The Microbiome of Complicated Diverticulitis: An Imbalance of Sulfur-Metabolizing Bacteria

Abstract

BACKGROUND:The progression to acute diverticulitis from the relatively benign condition of colonic diverticulosis is not well characterized. A smaller subset may even develop complicated (perforated) diverticulitis resulting in sepsis and/or death. Characterizing the differences between recurrent, uncomplicated diverticulitis, and the more virulent, complicated diverticulitis is necessary to guide clinical decision-making. Alterations to the microbiome offer a possible explanation for local inflammation and the pathophysiology of diverticular disease. OBJECTIVE:This study aimed to characterize the mucosal-associated microbiome in patients with recurrent uncomplicated diverticulitis and complicated (perforated) diverticulitis.DESIGN: Microbial DNA was extracted from full-thickness surgical specimens for 16S rRNA gene sequencing, targeting the V4 hypervariable region. Sequences were analyzed and a quantitative characterization based on taxonomic classification was performed.SETTING: A tertiary care academic medical center.PATIENTS: This study compared 48 patients with recurrent, uncomplicated diverticulitis and 35 patients with radiographically confirmed perforated (complicated) diverticulitis. Tissues were harvested from surgical resection specimens to include both diseased regions and nondiseased (adjacent normal) regions. MAIN OUTCOME MEASURES:We assessed differences in relative abundance and taxonomic classification of mucosal-associated microbes in surgical resection specimens from diverticular disease. RESULTS:When analyzing the tissue of diverticular resection specimens, the complicated diseased segments demonstrated an increased abundance of sulfurreducing and sulfur-oxidizing bacteria compared to nondiseased, adjacent normal regions. When comparing diseased segments, tissues of patients with complicated diverticulitis had a marked increase in sulfur-reducing microbes. LIMITATIONS:We characterized the mucosal-associated microbiome present at the time of surgical resection, limiting conclusions on its role in pathophysiology. Furthermore, antibiotic usage and bowel preparation before surgery may result in perturbations to microbial flora. CONCLUSIONS:The microbiome of complicated diverticulitis is marked by a localized imbalance of sulfur-metabolizing microbes. The abundance of sulfurreducing microbes may lead to an excess of hydrogen sulfide and subsequent inflammation. See Video Abstract at http://links.lww.com/DCR/C175.

Management of Diverticulitis

“…A 2023 study, the largest of its kind, used RNA sequencing to compare harvested diseased and nondiseased tissue from the surgical resections of 48 patients with recurrent, uncomplicated diverticulitis and 35 patients with complicated acute diverticulitis. 28 The results showed that complicated diverticulitis tissue samples had increased sulfur-reducing bacteria compared with adjacent normal-appearing tissue and tissue samples from uncomplicated diverticulitis. Another contemporary review on the microbiome and its association with diverticulitis (which did not include the aforementioned study) delineated the limitations of the current data and use of available evidence and proposed a link between fiber intake and the microbiome in the development of diverticulitis.…”

“…There is a burgeoning field of study examining how the microbiome shapes the development of diverticulitis and the severity of diverticular disease. A 2023 study, the largest of its kind, used RNA sequencing to compare harvested diseased and nondiseased tissue from the surgical resections of 48 patients with recurrent, uncomplicated diverticulitis and 35 patients with complicated acute diverticulitis . The results showed that complicated diverticulitis tissue samples had increased sulfur-reducing bacteria compared with adjacent normal-appearing tissue and tissue samples from uncomplicated diverticulitis.…”

Creating a Surgical Biobank: The Hershey Medical Center Experience

“…Over 100 original clinical and scientific research articles have been published using these specimens. These publications have been the result of work with more than 30 collaborating scientists and relate to the genetics and pathophysiology diverticulitis, 31,32 the genetic basis of IBD, 33,34 disease phenotype/ genotype correlations, [35][36][37] mucus defense, 38,39 bowel permeability and myofibroblast function in IBD, [40][41][42][43] and colorectal cancer. 44,45…”