A murine model of tuberculosis/type 2 diabetes comorbidity for investigating the microbiome, metabolome and associated immune parameters

• 作者: Harindra D.Sathkumara Janet L.Eaton Matt A.Field Brenda L.Govan Natkunam Ketheesan Andreas Kupz
• 来源期刊: 动物模型与实验医学（英文）
• 年，卷（期）: 2021,（2）
• 所属期刊栏目: Short Communication
• 页码范围: 181-188
• 页数: 8页
• 语种: 英文
• DOI: 10.1002/ame2.12159

摘要

Tuberculosis (TB) is one of the deadliest infectious diseases in the world. The meta-bolic disease type 2 diabetes (T2D) significantly increases the risk of developing ac-tive TB. Effective new TB vaccine candidates and novel therapeutic interventions are required to meet the challenges of global TB eradication. Recent evidence suggests that the microbiota plays a significant role in how the host responds to infection, in-jury and neoplastic changes. Animal models that closely reflect human physiology are crucial in assessing new treatments and to decipher the underlying immunological defects responsible for increased TB susceptibility in comorbid patients. In this study, using a diet-i nduced murine T2D model that reflects the etiopathogenesis of clinical T2D and increased TB susceptibility, we investigated how the intestinal microbiota may impact the development of T2D, and how the gut microbial composition changes following a very low- dose aerosol infection with Mycobacterium tuberculosis ( Mtb ). Our data revealed a substantial intestinal microbiota dysbiosis in T2D mice compared to non- diabetic animals. The observed differences were comparable to previous clini-cal reports in TB patients, in which it was shown that Mtb infection causes rapid loss of microbial diversity. Furthermore, diversity index and principle component analyses demonstrated distinct clustering of Mtb -i nfected non- diabetic mice vs. Mtb -i nfected T2D mice. Our findings support a broad applicability of T2D mice as a tractable small animal model for studying distinct immune parameters, microbiota and the immune- metabolome of TB/T2D comorbidity. This model may also enable answers to be found to critical outstanding questions about targeted interventions of the gut mi-crobiota and the gut-l ung axis.