A population-based nationwide study on total colectomy for ulcerative colitis and risk of ten prevalent inflammatory or autoimmune diseases

Abstract

Background

There is growing evidence to support a role of the gut microbiome in the development of chronic inflammatory and autoimmune disease (IAD). We used total colectomy (TC) for ulcerative colitis (UC) as a model for a significant disruption in gut microbiome to explore an association with subsequent risk of IAD.

Methods

We identified all patients with UC and no diagnosis of IAD prior to their UC diagnosis in Denmark from 1988 to 2015. Patients were followed from the date of UC to a diagnosis of IAD, death or end of follow-up, whichever occurred first. We used Cox regression to estimate hazard ratios (HRs) of IAD associated with TC, adjusting for age, sex, Charlson Comorbidity Index, and calendar year of UC diagnosis.

Results

30,507 patients with UC (3,155 with TC and 27,352 without) were identified from the Danish National Patient Registry. During 43,266 person-years of follow-up, 2733 patients were diagnosed with an IAD. The risk of any IAD was higher for patients with TC compared to patients without (adjusted HR [aHR] 1.39 (95% CI: 1.24–1.57)). When the analyses were adjusted for exposure to antibiotics, immunomodulatory medicine and biologics (covering 2005–2018), the risk of IAD was still higher for patients with total colectomy (aHR = 1.41 (95% CI: 1.09;1.83)). Disease-specific analyses were weakened by a low number of outcomes.

Conclusions

The risk of IAD was higher for patients who underwent TC for UC compared to patients who did not.

KEY MESSAGES

• What is already known?

  • o The gut microbiome plays an important role in host immune homeostasis, and changes in gut bacterial diversity and composition may change the individual’s risk of inflammatory and autoimmune disease (IAD).

• What is new here?

  • o Patients with ulcerative colitis who undergo total colectomy have a higher risk of being diagnosed with IAD, compared to patients with ulcerative colitis who do not undergo total colectomy.

• How can this study help patient care?

  • o Future research can help uncover the mechanisms responsible for the higher risk of certain IADs after total colectomy. If the microbiome plays a role, modifying the gut microbiome could prove a viable therapeutic strategy to reduce the risk of developing IADs.

SUMMARY

In this nationwide Danish cohort study of all Danish UC patients diagnosed in the period from 1988 to 2015, the risk of being diagnosed with inflammatory and autoimmune disease is higher for patients who underwent total colectomy compared to UC patients without total colectomy.

Keywords:

• Ulcerative colitis
• total colectomy
• autoimmune disease
• cohort study

Author contribution

All authors contributed to the concept and design of the study. LRJ, PLA, and BMN collected and analyzed the data, which were interpreted by all authors. AMC drafted the manuscript, which was reviewed for intellectual content by all authors. The final manuscript version was approved by all authors.

Data sharing/data availability

Data from this study will not be made available to other researchers as per Danish law.

Disclosure statement

JAM received study grants from Nexpep/ImmusanT, National Institutes of Health, Immunogenix, Teva Pharmaceuticals, Takeda Pharmaceutical, Allakos, Oberkotter, and Cour; consultancy fees from Bionix, Lilly Research Laboratory, Johnson & Johnson, Dr. Schar USA, UCB Biopharma, Celimmune, Intrexon Corporation, Chugai Pharma, and Kanyos; holds patents licensed to Evelo Biosciences; and receives royalties from Torax Medical. The other authors have no potential conflicts of interest or financial ties to disclose.