High Schistosoma mansoni infection intensity is associated with distinct gut microbiota and low levels of systemic cytokines in children along the Albert-Nile, Northern Uganda.

BACKGROUND: Schistosomiasis disease that affects millions of people in sub-Saharan Africa, with a range of impacts on both host immune responses and the gut microbiome. The gut microbiota plays a fundamental role in the host's nutrition, metabolism, protection against pathogens, and modulation of host immunity. Understanding the role of the gut microbiome in pathophysiology of Schistosoma mansoni infection and how it influences host immune response, is essential for developing a more comprehensive view of disease progression and potential therapeutic strategies. METHODOLOGY: A cross-sectional study was carried out on 140 faecal samples collected from school children aged 10-15years residing in the schistosomiasis endemic hot spots of the Albert-Nile, Pakwach district, Northern Uganda. The samples were categorised by S. mansoni infection intensity based on the Kato Katz test. Faecal DNA was isolated, and microbiota composition was determined by 16 S rRNA V3-V4 sequencing. Plasma Th1/Th2 profiling of 13 cytokines was carried out on the Luminex platform and compared with respect to S. mansoni infection intensities. RESULTS: The genera Phascolarctobaterium and Prevotella_7 were significantly enriched (padj < 0.05, LDA > 3.0) in the high S. mansoni infection intensity group whereas, Ruminobacter and Alloprevotella were enriched in the low infection intensity group. We observed significantly lower systemic Th1/Th2 cytokine levels between the high intensity infection and the control samples (padj < 0.05). Linear regression analysis using all cytokines as covariates showed that the genus Alloprevotella, Streptococcus, Gastranaerophilales and Ruminobacter were associated with systemic IL6 response. CONCLUSION: There are alterations in the gut microbiota of S. mansoni infected children with distinct genera that discriminate the high and low infection intensity that could be potentially used as biomarkers. There is an association between the gut microbiota and systemic cytokine response whose mechanism in chronic disease pathophysiology needs to be further investigated.