The gut microbiome and metabolome associate with Schistosoma mansoni infection and cardiovascular disease risk in Uganda.

S. mansoni infection was associated with increased gut microbial diversity in a cross-sectional study of 209 individuals in Uganda.

• Study design was cross-sectional involving 209 individuals living in communities with contrasting S. mansoni endemicity
• Gut microbiome was profiled using 16S rRNA gene sequencing
• Increased alpha diversity was observed in S. mansoni-infected individuals compared to uninfected individuals
• The study was conducted in Uganda in communities with differing levels of schistosomiasis transmission

S. mansoni infection was associated with distinct taxonomic signatures in the gut microbiome, including enrichment of Treponema and depletion of Prevotella and Streptococcus.

• Treponema was among the taxa enriched in S. mansoni-infected individuals
• Prevotella and Streptococcus were depleted in S. mansoni-infected individuals
• These taxonomic differences represent distinct microbial profiles associated with helminth infection
• 16S rRNA gene sequencing was used to characterize the taxonomic signatures

Several infection-associated microbial taxa statistically mediated the relationships between S. mansoni infection and cardiovascular disease risk.

• Mediation analyses were performed to assess whether gut microbial taxa mediated associations between S. mansoni infection and CVD risk
• Multiple microbial taxa were identified as statistical mediators of the infection-CVD risk relationship
• This finding suggests a potential biological pathway linking helminth infection to reduced CVD risk via gut microbiome changes
• Causality could not be inferred due to the cross-sectional study design

Faecal metabolomic profiling identified infection-associated metabolites linked to cardiovascular risk.

• Faecal metabolome was profiled using liquid chromatography-mass spectrometry (LC-MS)
• Distinct infection-associated metabolites were identified in S. mansoni-infected versus uninfected individuals
• Integrative analyses revealed linked microbe-metabolite networks associated with cardiovascular risk
• The metabolomic findings complement the microbial diversity and taxonomic findings

Helminth infections are consistently associated with reduced cardiovascular disease risk, yet the biological mechanisms underlying this relationship remain unclear.

• The gut microbiome and metabolome are described as 'key regulators of cardiometabolic health' that may mediate infection-associated effects on host physiology
• This study was motivated by the unexplained inverse relationship between helminth infections and CVD risk
• The study aimed to identify microbial and metabolic pathways relevant to cardiometabolic health in the context of S. mansoni infection
• Prior literature consistently links helminth infection to reduced CVD risk but mechanisms were not established

Integrative microbiome-metabolome analyses identified linked microbe-metabolite networks associated with cardiovascular risk in the context of S. mansoni infection.

• Both gut microbiome and faecal metabolome data were integrated in network analyses
• The integrative approach identified coordinated microbe-metabolite associations relevant to CVD risk
• These findings highlight microbial and metabolic pathways relevant to cardiometabolic health
• The study provides insight into host-parasite-microbiome interactions