Gut Bacteroides act in a microbial consortium to cause susceptibility to severe malaria

Abstract

Malaria is caused by Plasmodium species and remains a significant cause of morbidity and mortality globally. Gut bacteria can influence the severity of malaria, but the contribution of specific bacteria to the risk of severe malaria is unknown. Here, multiomics approaches demonstrate that specific species of Bacteroides are causally linked to the risk of severe malaria. Plasmodium yoelii hyperparasitemia-resistant mice gavaged with murine-isolated Bacteroides fragilis develop P. yoelii hyperparasitemia. Moreover, Bacteroides are significantly more abundant in Ugandan children with severe malarial anemia than with asymptomatic P. falciparum infection. Human isolates of Bacteroides caccae, Bacteroides uniformis, and Bacteroides ovatus were able to cause susceptibility to severe malaria in mice. While monocolonization of germ-free mice with Bacteroides alone is insufficient to cause susceptibility to hyperparasitemia, meta-analysis across multiple studies support a main role for Bacteroides in susceptibility to severe malaria. Approaches that target gut Bacteroides present an opportunity to prevent severe malaria and associated deaths.

Altered Gut Microbiota as a Potential Risk Factor for two types of anemia: insights from Mendelian randomization analysis

“…Moreover, their fecal metagenomics and metabolomics analyses showed a decrease in Bacteroides abundance among IDA patients, which contrasted with our ndings linking Bacteroides to IDA; the discrepancy could be related to bias from the use of fecal samples. Additionally, Mandal et al found a signi cant increase in Bacteroides abundance among children with severe malaria anemia, validating the ndings in a mouse model that simulated a comparable microbial background, and suggesting that a Bacteroides-targeting treatment strategy could be feasible [41].…”

Susceptibility to febrile malaria is associated with an inflammatory gut microbiome

“…Bacteroides were recently demonstrated to be signi cantly increased in Ugandan infants with severe malaria anemia compared to infants with asymptomatic P. falciparum infection 12 . Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides fragilis and Bacteroides uniformis were signi cantly increased in the susceptible Malian children (Table 6), although this appears to be largely the result of outliers (Supp Fig.…”

“…The gut microbiome is increasingly recognized as playing a role in the etiology of numerous diseases [6][7][8] , including those caused by intestinal and extraintestinal pathogens [9][10][11] . The susceptibility of mice to Plasmodium infection, as measured by their parasite burden, has been established to be highly dependent on the composition of their gut microbiome 10,12 , but the in uence of the gut microbiome on clinical malaria outcomes in humans is less well characterized. In a cross-sectional study, the composition of the fecal microbiome was shown to be different between Ugandan infants (aged 0.5-4 years) with severe malarial anemia and those with asymptomatic P. falciparum infection 12,13 , but whether the differences in the microbiome engendered the differences in malaria severity or were the result of the differential severity is unclear.…”

“…The susceptibility of mice to Plasmodium infection, as measured by their parasite burden, has been established to be highly dependent on the composition of their gut microbiome 10,12 , but the in uence of the gut microbiome on clinical malaria outcomes in humans is less well characterized. In a cross-sectional study, the composition of the fecal microbiome was shown to be different between Ugandan infants (aged 0.5-4 years) with severe malarial anemia and those with asymptomatic P. falciparum infection 12,13 , but whether the differences in the microbiome engendered the differences in malaria severity or were the result of the differential severity is unclear. Additionally, a longitudinal study in a cohort of Malian children and adults (aged 0.25-25 years) found that the fecal microbiome composition before the start of the malaria season correlated with the prospective risk of P. falciparum infection, but not with the development of febrile malaria 14 .…”

Top-Down Characterization of Bacterial Lipopolysaccharides and Lipooligosaccharides Using Activated-Electron Photodetachment Mass Spectrometry

“…coli Nissle, a probiotic that modulates gut microbiota, − and Bacteroides fragilis (B. fragilis), a representative human gut symbiont with host immune modulatory activities. − a-EPD yields extensive fragmentation across the polysaccharide region of LPS, including cross-ring and glycosidic cleavages, while providing less congested spectra and fewer redundant ions, thus retaining beneficial traits of both CID and UVPD. The structural details presented here are a major step in better understanding the structure–function relationship of commensal LPS in human gut microbiota.…”