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

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Animal Models and Experimental Medicine 2021年第2期4卷 181-188页

作者： harindra d.sathkumara Janet L.Eaton Matt A.Field Brenda L.Govan Natkunam Ketheesan Andreas Kupz Centre for Molecular Therapeutics Australian Institute of Tropical Health and MedicineJames Cook UniversityCairns&TownsvilleQLDAustralia College of Public Health Medical and Veterinary SciencesJames Cook UniversityTownsvilleQLDAustralia Centre for Tropical Bioinformatics and Molecular Biology James Cook UniversityCairnsQLDAustralia John Curtin School of Medical Research Australian National UniversityCanberraACTAustralia Science and Technology University of New EnglandArmidaleNSWAustralia

Tuberculosis(TB)is one of the deadliest infectious diseases in the *** meta-bolic disease type 2 diabetes(T2d)significantly increases the risk of developing ac-tive *** new TB vaccine candidates and novel therapeutic interventions are required to meet the challenges of global TB *** evidence suggests that the microbiota plays a significant role in how the host responds to infection,in-jury and neoplastic *** 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 *** this study,using a diet-induced 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 *** 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 index and principle component analyses demonstrated distinct clustering of Mtb-infected non-diabetic mice ***-infected T2d *** 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 *** model may also enable answers to be found to critical outstanding questions about targeted interventions of the gut mi-crobiota and the gut-lung axis.

关键词： gut microbiota host microbe interaction infectious diseases tuberculosis type 2 diabetes

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