Inniss, Saskia; (2024) An exploration of the relationship between malnutrition, sarcopenia and the microbiome on treatment outcomes in Crohn’s disease. Doctoral thesis (Ph.D), UCL (University College London).

Text Saskia Inniss - 18147397 - PhD thesis (Final copy).pdf - Accepted Version Access restricted to UCL open access staff until 1 October 2025. Download (39MB)

Abstract

Crohn’s disease (CD) is an incurable disease. As such treatments focus on controlling the inflammatory response through the use of medication and gastrointestinal surgery. Despite significant improvements in the management of CD over the last decades, many patients do not respond or eventually lose response to drug therapies, leading to up to 80% of patients requiring surgery during their lifetime, which is often complicated by disease recurrence. The reason for suboptimal treatment outcomes in patients is currently unknown. Many published studies focus on ways of predicting short-term outcomes for anti-TNF therapy and bowel resections but often neglecting its long-term effects and other types of CD treatments. Therefore, this thesis aims to explore the association between malnutrition, sarcopenia and both the oral and gut microbiome with short- and long-term outcomes of various biologic therapies and gastrointestinal surgery. To answer this aim, two retrospective (n=95 & n=131) and one prospective (n=80) observational studies were conducted, revealing that sarcopenia was highly prevalent in CD patients (60.9%-74.1%) in comparison to other markers of malnutrition (6.8%-53.0%). Sarcopenia, unlike other malnutrition markers, was associated with an increased risk of post- operative infectious complications 30 days after surgery (p=0.052), elevated disease activity six months after surgery (p=0.004) and not persisting on ustekinumab therapy by 18 months (p=0.043). CD patients’ stool, but not saliva, exhibited lower α-diversity and differences in β- diversity and bacterial taxa compared to healthy controls (p<0.05). However, the microbiome had no effect on whether or not patients persisted on biologic therapy (p≥0.05). The findings from this thesis suggest that sarcopenia is of particular importance when considering the success of CD patients starting biologic therapy or undergoing gastrointestinal surgery. Whilst larger studies are needed to confirm these findings, it is hoped that this thesis contributes to the growing evidence regarding the importance of sarcopenia in CD and leads to future research that explores the benefits of targeting sarcopenia to improve patient treatment outcomes.

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