Bugs as Features (Part I): Concepts and Foundations for the Compositional Data Analysis of the Microbiome-Gut-Brain Axis

There has been a growing acknowledgement of the involvement of the gut microbiome - the collection of microbes that reside in our gut - in regulating our mood and behaviour. This phenomenon is referred to as the microbiome-gut-brain axis. While our techniques to measure the presence and abundance of these microbes have been steadily improving, the analysis of microbiome data is non-trivial. Here, we present a perspective on the concepts and foundations of data analysis and interpretation of microbiome experiments with a focus on the microbiome-gut-brain axis domain. We give an overview of foundational considerations prior to commencing analysis alongside the core microbiome analysis approaches of alpha diversity, beta diversity, differential feature abundance and functional inference. We emphasize the compositional data analysis (CoDA) paradigm. Further, this perspective features an extensive and heavily annotated microbiome analysis in R in the supplementary materials, as a resource for new and experienced bioinformaticians alike.Comment: For main text: 23 pages, 3 figures; for supplementary demonstration analysis: 31 pages and 12 figures. Supplementary demonstration analysis generated using Rmarkdown by Thomaz F. S. Bastiaanssen. Part I of a two-part piec

Bugs as Features (Part II): A Perspective on Enriching Microbiome-Gut-Brain Axis Analyses with Multidisciplinary Techniques

The microbiome-gut-brain-axis field is multidisciplinary, benefiting from the expertise of microbiology, ecology, psychiatry, computational biology, and epidemiology amongst other disciplines. As the field matures and moves beyond a basic demonstration of its relevance, it is critical that study design and analysis are robust and foster reproducibility. In this companion piece to Bugs as Features (Part 1), we present techniques from adjacent and disparate fields to enrich and inform the analysis of microbiome-gut-brain-axis data. Emerging techniques built specifically for the microbiome-gut-brain axis are also demonstrated. All of these methods are contextualised to inform several common challenges: how do we establish causality? How can we integrate data from multiple 'omics techniques? How might we account for the dynamicism of host-microbiome interactions? This perspective is offered to experienced and emerging microbiome scientists alike, to assist with these questions and others, at the study conception, design, analysis and interpretation stages of research.Comment: For main text: 20 pages, 2 figures; for supplementary analysis: 31 pages and 6 figures. Supplementary analysis generated using Rmarkdown by Thomaz F. S. Bastiaanssen. arXiv admin note: substantial text overlap with arXiv:2207.1247

Diet quality and a traditional dietary pattern predict lean mass in Australian women: Longitudinal data from the Geelong Osteoporosis Study

Low muscle mass is associated with reduced independence and increased risk for falls and fractures. Identification of modifiable risk factors for low muscle mass is thus imperative. This study aimed to examine the longitudinal relationship between both diet quality and patterns and lean mass in Australian women. Data from n = 494 participants of the Geelong Osteoporosis Study's 10- and 15-year women's follow-ups were used (conducted in 2004–08 and 2011–14, respectively), and participants were aged 21–89 years. Self-reported lifestyle and demographics were collected, and food frequency questionnaire data informed the dietary exposure variables: the Australian Recommended Food Score (ARFS); the Dietary Inflammatory Index (DII); and a posteriori dietary patterns. The outcome, Skeletal Muscle Index (SMI), was calculated from DXA-derived appendicular lean mass (ALM) relative to height (ALM kg/m2). Analyses employed Generalised Estimating Equations. A higher ARFS score positively predicted SMI over 5-years, and adjustments for age and physical activity did not attenuate this relationship (B:0.044, (95%CI 0.004, 0.084) kg/m2). Following adjustment, both an anti-inflammatory diet (B:-0.034, (95%CI −0.070, −0.002) kg/m2) and a ‘traditional’ dietary pattern predicted higher SMI (B:0.081, (95%CI 0.004, 0.158) kg/m2). No other associations were observed. Our study reinforces the importance of diet quality for healthy, aging muscle mass. Furthermore, a less inflammatory diet and a diet comprising a wide variety of plant and animal foods may be conducive to maintenance of muscle mass in women. Further studies investigating diet quality's impact on various muscle health measures over longer time periods are warranted

Efficacy and safety of fecal microbiota transplantation for the treatment of diseases other than Clostridium difficile infection: a systematic review and meta-analysis

The intestinal microbiome has been identified as a key modifier for a variety of health conditions. Fecal Microbiota Transplantation (FMT) has emerged as a fast, safe, and effective means by which to modify the intestinal microbiome and potentially treat a variety of health conditions. Despite extensive research of FMT for CDI, there is a lack of clarity informed by systematic synthesis of data regarding the safety and efficacy of FMT for other health conditions. This systematic review used PRISMA guidelines and was prospectively registered with PROSPERO (CRD42018104243). In March 2020, a search of MEDLINE, EMBASE, and PsycINFO was conducted. We identified 26 eligible studies. A meta-analysis of FMT for active Ulcerative Colitis (UC) showed that FMT significantly improved rates of clinical remission (OR = 3.634, 95% CI = 1.940 to 6.808, I-2 = 0%, p< .001), clinical response (OR = 2.634, 95% CI = 1.441 to 4.815, I2 = 33%, p = .002) and endoscopic remission (OR = 4.431, 95% CI = 1.901 to 10.324, I2 = 0%, p = .001). With respect to Irritable Bowel Syndrome, a meta-analysis showed no significant change in symptoms following FMT (p = .739). Hepatic disorders, metabolic syndrome, and antibiotic-resistant organisms were conditions with emerging data on FMT. Serious adverse events (AE) were more often reported in control group participants (n = 43) compared with FMT group participants (n = 26). There were similar rates of mild to moderate AE in both groups. Preliminary data suggest that FMT is a potentially safe, well-tolerated and efficacious treatment for certain conditions other than CDI, with evidence for active UC being the most compelling

Strengthening The Organization and Reporting of Microbiome Studies (STORMS): A Reporting Checklist for Human Microbiome Research

Background Human microbiome research is a growing field with the potential for improving our understanding and treatment of diseases and other conditions. The field is interdisciplinary, making concise organization and reporting of results across different styles of epidemiology, biology, bioinformatics, translational medicine, and statistics a challenge. Commonly used reporting guidelines for observational or genetic epidemiology studies lack key features specific to microbiome studies. Methods A multidisciplinary group of microbiome epidemiology researchers reviewed elements of available reporting guidelines for observational and genetic studies and adapted these for application to culture-independent human microbiome studies. New reporting elements were developed for laboratory, bioinformatic, and statistical analyses tailored to microbiome studies, and other parts of these checklists were streamlined to keep reporting manageable. Results STORMS is a 17-item checklist for reporting on human microbiome studies, organized into six sections covering typical sections of a scientific publication, presented as a table with space for author-provided details and intended for inclusion in supplementary materials. Conclusions STORMS provides guidance for authors and standardization for interdisciplinary microbiome studies, facilitating complete and concise reporting and augments information extraction for downstream applications. Availability The STORMS checklist is available as a versioned spreadsheet from https://www.stormsmicrobiome.org/

Preventing mental health problems in children : the families in mind population-based cluster randomised controlled trial.

BackgroundExternalising and internalising problems affect one in seven school-aged children and are the single strongest predictor of mental health problems into early adolescence. As the burden of mental health problems persists globally, childhood prevention of mental health problems is paramount. Prevention can be offered to all children (universal) or to children at risk of developing mental health problems (targeted). The relative effectiveness and costs of a targeted only versus combined universal and targeted approach are unknown. This study aims to the effectiveness, costs and uptake of two approaches to early childhood prevention of mental health problems ie: a Combined universal-targeted approach, versus a Targeted only approach, in comparison to current primary care services (Usual care).DesignThree armed, population-level cluster randomised trial (2010-2014) within the universal, well child Maternal Child Health system, attended by more than 80% of families in Victoria, Australia at infant age eight months. Participants: Families of eight month old children from nine participating local government areas. Randomised to one of three groups: Combined, Targeted or Usual care. Intervention: (a) the Combined universal and targeted program where all families are offered the universal Toddlers Without Tears group parenting program followed by the targeted Family Check-Up one-on-one program or (b) the Targeted Family Check-Up program. The Family Check-Up program is only offered to children at risk of behavioural problems. Analysis: Participants will be analysed according to the trial arm to which they were randomised, using logistic and linear regression models to compare primary and secondary outcomes. An economic evaluation (cost consequences analysis) will compare incremental costs to all incremental outcomes from a societal perspective.DiscussionThis trial will inform public health policy by making recommendations about the effectiveness and cost-effectiveness of these early prevention programs. If effective prevention programs can be implemented at the population level, the growing burden of mental health problems could be curbed.<br /

Cognitive and psychosocial functioning in genetic generalised epilepsy

© 2017 Dr. Amy LoughmanGenetic generalised epilepsies (GGE) are a common, but under-studied cluster of epileptic syndromes of predominantly child and adolescent onset. The primary syndromes of GGE are childhood absence epilepsy (CAE), juvenile absence epilepsy(JAE), juvenile myoclonic epilepsy (JME), and genetic generalised epilepsy with generalised tonic-clonic seizures only (GTSCO). Important questions remain regarding: the degree of cognitive and psychopathological comorbidity, particularly in adults and in syndromes other than JME; effects of the disease on cognitive function; and psychopathology and psychosocial wellbeing in these patient groups. This thesis aimed to provide a detailed and quantitative description of cognitive function and psychopathology in GGE, assess the impact of contributing factors including subclinical epileptiform discharges on cognitive and psychopathology outcomes, and to evaluate the relationship between psychopathology and cognition. Methods employed include narrative systematic review, quantitative meta-analysis, and prospective assessment of cognitive and psychosocial functioning of a relatively large sample of people with GGE. Results indicated mild to moderately large reductions across most cognitive factors relative to that of healthy control participants and age-based normative data, with a relative weakness in long-term retrieval and memory function. Short-term memory function was not reduced relative to age-based normative data. Overall cognitive ability and memory function was negatively associated with total duration of epileptiform discharges during a 24-hour period. Approximately 50% of the sample reported elevated symptoms on a measure of psychopathology spanning six symptom types, with depression and anxiety the most common amongst these. Collectively, these findings highlight the need for increased awareness, screening and the provision of services for psychological comorbidities for people with GGE

Neuroscientific explanations and the stigma of mental disorder: a meta-analytic study

Abstract Genetic and other biological explanations appear to have mixed blessings for the stigma of mental disorder. Meta-analytic evidence shows that these “biogenetic” explanations reduce the blame attached to sufferers, but they also increase aversion, perceptions of dangerousness, and pessimism about recovery. These relationships may arise because biogenetic explanations recruit essentialist intuitions, which have known associations with prejudice and the endorsement of stereotypes. However, the adverse implications of biogenetic explanations as a set may not hold true for the subset of those explanations that invoke neurobiological causes. Neurobiological explanations might have less adverse implications for stigma than genetic explanations, for example, because they are arguably less essentialist. Although this possibility is important for evaluating the social implications of neuroscientific explanations of mental health problems, it has yet to be tested meta-analytically. We present meta-analyses of links between neurobiological explanations and multiple dimensions of stigma in 26 correlational and experimental studies. In correlational studies, neurobiological explanations were marginally associated with greater desire for social distance from people with mental health problems. In experimental studies, these explanations were associated with greater desire for social distance, greater perceived dangerousness, and greater prognostic pessimism. Neurobiological explanations were not linked to reduced blame in either set of studies. By implication, neurobiological explanations have the same adverse links to stigma as other forms of biogenetic explanation. These findings raise troubling implications about the public impact of psychiatric neuroscience research findings. Although such findings are not intrinsically stigmatizing, they may become so when viewed through the lens of neuroessentialism