Multi-kingdom microbiota analysis reveals bacteria-viral interplay in IBS with depression and anxiety.

Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder frequently accompanied by psychological symptoms. Bacterial microbiota plays a critical role in mediating local and systemic immunity, and alterations in these microbial communities have been linked to IBS. Emerging data indicate that other intestinal organisms, including bacteriophages, are closely interlinked with the bacterial microbiota and their host, yet their collective role remains to be elucidated. Here, we analyze the gut multi-kingdom microbiota of 360 IBS patients from a prospective cohort study in Hong Kong, with participants phenotyped through psychological assessment. Our findings reveal significantly lower intra-community correlations in IBS patients compared to healthy controls and highlight unique taxa patterns associated with IBS and mental disorders. Utilizing multi-omic data alongside machine learning techniques, we successfully predicted psychiatric comorbidities in IBS, achieving an average AUC of 0.78. Notably, gut viruses emerged as significant contributors to our predictive model, indicating a vital role for bacteriophages in the gut microbiome of IBS patients. We found that lysogenic phages in IBS displayed a broader host range, with Bilophia containing the most abundant prophages. Our analysis further indicates that IBS patients with depression exhibited a higher prevalence of viral-encoded auxiliary metabolic genes, specifically those involved in the sulfur metabolic pathway related to ubiquinone biosynthesis. The gut virome is increasingly reported to play an important role in the pathogenesis of many diseases. The study provides a systematic characterization of the drivers of the gut viral community and further expands our knowledge of the distinct interaction of gut viruses with their prokaryotic hosts, which is critical for understanding the viral-bacterial environment in IBS.