A Novel UC Exclusion Diet and Antibiotics for Treatment of Mild to Moderate Pediatric Ulcerative Colitis: A Prospective Open-Label Pilot Study

Chen Sarbagili-Shabat, Lindsey Albenberg, Johan Van Limbergen, Naomi Pressman, Anthony Otley, Michal Yaakov, Eytan Wine, Dror Weiner, Arie Levine, Chen Sarbagili-Shabat, Lindsey Albenberg, Johan Van Limbergen, Naomi Pressman, Anthony Otley, Michal Yaakov, Eytan Wine, Dror Weiner, Arie Levine

Abstract

Background: As the microbiome plays an important role in instigating inflammation in ulcerative colitis (UC), strategies targeting the microbiome may offer an alternative therapeutic approach. The goal of the pilot trial was to evaluate the potential efficacy and feasibility of a novel UC exclusion diet (UCED) for clinical remission, as well as the potential of sequential antibiotics for diet-refractory patients to achieve remission without steroids.

Methods: This was a prospective, single-arm, multicenter, open-label pilot study in patients aged 8-19, with pediatric UC activity index (PUCAI) scores >10 on stable maintenance therapy. Patients failing to enter remission (PUCAI < 10) on the diet could receive a 14-day course of amoxycillin, metronidazole and doxycycline (AMD), and were re-assessed on day 21. The primary endpoint was intention-to-treat (ITT) remission at week 6, with UCED as the only intervention.

Results: Twenty-four UCED treatment courses were given to 23 eligible children (mean age: 15.3 ± 2.9 years). The median PUCAI decreased from 35 (30-40) at baseline to 12.5 (5-30) at week 6 (p = 0.001). Clinical remission with UCED alone was achieved in 9/24 (37.5%). The median fecal calprotectin declined from 818 (630.0-1880.0) μg/g at baseline to 592.0 (140.7-1555.0) μg/g at week 6 (p > 0.05). Eight patients received treatment with antibiotics after failing on the diet; 4/8 (50.0%) subsequently entered remission 3 weeks later.

Conclusion: The UCED appears to be effective and feasible for the induction of remission in children with mild to moderate UC. The sequential use of UCED followed by antibiotic therapy needs to be evaluated as a microbiome-targeted, steroid-sparing strategy.

Keywords: antibiotics; child; diet; remission; treatment; ulcerative colitis.

Conflict of interest statement

C.S.-S.: potential IP for Nestle Health Science. LA. has received grants, honoraria, and speaker or consulting fees from Abbott Nutrition, Nestle Health Science, and Seres Therapeutics. J.V.L.: consulting, travel and/or speaker fees and research support from AbbVie, Janssen, Nestlé Health Science, Merck, P&G, GSK, Illumina and Otsuka. The conduct of the study in Halifax, Canada, was supported by local divisional funds, a Canadian Institutes of Health Research (CIHR: Canadian Association of Gastroenterology—Crohn’s Colitis Canada) New Investigator award (J.V.L.) and a Canada Research Chair Tier 2 in Translational Microbomics (J.V.L.). A.O. has received grants and consulting fees, and/or sits on advisory boards for Janssen, AbbVie, Pfizer, Eli Lily and Nestle Health Science. M.Y. has no conflicts of interest. E.W. has received honoraria from Janssen & Mead Johnson Nutrition (speaker fee) and from AbbVie and Nestle Health Sciences (advisory board and speaker fees). D.W. has no conflicts of interest. A.L. has received grants, honoraria, speaker or consulting fees, or IP licensing from Janssen, Megapharm, Takeda, Ferring, Galapagos and Nestle Health Science.

Figures

Figure 1
Figure 1
Trial design.
Figure 2
Figure 2
Response and remission rates according to intention-to-treat analysis with UC exclusion diet (UCED) as sole intervention; amoxycillin, metronidazole and doxycycline (AMD) antibiotic treatment; and either UCED or the AMD antibiotic treatment.
Figure 3
Figure 3
Change in PUCAI with UC exclusion diet between baseline and week 6, including all patients in a last-observation-carried-forward analysis.
Figure 4
Figure 4
Dietary intake of macronutrients and micronutrient targets for UCED at baseline and after diet treatment: total protein (g/kg, n = 20), saturated fat (g, n = 19), monounsaturated fat (g, n = 19), fiber (g, n = 20), cysteine (g, n = 15), methionine (g, n = 15), and iron (mg, n = 19).

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