Gaseous metabolites as therapeutic targets in ulcerative colitis

Table 2 Summary of studies clinical outcomes by dietary interventions for ulcerative colitis as a possible strategy to modify hydrogen sulfide production

Ref.	Dietary intervention	Study design	Main outcomes	Limitations
Roediger[9], 1998	Low sulfur diet	Open-label, prospective pilot study. Patients were instructed to follow low sulfur diet + stable dose of salazopyrin for 12 mo (n = 4 adults)	All patients showed clinical and histological improvement and no relapse attacks were observed	Very small sample size
Bhattacharyya et al[43], 2017	No-carrageenan diet	Double-blind RCT: Carrageenan capsules versus placebo. Patients with remission were followed up until relapse or of 12 mo (n = 12 adults)	The carrageenan group demonstrated significant higher relapse rate and an increase in FC and IL-6 values from study onset	Small sample size in each group. The effects on the microbiome were not addressed and precise measurements of compliance with the diet were not performed
Chiba et al[58], 2019	Lacto-ovo-semivegetarian diet-PBD	Prospective single arm study. Patients were followed after induction therapy incorporating PBD (n = 92 children and adults)	The cumulative relapse rates at 1 and 5 yr were 14% and 27% respectively, which is indicated by the authors to be lower than those previously reported	Small sample size without control group. The mechanistic effect of the diet was not addressed
Sarbagili Shabat et al[48], 2022	UCED	Single-blind RCT in adults with active refractory UC: Group1: FT alone; group2: FT with UCED; group3: UCED alone. The primary endpoint was week 8 clinical remission (n = 51)	UCED alone demonstrated the greatest clinical and endoscopic remission rates compared to single donor FT with or without diet	Small sample size in each group. Eligibility criteria include patients with severe UC, of whom none obtain remission. The effects on the microbiome were not addressed
Sarbagili-Shabat et al[49], 2021	UCED	Open-label, prospective pilot study in children with active UC. The primary endpoint was week 6 clinical remission (n = 24)	UCED lead to 38% clinical remission and FC improvement	Small sample size without control group. The effects on the microbiome were not addressed
Day et al[47], 2022	4-SURE	Open-label, prospective pilot study in adults with active UC. The primary endpoint was week 8 tolerability (n = 28)	The 4-SURE diet was well tolerated and lead to 46% clinical response and 36% endoscopic improvement. Fecal excretion of SCFAs increased while BCFAs decreased	Changes in colonic H2S not able to be measured. Lack of control and inadequate power for interpretation of secondary clinical end-points

RCT: Randomized controlled trial; FC: Fecal calprotectin; IL-6: Interleukin-6; PBD: Plant-based diet; UCED: Ulcerative colitis exclusion diet; FT: Faecal transplantation; UC: Ulcerative colitis; 4-SURE: 4 Strategies to SUlfide-Reduction; SCFA: Short chain fatty acid; BCFA: Branched chain fatty acid; H₂S: Hydrogen sulfide.