Metatranscriptomic analysis of colonic mucosal samples exploring the functional role of active microbial consortia in complicated diverticulitis

ABSTRACT In this study, we investigated complicated diverticulitis, an inflammatory condition associated with abscesses, fistulas, intestinal obstructions, perforations, and primarily affects adults over the age of 60. Although the exact etiology remains unclear, the gut microbiome has been suggested as a contributing factor. Previous studies have used 16S rRNA gene analysis from patient fecal samples, which is limited to identifying the bacterial communities present. Herein, we employed shotgun metatranscriptomics on 40 patient-matched samples of diseased and adjacent normal colonic mucosal tissues from 20 patients with complicated diverticulitis to gain a more comprehensive understanding of active microbial taxa and gene expression patterns that may be involved in this disease state. Our findings revealed distinct beta diversity and a conglomerate of pathogenic microbiota in the diseased tissues, including Staphylococcus cohnii, Corynebacterium jeikeium, Kineococcus, Talaromyces rugulosus, Campylobacteraceae, and Ottowia, among others. The adjacent normal tissues were a stark contrast, harboring anti-inflammatory taxa such as Streptococcus salivarius and housekeeping genes and pathways such as the ABC-2 type transport system ATP-binding protein. These results align with previous amplicon sequencing studies and provide novel functional insights that may be crucial for understanding the etiology of complicated diverticulitis. IMPORTANCE Complicated diverticulitis is a virulent condition with no clear cause other than the association with colonic diverticulosis. We assessed the microbial gene expression in complicated diverticulitis patients using colonic tissue samples, revealing microbes in the diseased tissue known to exacerbate the diverticular condition and to live in extreme places, and microbes in patients’ normal tissue known to maintain normal bodily functions. This functional information is therefore important for understanding what microbial taxa are present and what they are doing. It is possible clinicians could someday harness this information to more effectively treat complicated diverticulitis symptoms. For example, clinicians may suggest dietary changes and prescribe probiotics to increase beneficial bacteria. Clinicians may also prescribe targeted antibiotics or consider the emerging treatment option of fecal transplants in complicated diverticulitis patients. While not curing complicated diverticulitis, each potential treatment option mentioned addresses balancing out dysbiosis of the gut microbiome, therefore alleviating associated symptoms.