Diet, ageing and genetic factors in the pathogenesis of diverticular disease

Abstract

Diverticular disease (DD) is an age-related disorder of the large bowel which may affect half of the population over the age of 65 in the UK. This high prevalence ranks it as one of the most common bowel disorders in western nations. The majority of patients remain asymptomatic but there are associated life-threatening co-morbidities, which, given the large numbers of people with DD, translates into a considerable number of deaths per annum. Despite this public health burden, relatively little seems to be known about either the mechanisms of development or causality. In the 1970s, a model of DD formulated the concept that diverticula occur as a consequence of pressure-induced damage to the colon wall amongst those with a low intake of dietary fiber. In this review, we have examined the evidence regarding the influence of ageing, diet, inflammation and genetics on DD development. We argue that the evidence supporting the barotrauma hypothesis is largely anecdotal. We have also identified several gaps in the knowledge base which need to be filled before we can complete a model for the etiology of diverticular disease.

Figure 1

Prevalence of DD in intestines obtained at necropsy by age, gender and region. A: Increasing prevalence of DD with age in western populations. In contrast DD peaked amongst individuals in their late fifties and early sixties in Singapore. The Singapore study however is based on diverse ethnic populations which may be confounding these observations; B: Percentages of intestine shown to have DD present at necropsy by gender. Data obtained on individuals from the Trømso region of northern Norway between 1974 and 1976, Northern Irish subjects in 1968, Cretan subjects 1997-1999, and Singapore prior to 1986. Note: The data presented for the Cretan-, Belfast- and Singapore-based studies are adjusted for age groups used by the Norwegian study using slopes obtained from the published data. Figures adapted from reference[–4].

Figure 2

Physiological activity within the large bowel. Schematic of the human colon highlighting functional roles; the right colon is associated with high microbial activity, larger fecal volume and parasympathetic control. DD in the right colon is infrequently observed in western populations but commonly found in Asian populations. The left colon is the primary site of diverticula in western populations and has lower microbial activity, decreased fecal volume and is more responsive to voluntary control.

Figure 3

Consumption of major sources of dietary fiber in the UK in grams per person per week since 1942. Data shows a steadily decreasing consumption of dietary fiber-rich foods in the UK population since 1942. Adapted from data produced in the National Food Survey[64].

Figure 4

Graph showing the relationship of age with mitochondrial DNA damage and risk of hospital admissions for DD. Graph showing the correlation between the percentage accumulation mitochondrial (mt) DNA damage in the colonic mucosa - right hand y axis whilst left hand y axis shows hospital admissions for DD/10⁵ in the UK. Ageing is expressed on the x axis in decades. The incidence of asymptomatic disease is considerably higher but the rate of hospital admissions may mirror DD incidence in the population as a whole. Mitochondrial DNA mutations are inferred from level of deficiency/inactivity in the respiratory chain mitochondrial protein Cytochrome C oxidase[102].