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

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-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 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-infected non-diabetic mice vs.Mtb-infected 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-lung axis.

Exploring behavioral traits over different contexts in four species of Australian funnel-web spiders

Australian funnel-web spiders are arguably the most venomous spiders in the world,with much research focusing on this aspect of their biology.However,other aspects related to their life history,ecology and behaviour have been overlooked.For the first time,we assessed repeatability.namely risk-taking behaviour,aggressiveness and activity in the contexts of predation,conspecific tolerance and exploration of a new territory in four species of Australian funnel-web spiders:two are closely related,Hadronyche valida and H.infensa,and two have overlapping distributions but occupy different habitats,H.cerberea and Atrax robustus.We also compared behaviors between species.At the species level,we found that H.valida showed consistency in risk-taking behavior when exposed to a predator stimulus,aggressiveness against conspecifics,and exploration of a new territory.In contrast,in the other species,only A.robustus showed repeatability in the context of exploration of a new territory.These results suggest that some behavioral traits are likely more flexible than others,and that the repeatability of behaviors may be species-specific in funnel-webs.When we compared species,we found differences in risk-taking behavior and defensiveness.This study provides novel insights to understanding variation in behavioral traits within and between species of funnel-web spiders,suggesting that some behavioral traits are likely context and/or species dependent,as a result of their evolutionary history.These findings provide key insights for understanding the ecological role of behavior and venom deployment in venomous animals,and a greater understanding of behavior in these medically significant and iconic spiders thatareof conservation concern.