Uncovering the role of the gut microbiome and metabolome in Schistosoma mansoni-induced modulation of cardiovascular disease risk in humans
Abstract
Background Helminth infections have been consistently associated with reduced cardiovascular disease (CVD) risk, yet the underlying mechanisms remain poorly understood. We hypothesized that Schistosoma mansoni infection alters the gut microbiome and metabolome in ways that modulate CVD risk factors—specifically high total cholesterol, LDL cholesterol, and blood pressure. We further hypothesized that S. mansoni-associated microbes linked with these risk factors would correlate with similarly associated metabolites. Methods We profiled the gut microbiome (using 16S rRNA gene sequencing) and faecal metabolome (using liquid chromatography–mass spectrometry) of 216 individuals from two settings in Uganda with contrasting S. mansoni endemicity. We conducted differential abundance, linear discriminant, linear regression, mediation, pathway enrichment, and integrative multi-omics analyses to investigate associations between S. mansoniinfection, microbial and metabolite profiles, and CVD risk factors. Results S. mansoni (S. m) infection was associated with increased microbiome alpha diversity (Shannon index p = 0.048; observed richness p = 0.008), though beta diversity separation was observed only in urban communities (PERMANOVA p = 0.011). Linear discriminant analysis (LDA) and differential abundance testing revealed distinct taxa enriched in S. m+ individuals, including Lysobacter, Domibacillus, and Treponema, while Prevotella and Streptococcus were consistently depleted. Mediation analysis identified several taxa such as Treponema, Roseburia, Lachnospiraceae_UCG.00 4 andMethanobrevibacter, that significantly mediated the relationship between S. mansoni infection and reduced cardiovascular disease (CVD) risk factors. Metabolomic profiling of faecal samples identified differentially abundant metabolites (p< 0.05) present in each group, although the overall global metabolomic separation between S. m+ and S. m– groups was not significant. Integrative analyses revealed coherent microbe–metabolite–CVD networks present; one example identified were those bacterial species belonging to Lysobacter and Arthrobacter were inversely correlated with metabolites such as glycerolipids, steroids, and fatty acyls which are associated with both total and LDL cholesterol levels found in blood. These findings support a putative helminth–microbiome–metabolome axis that may modulate host cardiometabolic risk. Conclusion Our findings reveal a gut microbiome–metabolome pathway induced from S. m infection that may reduce CVD risk. Collectively this research provides novel insight into host-parasite interactions and identifying microbial and metabolic signatures that could offer new strategies to mimic the cardioprotective effects of helminth infections.
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