Gut metagenome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA925433 | ENA |
REPOSITORIES: ENA
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Project description:Background: Iron deficiency, anaemia and Plasmodium infection represent significant global health challenges with overlapping geographical distributions, particularly affecting pregnant women in Africa. Previous evidence suggests complex interactions between iron status and malaria susceptibility. However, the mechanisms and clinical implications of this relationship remain poorly understood. Methods: We employed a multi-layered approach to clarify the association between iron deficiency and malaria infection risk. First, we analysed clinical data from Malawian pregnant women (n=711) participating in the REVAMP clinical trial—an RCT of intravenous iron versus oral iron—to assess associations between iron status and P. falciparum parasitaemia detected by ultra-sensitive qPCR. All eligible women received intermittent preventive anti-malaria treatment. Then, we utilised a genetic mouse model (Tmprss6-knockout) to isolate the effect of iron deficiency on P. berghei infection and progression to clinical disease. Finally, we explored direct effects of iron chelation on cultured P. falciparum parasites through transcriptomic and proteomic analyses. Results: In REVAMP, iron deficiency was associated with a 50% reduced probability of P. falciparum qPCR positivity at baseline (95% CI [30%-64%], p<0·0001). Iron intervention given at baseline did not significantly modify the probability of subsequent parasitaemia across the pregnancy. In the murine model, iron-deficient Tmprss6-knockout mice exhibited significantly improved survival compared to controls (median survival 15·5 vs 7·0 days) and protection from cerebral malaria (survival 83% vs 17%). Iron chelation in P. falciparum cultures induced substantial transcriptomic (1,397 differentially expressed genes) and proteomic changes (121 differentially expressed proteins; 46 matched differentially expressed gene/protein pairs), primarily affecting processes involved in host cell invasion, protein export, and nutrient acquisition. Conclusion: Our findings consistently demonstrate that iron deficiency protects against Plasmodium infection across clinical, pre-clinical, and in vitro models. Importantly, in the presence of adequate malaria prevention intravenous iron supplementation did not significantly increase subsequent parasitemia prevalence. These results provide mechanistic insights into iron and malaria interactions and support current WHO recommendations for iron supplementation in pregnant women in malaria-endemic regions when coupled with adequate malaria prevention strategies.
2026-01-04 | GSE302727 | GEO
Project description:Gut microbiome research is rapidly moving towards the functional characterization of the microbiota by means of shotgun meta-omics. Here, we selected a cohort of healthy subjects from an indigenous and monitored Sardinian population to analyze their gut microbiota using both shotgun metagenomics and shotgun metaproteomics. We found a considerable divergence between genetic potential and functional activity of the human healthy gut microbiota, in spite of a quite comparable taxonomic structure revealed by the two approaches. Investigation of inter-individual variability of taxonomic features revealed Bacteroides and Akkermansia as remarkably conserved and variable in abundance within the population, respectively. Firmicutes-driven butyrogenesis (mainly due to Faecalibacterium spp.) was shown to be the functional activity with the higher expression rate and the lower inter-individual variability in the study cohort, highlighting the key importance of the biosynthesis of this microbial by-product for the gut homeostasis. The taxon-specific contribution to functional activities and metabolic tasks was also examined, giving insights into the peculiar role of several gut microbiota members in carbohydrate metabolism (including polysaccharide degradation, glycan transport, glycolysis and short-chain fatty acid production). In conclusion, our results provide useful indications regarding the main functions actively exerted by the gut microbiota members of a healthy human cohort, and support metaproteomics as a valuable approach to investigate the functional role of the gut microbiota in health and disease.
2017-07-19 | PXD005780 | Pride
Project description:Administration of iron as drops has significant effects on the gut microbiota of iron-sufficient infants: a randomized controlled study
| PRJNA475589 | ENA
Project description:Background: Host iron deficiency is protective against severe malaria as the human malaria parasite Plasmodium falciparum depends on free iron from its host to proliferate. Due to the absence of transferrin, ferritin, ferroportin, and a functional heme oxygenase, the parasite’s essential pathways of iron acquisition, storage, export, and detoxification differ from those in humans and may thus be excellent targets for therapeutic development. However, the proteins involved in these processes in P. falciparum remain largely unknown. Experimental design: To identify iron-regulated mechanisms and putative iron transporters in the human malaria parasite Plasmodium falciparum 3D7, we carried out whole-transcriptome profiling using bulk RNA-sequencing. The parasites were cultured either using erythrocytes from a donors with high, medium (healthy) or low iron status (experiment 1); or with red blood cells from another healthy donor in the presence or absence of 0.7 µM hepcidin, a specific ferroportin inhibitor and iron-regulatory hormone (experiment 2). This concentration of hepcidin was reported to reduce binding of ferrous iron to ferroportin by 50% in vitro (39). Samples from three biological replicates each were harvested at the ring and trophozoite stage (6 – 9 and 26 – 29 hours post invasion, hpi) during the second intra-erythrocytic developmental cycle under the conditions specified.
2024-04-08 | E-MTAB-13411 | biostudies-arrayexpress
Project description: Not available
| S-EPMC10477861 | biostudies-literature
Project description:The mechanism by which artemisinin and its derivatives (ARTs) kill malaria parasites remains unclear. Haem or iron activates ARTs to produce free radicals that kill malaria parasites. However, adding iron or haem supply did not enhance, but instead attenuated, the antimalarial effect of ARTs, suggesting that the free-radical effect (FRE) is not the only antimalarial mechanism of ARTs. Here, through the single-cell RNA sequencing analysis of Plasmodium yoelii 17XNL and P. falciparum 3D7 in vivo and in vitro, we found that the sensitive stages to ARTs were associated with the expression of genes related to haem and iron (HI), DNA synthesis, antioxidation and the pentose-phosphate-pathway (PPP). Furthermore, the stages included an ART-sensitive cycle crucial for DNA synthesis that encompassed the release of iron through haem degradation to the activation of the PPP by iron. Additionally, the mechanism of haemozoin formation created a unique condition for interaction between ARTs and HI. In particular, HI can attenuate the antimalarial action of ARTs, strongly suggesting the existence of a HI-use-disturbance effect that combined with FRE to confer ARTs with a double-kill antimalarial mechanism different from the effect of iron chelators.
2024-06-08 | GSE234872 | GEO
Project description:16S sequencing of gut microbiota of malaria-infected mice
| PRJDB3900 | ENA
Project description: Not available
| S-EPMC3538954 | biostudies-literature
Project description: Not available
| S-EPMC7109134 | biostudies-literature