Epidemiological and pathophysiological studies on diverticular disease in the colon

Background: Diverticular disease of the colon is common and is associated with a high and increasing societal burden with great economical and human costs. Prevalence increases with age and with an overall aging population, investigating risk factors are important. The pathogenesis is complex and poorly understood. Low-grade inflammation and gut dysbiosis have been suggested to play a role but population studies are lacking. While genetic and lifestyle factors have been associated with increased risk for complicated diverticular disease in adults, environmental risk factors are underexplored. The aim of this thesis was to investigate the prevalence of diverticulosis, its association with gastrointestinal symptoms and colonic inflammation in a general population, and to identify early lifestyle and environmental risk factors for developing future symptomatic diverticular disease, in a young population.

Methods and Main results: In paper I, we performed a population-based colonoscopy study of randomly selected adults born in Sweden (18–70 years old) assessing the association between abdominal symptoms, mental health, colonoscopy findings and diverticulosis (n=742). We found the prevalence of diverticulosis to be age-dependent and diverticulosis was associated with diarrhea across all age groups. In those older than 60 years of age, diverticulosis was further associated with abdominal pain and diarrhea-predominant IBS. In paper II, a nested case control study from paper I was performed (n=127 cases with diverticulosis and n=127 controls). The findings were that in a general community sample, neither asymptomatic nor symptomatic diverticulosis, were associated with serological or colonic mucosal inflammation. Other explanations for symptomatic colonic diverticulosis need to be identified. Papers III and IV were population-based cohort studies of Swedish male conscripts ages 18-20, investigating the association between lifestyle and environmental exposure variables, and symptomatic diverticular disease requiring hospitalization from 1969-2009 (n=49,321). In papers III and IV, we found that exposure to parental divorce, being overweight or obese, a smoker, a risk user of alcohol and/or having low cardiovascular fitness in late adolescence is associated with an increased risk of hospitalized diverticular disease later in life.

Conclusions: Diverticulosis is common, age-dependent and associated with diarrhea and age-specific symptoms but not inflammation. Early adulthood lifestyle and environmental factors such as obesity, smoking, risky alcohol use, physical inactivity and early adverse events such as parental divorce increase the risk for developing severe diverticular disease. Future studies investigating alternate pathophysiologic mechanisms for diverticulosis are needed and prospective age-specific studies evaluating early life events and the role of modified lifestyle risk factors and course of diverticular disease are recommended.

List of scientific papers

I. M. Ellionore Järbrink-Sehgal, Anna Andreasson, Nicholas J. Talley, Lars Agréus, Jeong-Yeop Song, Peter T. Schmidt. Symptomatic Diverticulosis is Characterized By Loose stools. Clin Gastroenterol Hepatol. 2016;14(12):1763-1770.
https://doi.org/10.1016/j.cgh.2016.06.014

II. M. Ellionore Järbrink-Sehgal, Loui Rassam, Aws Jasim, Marjorie M. Walker, Nicholas J. Talley, Lars Agréus, Anna Andreasson, Peter T. Schmidt. Diverticulosis, Symptoms And Colonic Inflammation - A Population-Based Colonoscopy Study. [Submitted]

III. M. Ellionore Järbrink-Sehgal, Peter T. Schmidt, Filip Sköldberg, Tomas Hemmingsson, Hannes Hagström, Anna Andreasson. The Influence of Environmental Factors in Late Adolescence on Future Symptomatic Diverticular Disease Requiring Hospitalization: A 39 Year Follow Up Study. [Manuscript]

IV. M. Ellionore Järbrink-Sehgal, Peter T. Schmidt, Filip Sköldberg, Tomas Hemmingsson, Hannes Hagström, Anna Andreasson. Lifestyle Factors in Late Adolescence Associate with Later Development of Diverticular Disease. Clin Gastroenterol Hepatol. 2018;16(9):1474-1480.
https://doi.org/10.1016/j.cgh.2018.04.006