The new face of dietary therapy in pouchitis: targeting pathogenic factors from the pouch microbiota

Restorative proctocolectomy with an ileal-anal pouch anastomosis (IPAA) is the surgical treatment of choice for refractory ulcerative colitis (UC). Whilst quality of life following IPAA is generally good, a considerable number of patients have persistent pouch-related symptoms of increased frequency, urgency, leakage and incontinence. Additionally, around 40-50% of UC-IPAA patients develop
inflammation of the pouch, called pouchitis. The first-line treatment for pouchitis is repeated courses of antibiotics, suggesting that the inflammation ensues from interactions with the microbial component of the pouch, but this approach remains underexplored.

To date, only a small handful of dietary interventions have been trialled in patients with pouchitis to improve pouch symptoms and inflammation. No single strategy has been consistently effective. This likely reflects a limited understanding of the interactions between diet and the pathophysiology of pouchitis. Given the strong influence of the microbial component in pouch phenotypes, there is evidence to indicate the role of a dysbiotic pouch microbiota that is characterised by a reduction in major butyrate-producing microbial communities and an increase in pathogenically-invasive microbes that favour production of a potentially toxic gas called hydrogen sulphide. Additionally, there is accumulating research to suggest that excessive exposure of the pouch mucosa to these microbial end-products, namely hydrogen sulphide and
nitric oxide, is a key factor driving mucosal inflammation in pouchitis. In turn, the production of hydrogen sulphide is largely influenced by a range of dietary components such as dietary protein (red meat) and the food preservatives, sulphates, sulphites and carrageenan, a sulphated-polysaccharide. Hence, factors that demand further exploration of a pathogenically-driven dietary strategy includes (i) the improved understanding of dietary factors that modulate hydrogen sulphide, and the need to tailor dietary intervention the pouch phenotype and risk of pouchitis, (ii) the development of a novel diet strategy called “5-strategies to a sulphide-reducing (5URE) diet” targeting microbial hydrogen sulphide production and the preliminary success of a pilot tolerability study in patients with a symptomatic pouch and a history of pouchitis.
Hence, the aims of this randomized, double-blind, placebo-controlled dietary feed study are to investigate in a cohort of patients with symptomatic pouches and a history of pouchitis, the effects of a 7-week 5URE diet intervention on (i) pouch-related symptoms, pouch inflammation, quality of life, (ii) correlate these
with changes in biomarkers of microbial fermentation in the pouch and (iii) demonstrate tolerability and acceptability of the diet compared to a control diet.