DOI: 10.1002/ame2.12159
A murine model of tuberculosis/type 2 diabetes comorbidity for investigating the microbiome, metabolome and associated immune parameters
Harindra D.Sathkumara1
Janet L.Eaton2
Matt A.Field3
Brenda L.Govan4
Natkunam Ketheesan5
Andreas Kupz1
1.Centre for Molecular Therapeutics,Australian Institute of Tropical Health and Medicine,James Cook University,Cairns&Townsville,QLD,Australia2.College of Public Health,Medical and Veterinary Sciences,James Cook University,Townsville,QLD,Australia3.Centre for Molecular Therapeutics,Australian Institute of Tropical Health and Medicine,James Cook University,Cairns&Townsville,QLD,Australia;Centre for Tropical Bioinformatics and Molecular Biology,James Cook University,Cairns,QLD,Australia;John Curtin School of Medical Research,Australian National University,Canberra,ACT,Australia4.Centre for Molecular Therapeutics,Australian Institute of Tropical Health and Medicine,James Cook University,Cairns&Townsville,QLD,Australia;College of Public Health,Medical and Veterinary Sciences,James Cook University,Townsville,QLD,Australia5.Science and Technology,University of New England,Armidale,NSW,Australia
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.
机标关键词：
论文发表日期：2021-06-25
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：8( 181-188 )
英文信息