Investigating the role of the gut microbiome in modulating the development of konzo

Konzo is a distinct upper motor neuron disease prevalent in several sub-Saharan African countries and is strongly associated with a reliance on toxic cassava, chronic malnutrition and a deficiency in dietary sulfur amino acids. Konzo predominately affects children and women of childbearing ages, with the Democratic Republic of the Congo (DRC) having one of the highest incidences of cases. The exact molecular mechanisms behind the pathophysiology of konzo remain poorly understood, but the gut microbiome has been implicated as a possible modulatory factor in disease development. While there is evidence in non-human models indicating that the gut microbiome may exacerbate the cyanide toxicity found in cassava, the gut microbiome of individuals affected with konzo had yet to be characterized. Using shotgun metagenomics sequencing, metatranscriptomics sequencing, and metabolomics, the gut microbiome of children affected with konzo was assessed, along with unaffected populations of the DRC who reside outside the historical konzo risk zone of Kahemba. The findings indicate that the bacterial composition and metabolites present in the gut microbiome of individuals from different geographic regions of the DRC are distinct, however, differences in the gut flora composition between those discordant for disease from the Kahemba region are similar. The data have identified numerous metabolic differences between study groups, which now provide novel variables for hypothesis testing in future experimentation to better understand the biological relevance that these metabolites may contribute to disease development. Most interestingly, these data highlight key differences between populations residing in konzo risk zones compared to those in rural regions where konzo has yet to be documented. This study identified a strong influence of diet and geography on the gut microbiome, while highlighting key differences in bacterial composition between populations that possibly put the children residing in Kahemba, the epicenter of konzo, at highest risk for disease development.

Author

• Vashist, Neerja Nisha

Language

• en

Keyword

• Multi-omics
• Gut Microbiome
• Democratic Republic of the Congo
• Cassava
• Konzo
• Africa

Date created

• 2023

Type of Work

• Dissertation

License

• All rights reserved

Rights statement

• In Copyright

GW Unit

• Genomics and Bioinformatics

Degree

• Ph.D.

Advisor

• Vilain, Eric J.N.
• Freishtat, Robert J.

Committee Member(s)

• Mazumder, Raja
• Caldovic, Ljubica

Persistent URL

•  https://scholarspace.library.gwu.edu/etd/02870w629