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Health Protocols

Diverticulosis and Diverticular Disease

Novel and Emerging Strategies

Fecal Calprotectin Testing

Calprotectin is a protein released from white blood cells during inflammation. Fecal calprotectin, a non-invasive stool test, is under investigation as a biomarker that may help identify diverticular disease. Fecal calprotectin can distinguish inflammatory bowel diseases, such as Crohn’s or ulcerative colitis, from functional disorders such as irritable bowel syndrome (IBS). Fecal calprotectin is also being investigated as a biomarker for colorectal cancer and as a clinical tool in patients with inflammatory bowel disease to identify risk of relapse (Burri 2014; Henderson 2014; Fengming 2014).

Two studies have found that fecal calprotectin is higher in active diverticular disease than in healthy individuals and those with IBS. In asymptomatic diverticulosis, however, fecal calprotectin was not elevated; and in segmental colitis associated with diverticula (SCAD) it was higher than in other types of diverticular disease. In these studies, treatment of uncomplicated acute diverticulitis and symptomatic uncomplicated diverticular disease (SUDD) reduced fecal calprotectin to normal levels (Tursi 2009; Tursi 2011).

Persistently high fecal calprotectin may indicate a high risk of recurrence. In one study, 54 people were followed for an average of 20 months after a bout of acute uncomplicated diverticulitis; seven of the eight people who had a recurrence during the study had elevated fecal calprotectin, while only one person who experienced a recurrence had normal fecal calprotectin (Tursi, Elisei, Picchio 2014).

Taken together, these preliminary findings suggest fecal calprotectin may distinguish diverticular disease from IBS; help monitor severity of diverticulitis and response to treatment; and predict risk of disease recurrence (Tursi, Elisei 2015; Tursi 2009; Erbayrak 2009).


Rifaximin (Xifaxan) is an antibiotic that is poorly absorbed into the bloodstream and so has a favorable safety profile (Gold Standard 2014). Rifaximin targets the microbial community in the gut and has been studied for the treatment of SUDD (Sopena 2011; Strate, Modi 2012). A comprehensive literature review analyzed four randomized controlled trials that compared treatment of SUDD using fiber supplementation plus seven days per month of rifaximin with fiber supplementation alone. This analysis found that rifaximin was associated with better symptom relief, fewer complications, and a better chance of being symptom-free after one year (Bianchi 2011).

An interesting study in 40 patients with uncomplicated diverticular disease found that rifaximin treatment reduced the interaction of gut bacteria with specialized receptors on immune cells, called toll-like receptors, which are involved in the induction of the inflammatory immune response to microorganisms. This study showed that rifaximin reduced the activation of toll-like receptors, thereby reducing gut inflammation. These findings prompted the researchers who conducted the study to postulate that rifaximin might have anti-inflammatory activity in the gut lining, as well as systemic immune-modulating effects, through its impact on pathogenic microbes residing in the gut (Cianci 2014).


Mesalamine (also called mesalazine) (Asacol) belongs to a class of medications that contain 5-aminosalicylic acid (5-ASA), which have anti-inflammatory and free radical-scavenging effects. Medications in this drug class are used in the treatment of inflammatory bowel disease (CCFA 2013; Tursi 2014; Thaha 2015). Mesalamine has also been studied in diverticular disease (Thaha 2015; Collins 2015; Morris 2014). One rigorous review of the scientific literature examined six randomized controlled trials of 5-ASA medications for uncomplicated diverticulitis in a total of 818 patients, and found that these medications led to significantly better outcomes than placebo (Gatta 2010).

A randomized controlled trial in 117 patients who had acute diverticulitis found that the rate of complete response, in which patients became asymptomatic, was significantly higher in patients receiving mesalamine than in those who received placebo (Stollman 2013). Additional rigorous studies are needed to clarify the role of mesalamine in the treatment of diverticular disease.