INDIANAPOLIS — New research conducted by Indiana University School of Medicine scientists emphasizes the gut microbiome's significant role in febrile malaria development. The findings, recently published in Nature Communications, suggest that treatments targeting gut bacteria could offer promising strategies to decrease the risk of the disease, particularly in children.
Five mosquito-transmitted parasite species cause malaria in humans, with Plasmodium falciparum being the deadliest and most prevalent in Africa. According to the latest World malaria report, P. falciparum infections in 2022 caused more than 200 million cases of malaria and around 600,000 deaths.
"In a prior study, my research team found that children with asymptomatic P. falciparum infections have different gut bacteria populations than children with severe malaria," said Nathan Schmidt, PhD, the study's lead author and an associate professor of pediatrics at the IU School of Medicine. "However, it was not known if the different bacteria communities were the cause or consequence of severe malaria, so our goal was to assess potential causality between gut bacteria and disease outcomes."
The research was led by the Schmidt lab in collaboration with colleagues from the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health and the University of Sciences, Techniques and Technologies of Bamako (USTTB). The team analyzed results from a field study led by Peter Crompton, MD, MPH, a senior investigator at NIAID, and Boubacar Traore, PharmD, PhD, a professor at USTTB, involving Malian children who were infected with P. falciparum.
The investigators collected stool samples from children before Mali’s six-month rainy season, which coincides with malaria transmission. During the rainy season, the children were closely monitored for infections and symptoms of malaria, such as fevers, chills and headaches. The research found that most children developed one or more P. falciparum infections that led to febrile malaria. However, a small subset of children only had asymptomatic infections. When the researchers compared the gut bacteria from the pre-rainy season stool samples of these two groups, they found distinct differences in bacterial communities. This suggests that gut bacteria may have influenced the different outcomes following P. falciparum infection. Similar trends were also observed in a controlled environment using mouse models, reinforcing the results from the Malian children study.
"My laboratory plans to continue investigating the contribution of gut bacteria towards malaria pathogenesis in African children using stool samples collected in separate clinical observation studies of severe malaria," Schmidt said. "If these studies provide additional support towards gut bacteria contributing to severe malaria in African children, then it may suggest that methods to manipulate gut bacteria could be a novel approach to prevent children from dying of severe malaria."
Schmidt's recent research strengthens his lab's previous findings involving the interplay between the gut microbiome and malaria susceptibility. In 2023, the researchers from the Ryan White Center for Pediatric Infectious Disease and Global Health and the Herman B Wells Center for Pediatric Research published similar discoveries linking specific gut bacteria to an increased risk of severe malaria development in Ugandan children.
About the IU School of Medicine
The IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability. According to the Blue Ridge Institute for Medical Research, the IU School of Medicine ranks No. 13 in 2023 National Institutes of Health funding among all public medical schools in the country.
Writer: Jackie Maupin, jacmaup@iu.edu
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