A pinboard by
Jacob Mills

Student, University of Adelaide


Exploring ways to engineer microbiomes to install human immune protection in urban landscapes

Urbanisation, the great concrete expansion, has lead to the removal of humans from our coevolved natural habitat. This has had health ramifications in the form of increased incidences of allergic, autoimmune, and chronic inflammatory diseases relative to rural populations. Symbiotic microbiota are known to develop and maintain the immune system, and many of these microbes colonise us during infancy and childhood. Imbalance in the human microbiome - microbial communities of the body - is known to lead to these diseases. My research is about understanding if returning natural environmental microbiomes to the lived human experience, which is now predominantly urban, can improve public health through adequate exposure to beneficial microbiota. By taking advantage of plant-microbe symbiotic relationships to engineer urban green spaces to harbour microbiota symbiotic to humans, I hope to find out if the modern human habitat can be rewilded - the return of natural processes (ecosystem services) to dominance. In preliminary results, I have seen that engineering natural microbiomes in an urban green spaces is plausible, and that bacteria transfer to humans readily.


Acinetobacter species in the skin microbiota protect against allergic sensitization and inflammation.

Abstract: The human commensal microbiota interacts in a complex manner with the immune system, and the outcome of these interactions might depend on the immune status of the subject.Previous studies have suggested a strong allergy-protective effect for Gammaproteobacteria. Here we analyze the skin microbiota, allergic sensitization (atopy), and immune function in a cohort of adolescents, as well as the influence of Acinetobacter species on immune responses in vitro and in vivo.The skin microbiota of the study subjects was identified by using 16S rRNA sequencing. PBMCs were analyzed for baseline and allergen-stimulated mRNA expression. In in vitro assays human monocyte-derived dendritic cells and primary keratinocytes were incubated with Acinetobacter lwoffii. Finally, in in vivo experiments mice were injected intradermally with A lwoffii during the sensitization phase of the asthma protocol, followed by readout of inflammatory parameters.In healthy subjects, but not in atopic ones, the relative abundance of Acinetobacter species was associated with the expression of anti-inflammatory molecules by PBMCs. Moreover, healthy subjects exhibited a robust balance between anti-inflammatory and TH1/TH2 gene expression, which was related to the composition of the skin microbiota. In cell assays and in a mouse model, Acinetobacter species induced strong TH1 and anti-inflammatory responses by immune cells and skin cells and protected against allergic sensitization and lung inflammation through the skin.These results support the hypothesis that skin commensals play an important role in tuning the balance of TH1, TH2, and anti-inflammatory responses to environmental allergens.

Pub.: 30 Sep '14, Pinned: 27 Jul '17

Markedly Elevated Antibody Responses in Wild versus Captive Spotted Hyenas Show that Environmental and Ecological Factors Are Important Modulators of Immunity.

Abstract: Evolutionary processes have shaped the vertebrate immune system over time, but proximal mechanisms control the onset, duration, and intensity of immune responses. Based on testing of the hygiene hypothesis, it is now well known that microbial exposure is important for proper development and regulation of the immune system. However, few studies have examined the differences between wild animals in their natural environments, in which they are typically exposed to a wide array of potential pathogens, and their conspecifics living in captivity. Wild spotted hyenas (Crocuta crocuta) are regularly exposed to myriad pathogens, but there is little evidence of disease-induced mortality in wild hyena populations, suggesting that immune defenses are robust in this species. Here we assessed differences in immune defenses between wild spotted hyenas that inhabit their natural savanna environment and captive hyenas that inhabit a captive environment where pathogen control programs are implemented. Importantly, the captive population of spotted hyenas was derived directly from the wild population and has been in captivity for less than four generations. Our results show that wild hyenas have significantly higher serum antibody concentrations, including total IgG and IgM, natural antibodies, and autoantibodies than do captive hyenas; there was no difference in the bacterial killing capacity of sera collected from captive and wild hyenas. The striking differences in serum antibody concentrations observed here suggest that complementing traditional immunology studies, with comparative studies of wild animals in their natural environment may help to uncover links between environment and immune function, and facilitate progress towards answering immunological questions associated with the hygiene hypothesis.

Pub.: 09 Oct '15, Pinned: 27 Jul '17

Environmental and mucosal microbiota and their role in childhood asthma.

Abstract: High microbial diversity in the environment has been associated with lower asthma risk, particularly in children exposed to farming. It remains unclear whether this effect operates through an altered microbiome of the mucosal surfaces of the airways.DNA from mattress dust and nasal samples of 86 school-age children was analyzed by 454-pyrosequencing of the 16S rRNA gene fragments. Based on operational taxonomic units bacterial diversity and composition was related to farm exposure and asthma status.Farm exposure was positively associated with bacterial diversity in mattress dust samples as determined by richness (p=8.1 * 10(-6) ) and Shannon index (p=1.3 * 10(-5) ). Despite considerable agreement of richness between mattress and nasal samples, the association of richness with farming in nasal samples was restricted to a high gradient of farm exposure, i.e. exposure to cows and straw versus no exposure at all. In mattress dust the genera Clostridium, Facklamia, an unclassified genus within the family of Ruminococcaceae and six OTUs were positively associated with farming. Asthma was inversely associated with richness (aOR= 0.48 [0.22-1.02]) and Shannon Index (aOR=0.41 [0.21-0.83]) in mattress dust and to a lower extent in nasal samples (richness aOR 0.63[0.38-1.06], Shannon Index aOR= 0.66 [0.39-1.12]).The stronger inverse association of asthma and bacterial diversity in mattress dust as compared to nasal samples suggests microbial involvement beyond mere colonization of the upper airways. Whether inhalation of metabolites of environmental bacteria contributes to this phenomenon should be the focus of future research. This article is protected by copyright. All rights reserved.

Pub.: 10 Aug '16, Pinned: 27 Jul '17

Revegetation rewilds the soil bacterial microbiome of an old field.

Abstract: Ecological restoration is a globally important and well-financed management intervention used to combat biodiversity declines and land degradation. Most restoration aims to increase biodiversity towards a reference state, but there are concerns that intended outcomes are not reached due to unsuccessful interventions and land use legacy issues. Monitoring biodiversity recovery is essential to measure success, however most projects remain insufficiently monitored. Current field-based methods are hard to standardise and are limited in their ability to assess important components of ecosystems, such as bacteria. High-throughput amplicon sequencing of environmental DNA (metabarcoding of eDNA) has been proposed as a cost-effective, scalable and uniform ecological monitoring solution, but its application in restoration remains largely untested. Here we show that metabarcoding of soil eDNA is effective at demonstrating the return of the native bacterial community in an old field following native plant revegetation. Bacterial composition shifted significantly after 8 years of revegetation, where younger sites were more similar to cleared sites and older sites were more similar to remnant stands. Revegetation of the native plant community strongly impacted on the belowground bacterial community, despite the revegetated sites having a long and dramatically altered land use history (i.e. >100 years grazing). We demonstrate that metabarcoding of eDNA provides an effective way of monitoring changes in bacterial communities that would otherwise go unchecked with conventional monitoring of restoration projects. With further development, awareness of microbial diversity in restoration has significant scope for improving the efficacy of restoration interventions more broadly. This article is protected by copyright. All rights reserved.

Pub.: 07 Mar '17, Pinned: 27 Jul '17