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

Abstract

<title>Abstract</title> Background Schistosomiasis is a chronic neglected 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 in role in the host’s nutrition, metabolism, protection against pathogens, and modulation of host immunity. There is a need to understand the role of the gut microbiome in pathophysiology of <italic>Schistosoma mansoni</italic> infection and how this influences the host’s immune response. 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 <italic>S. mansoni</italic> infection intensity based on the Kato Katz test. Faecal DNA was isolated and microbiome composition was determined by 16S rRNA V3-V4 sequencing. Plasma Th1/Th2 profiling of 13 cytokines was carried out on the Luminex platform and compared with respect to <italic>S. mansoni</italic> infection intensities. Results The genera <italic>Phascolarctobaterium</italic> and <italic>Prevotella_7</italic> were significantly enriched (padj &lt; 0.05, LDA &gt; 3.0) in the high <italic>S. mansoni</italic> infection intensity group whereas, <italic>Ruminobacter</italic> and <italic>Alloprevotella</italic> 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 &lt; 0.05). Linear regression analysis using all cytokines as covariates showed that the genus <italic>Alloprevotella, Streptococcus, Gastranaerophilales</italic> and <italic>Ruminobacter</italic> were associated with systemic IL6 response. Conclusion There are alterations in the gut microbiome of <italic>S. mansoni</italic> 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 microbiome and systemic cytokine response whose mechanism in chronic disease pathophysiology can be further investigated.