http://hdl.handle.net/10453/35220 2026-04-09T22:52:52Z http://hdl.handle.net/10453/194309 Title: SCFA biotherapy delays diabetes in humanized gnotobiotic mice by remodeling mucosal homeostasis and metabolome. Authors: Tillett, BJ; Dwiyanto, J; Secombe, KR; George, T; Zhang, V; Anderson, D; Duggan, E; Giri, R; Loo, D; Stoll, T; Morrison, M; Begun, J; Hill, MM; Gurzov, EN; Bell, KJ; Saad, S; Barlow, CK; Creek, DJ; Chong, CW; Mariño, E; Hamilton-Williams, EE Abstract: Type 1 diabetes (T1D) is linked to an altered gut microbiota characterized by reduced short-chain fatty acid (SCFA) production. Oral delivery of a SCFA-yielding biotherapy in adults with T1D was followed by increased SCFAs, altered gut microbiota and immunoregulation, as well as delaying diabetes in preclinical models. Here, we show that SCFA-biotherapy in humans is accompanied by remodeling of the gut proteome and mucosal immune homeostasis. Metabolomics showed arginine, glutamate, nucleotide and tryptophan metabolism were enriched following the SCFA-biotherapy, and found metabolites that correlated with glycemic control. Fecal microbiota transfer demonstrated that the microbiota of SCFA-responders delayed diabetes progression in humanized gnotobiotic mice. The protected mice increased similar metabolite pathways to the humans including producing aryl-hydrocarbon receptor ligands and reducing inflammatory mucosal immunity and increasing IgA production in the gut. These data demonstrate that a potent SCFA immunomodulator promotes multiple beneficial pathways and supports targeting the microbiota as an approach against T1D. Trial registration: Australia New Zealand Clinical Trials Registry ACTRN12618001391268. 2025-03-25T00:00:00Z http://hdl.handle.net/10453/194308 Title: Nedd4-2 ablation in kidney improves glycaemic control in diabetic mice. Authors: Manning, JA; Jesudason, S; Moretti, PAB; Pitson, SM; Chou, ASY; Shabbar, M; Saad, S; Pollock, C; Kumar, S Abstract: NEDD4-2, a ubiquitin ligase, regulates a number of ion channels and transporters by promoting their ubiquitination, internalisation and degradation, thereby affecting many signalling and physiological outcomes. Loss of this gene in mice results in tubular cell death and a chronic kidney disease (CKD)-like phenotype due to aberrant Na+ transport, caused by elevated expression of NEDD4-2 substrates including the epithelial sodium channel (ENaC). One of the biggest risk factors for CKD is diabetes, as up to 50% of diabetic patients develop diabetic kidney disease (DKD). Reduced levels of Nedd4-2 are associated with DKD in patients, therefore we investigated if this gene contributes to the development of this disease. In a diabetic (db/db) mouse model that develops DKD, we observed reduced expression of Nedd4-2 that correlated with disease progression. Substrates of NEDD4-2, including ENaC, were elevated in db/db mice, suggesting that NEDD4-2 dysfunction is involved in disease pathology. Intriguingly, genetic ablation of Nedd4-2 in this diabetic model did not exacerbate kidney disease severity beyond Nedd4-2 loss alone, but corrected metabolic parameters via a reduction of aldosterone levels, restoration of insulin signaling and reduced blood glucose levels. Hence, we conclude that a reduced Nedd4-2 level is detrimental for kidney health, however unexpectedly improves glycemic control in diabetes. 2025-07-05T00:00:00Z http://hdl.handle.net/10453/193708 Title: Hydrogeology, European colonialism, local communities and First Peoples: moving beyond business as usual Authors: Bourke, SA; Taucare, M; Devoie, É; Hansen, C; N. Wright, S; Shanafield, M; Re, V; Kagawa-Viviani, A; Kenny, A; Bell, G; Diene, M; Kreamer, DK; Gurmessa, SK; Mulligan, B; Sarris, TS; Cuthbert, MO; Wallis, KJ; Moggridge, B Abstract: European colonialism altered the connections between First Peoples, local communities, and groundwater systems across the world. In many countries, the practice of hydrogeology remains intertwined with the economic agendas of colonial settler communities, making colonialism a useful lens through which to consider our work. This paper briefly summarizes connections between First Peoples, local communities and groundwater, as well as the role of groundwater as a resource in the process of European colonization. The key contemporary legacies of colonization pertaining to groundwater resource utilization and management are outlined, and established human rights that relate to the practice of hydrogeology are highlighted. The paper concludes with a call for more meaningful relationships between hydrogeologists and local communities, a broader practice of hydrogeology that respects and integrates traditional knowledge and community perspectives so that we can walk together into a better future. 2025-01-01T00:00:00Z http://hdl.handle.net/10453/193522 Title: Quantitative metagenomics for marine prokaryotes and photosynthetic eukaryotes. Authors: Bei, Q; Williams, NLR; Furtado, LE; Blasi, DD; Williams, J; Brotas, V; Tarran, G; Rees, AP; Bowler, C; Fuhrman, JA Abstract: High-throughput sequencing has provided unprecedented insights into microbial biodiversity in marine and other ecosystems. However, most sequencing-based studies report only relative (compositional) rather than absolute abundance, limiting their application in ecological modeling and biogeochemical analyses. Here, we present a metagenomic protocol incorporating genomic internal standards to quantify the absolute abundances of prokaryotes and eukaryotic phytoplankton, which together form the base of the marine food web, in unfractionated seawater. We applied this method to surface waters collected across 50°N to 40°S during the 29th Atlantic Meridional Transect. Using the single-copy recA gene, we estimated an average bacterial abundance of 1.0 × 109 haploid genome equivalents per liter. Leveraging a recent report that the psbO gene is typically single-copy in phytoplankton, we also quantified eukaryotic phytoplankton. Metagenomic estimates closely aligned with flow cytometry data for cyanobacteria (slope = 1.03, Pearson's r = 0.89) and eukaryotic phytoplankton (slope = 0.72, Pearson's r = 0.84). Compared to flow cytometry, taxonomic resolution for nano- and picoeukaryotes was greatly improved. Estimates for diatoms, dinoflagellates, and Trichodesmium were considerably higher than microscopy counts, likely reflecting microscopy undercounts and potential ploidy variation. These findings highlight the value of absolute quantification by metagenomics and offer a robust framework for quantitative assessments in microbial oceanography. 2025-01-01T00:00:00Z