Substitution of Refined Conventional Wheat Flour with Wheat High in Resistant Starch Modulates the Intestinal Microbiota and Fecal Metabolites in Healthy Adults: A Randomized, Controlled Trial.

BACKGROUND: Resistant starch (RS) confers many health benefits, mostly through the microbial production of SCFAs, but foods containing appreciable RS are limited. High-amylose wheat (HAW) is high in RS and lowers the glycemic response of foods, but whether it can improve gastrointestinal health measures is unknown. OBJECTIVES: The objective of this study was to determine whether daily consumption of HAW food products improved markers of gastrointestinal health in healthy men and women compared with similar foods made from conventional wheat. METHODS: Eighty healthy adults (47 women and 33 men) were enrolled in a 4-arm parallel, randomized-controlled, double-blind trial. After a 2-wk low-dietary fiber run-in period, they were randomly allocated to 1 of 4 treatment groups: low-amylose wheat (LAW)-refined (LAW-R), LAW-wholemeal (LAW-W), HAW-refined (HAW-R), and HAW-wholemeal (HAW-W) and consumed the assigned test bread (160 g/d) and biscuits (75 g/d) for 4 wk. Fecal biochemical markers were measured at baseline and 4 wk. Microbial abundance and diversity were quantified using 16S ribosomal RNA sequencing and perceived gut comfort by a semiquantitative questionnaire completed at baseline, 2 wk, and 4 wk. RESULTS: HAW showed similar effects on fecal output and excretion of total SCFA compared with LAW, but changes were observed in secondary measures for the refined treatment groups. At 4 wk, the HAW-R group had 38% higher fecal butyrate excretion than the LAW-R group (P < 0.05), and higher fecal SCFA-producing bacteria, Roseburia inulinivorans (P < 0.001), than at baseline. In comparison with baseline, LAW-R increased fecal p-cresol concentration, and fecal abundance of a p-cresol-producing bacterium, Clostridium from the Peptostreptococcaceae family, but both were reduced by HAW-R. Amylose level did not affect measures of fecal consistency or adversely affecting digestive comfort. CONCLUSIONS: Increasing RS intake of healthy adults by substituting refined conventional wheat with refined HAW modulates fecal metabolites and microbes associated with gastrointestinal health.This trial was registered at anzctr.org.au as ACTRN12618001060235.

Precision health in behaviour change interventions: A scoping review.

Precision health seeks to optimise behavioural interventions by delivering personalised support to those in need, when and where they need it. Conceptualised a decade ago, progress toward this vision of personally relevant and effective population-wide interventions continues to evolve. This scoping review aimed to map the state of precision health behaviour change intervention research. This review included studies from a broader precision health review. Six databases were searched for studies published between January 2010 and June 2020, using the terms 'precision health' or its synonyms, and including an intervention targeting modifiable health behaviour(s) that was evaluated experimentally. Thirty-one studies were included, 12 being RCTs (39%), and 17 with weak study design (55%). Most interventions targeted physical activity (27/31, 87%) and/or diet (24/31, 77%), with 74% (23/31) targeting two to four health behaviours. Interventions were personalised via human interaction in 55% (17/31) and digitally in 35% (11/31). Data used for personalising interventions was largely self-reported, by survey or diary (14/31, 45%), or digitally (14/31, 45%). Data was mostly behavioural or lifestyle (20/31, 65%), and physiologic, biochemical or clinical (15/31, 48%), with no studies utilising genetic/genomic data. This review demonstrated that precision health behaviour change interventions remain dependent on human-led, low-tech personalisation, and have not fully considered the interaction between behaviour and the social and environmental contexts of individuals. Further research is needed to understand the relationship between personalisation and intervention effectiveness, working toward the development of sophisticated and scalable behaviour change interventions that have tangible public health impact.

Synbiotic supplementation with prebiotic green banana resistant starch and probiotic Bacillus coagulans spores ameliorates gut inflammation in mouse model of inflammatory bowel diseases.

PURPOSE: The research goal is to develop dietary strategies to help address the growing incidence of inflammatory bowel diseases (IBD). This study has investigated the effectiveness of green banana resistant starch (GBRS) and probiotic Bacillus coagulans MTCC5856 spores for the amelioration of dextran-sulfate sodium (DSS)-induced colitis in mice. METHODS: Eight-week-old C57BL/6 mice were fed standard rodent chow diet supplemented with either B. coagulans, GBRS or its synbiotic combination. After 7 days supplementation, colitis was induced by adding 2% DSS in drinking water for 7 days while continuing the supplemented diets. Animal health was monitored and after 14 days all animals were sacrificed to measure the biochemical and histochemical changes associated with each supplement type. RESULTS: The disease activity index and histological damage score for DSS-control mice (6.1, 17.1, respectively) were significantly higher (p < 0.0001) than the healthy mice. Synbiotic supplementation alleviated these markers (- 67%, - 94% respectively) more adequately than B. coagulans (- 52%, - 58% respectively) or GBRS (- 57%, - 26%, respectively) alone. Compared to DSS-control synbiotic supplementation significantly (p < 0.0001) maintained expressions of tight junction proteins. Moreover, synbiotic effects accounted for ~ 40% suppression of IL-1ß and ~ 29% increase in IL-10 levels in serum while also reducing C-reactive protein (- 37%) compared to that of the DSS-control. While, B. coagulans alone could not induce additional levels of short-chain fatty acid (SCFA) production beyond the caecum, the synbiotic combination with GBRS resulted in substantial increased SCFA levels across the whole length of the colon. CONCLUSION: The synbiotic supplementation with B. coagulans and GBRS ameliorated the overall inflammatory status of the experimental IBD model via synergistic functioning. This supports researching its application in mitigating inflammation in human IBD.

The Australian Research Council Longevity Intervention (ARCLI) study protocol (ANZCTR12611000487910) addendum: neuroimaging and gut microbiota protocol.

BACKGROUND: The Australian Research Council Longevity Intervention (ARCLI) was designed to investigate the effects of two active supplements, Pycnogenol and Bacopa monnieri (CDRI08) on cognitive performance in a cohort of elderly participants. An additional antioxidant supplement has been included into the trial. A neuroimaging component has also been added to the ARCLI study to investigate the neurochemical biomarkers of oxidative stress in vivo, as well as structural and functional changes associated with ageing and oxidative stress. Faecal biomarkers of gut microflora will also be analysed to investigate if gut microbiota are associated with domains of cognition (e.g., attention, processing speed, memory), mood or other ARCLI outcome variables. The aim of this paper is to update the published methods of the ARCLI clinical trial before it is completed, and data analysis commences. METHODS: ARCLI is a randomised, placebo controlled, double-blind, now 4-arm clinical trial including neuroimaging and gut microflora sub-studies. Along with the demographic, haematological, mood, cardiovascular and cognitive assessments described in the initial protocol, 80 eligible participants from the overall study pool of ~ 400 will be recruited into the neuroimaging study and undergo scans at baseline, 3 months and 12 months. Proton magnetic resonance spectroscopy, resting state functional connectivity and arterial spin labelled perfusion sequences are neuroimaging techniques included for each MRI visit in the study. Similarly, approximately 300 participants from the main study pool will be recruited to provide faecal samples at baseline, 3 months and 12 months so that the gut microbiome can be studied. DISCUSSION: ARCLI is 12-month intervention study, currently underway with a group of older adults, investigating a range of outcomes and their association with ageing. The additional measurements in the ARCLI trial will further the understanding of the underlying mechanisms associated with healthy ageing and may provide insights into novel preventative therapeutic strategies for maintaining cognitive and brain health into old age. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000487970 .

Genetic variation associated with hypersensitivity to mercury.

OBJECTIVES: Very little is known about mechanisms of idiosyncratic sensitivity to the damaging effects of mercury (Hg); however, there is likely a genetic component. The aim of the present study was to search for genetic variation in genes thought to be involved in Hg metabolism and transport in a group of individuals identified as having elevated Hg sensitivity compared to a normal control group. MATERIALS AND METHODS: Survivors of pink disease (PD; infantile acrodynia) are a population of clinically identifiable individuals who are Hg sensitive. In the present study, single nucleotide polymorphisms in genes thought to be involved in Hg transport and metabolism were compared across two groups: (i) PD survivors (n = 25); and (ii) age- and sex-matched healthy controls (n = 25). RESULTS: Analyses revealed significant differences between groups in genotype frequencies for rs662 in the gene encoding paraoxanase 1 (PON1) and rs1801131 in the gene encoding methylenetetrahydrofolate reductase (MTHFR). CONCLUSIONS: We have identified two genetic polymorphisms associated with increased sensitivity to Hg. Genetic variation in MTHFR and PON1 significantly differentiated a group formerly diagnosed with PD (a condition of Hg hypersensitivity) with age- and gender-matched healthy controls.

Defining precision health: a scoping review protocol.

INTRODUCTION: Precision health is a nascent field of research that would benefit from clearer operationalisation and distinction from adjacent fields like precision medicine. This clarification is necessary to enable precision health science to tackle some of the most complex and significant health problems that are faced globally. There is a pressing need to examine the progress in human precision health research in the past 10 years and analyse this data to first, find similarities and determine discordances in how precision health is operationalised in the literature and second, identify gaps and future directions for precision health research. METHODS AND ANALYSIS: To define precision health and map research in this field, a scoping review will be undertaken and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Scoping Review Extension guidelines. Systematic searches of scientific databases (Medline, Embase, Scopus, Web of Science and PsycINFO) and grey literature sources (Google Scholar, Google Patents) identified 8053 potentially eligible articles published from 1 January 2010 to 30 June 2020. Following removal of duplicates, a total of 3190 articles were imported for screening. Article data will be extracted using a customised extraction template on Covidence and analysed descriptively using narrative synthesis. ETHICS AND DISSEMINATION: Ethics approval is not required. Findings will be disseminated through professional networks, conference presentations and publication in a scientific journal.

The Relationship between Gut Microbiome and Cognition in Older Australians.

Ageing is associated with changes in biological processes, including reductions in cognitive functions and gut microbiome diversity. However, not much is known about the relationship between cognition and the microbiome with increasing age. Therefore, we examined the relationship between the gut microbiome and cognition in 69 healthy participants aged 60-75 years. The gut microbiome was analysed with the 16S rRNA sequencing method. The cognitive assessment included the Cognitive Drug Research computerised assessment battery, which produced five cognitive factors corresponding to 'Quality of Episodic Secondary Memory', 'Quality of Working Memory', 'Continuity of Attention, 'Speed of Memory' and 'Power of Concentration'. Multiple linear regression showed that the bacterial family Carnobacteriaceae explained 9% of the variance in predicting Quality of Episodic Secondary Memory. Alcaligenaceae and Clostridiaceae explained 15% of the variance in predicting Quality of Working Memory; Bacteroidaceae, Barnesiellaceae, Rikenellaceae and Gemellaceae explained 11% of the variance in Power of Concentration. The present study provides specific evidence of a relationship between specific families of bacteria and different domains of cognition.

Trends and gaps in precision health research: a scoping review.

OBJECTIVE: To determine progress and gaps in global precision health research, examining whether precision health studies integrate multiple types of information for health promotion or restoration. DESIGN: Scoping review. DATA SOURCES: Searches in Medline (OVID), PsycINFO (OVID), Embase, Scopus, Web of Science and grey literature (Google Scholar) were carried out in June 2020. ELIGIBILITY CRITERIA: Studies should describe original precision health research; involve human participants, datasets or samples; and collect health-related information. Reviews, editorial articles, conference abstracts or posters, dissertations and articles not published in English were excluded. DATA EXTRACTION AND SYNTHESIS: The following data were extracted in independent duplicate: author details, study objectives, technology developed, study design, health conditions addressed, precision health focus, data collected for personalisation, participant characteristics and sentence defining 'precision health'. Quantitative and qualitative data were summarised narratively in text and presented in tables and graphs. RESULTS: After screening 8053 articles, 225 studies were reviewed. Almost half (105/225, 46.7%) of the studies focused on developing an intervention, primarily digital health promotion tools (80/225, 35.6%). Only 28.9% (65/225) of the studies used at least four types of participant data for tailoring, with personalisation usually based on behavioural (108/225, 48%), sociodemographic (100/225, 44.4%) and/or clinical (98/225, 43.6%) information. Participant median age was 48 years old (IQR 28-61), and the top three health conditions addressed were metabolic disorders (35/225, 15.6%), cardiovascular disease (29/225, 12.9%) and cancer (26/225, 11.6%). Only 68% of the studies (153/225) reported participants' gender, 38.7% (87/225) provided participants' race/ethnicity, and 20.4% (46/225) included people from socioeconomically disadvantaged backgrounds. More than 57% of the articles (130/225) have authors from only one discipline. CONCLUSIONS: Although there is a growing number of precision health studies that test or develop interventions, there is a significant gap in the integration of multiple data types, systematic intervention assessment using randomised controlled trials and reporting of participant gender and ethnicity. Greater interdisciplinary collaboration is needed to gather multiple data types; collectively analyse big and complex data; and provide interventions that restore, maintain and/or promote good health for all, from birth to old age.

An Integrated Multi-Disciplinary Perspectivefor Addressing Challenges of the Human Gut Microbiome.

Our understanding of the human gut microbiome has grown exponentially. Advances in genome sequencing technologies and metagenomics analysis have enabled researchers to study microbial communities and their potential function within the context of a range of human gut related diseases and disorders. However, up until recently, much of this research has focused on characterizing the gut microbiological community structure and understanding its potential through system wide (meta) genomic and transcriptomic-based studies. Thus far, the functional output of these microbiomes, in terms of protein and metabolite expression, and within the broader context of host-gut microbiome interactions, has been limited. Furthermore, these studies highlight our need to address the issues of individual variation, and of samples as proxies. Here we provide a perspective review of the recent literature that focuses on the challenges of exploring the human gut microbiome, with a strong focus on an integrated perspective applied to these themes. In doing so, we contextualize the experimental and technical challenges of undertaking such studies and provide a framework for capitalizing on the breadth of insight such approaches afford. An integrated perspective of the human gut microbiome and the linkages to human health will pave the way forward for delivering against the objectives of precision medicine, which is targeted to specific individuals and addresses the issues and mechanisms in situ.

Modulating the Microbiome and Immune Responses Using Whole Plant Fibre in Synbiotic Combination with Fibre-Digesting Probiotic Attenuates Chronic Colonic Inflammation in Spontaneous Colitic Mice Model of IBD.

A probiotic and prebiotic food ingredient combination was tested for synergistic functioning in modulation of the colonic microbiome and remediation of the gastrointestinal immune and inflammatory responses in a spontaneous colitic mouse model. Bacillus coagulans MTCC5856 spores with capability to metabolise complex plant polysaccharides were supplemented with complex whole-plant prebiotic sugarcane fibre (PSCF). The combined and individual efficacies were tested for their influence on the outcomes of chronic inflammation in Muc2 mutant colitic Winnie mice. The mice were fed normal chow diet supplemented with either ingredient or a combination for 21 days. Synbiotic combined supplementation ameliorated clinical symptoms and histological colonic damage scores more effectively than either B. coagulans or PSCF alone. PSCF and B. coagulans alone also induced considerable immunomodulatory effects. Synbiotic supplementation however was the most efficacious in modulating the overall immune profile compared to the unsupplemented Winnie-control. The augmented synbiotic effect could potentially be due to a combination of increased levels of fermentation products, direct immune-modulating abilities of the components, their capability to reduce colonic epithelial damage and/or modulation of the microbiota. The beneficial effects of the supplementation with a complex plant fibre and a fibre-degrading probiotic parallel the effects seen in human microbiota with high plant fibre diets.

Gut microbiota and bipolar disorder: a review of mechanisms and potential targets for adjunctive therapy.

There is increasing evidence that connections formed between microbiome, the gut, and the brain play a role in health and well-being. Non-pharmaceutical targets for management of mood disorders, such as bipolar disorder, are relatively under-researched. At the same time, it is clear that there is an intimate connection between psychiatry and gastrointestinal health. Here, we have discussed various comorbid conditions associated with bipolar disorders such as inflammation, irritable bowel disease and antibiotic induced mania with importance to demonstrate possible involvement of the gut microbiota. Gut microbiota-targeted preclinical and clinical interventions have demonstrated enhancement in various psychological conditions. Further in this review, we explore links between bipolar disorder, inflammation and gut microbiome with a focus on dietary, pro- and pre-biotic interventions as potential adjuvant therapies for use in the management of mood disorders such as bipolar disorder.

The microbiome and cognitive aging: a review of mechanisms.

Gut microbiota plays an intrinsic role in communication between the gut and the brain and is capable of influencing the host brain by producing neurotransmitters and neurotrophins, the modulation of inflammatory processes amongst other key mechanisms. Increased age is also associated with changes in these key biological processes and impairments in a range of cognitive processes. We hypothesise several mechanisms in which gut microbiota may modulate changes in cognitive function with age. In this review, we discuss issues related to the measurement of cognition in the elderly and in particular outline a standardised model of cognition that could be utilised to better understand cognitive outcomes in future studies examining the relationship between gut microbiota and cognition in the elderly. We then review biological processes such as oxidative stress and inflammation which are related to cognitive changes with age and which are also influenced by our gut microbiota. Finally, we outline other potential mechanisms by which the gut microbiota may influence cognition.

Synbiotic Supplementation Containing Whole Plant Sugar Cane Fibre and Probiotic Spores Potentiates Protective Synergistic Effects in Mouse Model of IBD.

Inflammatory bowel diseases (IBD) are a chronic inflammatory disorders with increasing global incidence. Synbiotic, which is a two-point approach carrying probiotic and prebiotic components in mitigating inflammation in IBD, is thought to be a pragmatic approach owing to the synergistic outcomes. In this study, the impacts of dietary supplementation with probiotic Bacillus coagulans MTCC5856 spores (B. coagulans) and prebiotic whole plant sugar cane fibre (PSCF) was assessed using a murine model of IBD. Eight-week-old C57BL/6 mice were fed a normal chow diet supplemented with either B. coagulans, PSCF or its synbiotic combination. After seven days of supplementation, colitis was induced with dextran sulfate sodium (DSS) in drinking water for seven days during the continuation of the supplemented diets. Synbiotic supplementation ameliorated disease activity index and histological score (-72%, 7.38, respectively), more effectively than either B. coagulans (-47%, 10.1) and PSCF (-53%, 13.0) alone. Synbiotic supplementation also significantly (p < 0.0001) prevented the expression of tight junction proteins and modulated the altered serum IL-1ß (-40%), IL-10 (+26%), and C-reactive protein (CRP) (-39%) levels. Synbiotic supplementations also raised the short-chain fatty acids (SCFA) profile more extensively compared to the unsupplemented DSS-control. The synbiotic health outcome effect of the probiotic and prebiotic combinations may be associated with a synergistic direct immune-regulating efficacy of the components, their ability to protect epithelial integrity, stimulation of probiotic spores by the prebiotic fibre, and/or with stimulation of greater levels of fermentation of fibres releasing SCFAs that mediate the reduction in colonic inflammation. Our model findings suggest synbiotic supplementation should be tested in clinical trials.

Lactobacillus acidophilus DDS-1 Modulates Intestinal-Specific Microbiota, Short-Chain Fatty Acid and Immunological Profiles in Aging Mice.

Distribution of the microbiota varies according to the location in the gastrointestinal (GI) tract. Thus, dysbiosis during aging may not be limited to faecal microbiota and extend to the other parts of the GI tract, especially the cecum and colon. Lactobacillus acidophilus DDS-1, a probiotic strain, has been shown to modulate faecal microbiota and its associated metabolic phenotype in aging mice. In the present study, we investigated the effect of L. acidophilus DDS-1 supplementation on caecal- and mucosal-associated microbiota, short-chain fatty acids (SCFAs) and immunological profiles in young and aging C57BL/6J mice. Besides differences in the young and aging control groups, we observed microbial shifts in caecal and mucosal samples, leading to an alteration in SCFA levels and immune response. DDS-1 treatment increased the abundances of beneficial bacteria such as Akkermansia spp. and Lactobacillus spp. more effectively in caecal samples than in mucosal samples. DDS-1 also enhanced the levels of butyrate, while downregulating the production of inflammatory cytokines (IL-6, IL-1ß, IL-1α, MCP-1, MIP-1α, MIP-1ß, IL-12 and IFN-γ) in serum and colonic explants. Our findings suggest distinct patterns of intestinal microbiota, improvements in SCFA and immunological profiles with DDS-1 supplementation in aging mice.

Oxaliplatin-induced changes in microbiota, TLR4+ cells and enhanced HMGB1 expression in the murine colon.

Oxaliplatin is a platinum-based chemotherapeutic used for cancer treatment. Its use associates with peripheral neuropathies and chronic gastrointestinal side-effects. Oxaliplatin induces immunogenic cell death by provoking the presentation of damage associated molecular patterns. The damage associated molecular patterns high-mobility group box 1 (HMGB1) protein exerts pro-inflammatory cytokine-like activity and binds to toll-like receptors (namely TLR4). Gastrointestinal microbiota may influence chemotherapeutic efficacy and contribute to local and systemic inflammation. We studied effects of oxaliplatin treatment on 1) TLR4 and high-mobility group box 1 expression within the colon; 2) gastrointestinal microbiota composition; 3) inflammation within the colon; 4) changes in Peyer's patches and mesenteric lymph nodes immune populations in mice. TLR4+ cells displayed pseudopodia-like extensions characteristic of antigen sampling co-localised with high-mobility group box 1 -overexpressing cells in the colonic lamina propria from oxaliplatin-treated animals. Oxaliplatin treatment caused significant reduction in Parabacteroides and Prevotella1, but increase in Prevotella2 and Odoribacter bacteria at the genus level. Downregulation of pro-inflammatory cytokines and chemokines in colon samples, a reduction in macrophages and dendritic cells in mesenteric lymph nodes were found after oxaliplatin treatment. In conclusion, oxaliplatin treatment caused morphological changes in TLR4+ cells, increase in gram-negative microbiota and enhanced HMGB1 expression associated with immunosuppression in the colon.

Lactobacillus acidophilus DDS-1 Modulates the Gut Microbiota and Improves Metabolic Profiles in Aging Mice.

Recent evidence suggests that gut microbiota shifts can alter host metabolism even during healthy aging. Lactobacillus acidophilus DDS-1, a probiotic strain, has shown promising probiotic character in vitro, as well as in clinical studies. The present study was carried out to investigate whether DDS-1 can modulate the host metabolic phenotype under the condition of age-affected gut microbial shifts in young and aging C57BL/6J mice. Collected fecal samples were analyzed using 16S rRNA gene sequencing for identifying gut microbiota and untargeted gas chromatography-mass spectrometry (GC-MS) metabolomics analysis. Gut microbial shifts were observed in the control groups (young and aging), leading to an alteration in metabolism. Principal coordinate analysis (PCoA) of microbiota indicated distinct separation in both the DDS-1-treated groups. L. acidophilus DDS-1 increased the relative abundances of beneficial bacteria, such as Akkermansia muciniphila and Lactobacillus spp., and reduced the relative levels of opportunistic bacteria such as Proteobacteria spp. Metabolic pathway analysis identified 10 key pathways involving amino acid metabolism, protein synthesis and metabolism, carbohydrate metabolism, and butanoate metabolism. These findings suggest that modulation of gut microbiota by DDS-1 results in improvement of metabolic phenotype in the aging mice.

Anti-Stress, Behavioural and Magnetoencephalography Effects of an L-Theanine-Based Nutrient Drink: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial.

L-theanine (γ-glutamylethylamide) is an amino acid found primarily in the green tea plant. This study explored the effects of an L-theanine-based nutrient drink on mood responses to a cognitive stressor. Additional measures included an assessment of cognitive performance and resting state alpha oscillatory activity using magnetoencephalography (MEG). Thirty-four healthy adults aged 18-40 participated in this double-blind, placebo-controlled, balanced crossover study. The primary outcome measure, subjective stress response to a multitasking cognitive stressor, was significantly reduced one hour after administration of the L-theanine drink when compared to placebo. The salivary cortisol response to the stressor was reduced three hours post-dose following active treatment. No treatment-related cognitive performance changes were observed. Resting state alpha oscillatory activity was significantly greater in posterior MEG sensors after active treatment compared to placebo two hours post-dose; however, this effect was only apparent for those higher in trait anxiety. This change in resting state alpha oscillatory activity was not correlated with the change in subjective stress response or the cortisol response, suggesting further research is required to assess the functional relevance of these treatment-related changes in resting alpha activity. These findings further support the anti-stress effects of L-theanine.

Fecal Microbiota and Metabolome in a Mouse Model of Spontaneous Chronic Colitis: Relevance to Human Inflammatory Bowel Disease.

BACKGROUND: Dysbiosis of the gut microbiota may be involved in the pathogenesis of inflammatory bowel disease (IBD). However, the mechanisms underlying the role of the intestinal microbiome and metabolome in IBD onset and its alteration during active treatment and recovery remain unknown. Animal models of chronic intestinal inflammation with similar microbial and metabolomic profiles would enable investigation of these mechanisms and development of more effective treatments. Recently, the Winnie mouse model of colitis closely representing the clinical symptoms and characteristics of human IBD has been developed. In this study, we have analyzed fecal microbial and metabolomic profiles in Winnie mice and discussed their relevance to human IBD. METHODS: The 16S rRNA gene was sequenced from fecal DNA of Winnie and C57BL/6 mice to define operational taxonomic units at ≥97% similarity threshold. Metabolomic profiling of the same fecal samples was performed by gas chromatography-mass spectrometry. RESULTS: Composition of the dominant microbiota was disturbed, and prominent differences were evident at all levels of the intestinal microbiome in fecal samples from Winnie mice, similar to observations in patients with IBD. Metabolomic profiling revealed that chronic colitis in Winnie mice upregulated production of metabolites and altered several metabolic pathways, mostly affecting amino acid synthesis and breakdown of monosaccharides to short chain fatty acids. CONCLUSIONS: Significant dysbiosis in the Winnie mouse gut replicates many changes observed in patients with IBD. These results provide justification for the suitability of this model to investigate mechanisms underlying the role of intestinal microbiota and metabolome in the pathophysiology of IBD.

A randomized controlled trial investigating the neurocognitive effects of Lacprodan® PL-20, a phospholipid-rich milk protein concentrate, in elderly participants with age-associated memory impairment: the Phospholipid Intervention for Cognitive Ageing Reversal (PLICAR): study protocol for a randomized controlled trial.

BACKGROUND: Age-related cognitive decline (ARCD) is of major societal concern in an ageing population, with the development of dietary supplements providing a promising avenue for amelioration of associated deficits. Despite initial interest in the use of phospholipids (PLs) for ARCD, in recent years there has been a hiatus in such research. Because of safety concerns regarding PLs derived from bovine cortex, and the equivocal efficacy of soybean-derived PLs, there is an important need for the development of new PL alternatives. Phospholipids derived from milk proteins represent one potential candidate treatment. METHODS: In order to reduce the effects of age-associated memory impairment (AAMI) the Phospholipid Intervention for Cognitive Ageing Reversal (PLICAR) was developed to test the efficacy of a milk protein concentrate rich in natural, non-synthetic milk phospholipids (Lacprodan® PL-20). PLICAR is a randomized, double-blind, placebo-controlled parallel-groups study where 150 (N = 50/group) AAMI participants aged > 55 years will be randomized to receive a daily supplement of Lacprodan® PL-20 or one of two placebos (phospholipid-free milk protein concentrate or inert rice starch) over a 6-month (180-day) period. Participants will undergo testing at baseline, 90 days and 180 days. The primary outcome is a composite memory score from the Rey Auditory Verbal Learning Test. Secondary outcomes include cognitive (verbal learning, working memory, prospective and retrospective memory, processing speed and attention), mood (depression, anxiety, stress and visual analogue scales), cardiovascular (blood pressure, blood velocity and pulse wave pressure), gastrointestinal microbiota and biochemical measures (oxidative stress, inflammation, B vitamins and Homocysteine, glucoregulation and serum choline). Allelic differences in the Apolipoprotein E and (APOE) and Methylenetetrahydrofolate reductase (MTHFR) gene will be included for subgroup analysis. A subset (N = 60; 20/group)) will undergo neuroimaging using functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in order to further explore in vivo central mechanisms of action of Lacprodan® PL-20. This study will enable evaluation of the efficacy of milk-derived phospholipids for AAMI, and their mechanisms of action. TRIAL REGISTRATION: The trial is jointly funded by Arla Foods and Swinburne University of Technology, currently recruiting and is registered on the Australian New Zealand Clinical Trials Registry as ACTRN12613000347763.

Molecular characterisation of gastrointestinal microbiota of children with autism (with and without gastrointestinal dysfunction) and their neurotypical siblings.

Many children with autism spectrum disorders (ASDs) suffer from gastrointestinal problems such as diarrhoea, constipation and abdominal pain. This has stimulated investigations into possible abnormalities of intestinal microbiota in autistic patients. Therefore, we designed this study to identify differences (and/or similarities) in the microbiota of children with autism (without gastrointestinal dysfunction: n = 23; with gastrointestinal dysfunction: n = 28) and their neurotypical siblings (n = 53) who share a similar environment using bacterial tag-encoded FLX amplicon pyrosequencing. Regardless of the diagnosis and sociodemographic characteristics, overall, Firmicutes (70%), Bacteroidetes (20%) and Proteobacteria (4%) were the most dominant phyla in samples. Results did not indicate clinically meaningful differences between groups. The data do not support the hypothesis that the gastrointestinal microbiota of children with ASD plays a role in the symptomatology of ASD. Other explanations for the gastrointestinal dysfunction in this population should be considered including elevated anxiety and self-restricted diets.