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Research

A sustained energy food for weaning infants

Mother feeding baby

Tannock, G.W.; Heath A-L., Sims, I.M., Galland, B.; Rehrer, N.; Drummond, L. and Wu, K.
National Science Challenge High Value Nutrition Contestable Funding. Novel dietary fibres in weaning food for sustained energy generation in the bowel and a good night’s sleep, 2016-2018.

Food contains complex carbohydrates (dietary fibre) that are not digested by humans. The large bowel (colon), however, is home to a multitude of bacteria that degrade and ferment these carbohydrates. The fermentation products that are produced are organic acids that are absorbed from the bowel and provide energy for the human. The degradation and fermentation of complex carbohydrates takes time and provides a slower, sustained energy harvest compared to the easily digested food components that provide most of human energy requirements. The amount of energy required by the body is less during periods of sleep, but infant waking in the night is commonly believed by parents to be due to hunger. A good night’s sleep could be achieved by providing baby food (weaning food) with optimal mixtures of dietary fibres that would enable a sustained energy harvest by bowel bacteria during the night so as to satisfy the body’s needs. Optimal mixtures of dietary fibres will be defined through laboratory experiments based on the applicants’ knowledge of the bacterial species present in the bowel of children during weaning as well as of new complex polysaccharides. Asia provides excellent opportunities to market new weaning foods: there are 50 million children aged 0-3 years and 40 million aged 3-5 years in China where there is consumer-driven preference for “a good night’s sleep” for baby. An eclectic team of scientists, with expertise in microbiology, nutrition, carbohydrate chemistry, food science, sleep, energetics, and food formulation (including associated health claims) has been assembled to carry out the research. The aim is to produce a premium weaning food for evening consumption that will sustain energy harvest in the bowel through the night.

Improved detection and monitoring of Crohn's disease

Tannock, G.W.; Lawley, B.; Day, A.; Wall, C.; Gearry, R. and Young, W.
Broad Medical research Foundation, USA grant. Short-term exclusive enteral nutrition (EEN) of CD patients in the recognition of urine biomarkers of bowel inflammation, 2016-2017.

The aim of the study is to use Exclusive Enteral Nutrition (EEN) to simplify the collection of metabolic substances in the urine of Crohn’s Disease patients. Patients and controls will obtain their nutrition from a standardized liquid diet. Since many of the substances present in urine are derived from the metabolism of food, a standardized diet, by removing ‘background’, will improve the ability to detect molecules in urine that are associated with inflammation. Moreover, EEN helps the healing of inflamed bowel tissues. The use of EEN and urine samples in developing monitoring tests for Crohn’s disease patients has not been investigated previously. Sophisticated analytical methods will be used to determine the profile of metabolites in urine collected from patients and controls. Comparison of these profiles and detection of suitable ‘biomarkers’ of inflammation will lead to the development of assays by which the healing process in the bowel can be monitored without the use of invasive procedures such as colonoscopy.

The role of immune cells in Crohn's disease

Hamish Angus (PhD student), Kemp, R.; Butt, G.
PhD research project: Interactions between immune cells and bacteria in Inflammatory Bowel Diseases, 2017-2019.

Our research proposal is to use an organoid model to investigate the role of T cells in Crohn’s disease. We will do this by exposing mature organoids derived from human patients, to a variety of different environments including, but not limited to: a Crohn’s disease patient immune system, a ‘healthy’ patient immune system, pathogenic bacteria, commensal bacteria, and bacterial antigens.

The impact of altered nutrition on Crohn's disease patients

Morgan, X.; Day, A.; Gearry, R.; Wall, C.; Tannock, G.W.
Otago Medical School and Division of Health Sciences Collaborative Grant. Impact of enteral nutrition on the fecal microbiome of Crohn’s disease patients, 2017.

The complex bacterial community (microbiome) of the intestine biotransforms and digests almost everything eaten, as well as the intestinal mucus lining. The microbiome also produces both pro- and anti-inflammatory products, forming an intricate balance with the immune system that becomes disrupted in Crohn’s disease (CD). CD is typically treated with immunosuppressants, many of which have undesirable side effects. However, limiting the diet to a highly digestible formula, called ‘exclusive enteral nutrition’ (EEN), induces clinical remission in most paediatric CD patients. Because research on adult CD patients and EEN is limited, we will study how adult CD microbiomes change during EEN. We will determine what bacteria thrive in this nutrient-restricted environment, and which are permanently lost, and will associate these changes to patient health. Detection of changes in the microbiome and its functions, common to all patients, may result in new, non-invasive tests (biomarkers) to monitor the health of CD patients.

Changes to microbial communities in inflammatory bowel disease

Alice Withers (BSc Hons student), Morgan, X., Day, A.
University of Otago, Biomedical Sciences, Dean’s Bequest Fund, 2017. The longitudinal dynamics of the IBD microbiome.

Although inflammatory bowel disease (IBD) has no single cause, over 150 host genes are confidently linked, as are many environmental factors, chief among them the gut microbiome. Gut dysbiosis is a feature of established IBD and begins very early in disease establishment. However, longitudinal data is required to answer many fundamental questions about dysbiosis, including its temporal relationships with disease flares and remission. This research project will analyse a longitudinal dataset comprising 319 stool metagenomic samples from 76 pediatric IBD patients in order to better understand how gut microbial communities change during active disease and remission.

The genetics of antibiotic-resistant gut bacteria

Ro Rushton-Green (BSc Hons student), Morgan, X. and Cook, G.
Comparative genomics of vancomycin-resistant Enterococci, 2017.

Enterococci are among the most antibiotic-resistant of human-associated bacteria, and vancomycin-resistant Enterococcus (VRE) in particular is a matter of great public health concern. However, the relationship between clinical VRE strains and agricultural VRE strains is still not well understood. This research project will analyse a dataset comprising 105 recently-sequenced VRE isolates from New Zealand poultry farms in order to better understand the interactions between genetic background and further acquisition of antibiotic resistance, and phylogenetic relationships between commensal, poultry, and pathogenic strains.

Yeast colonisation of dentures

Dentures

Khai How Choo, Hee Ji Lee, Nicholas J. Knight, Ann R. Holmes and Richard D. Cannon.

Multilocus sequence typing (MLST) analysis of Candida albicans isolates colonizing acrylic dentures before and after denture replacement, 2017.

Denture stomatitis is a condition where inflammation of the palatal mucosa occurs beneath maxillary dentures. Denture stomatitis affects 11-67% of complete denture wearers and is often caused by Candida yeast species. Many aspects of the microbial ecology of denture colonisation are unknown. We are interested in discovering which yeast species and strains colonise dentures – are there specific strains well adapted to colonising dentures that could be responsible for denture stomatitis? We are also interested in strains of C. albicans that might be associated with the progression of oral cancer.

The effects of oral probiotics on the dental microbiome

Gareth Benic (DClinDent student) and Li Mei, Nick Heng, Mauro Farella and R. Cannon.
Biofilm management with oral probiotics in patients with fixed orthodontic appliances, 2017. 

Oral biofilms can cause a number of oral diseases such as dental caries, periodontitis, gingivitis, halitosis and candidosis. Mechanical and chemical methods have traditionally been used to remove oral biofilms but they have limitations. Oral probiotics have shown potential in affecting pathogens found in biofilms without impacting negatively on the normal oral microbiota and thus their application in dental patients has garnered much attention. Our research is investigating the effects or oral priobiotics on the dental plaque microbiome around orthodontic appliances.

Changes to the microbiome in type 2 diabetes

Naomi Davies (PhD Student), Rinki Murphy, Lindsay Plank and Justin O’Sullivan.
Comparative gut hormone, gut bacteria and metabolic changes in patients with type 2 diabetes undergoing sleeve gastrectomy or gastric bypass surgery, 2016-2019.


Our research aims to evaluate gut microbiota changes in relation to clinical improvements in weight and remission of type 2 diabetes after 2 contrasting bariatric surgeries – Sleeve Gastrectomy (SG) and Roux en Y Gastric Bypass (RYGB). This project will utilise DEXA scan and energy expenditure data, OGTT samples, fecal samples, food diaries and satiety questionnaires collected from patients receiving either SG or RYGB, at baseline, 1 year and 5 years post op to analyse these effects in relation to changes in satiety, resting energy expenditure, body composition, inflammatory markers and gut hormones.

Dietary fibre intake affects how gut microbiota respond to a prebiotic

Genelle Healey (PhD student), Jane Coad, Rinki Murphy, Chrissie Butts and Louise Brough.
Influence of habitual dietary fibre intake on the responsiveness of the gut microbiota to a prebiotic, 2014-2017.

Dysbiotic gut microbiota have been implicated in human disease. Diet-based therapeutic strategies have been utilised to manipulate the gut microbiota towards a more favourable profile. However, it has been demonstrated that large inter-individual variability in gut microbiota response to a dietary intervention exist. An in vitro three-stage continuous culture system experiment and a randomised, double-blind, placebo-controlled, cross-over study were undertaken to investigate whether low versus high dietary fibre intakes influence how the gut microbiota respond to a fructan-based prebiotic using an in vitro and via a randomised clinical trial. Our results show that habitual dietary fibre intakes influence how the gut microbiota respond to a prebiotic. Future studies aiming to modulate the gut microbiota should take habitual dietary fibre intake into account.

The impact of fasting and prebiotics in prediabetic obesity

Elise Penning (Masters student), Rinki Murphy and Lindsay Plank. 
The Profast Feasibility Study: Probiotics and intermittent fasting trial to improve prediabetes. 2016-2017.

Our study is designed to examine the efficacy of intermittent fasting (IF), with or without probiotic supplementation using Lactobacillus rhamnosus, in obese adults with prediabetes, to improve glucose control and weight. This feasibility study will evaluate the adherence and acceptability of IF and the efficacy of probiotics combined with IF in 44 participants of different ethnic groups with prediabetes randomised to IF with lactobacillus rhamnosus HN001 dose 6x109 or matching placebo supplementation daily. Food diaries, satiety questionnaires, blood samples during an oral glucose tolerance test, for gut hormones and inflammatory markers will be collected, along with resting energy expenditure, MRI and MRS for pancreatic and liver fat, resting energy expenditure, and fecal samples for gut microbiota analysis to evaluate any differences between the two groups.

Controlling enterococci in the gut

Enterococci

Jocelyn Griffith (Postdoctoral Fellow), Xochitl Morgan and James Ussher, funded by a University of Otago research grant.

Enterococci are commensal occupants of the human gut and are present at low levels (< 1%) in many people. However, antibiotic treatment, particularly broad-spectrum or long-term, can cause Enterococcus overgrowth. Higher Enterococcus overgrowth is associated with a variety of negative outcomes, including translocation from the gut, bloodstream infection, and increased likelihood of graft versus host disease. This research project will analyse the ability of commensal gut microbial communities in healthy populations to inhibit the growth of Enterococcus by producing inhibitory substances. A chemostat will be used as a model system for next-generation sequencing characterisation of the simplest model human gut community that can eliminate an Enterococcus challenge.

The impact of enteric protistan parasites on gut microbiota

John YASON (Postdoc), Chin Wen PNG (Postdoc), Yi Ran LIANG (BSc Honours Student), YL Zhang, KSW Tan, National University of Singapore, funded by a National University of Singapore Seed Grant.

Our research on the gut microbiome focusses on the role of the ubiquitous protistan parasite Blastocystis on the microbiota and host response. There is much controversy on whether the protist contributes to dysbiosis or is an indicator of a healthy gut. Our research seeks to resolve the conflicting data with unique in vitro platforms and animal models. Recent data suggests that pathogenic outcomes are strain dependent, and current projects seek to characterize the molecular mechanisms involved in Blastocystis-microbiota-host interactions. Another related interest is the role of Blastocystis in colorectal cancer (CRC). There is accumulating data suggesting that the protist plays a role in CRC and our projects seek to understand the molecular mechanisms underlying Blastocystis-CRC pathology.

A new pathway to obesity prevention and metabolic health

Bernhard Breier, Rozanne Kruger, Jeroen Douwes, Ridvan Firestone, Gerald Tannock, Anne-Thea McGill, Lisa Te Morenga, Leigh Signal, Philippa Gander, Stephen Stannard, Blair Lawley, Moana Manukia, Marilize Richter, and Niamh Brennan. PhD students Sophie Kindleysides, Jo Slater and Nikki Renall. MSc students Lizzie Cullen, Bronte Anscombe, Shivon Singh, Beatrice Drury and Laura Mickleson.
The PROMISE Study (PRedictors linking Obesity and gut MIcrobiomE) aka The gut microbiome: a new pathway to obesity prevention and metabolic health, funded by the Health Research Council of New Zealand.

The prevalence of obesity has increased substantially over recent decades and interventions to halt the epidemic have been unsuccessful. Although the causes of obesity are complex, key drivers include the over-consumption of highly palatable energy-dense and nutrient-poor foods. These dietary changes have had a profound impact on our gut microbiome, which comprises the bacterial community of the bowel. Tantalising new evidence suggests that microbial complexity and functionality in the gut may play a crucial role in obesity. In the proposed study we will characterise the gut microbiome in two populations with markedly different metabolic disease risk (Pacific and European women) and different body fat profiles (normal and obese). We will test whether taste perception, diet, sleep and physical activity are key pathways that modify the gut microbiome and its impact on obesity. This new knowledge will help us understand obesity and how best to prevent it. Study website: www.massey.ac.nz/promise

Gut parasites as a cause of dysbiosis

Blastocystis and E. coliTan, K.S.W.; Zhang, Y.L.; and Chen, J.
Interactions of the Ubiquitous Intestinal Protist Blastocystis with Host Microbiota: Implications for Dysbiosis. Funded by a Ministry of Education Academic Research Fund Tier-1 Grant.

Blastocystis is a ubiquitous enteric protist that inhabits the large intestine. It is estimated that there are approximately 1 billion infections globally, and 4% of individuals in Singapore harbour the parasite. Although the clinical importance of Blastocystis is considered controversial, it has been associated with several gastrointestinal diseases that include mucus diarrhoea, gastroenteritis and irritable bowel syndrome (IBS). IBS is a functional disorder that has been linked to disruption in the normal gut microbiota. There are accumulating reports indicating that the parasite is associated with changes in microbiota composition of the gut, but a causal link has not been established. Our preliminary experiments suggest that Blastocystis is able to destabilize representative members of the microbiota. This project aims to explore in vitro and in vivo effects of Blastocystis on these prokaryotic organisms with detailed investigations on the processes which are implicated in microbiota disruption, including parasite and parasite-induced host factors. Parasite secreted compounds and metabolites will also be identified as well as underlying mechanisms that could explain the parasite’s contribution to gut dysbiosis. We have recently established an experimental infection model for Blastocystis in C57BL/6 mice and show that the parasite is able to cause significant pathology in mouse colonocytes. We intend to leverage on this platform to study microbiota changes during acute Blastocystis infection. The results of this study will help to clarify the role of Blastocystis in gut homeostasis with emphasis on its effects on gut microbiota populations.