McMullen Brittney N, Chen See Jeremy, Baker Samantha, Wright Justin R, Anderson Samantha L C, Yochum Gregory, Koltun Walter, Portolese Austin, Jeganathan Nimalan A, Lamendella Regina
Department of Biology, Juniata College, Huntingdon, Pennsylvania, USA.
Wright Labs, LLC, Huntingdon, Pennsylvania, USA.
Microbiol Spectr. 2025 Jul;13(7):e0243124. doi: 10.1128/spectrum.02431-24. Epub 2025 May 22.
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 and among others. The adjacent normal tissues were a stark contrast, harboring anti-inflammatory taxa such as 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.IMPORTANCEComplicated 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.
在本研究中，我们调查了复杂性憩室炎，这是一种与脓肿、瘘管、肠梗阻、穿孔相关的炎症性疾病，主要影响60岁以上的成年人。尽管确切病因尚不清楚，但肠道微生物群被认为是一个促成因素。先前的研究使用患者粪便样本进行16S rRNA基因分析，该方法仅限于识别存在的细菌群落。在此，我们对20例复杂性憩室炎患者的40份患病及相邻正常结肠黏膜组织的配对样本进行了鸟枪法宏转录组学分析，以更全面地了解可能与这种疾病状态相关的活跃微生物分类群和基因表达模式。我们的研究结果揭示了患病组织中明显的β多样性和致病性微生物群的聚集，包括 等。相邻的正常组织则形成鲜明对比，含有抗炎分类群，如 以及管家基因和途径，如ABC-2型转运系统ATP结合蛋白。这些结果与先前的扩增子测序研究一致，并提供了新的功能见解，这可能对理解复杂性憩室炎的病因至关重要。
重要性
复杂性憩室炎是一种严重疾病，除了与结肠憩室病相关外，没有明确病因。我们使用结肠组织样本评估了复杂性憩室炎患者的微生物基因表达，揭示了患病组织中已知会加重憩室病情并存在于极端环境中的微生物，以及患者正常组织中已知能维持身体正常功能的微生物。因此，这些功能信息对于了解存在哪些微生物分类群以及它们在做什么很重要。临床医生有朝一日可能会利用这些信息更有效地治疗复杂性憩室炎症状。例如，临床医生可能会建议改变饮食并开益生菌以增加有益细菌。临床医生也可能会开有针对性的抗生素，或者考虑对复杂性憩室炎患者采用新兴的粪便移植治疗方案。虽然不能治愈复杂性憩室炎，但上述每种潜在治疗方案都旨在平衡肠道微生物群的生态失调，从而缓解相关症状。
