DIVERTICULAR DISEASE (DD): EPIDEMIOLOGY AND CLINICAL PRESENTATION
DD is an important gastrointestinal disease in terms of health care costs in western countries, with highest rates in the United States and Europe. All age groups can be affected and the prevalence increases with age.1 The term DD is used to denote a clinically significant and symptomatic condition or asymptomatic diverticulosis. In many individuals, colonic diverticula remain symptomless (diverticulosis), whereas about 20% of them develop symptoms, including recurrent abdominal pain or discomfort, bloating, and change in bowel habits (symptomatic DD). In contrast to the common belief that diverticulosis has a high rate of progression, only about 4% of patients develop acute diverticulitis.2
In a significant proportion of DD patients symptoms resembling or overlapping those of irritable bowel syndrome (IBS) are present, making a differential diagnosis between the two conditions challenging.3 According to recent studies, beyond abdominal symptoms, symptomatic DD is associated with impaired quality of life, in particular vitality and emotional health, as DD may be experienced as a chronic illness characterized by ongoing abdominal symptoms and psychosocial distress.4 Patients with acute diverticulitis may be at risk for subsequent development of IBS, a condition for which the term postdiverticulitis IBS has been proposed, analogously to postinfectious IBS proposed some years ago.5 Some pathophysiological factors leading to symptom generation as low-grade inflammation, visceral hypersensitivity, abnormal colonic motility, and altered intestinal microbiota, are probably shared by both conditions, DD and IBS.6 As a potential key step in the pathogenesis of diverticular inflammation and abdominal symptoms in DD, alteration of the peridiverticular bacterial flora has been suggested6; therefore, probiotics may be an appealing treatment option for this condition.7
PROBIOTICS: A PROMISING TREATMENT OPTION FOR DD?
Probiotics may modify the gut microbial balance leading to health benefits due to their anti-inflammatory effects and capability to enhance anti-infective defences by maintaining an adequate bacterial colonization in the gastrointestinal tract and by inhibiting colonic bacterial overgrowth and metabolism of pathogens.8 A recent meta-analysis showed that probiotics were effective treatments in IBS.9 Previous reviews on the use of probiotics in DD suggested a potential usefulness of this treatment in the management of DD.7,10 In contrast, a recent consensus report stated with a 97% level of agreement that to date there is insufficient evidence to judge probiotics as effective in reducing symptoms in DD.11 A recent systematic review on the efficacy of probiotics treatment in DD in terms of remission of abdominal symptoms, retrieved 11 articles, which were performed over a period of 20 years mainly in Europe on an overall total number of about 760 patients with DD, with a slight female prevalence (55.1%), and an age range from 58 to 75 years (unpublished data). Table 1 shows the strains of probiotics used in these studies to treat abdominal symptoms related to DD. In many studies patients were treated with a single probiotic strain. The most frequently investigated probiotics were different strains of Lactobacilli, whereas Bifidobacteria or other probiotic strains were less frequently used. The interventions varied between studies, as the probiotics were administered together with drugs (antibiotics, anti-inflammatory agents as mesalamine or beclomethasone) and compared with the efficacy of the drug alone, or, in other studies, a probiotic treatment arm was used without any associated drug or compared with a high-fiber diet. The variable nature and the relative poor quality of the available studies on the use of probiotics in DD make it difficult to evaluate the cumulative efficacy of these treatments. Only 2 of these studies were double-blinded randomized controlled trials. Moreover, 5 of the 11 studies were performed by the same authors. The follow-up periods in the single studies were very variable. Not only the probiotic strains used as treatment were very different, but also the treatment protocols with regard to timing, dosage, or combination with other drugs differed. Pooling different studies using different strains may not be a suitable method to evaluate their efficacy, because specific strains of probiotics may have different effects in patients with DD. Moreover, the type of DD was not homogenous between studies: some studies investigated patients with uncomplicated DD, other studies patients with acute diverticulitis in remission. Some studies investigated the reduction of abdominal symptoms, while other studies evaluated the maintenance of remission of abdominal symptoms. The clinical response to probiotics treatment may be potentially influenced by all these variables.
To date, the evidence on the efficacy of probiotics in DD still remains poor as high-quality studies are very few. At this point, available data do not allow to draw definite conclusions. Further work is needed to understand how probiotics can be used in the management of patients with DD.
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