Immunological and microbiological studies in post-operative Crohn's disease
AuthorHamilton, Amy Louise
AffiliationMedicine (St Vincent's)
Document TypePhD thesis
Access StatusOpen Access
© 2018 Dr. Amy Louise Hamilton
Crohn’s disease is a chronic, inflammatory condition of the bowel. The aetiology of Crohn’s has not been fully elucidated, but is believed to arise from the interaction between the gut microbiota, the host immune system and environmental factors. A majority of Crohn’s disease patients will require a bowel resection as a result of disease, which causes significant morbidity and impacts on quality of life. While surgery can ameliorate clinical symptoms, the disease often initially recurs at the site of the resection. This may be sub-clinical initially, and can be identified endoscopically. This thesis investigates the immunological and microbiological characteristics of post-operative Crohn’s disease recurrence in, addressing serologic markers, the faecal microbiome and the possible contribution of Proteus species to gastrointestinal disease. Serologic markers, while disappointing for prediction of disease recurrence, did have some utility for identifying patients at the highest risk of disease recurrence. I also demonstrated lower rates of antibody positivity in Crohn’s patients who smoke for the first time, indicating that these results should be interpreted with caution in current and past smokers. I have further evaluated the faecal microbiome in the setting of post-operative disease using metagenomic techniques. This work showed that after resection for Crohn's disease, enrichment of the bacterial family Lachnospiraceae is associated with maintenance of disease remission, while patients enriched for the Enterobacteriaceae are more likely to recur. Recurrence may result from a higher abundance of enteric pathobionts such as Proteus, Klebsiella, Serratia, and Escherichia. The Lachnospiraceae are an important family of butyrate producing bacteria in the gut, and depletion of this bacterial family may perpetuate the expansion of Enterobacteriaceae via environmental perturbation and ecologic shifts. These findings indicate possible protective and pathogenic bacteria in post-operative recurrence. Finally, I addressed the potential contribution of Proteus species (from the Enterobacteriaceae family) to gastrointestinal diseases including to inflammatory bowel disease. Proteus spp. are low-abundance commensals of the human gut that harbour significant pathogenic potential. Preliminary evidence of a pathogenic role in the gut should stimulate further investigation. I have elucidated some aspects of the microbiome and host immune factors involved, in the pathophysiology of post-operative Crohn’s disease recurrence. This work should encourage further work on a unifying hypothesis for the aetiology of disease recurrence after resectional surgery for Crohn’s disease.
KeywordsCrohn's disease; microbiota; post-operative; serology; Enterobacteriaceae; Proteus
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