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Past Events·

Monday, April 11, 2022

MVIF.8 | 11/12 & 13 April 2022

with Keynote talk by Prof. Suhelen Egan

Suhelen Egan is an Associate Professor at the School of Biological, Earth and Environmental Sciences (BEES) UNSW.  She is a microbiologist with experience in the areas of molecular microbiology, microbial symbioses and marine biotechnology. Her current research interests include understanding the role of microorganisms for the heath and function of marine plants and animals.

Seaweeds are a ubiquitous group of photosynthetic organisms that play an essential role in many aquatic ecosystems. Seaweeds also host complex microbiomes. While symbiotic interactions with these microbiomes are essential for seaweeds, we now also know that microorganisms can be responsible for negative outcomes, such as disease of the host.  
In this seminar I will firstly discuss how ecological principles such as the “lottery hypothesis” and “priority effects” determine how microbiomes assemble on seaweeds.  Secondly, I will discuss how anthropogenic stressors can disturb the microbiome (i.e. cause dysbiosis) resulting in the proliferation of opportunistic pathogens leading to disease. Finally, I will describe recent studies that show mitigation of disease through the addition of beneficial microorganisms and their possible mode of action.


Illuminating the black box: developing new genetic systems for genetically intractable microbiome species

With the recent explosion of next-generation sequencing and OMICS studies of human microbiome communities, a surprisingly broad diversity of diseases have been found to correlate with mucosal dysbiosis. Another consequence of such studies is an exponential increase in the number of uncharacterized and understudied microbes identified as potential drivers of mucosal health and disease. Thus, there is an impending challenge looming on the horizon to reveal the molecular basis for these observations. To meet this challenge, many newly identified microbes will require the development of new genetic systems useful for interrogating experimental models. Our laboratory has devoted a significant effort to improve the genetic tractability of a variety of important understudied microbiome species, especially those that have been traditionally considered as “genetically intractable”. Here, we will discuss a recently developed genetic system for one such pathobiont species, Parvimonas micra. Our preferred approach to develop new genetic systems begins with identifying and exploiting endogenous natural competence abilities (i.e. energy-dependent exogenous DNA uptake). Accordingly, we identified a natural competence ability in P. micra, which allowed us to employ cloning-independent methodologies to construct a variety of targeted genetic mutations directly within low-passage clinical isolates. In addition, we successfully developed a luciferase-based reporter system, a theophylline-inducible gene expression system, and a Mariner transposon mutagenesis system for Tn-seq studies of P. micra. While natural competence is widely believed to be a specialized ability of a small number of prokaryotes, we have reason to believe that it is likely to be quite common among bacteria. As such, natural competence could provide a clear path to investigate the genetics of the numerous novel organisms identified from microbiome studies.

Justin Merritt

Oregon Health & Science University

Urinary microbiome resistance: urinary lactobacilli inhibit three major uropathogens in vitro

The human urinary microbiome is thought to affect the development and progression of urinary tract infections (UTI), particularly recurrent UTIs in aging women. To understand the possible interactions of urinary pathogens with commensal bacteria inhabiting the aging bladder, we conducted an initial functional assessment of a representative set of urinary lactobacilli that dominate this niche in pre- and postmenopausal women. We created a repository of urinary bladder bacteria isolated via Enhanced Quantitative Urinary Culture (EQUC) from healthy postmenopausal women, as well as those with culture-proven recurrent UTI diagnosis. This repository contains lactobacilli strains from eight different species. As many other lactobacilli are known to inhibit human pathogens, including typical uropathogens, we screened the urinary lactobacilli in our repository for their ability to inhibit model uropathogens in vitro. We observed that many urinary lactobacilli strongly inhibit model gram-negative pathogens Escherichia coli and Klebsiella pneumoniae but demonstrate less inhibition of gram-positive pathogen Enterococcus faecalis. The observed inhibition is not specific to these model uropathogens and also affects clinical and multidrug-resistant isolates. Our preliminary analysis of inhibition mechanisms implicates pH as an important factor with additional cell-dependent inhibition mechanisms that differ amongst species and strains of urinary lactobacilli. Overall, our data show that urinary lactobacilli are broadly inhibiting uropathogen growth in vitro via a combination of different mechanisms. Nevertheless, simple measured inhibition level is not predictive of health outcomes in colonized patients, and species and strain level diversity of urinary lactobacilli is high.

Tatyana Sysoeva

University of Alabama in Huntsville

Axial spondyloarthritis patients have altered mucosal IgA response to oral and fecal microbiota

Objective To investigate whether axial spondyloarthritis (AxSpA) patients have an altered immunoglobulin A (IgA) response in the gut and oral microbial communities. Methods We performed 16S rRNA gene (16S) sequencing on IgA positive (IgA+) and IgA negative (IgA−) fractions (IgA-SEQ) from feces (n=17 AxSpA; n=14 healthy) and saliva (n=17 AxSpA; n=12 healthy), as well as on IgA-unsorted fecal and salivary samples. PICRUSt2 was used to predict microbial metabolic potential in AxSpA patients and healthy controls (HCs). Results IgA-SEQ revealed enrichment of several microbes in the fecal (Akkermansia, Ruminococcaceae, Lachnospira) and salivary (Prevotellaceae, Actinobacillus) microbiome in AxSpA patients as compared with HCs. Fecal microbiome from AxSpA patients showed a trend towards increased alpha diversity of the IgA+ fraction and decreased diversity in the IgA− fraction in comparison with HCs, while the salivary microbiome exhibits a significant decrease in alpha diversity in both IgA+ and IgA− fractions. Increased IgA coating of Clostridiales Family XIII correlated with disease severity. Inferred metagenomic analysis suggests perturbation of metabolites and metabolic pathways for inflammation (oxidative phosphorylation, glutathione metabolism) and metabolism (propanoate and butanoate metabolism) in AxSpA patients. Conclusions Analyses of fecal and salivary microbes from AxSpA patients reveal distinct populations of immunoreactive microbes using novel IgA-SEQ approach, which were not captured by comparing their relative abundance with HCs. Predictive metagenomic analysis revealed perturbation of metabolites/metabolic pathways in AxSpA patients. Future studies on these immunoreactive microbes may lead to better understanding of the functional role of IgA in maintaining microbial structure and human health.

Tejpal Gill

Division of Arthritis and Rheumatic Diseases, OHSU


Not all stool is created equal: Strain engraftment competition and functional augmentation in a multi-donor faecal microbiota transplantation trial for obesity

Transplantation of faecal microbiota (FMT) from healthy lean donors has been shown to transiently improve insulin sensitivity and alter fat distribution in individuals with obesity and metabolic syndrome. However, the mechanisms and levels of donor strain engraftment required to elicit these effects remain poorly characterised. To address this, we performed a double-blinded randomised placebo-controlled trial for FMT in 87 adolescents with obesity.  Participants were randomized to receive multi-donor FMT (capsules containing the fecal microbiota of four healthy, lean, sex-matched donors) or placebo (saline capsules). Following a bowel cleanse, participants ingested a total of 28 capsules over two consecutive days. FMT capsules and recipient stool samples collected at baseline, 6-, 12- and 26-weeks post-treatment were analysed by shotgun metagenomic sequencing allowing us to track donor strain engraftment and monitor changes in the recipient gut microbiome over time.   We found that multi-donor FMT sustainably altered the structure and functional potential of the gut microbiome for up to six months. In what was effectively a microbiome competition experiment, we discovered that two donor microbiomes (one female, one male) dominated strain engraftment. These ‘super-donor’ microbiomes were characterized by high microbial diversity and a high Prevotella to Bacteroides ratio. Engrafted strains led to enterotype-level shifts in community composition and provided genes that altered the metabolic potential of the microbiome, including pathways previously shown to be important in energy balance homeostasis (e.g. NAD biosynthesis). Despite our attempts to standardize FMT dose and donors, FMT recipients varied widely in their engraftment of donor strains suggesting the host environment plays a critical role in mediating FMT receptivity. Further work is required to better understand the various host-microbe interactions that determine engraftment success to help in developing more effective and personalised microbial therapies.

Brooke Wilson

Liggins Institute, University of Auckland

A systematic review of gut microbiota composition in observational studies of major depressive disorder, bipolar disorder and schizophrenia

The emerging understanding of gut microbiota as ‘metabolic machinery’ influencing many aspects of physiology has gained substantial attention in the field of psychiatry. This is largely due to the many overlapping pathophysiological mechanisms associated with both the potential functionality of the gut microbiota and the biological mechanisms thought to be underpinning mental disorders. In this systematic review, we synthesised the current literature investigating differences in gut microbiota composition in people with the major psychiatric disorders, major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ), compared to ‘healthy’ controls. We also explored gut microbiota composition across disorders in an attempt to elucidate potential commonalities in the microbial signatures associated with these mental disorders. Following the PRISMA guidelines, databases were searched from inception through to December 2021. We identified 44 studies (including a total of 2510 psychiatric cases and 2407 controls) that met inclusion criteria, of which 24 investigated gut microbiota composition in MDD, seven investigated gut microbiota composition in BD, and 15 investigated gut microbiota composition in SZ. Our syntheses provide no strong evidence for a difference in the number or distribution (α-diversity) of bacteria in those with a mental disorder compared to controls. However, studies were relatively consistent in reporting differences in overall community composition (β-diversity) in people with and without mental disorders. Our syntheses also identified specific bacterial taxa commonly associated with mental disorders, including lower levels of bacterial genera that produce short-chain fatty acids (e.g. butyrate), higher levels of lactic acid- producing bacteria, and higher levels of bacteria associated with glutamate and GABA metabolism. We also observed substantial heterogeneity across studies with regards to methodologies and reporting. Further prospective and experimental research using new tools and robust guidelines hold promise for improving our understanding of the role of the gut microbiota in mental and brain health and the development of interventions based on modification of gut microbiota.

Amelia McGuinness

The Institute for Mental and Physical Health and Clinical Translation (IMPACT), Food & Mood Centre, School of Medicine and Barwon Health, Deakin University, Geelong, VIC, Australia