Altered Gut Microbiota in Patients With Peutz–Jeghers Syndrome

Abstract

BackgroundPeutz–Jeghers syndrome (PJS) is a rare genetic disorder characterized by the development of pigmented spots and gastrointestinal polyps and increased susceptibility to cancers. It remains unknown whether gut microbiota dysbiosis is linked to PJS.AimThis study aimed to assess the structure and composition of the gut microbiota, including both bacteria and fungi, in patients with PJS and investigate the relationship between gut microbiota dysbiosis and PJS pathogenesis.MethodsThe bacterial and fungal composition of the fecal microbiota was analyzed in 23 patients with PJS (cases), 17 first-degree asymptomatic relatives (ARs), and 24 healthy controls (HCs) using 16S (MiSeq) and ITS2 (pyrosequencing) sequencing for bacteria and fungi, respectively. Differential analyses of the intestinal flora were performed from the phylum to species level.ResultsAlpha-diversity distributions of bacteria and fungi indicated that the abundance of both taxa differed between PJS cases and controls. However, while the diversity and composition of fecal bacteria in PJS cases were significantly different from those in ARs and HCs, fungal flora was more stable. High-throughput sequencing confirmed the special characteristics and biodiversity of the fecal bacterial and fungal microflora in patients with PJS. They had lower bacterial biodiversity than controls, with a higher frequency of the Proteobacteria phylum, Enterobacteriaceae family, and Escherichia-Shigella genus, and a lower frequency of the Firmicutes phylum and the Lachnospiraceae and Ruminococcaceae families. Of fungi, Candida was significantly higher in PJS cases than in controls.ConclusionThe findings reported here confirm gut microbiota dysbiosis in patients with PJS. This is the first report on the bacterial and fungal microbiota profile of subjects with PJS, which may be meaningful to provide a structural basis for further research on intestinal microecology in PJS.

Alterations and clinical relevance of gut microbiota in patients with Peutz–Jeghers syndrome: A prospective study

“…17 Moreover, intestinal microbiome may be considered an organism that can affect brain activity through the gut microbiota-brain axis and thus influence many biological functions. 18 Wang et al 14 were the first to demonstrate the influence of gut microbiota dysbiosis on PJS in 23 patients. In the current prospective study, the sample size was increased and we further explored the association between gut microbiota and polyp growth in PJS.…”

“…All the participants were required to be 18 to 75 years of age. PJS was diagnosed in patients according to one of the following criteria: (a) any number of histologically confirmed PJS polyps and a positive family history of PJS; (b) characteristic prominent mucocutaneous pigmentation and a positive family history of PJS; (c) a negative family history of PJS and at least three histologically confirmed PJS polyps; and (d) a negative family history of PJS and any number of histologically confirmed PJS polyps and characteristic pigmentation 14 . For the control group, healthy spouses of the patients were preferred.…”

“…As PJS is rarely encountered, studies regarding intestinal microbial composition or a potential link between gut microbiota and hamartomatous polyps are quite limited. To our knowledge, only one study has been published which confirmed gut microbiota dysbiosis in 23 patients 14 …”

“…To our knowledge, only one study has been published which confirmed gut microbiota dysbiosis in 23 patients. 14 Therefore, we conducted this preliminary study to investigate the association between gut microbiota and intestinal polyps in patients with PJS.…”

Small Intestinal Polyp Burden in Pediatric Peutz-Jeghers Syndrome

“…There is some consensus on the relationship of the speci c PV present (i.e., genotype) in the patient and the clinical phenotype including polyp burden, polyp size and risk of intussusception, speci cally, truncating mutations of STK11 are thought to predispose to a greater risk of intussusception 12,13 . Other factors implicated in intussusception risk may include microbiologic factors but a direct causal association between microbiome factors and polyp size remains elusive 14,15 . Our cohort characteristics did not allow us to control for speci c genotypic subtypes but our observation on male patients harboring larger polyps may signal an independent factor in polyp growth and therefore intussusception risk.…”