**Background:** Diverticular disease (DD) is one of the most common gastrointestinal disorders in Western countries, with prevalence increasing globally. While most patients remain asymptomatic, approximately 10–25% develop acute diverticulitis (AD) due to obstruction of the diverticulum sac by fecalith, leading to inflammation. The pathogenesis of DD remains poorly understood, though genetic, dietary, and lifestyle factors are implicated. Growing evidence suggests the intestinal microbiome may play a role in both DD pathogenesis and progression to AD. This systematic review aimed to clarify current knowledge on the association between intestinal microbiota and colonic diverticulitis at different disease stages.
**Methods:** The review was conducted according to PRISMA 2009 guidelines. Two independent reviewers searched Medline (PubMed), Scopus, Embase, Cochrane Oral Health Group Specialized Register, ProQuest Dissertations and Theses Database, and Google Scholar without date restriction. Keywords included diverticulosis, diverticulitis, diverticular disease, microbiome, and microbiota. Inclusion criteria followed the PICOS framework: adult patients with DD/AD at any stage; analysis of luminal or mucosa-associated microbiota from fecal samples or colorectal biopsies; comparisons between patients with and without DD/AD; outcomes including microbiota type and disease treatment; and study designs including randomized and non-randomized clinical trials, cohort, and case-control studies. Studies exclusively investigating other colorectal diseases or probiotic treatment effects were excluded. Quality assessment was performed using the Newcastle-Ottawa Scale (NOS).
**Key Results:** The initial search yielded 79 results; after duplicate removal, 78 articles were screened, and 9 studies published between 2007 and 2018 met inclusion criteria (3 cohort studies, 6 case-control studies). Seven studies were conducted in Europe and two in the USA. Only one study (Daniels et al., 2014) focused on patients with AD and reported disease stage according to current classification. Four studies considered symptomatic uncomplicated DD without specifying stage. Four studies collected fecal samples via rectal swabs or stool samples; five collected mucosa samples during colonoscopy or surgery. All studies used microbial DNA analysis; five used 16S rRNA gene amplification, and four used real-time quantitative PCR. Quality assessment yielded NOS scores of 7/9 (3 studies), 6/9 (3 studies), and 5/9 (3 studies).
KEY MICROBIOTA ASSOCIATIONS
Enterobacteriaceae (phylum Proteobacteria) was positively correlated with AD (Daniels et al., 2014) and DD (Linninge et al., 2019). Kvasnovsky et al. (2017) found overgrowth of Pseudobutyrivibrio, Bifidobacterium, and Christensenellaceae in patients with recurrent AD, with overall biodiversity positively correlated with fecal calprotectin. Gueimonde et al. (2007) reported overrepresentation of Bifidobacterium longum associated with colonic inflammation. Barbara et al. (2017) demonstrated significantly lower abundance of Clostridium cluster IV in patients with diverticula, along with depletion of taxa with anti-inflammatory activity. However, three studies focusing on DD (Lopetuso et al., 2017; Jones et al., 2018; Schieffer et al., 2017) found limited or absent association between DD and microbiota composition. The largest study (Jones et al., 2018), including 226 DD patients and 309 controls, showed no differences between groups except for underrepresentation of Proteobacteria and Comamonadaceae in cases.
**Clinical Implications:** The review highlights that asymptomatic DD does not appear to be consistently linked to significant gut microbiota alterations, whereas progression to AD involves inflammatory changes with microbial shifts—specifically, reduction of anti-inflammatory taxa (Clostridium cluster IV, Lactobacilli, Bacteroides) and overgrowth of potentially pro-inflammatory bacteria (Enterobacteriaceae, Bifidobacteria, Akkermansia). However, the definitive role of these taxa remains unclear, as some (Bifidobacteria, Akkermansia) exhibit both anti-inflammatory and pro-inflammatory properties depending on context. The authors note that the high heterogeneity in study design, population characteristics, sampling methods (stool vs. mucosa), laboratory techniques (PCR vs. metagenomics), and insufficient clinical characterization of disease stage precluded meta-analysis. They emphasize the need for future studies aligned with current DD management guidelines, with standardized sampling methods and stratification by disease stage. Given the high prevalence of DD, identifying specific microbiota signatures could serve as biomarkers for diagnosis, screening, and progression, potentially enabling targeted probiotic therapies and reducing emergency surgery requirements.