Management of colonic diverticular disease in the third millennium: Highlights from a symposium held during the United European Gastroenterology Week 2017

Abstract

Diverticulosis is a common anatomical condition, which appears to be age-dependent. Individuals who develop chronic gastrointestinal symptoms or complications are referred to as having diverticular disease. Although the diagnosis of this condition can be relatively straightforward, randomized controlled trials are scarce and management often follows tradition rather than principles of evidence-based medicine. This report deals with the topics discussed during a symposium held during the United European Gastroenterology Week (Barcelona, October 2017). During the meeting, the role of dysbiosis in the pathogenesis of diverticular disease and its treatment were thoroughly discussed, by examining the efficacy and mechanisms of action of the currently used drugs. Recent studies have shown the presence of dysbiosis in patients with diverticular disease and suggest an imbalance in favor of bacteria with pro-inflammatory and pathogenetic potential. These microbiota changes correlate with mucosal immune activation, mirrored by a marked increase of macrophages in colonic mucosa, both in the diverticular region and at distant sites. The low-grade inflammation, driven by bacteria-induced immune activation, could be involved in the pathophysiology of symptoms. As a consequence, pharmacological approaches targeting enteric bacteria (with poorly absorbed antibiotics, like rifaximin, or probiotics) or intestinal inflammation (with 5-ASA derivatives or rifaximin) have shown capability of controlling symptoms and also preventing complications, albeit more research is needed to establish the optimal regimen (daily dose and duration) of therapy. Well-designed randomized-controlled trials (RCTs), including homogeneous populations of patients, are therefore needed. The future of management of many GI diseases, including symptomatic uncomplicated diverticular disease, will rely on the so-called 'microbiota-directed therapies'.

Keywords: diverticular disease; dysbiosis; mesalazine; microbiota; mucosal inflammation; probiotics; rifaximin.

Figure 1.

Most common non-neoplastic findings at screening colonoscopy (data from Bevan et al.). IBD, inflammatory bowel disease.

Figure 2.

Pathophysiology of diverticular disease: from fiber hypothesis to mucosal inflammation.

Figure 3.

Clinical spectrum of diverticular disease. IBS, irritable bowel syndrome; SUDD, symptomatic uncomplicated diverticular disease.

Figure 4.

Low-grade inflammation in diverticular disease (modified from Barbara et al.). SUDD, symptomatic uncomplicated diverticular disease.

Figure 5.

Microbiota composition in healthy subjects, subjects with diverticulosis or patients with symptomatic uncomplicated diverticular disease (data from Barbara et al.). SCFA, short-chain fatty acids; SUDD, symptomatic uncomplicated diverticular disease.

Figure 6.

Relationship between fiber intake and risk of diverticulitis in the EPIC study (from Crowe et al.). RR, relative risk.

Figure 7.

Relationship between dietary patterns and risk of diverticulitis (from Strate et al.).

Figure 8.

Efficacy of rifaximin for symptom relief in symptomatic uncomplicated diverticular disease: meta-analysis of randomized-controlled trials (from Bianchi et al.). CI, confidence interval; NNT, number needed to treat; RD, rate difference.

Figure 9.

Eubiotic effects of rifaximin on gut microbiota in patients with irritable-bowel-syndrome-associated constipation (from Soldi et al.).

Figure 10.

Multiple mechanisms of action of rifaximin in the treatment of diverticular disease (from Cuomo et al.). AB, antibiotic.

Figure 11.

Mean rifaximin plasma concentration time (top panel) and cumulative urinary excretion (bottom panel) profiles following administration of 400 mg single-dose generic or branded (polymorph-α) rifaximin to healthy volunteers. Each point or column represents the mean ± SEM (vertical lines) obtained from 24 subjects (from Blandizzi et al.). SEM, standard error of the mean.

Figure 12.

Potential role of intestinal bacterial overgrowth in symptom development in patients with diverticular disease (derived from Colecchia et al.).

Figure 13.

Benefits of poorly absorbed antibiotics in patients with diverticular disease (derived from Frieri et al.).

Figure 14.

Representation of the impact of antimicrobial administration on bacterial community in the colon (from Jernberg et al.). Representation of the impact of antibiotic administration on the bacterial community of the colon. After the onset of treatment, an increase in resistant bacteria (purple rods) can be seen. This increase is due to either a susceptible bacterium (green rods) becoming resistant or resistant bacteria, already present in low levels, increasing in number due to their ability to survive the selective pressure provided by the antibiotic. The acquired resistance is often due to horizontal gene transfer or mutation events (white arrow). As a consequence of treatment, a temporary decrease in diversity can also be seen. Some bacteria may be protected from antibiotic exposure in the mucin layer (yellow shading) or in grooves in between the villi formed by host epithelial cells that line the intestinal channel (not shown). The figure is not drawn to scale and the timescale is relative.