Sustained biochemical response to oral antibiotics in pediatric PSC and ASC is correlated to changes in gut microbiota and serum bile acids during therapy
(2018) 50th Annual Meeting ESPGHAN — Location: Genève, Suisse (9.May.2018)
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- Abstract
- Objectives and Study: Concomitant presence of autoimmune hepatitis and primary sclerosing cholangitis (PSC) is labelled as autoimmune sclerosing cholangitis (ASC) in children. Based upon the possible implication of microbiota and microbial metabolites, such as bile acids (BAs), in the pathogenesis of PSC, oral antibiotics are increasingly being used as a novel therapeutic approach and shown to have benefit in PSC but their role in pediatric ASC is not well evaluated. We prospectively analysed the gut microflora and serum BAs pool before and after antibiotic therapy in children with ASC or PSC alone, and evaluated whether changes in gut microflora and/or BAs correlated with response to treatment. Method: Patients diagnosed with ASC or PSC on basis of biochemical, liver biopsy and radiology findings were included. They prospectively received metronidazole (MTZ) for 14 days as induction or rescue therapy. MTZ were administrated in addition to the standard treatment of UDCA for PSC patients and azathioprine, and UDCA and/or steroids for ASC patients. Stool and serum samples were collected before and after MTZ therapy. DNA isolation, amplification and Illumina sequencing to profile the microbiota composition were performed using the bacterial 16s rRNA while serum BAs were assessed by ultraperformance liquid chromatography coupled to mass spectrometry. The beta-diversity measured the dissimilarity between each paired stool samples. The outcome parameters to assess the efficacy of antibiotics were reduction liver enzymes and subsequently achievement of sustained biochemical remission. Results: Seven children (4 ASC, 3 PSC) were included, of which 5 have a concomitant ulcerative colitis (UC). All patients showed a significant decrease in their AST (-55%, p< 0.025), ALT (-56%, p< 0.025) and GGT (-41%, p< 0.025) under MTZ. Three children relapsed after stopping MTZ while the four others children showed a sustained biochemical remission (liver enzymes below 1.5 times upper limit of normal) after a median follow-up of 375 days. Among these four patients, three exhibited a wide different microbial composition before and after MTZ as expressed by the beta-diversity variation. They also expanded their total serum BAs size (from 1542.96 to 2620.99 pmol/100μl, +69.87%), primarily due to the large increment of UDCA and its glycine- and taurine-conjugates which finally represented more than half of the total serum BAs. On the contrary, the microbiota of patients who relapsed remained unchanged pre- and post-MTZ and total BAs pool decreased. Conclusion: Our study suggests that oral antibiotic could be an effective treatment of ASC and PSC, especially those with a concomitant UC, and that intestinal microflora and BAs play a major role in these diseases as sustained biochemical remission is associated with wide changes in gut microbiota communities and BAs profile after taking antibiotics.
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Sambon, P., Everard, A., Varma, S., Stephenne, X., Smets, F., Scheers, I., Komuta, M., Muccioli, G., Cani, P., & Sokal, E. (2018). Sustained biochemical response to oral antibiotics in pediatric PSC and ASC is correlated to changes in gut microbiota and serum bile acids during therapy. 50th Annual Meeting ESPGHAN, Genève, Suisse.