Abstract
Background and aims: Disorders of gut-brain interactions (DGBIs), including irritable bowel syndrome (IBS), functional constipation (FC) and functional diarrhoea (FD), have a multifactorial aetiology, with colonic microbiota alterations likely contributing. To investigate how these changes relate to DGBIs, the faecal microbial taxonomic composition and gene abundance in DGBI subjects was characterised and integrated with gastrointestinal and non-gastrointestinal symptoms.
Methods: Microbial DNA was extracted and analysed by shotgun sequencing. 239 faecal samples (IBS-constipation/FC, n = 60; IBS-diarrhoea/FD, n = 66; controls, n = 113) were used for integrative analysis with Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO).
Results: High-level compositional patterns were similar between FD and IBS-diarrhoea but differed between FC and IBS-constipation, compared to controls. All DGBI subtypes showed altered relative abundance of hydrogen-metabolising taxa (Enterobacteriaceae, Lachnospiraceae, Bilophila, Desulphovibrio, Methanobrevibacter), compared to controls. Relative gene abundance associated to micronutrient homeostasis discriminated IBS-diarrhoea, IBS-constipation and FC, but not FD, from controls. Increased tyrosine metabolism relative gene abundance discriminated FC and IBS-diarrhoea from controls. FC was further distinguished from controls and other DGBIs by increased abundance of facultative anaerobes (Salmonella, Shigella, Escherichia) and genes related to aromatic amine catabolism, secretion systems, and virulence. In constipation- and diarrhoea-predominant DGBIs, Firmicutes negatively correlated with microbial “secondary metabolism” and “phages, prophages, transposable elements, plasmids”, while “aromatic compound metabolism” positively correlated with constipation severity and diarrhoea symptoms (abdominal pain).
Conclusion: Distinctive microbial changes suggested FC as a distinct condition from IBS-constipation. Despite taxonomic similarities between FD and IBS-diarrhoea, microbial gene abundance discriminated IBS-diarrhoea but not FD from controls. Integrative analysis revealed potential microbial-symptom relationships in DGBIs.