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.

Apolipoprotein E (APOE) is a lipid transporter involved in neural cholesterol metabolism. Highly expressed in astrocytes and microglia, APOE4, one of the three isoforms of the transporter, is a strong genetic risk factor for Alzheimer’s disease, while APOE3 is considered moderate risk and APOE2 protective. Despite recent advances in Alzheimer’s disease research, the exact mechanism by which APOE4 influences the progression of the disease has yet to be determined. One hallmark pathological feature of Alzheimer’s disease is the accumulation of hyperphosphorylated tau protein in the brain. To investigate the role of APOE isoform expression in the accumulation of hyperphosphorylated tau protein, a microglia‐specific cre‐ recombinase‐mediated APOE inducible mouse model was used. Phosphorylated‐tau accumulation, microglia activation, and neurodegeneration of the hippocampus and piriform cortex upon specific expression of APOE3 were quantified. APOE3 expressing mice had exacerbated neurodegeneration and tau accumulation in the hippocampus. Additionally, it appeared that APOE3 expressing mice had increased microglial activation. Thus, APOE expression may be involved in the activation of microglia in Alzheimer’s disease, eliciting an overactive immune response that accelerates disease progression.

Diverticulitis, a common inflammatory disease characterized by infected pouches in the intestinal wall, can become especially painful when complications, such as abscesses and fistulas, arise. Despite affecting over 58% of adults over the age of 60, not much is known how the gut microbiome may influence or change as a result. Herein we resected diseased and adjacent tissue from both complicated and uncomplicated diverticulitis patients, extracting DNA and RNA from all samples. 16S rRNA gene Illumina‐tag PCR was performed on all samples extracted, analysis revealing an abundance of sulfur oxidizing bacteria in complicated diseased tissue compared to their adjacent tissue counterpart. This discovery led us to perform microbial gene expression using shotgun meta‐transcriptomics analysis on these complicated diseased tissues and their adjacent counterpart tissue to confirm expression of sulfur oxidizing behavior. Instead, differential gene expression revealed a fascinating trend in the increased expression of microbial xenobiotic degradation pathways in diseased tissue. Specifically, an uptake in Cytochrome‐P450 and Glutathione S‐transferase was found. Detailing how these environmental toxin degradation enzymes could be activated or cause the excessive immune response notorious of complicated diverticulitis will have profound impacts of treatment of the disease, as well as our understanding of how xenobiotics affect human health.