The role of the gut microbiome in human health
The overarching goal of my lab is to unlock the potential of the gut microbiome for the benefit of human health, aiming to prevent and cure diseases. Currently, I am focused on three main projects:
- Project 1: Investigating the Role of Gut Bacteroides in Severe Malaria Malaria is a devastating disease caused by the Plasmodium parasite transmitted through the bite of female Anopheles mosquitoes that continue to pose a significant global health threat. Despite progress, the disease remains a burden, especially in sub-Saharan Africa, affecting young children which cause more than 600,000 deaths and 240 million cases annually. Our research has revealed that gut Bacteroides act in a microbial consortium to cause susceptibility to severe malaria. Bacteroides, normally beneficial gut commensals providing nutrition and supporting host immunity, are implicated in the severity of malaria. However, the mechanisms behind their involvement remain poorly understood. In this project, I aim to decipher how gut Bacteroides influence both gut and systemic immunity, exacerbating severe malaria, using a murine malaria model. Additionally, I am interested in developing a precision gut microbiota editing tool for fine-tuning gut Bacteroides levels to promote host health and mitigate severe malaria.
- Project 2: Exploring the Impact of Gut Microbiome on RBC Tension, Hematopoiesis, and Severe Malaria Our preliminary data indicate that naïve mice susceptible to hyperparasitemia caused by Plasmodium yoelii (Py) infection exhibit increased genetic potential for the alpha hemolysin/cyclolysin transport system in their gut microbiota, compared to mice resistant to hyperparasitemia. Moreover, hyperparasitemia susceptible naïve mice show enhanced expression of genes related to heme metabolism and increased RBC surface tension compared to resistant mice. This project aims to investigate the link between alpha toxin, heme metabolism, and severe malaria.
- Project 3: Studying the Role of Gut Microbiome in Sickle Cell Vaso-Occlusive Crises Sickle cell disease (SCD) affects millions of people globally each year and can be life-threatening, especially in children and in low- and middle-income countries. In Africa, approximately 240,000 children are born with SCD annually, which accounts for 75% of all cases of SCD. SCD is characterized by abnormal hemoglobin, leading to sickle-shaped RBCs prone to hemolysis, resulting in sickle cell anemia (SCA). Vaso-occlusive crises (VOC) are common complications of SCD, and the factors contributing to their incidence are not fully understood. Recent studies suggest a association between the gut microbiome, aged neutrophils, and VOC in SCD patients. However, the specific bacteria involved remain unknown. In this project, we will investigate differences in gut microbiota between children with and without SCD and explore how these differences relate to an increased presence of aged neutrophils and VOC. This research could pave the way for novel gut microbiota-based approaches to reduce SCD complications.