Peutz-Jeghers syndrome (PJS) is a rare hereditary disorder characterized by intestinal polyposis, and intestinal intussusception is one of the most urgent complications. While it is known that imbalance of the gut microbiota is highly associated with intestinal disorders, the role of the gut microbiome in the pathogenesis of PJS has not been reported. In this study, we performed 16S rRNA sequencing on stools from 168 patients and 68 healthy family members who lived together to determine the gut microbiome composition of PJS patients. Metagenomics sequencing was further performed on the representative samples (61 PJS patients and 27 healthy family members) to analyze the functional changes. We found that the fecal microbiome of patients with PJS showed a greater variation in β-diversity. An enhancement of Escherichia coli and a reduction of Faecalibacterium prausnitzii was identified in PJS patients. Further reduction of Faecalibacterium prausnitzii was the characteristic microbial change observed in patients with intussusception. Functional analysis revealed that the abundance of propanoate metabolism was enriched in PJS patients and further enriched in those with intussusception. Escherichia coli was the major contributor to the enrichment of this metabolism pathway, which was associated with the abnormal expression of methylglyoxal synthase (encoded by mgsA) and phosphate acetyltransferase (encoded by pta). Our findings showed a distinct gut microbiome signature in PJS patients and identified the connection between the gut microbiome and intussusception. Alterations in the gut microbiome might be involved in the pathogenesis of PJS and may serve as biomarkers for gastrointestinal surveillance. IMPORTANCE Recent research has established a link between the gut microbiome and polyps and neoplasia, and antibiotic use influences the microbiome and the development of colorectal polyps. Familial adenomatous polyposis (FAP), which is characterized by the early development of benign precursor lesions (polyps), is associated with enterotoxigenic Bacteroides fragilis and Escherichia coli biofilms. However, the relationship between the gut microbiome and the pathophysiology of PJS has not yet been established. In this study, we found that PJS patients had a distinct microbiome composition, with a greater variation in β-diversity, an increase in Escherichia coli, and a decrease in Faecalibacterium prausnitzii. A further reduction of Faecalibacterium prausnitzii was observed in patients with intussusception. Moreover, PJS involved increased propanoate metabolism as well as abnormal mgsA and pta expression. These findings may contribute to a better understanding of the etiology of PJS and improve disease control strategies.
Keywords: Peutz-Jeghers syndrome; biomarkers; functional analysis; gut microbiota; intussusception.