The first report on effect of fecal microbiota transplantation as a complementary treatment in a patient with steroid-refractory Cronkhite-Canada syndrome

Abstract

Rationale: Cronkhite-Canada syndrome (CCS) is a rare non-hereditary disease of unknown etiology that is characterized by the appearance of multiple polyps in the entire gastrointestinal (GI) tract, except in the esophagus, with GI and non-GI symptoms. Various factors are associated with the pathogenesis of CCS. Immune dysregulation has been discussed as one of the pathogeneses of CCS, and dysbiosis of the gut microbiota can affect the immune system. Currently, standard treatment has not been established. Patient concerns and diagnosis:We present the treatment with fecal microbiota transplantation (FMT) in a 67-year-old male patient with steroid-refractory CCS who could not undergo anti-tumor necrosis factor-a treatment due to suspected tuberculosis infection.Interventions: FMT has recently attracted attention as a method of overcoming drug resistance through immunomodulatory effects through microbiome regulation. We collected the patient's stool samples before FMT and 8 weeks after FMT.Outcomes: We analyzed the microbiome composition of patients by sequencing the V3-V4 region of the 16s rRNA gene (Miseq). After FMT, the number of episodes of diarrhea and hypoalbuminemia were also corrected. The Chao 1 index after FMT, which was significantly higher than that of donors before FMT, changed to a similar level for donors after FMT. Fusobacterium nucleatum, Pyramidobacter piscolens, and Campylobacter concisus disappeared after FMT, suggesting the presence of an association between gut microbiota and CCS.Lessons: Furthermore, we provide the possibility that microbiome modulation by FMT could serve as a complementary treatment in patients with steroid-refractory CCS.

Analyses of cytokine gene expression and fecal microbiota in a patient with Cronkhite‐Canada syndrome successfully treated with prednisolone

“… 1 , 4 In addition, recent reports identified intestinal dysbiosis as one of the risk factors for CCS because the replacement of intestinal bacteria by fecal microbiota transplantation or gut sterilization by antibiotics is effective in CCS. 5 , 6 These findings led us to hypothesize that PSL or TNF‐α‐inhibitors might achieve regression of CCS polyps through suppression of proinflammatory cytokines induced by intestinal dysbiosis. In this study, we provide evidence that regression of CCS polyps by PSL was accompanied by the downregulation of proinflammatory cytokine responses and alterations in intestinal microbiota composition.…”

“… 4 Furthermore, the effectiveness of the replacement of intestinal microbiota was reported in CCS. 6 Thus, it is likely that proinflammatory cytokine responses triggered by intestinal dysbiosis are involved in the development of CCS and that PSL mediates regression of CCS polyps via suppression of such responses. Notably, intestinal dysbiosis might also accelerate the development of CCS‐associated cancer since the colonization of B. fragilis and P. anaerobius with the promotion of inflammation and oncogenesis is enriched in this case before PSL treatment.…”

“…Although the etiology of CCS and CCS‐associated cancer is poorly defined, marked responses to PSL and TNF‐α inhibitors implicate the involvement of proinflammatory cytokine responses 1,4 . In addition, recent reports identified intestinal dysbiosis as one of the risk factors for CCS because the replacement of intestinal bacteria by fecal microbiota transplantation or gut sterilization by antibiotics is effective in CCS 5,6 . These findings led us to hypothesize that PSL or TNF‐α‐inhibitors might achieve regression of CCS polyps through suppression of proinflammatory cytokines induced by intestinal dysbiosis.…”

“…Therapeutic effects by PSL or TNF−α‐inhibitors with the ability to suppress proinflammatory cytokines are established in CCS 4 . Furthermore, the effectiveness of the replacement of intestinal microbiota was reported in CCS 6 . Thus, it is likely that proinflammatory cytokine responses triggered by intestinal dysbiosis are involved in the development of CCS and that PSL mediates regression of CCS polyps via suppression of such responses.…”

Comprehensive treatment and a rare presentation of Cronkhite–Canada syndrome: Two case reports and review of literature

“…Achieving a sustained endoscopic response is the therapeutic goal and associated with a reduced risk of cancer[ 4 , 25 ]. Kim et al [ 28 ] reported a successful case of fecal microbiota transplantation in the treatment of steroid-refractory CCS. The etiology and pathogenesis of this disease are not yet fully understood, and various other methods are still being explored.…”