G11-2017).
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Knowler, S.A., Shindler, A., Wood, J.L. et al. Altered gastrointestinal tract structure and microbiome following cerebral malaria infection. Parasitol Res 122, 789–799 (2023). https://doi.org/10.1007/s00436-022-07775-2
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DOI: https://doi.org/10.1007/s00436-022-07775-2