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Updated: Apr 18, 2026
Isolation and Analysis of Brain-sequestered Leukocytes from Plasmodium berghei ANKA-infected Mice
Published on: January 2, 2013
Gut microbiota bidirectionally influences protection and severity in cerebral malaria in mice
Tomoyo Taniguchi1,2,3,4, Eiji Miyauchi5,6, Reika Kawabata-Iwakawa7
1Department of Immunology and Parasitology, Graduate School of Medicine, University of the Ryukyus, 1076 Kiyuna, Ginowan, Okinawa, 901-2720, Japan. ttani@cs.u-ryukyu.ac.jp.
Background:
Malaria caused by Plasmodium parasites leads to severe complications, such as cerebral malaria; however, the influence of the gut microbiota on the pathogenesis of cerebral malaria remains unclear. Here, the effects of antibiotic-induced microbiota alteration on experimental cerebral malaria (ECM) were examined.
Methods:
Male C57BL/6N mice that were administered drinking water containing a four-antibiotic cocktail, ampicillin, neomycin, metronidazole and vancomycin, from 2 weeks before P. berghei ANKA (PbA) infection were used for the experiments. Disease progression, blood-brain barrier (BBB) integrity, immune responses, and gut microbiota composition were evaluated.
Results:
Approximately 80% of mice with modified gut microbiota avoided ECM and showed reduced BBB disruption and lymphocyte infiltration into the brain. 16S rRNA gene sequencing revealed specific bacterial species that contributed to either the protection or pathogenesis of ECM. The mono-colonization of germ-free mice revealed that distinct bacterial species could attenuate or exacerbate ECM symptoms, independent of antibiotic effects.
Conclusions:
The findings highlight that distinct gut microbial populations can modulate host susceptibility or resistance to ECM, underscoring the important influence of the intestinal microbiota on infectious disease outcomes. This work broadens the understanding of host‒microbe interactions and may inform new strategies for managing cerebral malaria through microbiota modulation.
Insights
Altering gut microbiota composition in mice significantly reduced the severity of experimental cerebral malaria (ECM). Specific bacteria were identified as key players in either protecting against or worsening ECM, independent of antibiotic treatment.
Area of Science:
- Microbiology
- Immunology
- Neuroscience
Background:
- Cerebral malaria (CM) is a severe complication of Plasmodium parasite infection.
- The role of gut microbiota in CM pathogenesis is not well understood.
Purpose of the Study:
- To investigate the impact of gut microbiota alterations on experimental cerebral malaria (ECM).
- To identify specific microbial contributions to ECM development and severity.
Main Methods:
- Mice were treated with a four-antibiotic cocktail to modify gut microbiota before Plasmodium berghei ANKA (PbA) infection.
- Evaluated disease progression, blood-brain barrier (BBB) integrity, immune responses, and gut microbiota composition using 16S rRNA gene sequencing.
- Germ-free mice were mono-colonized with specific bacterial species to assess their independent effects on ECM.
Main Results:
- Antibiotic-induced microbiota modification protected approximately 80% of mice from ECM.
- Reduced BBB disruption and lymphocyte infiltration into the brain were observed in mice with altered microbiota.
- Specific bacterial species were found to either protect against or promote ECM, with effects confirmed in germ-free mice.
Conclusions:
- Gut microbial populations significantly influence host susceptibility and resistance to ECM.
- These findings highlight the critical role of the intestinal microbiota in infectious disease outcomes.
- Modulating the gut microbiota may offer novel therapeutic strategies for managing cerebral malaria.
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