From hype to hope: Considerations in conducting robust microbiome science.

Microbiome science has been one of the most exciting and rapidly evolving research fields in the past two decades. Breakthroughs in technologies including DNA sequencing have meant that the trillions of microbes (particularly bacteria) inhabiting human biological niches (particularly the gut) can be profiled and analysed in exquisite detail. This microbiome profiling has profound impacts across many fields of research, especially biomedical science, with implications for how we understand and ultimately treat a wide range of human disorders. However, like many great scientific frontiers in human history, the pioneering nature of microbiome research comes with a multitude of challenges and potential pitfalls. These include the reproducibility and robustness of microbiome science, especially in its applications to human health outcomes. In this article, we address the enormous promise of microbiome science and its many challenges, proposing constructive solutions to enhance the reproducibility and robustness of research in this nascent field. The optimisation of microbiome science spans research design, implementation and analysis, and we discuss specific aspects such as the importance of ecological principals and functionality, challenges with microbiome-modulating therapies and the consideration of confounding, alternative options for microbiome sequencing, and the potential of machine learning and computational science to advance the field. The power of microbiome science promises to revolutionise our understanding of many diseases and provide new approaches to prevention, early diagnosis, and treatment.

Novel Methods for Leveraging Large Cohort Studies for Qualitative and Mixed-Methods Research.

Qualitative research methods, while rising in popularity, are still a relatively underutilized tool in public health research. Usually reserved for small samples, qualitative research techniques have the potential to enhance insights gained from large questionnaires and cohort studies, both deepening the interpretation of quantitative data and generating novel hypotheses that might otherwise be missed by standard approaches; this is especially true where exposures and outcomes are new, understudied, or rapidly changing, as in a pandemic. However, methods for the conduct of qualitative research within large samples are underdeveloped. Here, we describe a novel method of applying qualitative research methods to free-text comments collected in a large epidemiologic questionnaire. Specifically, this method includes: 1) a hierarchical system of coding through content analysis; 2) a qualitative data management application; and 3) an adaptation of Cohen's κ and percent agreement statistics for use by a team of coders, applying multiple codes per record from a large codebook. The methods outlined in this paper may help direct future applications of qualitative and mixed methods within large cohort studies.

Challenges and priorities for researching the gut microbiota in individuals living with anorexia nervosa.

OBJECTIVE: The gut microbiota is implicated in several symptoms and biological pathways relevant to anorexia nervosa (AN). Investigations into the role of the gut microbiota in AN are growing, with a specific interest in the changes that occur in response to treatment. Findings suggest that microbial species may be associated with some of the symptoms common in AN, such as depression and gastrointestinal disturbances (GID). Therefore, researchers believe the gut microbiota may have therapeutic relevance. Whilst research in this field is rapidly expanding, the unique considerations relevant to conducting gut microbiota research in individuals with AN must be addressed. METHOD: We provide an overview of the published literature investigating the relationship between the gut microbiota and symptoms and behaviors present in AN, discuss important challenges in gut microbiota research, and offer recommendations for addressing these. We conclude by summarizing research design priorities for the field to move forward. RESULTS: Several ways exist to reduce participant burden and accommodate challenges when researching the gut microbiota in individuals with AN. DISCUSSION: Recommendations from this article are foreseen to encourage scientific rigor and thoughtful protocol planning for microbiota research in AN, including ways to reduce participant burden. Employing such methods will contribute to a better understanding of the role of the gut microbiota in AN pathophysiology and treatment. PUBLIC SIGNIFICANCE: The field of gut microbiota research is rapidly expanding, including the role of the gut microbiota in anorexia nervosa. Thoughtful planning of future research will ensure appropriate data collection for meaningful interpretation while providing a positive experience for the participant. We present current challenges, recommendations for research design and priorities to facilitate the advancement of research in this field.

Ethical Challenges in AI Approaches to Eating Disorders.

The use of artificial intelligence (AI) to assist with the prevention, identification, and management of eating disorders and body image concerns is exciting, but it is not without risk. Technology is advancing rapidly, and ensuring that responsible standards are in place to mitigate risk and protect users is vital to the success and safety of technologies and users.

Gastrointestinal symptoms following treatment for anorexia nervosa: A systematic literature review.

OBJECTIVE: Gastrointestinal (GI) disturbances are a frequent and burdensome experience for patients with anorexia nervosa (AN). How GI symptoms respond to current interventions is not well characterized, yet is critical to facilitate treatment success, and to inform the development of new treatments for AN. Therefore, the aim of this systematic review was to identify which treatments are effective in improving GI symptoms in patients with AN. METHOD: A systematic search for studies of AN treatments measuring GI symptoms pre- and post-treatment was conducted in May 2020 (PROSPERO ID: CRD42020181328). After removal of duplicates, title and abstracts of 3,370 studies were screened. Methodological quality was assessed using National Institute of Health Quality Assessment Tool. RESULTS: Following full-text screening, 13 studies (12 observational studies and 1 randomized double-blind placebo-controlled trial) with 401 participants met eligibility criteria and were included. All observational studies included a component of nutritional rehabilitation, with half (n = 6) involving concurrent psychological treatment. The randomized controlled trial reported a drug therapy. Eleven studies reported an improvement in all (n = 6) or at least one (n = 5) patient-reported GI symptom following treatment. Two studies reported no change. Methodological quality was fair or poor across all studies. DISCUSSION: This is the first systematic review to synthesize available evidence on the trajectory of patient-reported GI symptoms from commencement to end of treatment for AN. The results suggest that most studies showed improvement in one or more GI symptom in response to current treatments. Future therapeutic approaches should consider GI symptoms within their design for optimal treatment adherence and outcomes.

OBJETIVO: Las alteraciones gastrointestinales (GI) son una experiencia frecuente y gravosa para los pacientes que padecen anorexia nerviosa (AN). La forma en que los síntomas gastrointestinales responden a las intervenciones actuales no está bien caracterizada, sin embargo es fundamental para facilitar el éxito del tratamiento, e informar el desarrollo de nuevos tratamientos para la AN. Por lo tanto, el objetivo de esta revisión sistemática fue identificar qué tratamientos son eficaces para mejorar los síntomas gastrointestinales en pacientes que padecen AN. MÉTODO: En mayo de 2020 se llevó a cabo una búsqueda sistemática de estudios de tratamientos para AN que midieron los síntomas gastrointestinales antes y después del tratamiento (PROSPERO ID: CRD42020181328). Después de la eliminación de duplicados, se examinaron el título y los resúmenes de 3370 estudios. La calidad metodológica fue evaluada utilizando la Herramienta de Evaluación de la Calidad del Instituto Nacional de Salud. RESULTADOS: Después de la detección completa de texto, 13 estudios (12 estudios observacionales y un ensayo aleatorizado doble ciego controlado con placebo) con 401 participantes cumplieron con los criterios de elegibilidad y fueron incluidos. Todos los estudios observacionales incluyeron un componente de rehabilitación nutricional, con la mitad (n=6) involucrando un tratamiento psicológico simultáneo. El ensayo controlado aleatorizado reportó tratamiento farmacológico. Once studies informaron de una mejora en todos (n=6) o al menos un (n=5) paciente reportó síntomas gastrointestinales después del tratamiento. Dos estudios no reportaron ningún cambio. La calidad metodológica fue justa o pobre en todos los estudios. DISCUSIÓN: Esta es la primera revisión sistemática que sintetiza la evidencia disponible sobre la trayectoria de los síntomas GI notificados por el paciente desde el inicio hasta el final del tratamiento para la AN. Los resultados sugieren que la mayoría de los estudios mostraron mejoría en uno o más síntomas gastrointestinales en respuesta a los tratamientos actuales. Los futuros abordajes terapéuticos deben considerar los síntomas gastrointestinales dentro de su diseño para una adherencia y resultados óptimos en el tratamiento.

A systematic review and meta-analysis of 24-h urinary output of children and adolescents: impact on the assessment of iodine status using urinary biomarkers.

PURPOSE: Urinary iodine concentration (UIC (µg/ml) from spot urine samples collected from school-aged children is used to determine the iodine status of populations. Some studies further extrapolate UIC to represent daily iodine intake, based on the assumption that children pass approximately 1 L urine over 24-h, but this has never been assessed in population studies. Therefore, the present review aimed to collate and produce an estimate of the average 24-h urine volume of children and adolescents (> 1 year and < 19 years) from published studies. METHODS: EBSCOHOST and EMBASE databases were searched to identify studies which reported the mean 24-h urinary volume of healthy children (> 1 year and < 19 years). The overall mean (95% CI) estimate of 24-h urine volume was determined using a random effects model, broken down by age group. RESULTS: Of the 44 studies identified, a meta-analysis of 27 studies, with at least one criterion for assessing the completeness of urine collections, indicated that the mean urine volume of 2-19 year olds was 773 (654, 893) (95% CI) mL/24-h. When broken down by age group, mean (95% CI) 24-h urine volume was 531 mL/day (454, 607) for 2-5 year olds, 771 mL/day (734, 808) for 6-12 year olds, and 1067 mL/day (855, 1279) for 13-19 year olds. CONCLUSIONS: These results demonstrate that the average urine volume of children aged 2-12 years is less than 1 L, therefore, misclassification of iodine intakes may occur when urine volumes fall below or above 1 L. Future studies utilizing spot urine samples to assess iodine status should consider this when extrapolating UIC to represent iodine intakes of a population.

Treatment interventions for Severe and Enduring Eating Disorders: Systematic review.

OBJECTIVE: Approximately 20% of people with Anorexia Nervosa (AN) and 10% with Bulimia Nervosa (BN) will eventually develop a long-standing illness. Although there is no set definition for Severe and Enduring eating Disorder (SE-ED), the common criteria relate to a long duration of the disorder and a number of unsuccessful treatment attempts. Research evidence for treatment of SE-ED remains limited, thus the objective of this systematic review was to describe different treatment interventions and their effects on SE-ED-related outcomes. METHOD: A systematic search for quantitative treatment studies of adult participants with SE-ED was conducted in June 2019 (PROSPERO, CRD42018115802) with no restriction on eating disorder type. Altogether, 2,938 studies were included for title and abstract screening. RESULTS: After systematic searches and article screening, 23 studies (3 randomized controlled trials, 3 open-label studies, 8 naturalistic follow-up studies, 8 case series and case studies, and 1 partially blinded pilot study) were included in the analysis and data extraction. Methodological quality of the included studies was generally low. Inpatient treatment programs (n = 5) were effective in short-term symptom reduction, but long-term results were inconsistent. Outpatient and day-hospital treatment programs (n = 5) seemed promising for symptom reduction. Drug interventions (n = 5) showed some benefits, especially as adjuvant therapies. Brain stimulation (n = 6) led to improvements in depressive symptoms. Other treatments (n = 2) produced mixed results. DISCUSSION: This is the first systematic review to examine all of the different treatment interventions that have been studied in SE-ED. The results will inform future interventions in research and clinical practice.

The Digital Education to Limit Salt in the Home Program Improved Salt-Related Knowledge, Attitudes, and Behaviors in Parents.

BACKGROUND: Currently, Australian children and adults are eating too much salt, increasing their risk of cardiovascular-related conditions. Web-based programs provide an avenue to engage the parents of primary schoolchildren in salt-specific messages, which may positively impact their own salt-related knowledge, attitudes, and behaviors (KABs). OBJECTIVE: This pilot study aimed to determine whether parents' salt-related KABs improved following participation in the Digital Education to LImit Salt in the Home (DELISH) Web-based education program. METHODS: The DELISH program was a 5-week, home-delivered, Web-based intervention, with a pre- and posttest design, targeting schoolchildren aged 7 to 10 years and their parents. Parents received weekly Web-based educational newsletters and text messages and completed online pre- and postprogram surveys assessing salt-related KABs. Upon completion of the program, all parents were also invited to complete an online evaluation survey. Changes in KABs outcomes were assessed using McNemar tests and paired t tests. RESULTS: Of the 80 parents that commenced the program, 73 parents (mean age 41.0, SD 7.0 years; 86% (63/73) females) completed both pre- and postsurveys. Overall, mean score for salt-related knowledge improved (+3.6 [standard error (SE) 0.41] points), and mean behavior score also improved (+4.5 [SE 0.61] points), indicating a higher frequency of engaging in behaviors to reduce salt in the diet, and mean attitude score decreased (-0.7 [SE 0.19] points), representing lower importance of using salt to enhance the taste of food (all P<.001). Following participation, the proportion of parents aware of the daily salt intake recommendation increased from 40% (29/73) to 74% (54/73) (P<.001), and awareness of bread as the main source of salt increased from 58% (42/73) to 95% (69/73) (P<.001). The proportion of parents who agreed that salt should be used in cooking to enhance the flavor of food decreased from 30% (22/73) to 11% (8/73) (P=.002) and the proportion who agreed that sodium information displayed on food labels was difficult to understand decreased from 52% (38/73) to 32% (23/73) (P=.009). There was a reduction in the proportion of parents who reported adding salt during cooking (55% [40/73] vs 41% [30/73]; P=.03) and at the table (32% [23/73] vs 18% [13/73]; P=.002). Of the 16 parents who completed the evaluation survey, 75% (12/16) enjoyed the program, and all parents found the newsletters to be useful. Almost all parents (15/16, 94%) agreed that the DELISH program would be useful to other parents. CONCLUSIONS: The improvement in salt-related KABs in the DELISH program indicates the potential for online technology, to disseminate simple salt reduction education messages to families with primary school-aged children. Future work should seek to improve the quality of data collected by including a larger sample size and a control group to integrate the program within the school setting to enable wider dissemination.

Kinetic evidence for multiple aggregation pathways in antibody light chain variable domains.

Aggregation of antibody light chain proteins is associated with the progressive disease light chain amyloidosis. Patient-derived amyloid fibrils are formed from light chain variable domain residues in non-native conformations, highlighting a requirement that light chains unfold from their native structures in order to aggregate. However, mechanistic studies of amyloid formation have primarily focused on the self-assembly of natively unstructured peptides, and the role of native state unfolding is less well understood. Using a well-studied light chain variable domain protein known as WIL, which readily aggregates in vitro under conditions where the native state predominates, we asked how the protein concentration and addition of pre-formed fibril "seeds" alter the kinetics of aggregation. Monitoring aggregation with thioflavin T fluorescence revealed a distinctly non-linear dependence on concentration, with a maximum aggregation rate observed at 8 µM protein. This behavior is consistent with formation of alternate aggregate structures in the early phases of amyloid formation. Addition of N- or C-terminal peptide tags, which did not greatly affect the folding or stability of the protein, altered the concentration dependence of aggregation. Aggregation rates increased in the presence of pre-formed seeds, but this effect did not eliminate the delay before aggregation and became saturated when the proportion of seeds added was greater than 1 in 1600. The complexity of aggregation observed in vitro highlights how multiple species may contribute to amyloid pathology in patients.

Exploration of parental consent for adolescent involvement in genital body image education research.

Genital body image is a highly understudied concept but is important for sexual health and broader body image satisfaction. Effective genital body image interventions for adolescents have been developed, however, parental consent can be a barrier to adolescent participation. The aim of this study was to conduct a novel exploration of parental consent for genital body image education research and factors related to this consent. Participants were 125 parents of adolescents in Australia who completed an online questionnaire including measures of demographic characteristics, personality traits and attitudes, and likelihood of consent for an adolescent son and daughter participating in hypothetical genital body image education research. The vast majority of parents indicated that they definitely would consent to their adolescent sons' and daughters' involvement in this hypothetical research. There was no significant difference in likelihood of consent based on the gender of the adolescent. Parents having more conservative attitudes towards sex was the only factor tested that reduced the likelihood of providing consent. Overall, our results suggest parents are generally supportive of adolescent involvement in genital body image education research. This concept should be included in broader body image educational programs so adolescents gain exposure to this important but neglected topic.

In their own words: a qualitative survey of healthcare providers' experiences with personal protective equipment during the COVID-19 pandemic.

BACKGROUND: At the beginning of the coronavirus disease (COVID-19) pandemic, healthcare personnel (HCP) faced a dire shortage of personal protective equipment (PPE). This shortage has been identified as a major source of distress among HCP during the early COVID-19 pandemic, though the specific consequences of this shortage have not been identified in the qualitative literature. METHODS: We sought to fill this gap by conducting a qualitative analysis of PPE related free-text comments from online surveys completed by 923 HCP during Spring 2020. RESULTS: We found that HCP used words such as "required" and "had" to describe how their use of non-standard PPE was imposed on them by their workplace, suggesting that they felt little control over their protection at work. HCP described cleaning PPE with novel methods, such as bleach, alcohol, hydrogen peroxide, and UV light, in addition to creating their own PPE out of materials such as garbage bags, sheets, and cloth. Furthermore, HCP expressed frustration with PPE policies at their workplaces, which continued throughout the early pandemic due to the rapidly changing guidelines and the inability to express their opinions to their institutions. The combination of these concerns left HCP scared of being infected with COVID-19 while at work and subsequently infecting their loved ones at home. CONCLUSION: It is critical that healthcare institutions understand HCP's experiences with and feelings towards PPE, as providing the proper protection is vital in ensuring an adequate HCP workforce.

ERK signaling promotes resistance to TRK kinase inhibition in NTRK fusion-driven glioma mouse models.

Pediatric-type high-grade gliomas frequently harbor gene fusions involving receptor tyrosine kinase genes, including neurotrophic tyrosine kinase receptor (NTRK) fusions. Clinically, these tumors show high initial response rates to tyrosine kinase inhibition but ultimately recur due to the accumulation of additional resistance-conferring mutations. Here, we developed a series of genetically engineered mouse models of treatment-naïve and -experienced NTRK1/2/3 fusion-driven gliomas. Both the TRK kinase domain and the N-terminal fusion partners influenced tumor histology and aggressiveness. Treatment with TRK kinase inhibitors significantly extended survival of NTRK fusion-driven glioma mice in a fusion- and inhibitor-dependent manner, but tumors ultimately recurred due to the presence of treatment-resistant persister cells. Finally, we show that ERK activation promotes resistance to TRK kinase inhibition and identify MEK inhibition as a potential combination therapy. These models will be invaluable tools for preclinical testing of novel inhibitors and to study the cellular responses of NTRK fusion-driven gliomas to therapy.

Kinetic evidence for multiple aggregation pathways in antibody light chain variable domains.

Aggregation of antibody light chain proteins is associated with the progressive disease light chain amyloidosis. Patient-derived amyloid fibrils are formed from light chain variable domain residues in non-native conformations, highlighting a requirement that light chains unfold from their native structures in order to aggregate. However, mechanistic studies of amyloid formation have primarily focused on the self-assembly of natively unstructured peptides, and the role of native state unfolding is less well understood. Using a well-studied light chain variable domain protein known as WIL, which readily aggregates in vitro under conditions where the native state predominates, we asked how the protein concentration and addition of pre-formed fibril "seeds" alter the kinetics of aggregation. Monitoring aggregation with thioflavin T fluorescence revealed a distinctly non-linear dependence on concentration, with a maximum aggregation rate observed at 8 µM protein. This behavior is consistent with formation of alternate aggregate structures in the early phases of amyloid formation. Addition of N- or C-terminal peptide tags, which did not greatly affect the folding or stability of the protein, altered the concentration dependence of aggregation. Aggregation rates increased in the presence of pre-formed seeds, but this effect did not eliminate the delay before aggregation and became saturated when the proportion of seeds added was greater than 1 in 1600. The complexity of aggregation observed in vitro highlights how multiple species may contribute to amyloid pathology in patients.

Factors contributing to the sustained implementation of an early childhood obesity prevention intervention: The INFANT Program.

Background: The INFANT Program is an efficacious, group-based program for first-time parents, delivered at three-monthly intervals when INFANT are aged 3-18 months through an existing universal care service in Victoria, Australia. Many lessons have been learnt from its origins as a cluster randomized control trial to its small-scale, community-level implementation. This study aimed to describe factors contributing to its sustained implementation to inform large-scale implementation across Australia. Methods: This study used a multi-site qualitative exploratory approach. INFANT facilitators trained between 2013 and 2017 were sent an online survey, with optional telephone interviews. The Consolidated Framework for Implementation Research (CFIR) was selected as the underpinning theoretical framework as it offered the opportunity to explore a breadth of possible barriers and enablers across patterns of implementation (never, discontinued, ongoing). Results: All participants were female (n = 31), the majority were Maternal and Child Health Nurses (48%), representing five regional and nine metro local government areas (LGAs), across all patterns of implementation (never implemented n = 4; discontinued implementation n = 5; ongoing implementation n = 5). All consenting participants were interviewed (n = 11) representing four regional and seven metro LGAs, across all patterns of implementation (never implemented n = 3; discontinued implementation n = 4; ongoing implementation n = 4). The main reason for attending INFANT Program training was to become skilled to implement the program. Mapping identified barriers and enablers to the CFIR revealed the inner and outer settings and implementation process to be of greatest influence. Main differences between LGAs with ongoing and discontinued implementation related to funding availability, organizational management support and endorsement, organizational resourcing and capacity, integration into routine practice and establishing role clarity with partner organizations, and planning for sustained implementation from the start. Conclusion: This study provides important insights into the barriers and enablers to the sustained implementation of an evidence-based intervention (the INFANT Program) during small scale community-level implementation. The authors therefore contend that the pre-requisite for scale-up of a population health intervention is not just proof of effectiveness but also proof of sustained implementation at the local/organizational level. Study findings have broad transferability given their similarity to those identified for health promotion interventions implemented globally, in healthcare, education and community settings.

Diet, Digestion, and the Dietitian: A Survey of Clinicians' Knowledge, Attitudes and Practices to Advance the Treatment of Gastrointestinal Disturbances in Individuals with Anorexia Nervosa.

Despite advances in treatment of anorexia nervosa (AN), current therapeutic approaches do not fully consider gastrointestinal disturbances (GID), often present in AN. Addressing GID, both symptoms and disorders, is likely to improve treatment adherence and outcomes in people with AN. GID are complex and are linked to a range of factors related to eating disorder symptomology and can be impacted by nutritional treatment. It is not known which dietetic practices are currently used to address GID in AN. Therefore, this survey aimed to explore the perceived knowledge, attitudes, and practices (KAP) of Australian dietitians treating AN and co-occurring GID. Seventy dietitians participated by completing an online survey. Knowledge scores were calculated based on correct responses to knowledge items (total: 12 points); and two groups were generated: higher knowledge (≥10 points, n = 31) and lower knowledge (≤9 points, n = 39). A greater proportion of dietitians with higher knowledge recognized the role of GID in pathogenesis of AN (p = 0.002) and its impact on quality of life (p = 0.013) and screened for GID (p ≤ 0.001), compared with those with lower knowledge. These results suggest that attitudes and practices toward patients presenting with AN and GID differ depending on level of knowledge. This may have important implications for treatment outcomes for individuals with AN and GID.

A qualitative analysis of psychosocial stressors and health impacts of the COVID-19 pandemic on frontline healthcare personnel in the United States.

There is a dearth of qualitative studies exploring the lived experiences of frontline healthcare personnel (HCP) during the coronavirus disease (COVID-19) pandemic. We examined workplace stressors, psychological manifestations of said stressors, and coping strategies reported through coded open-text responses from 1024 online surveys completed over two months by 923 HCP participating in three nationwide cohorts from Spring 2020. Our findings suggest that risk, job insecurity, frustration with hospital administration, inadequate access to personal protective equipment, and witnessing patient suffering and death contributed to deteriorating mental and physical health. Negative health impacts included the onset or exacerbation of anxiety, depression, and somatic symptoms, including weight fluctuation, fatigue, and migraines. Coping mechanisms included substance use and food consumption, meditation and wellness, fitness, socializing with loved ones, and religious activities. Insights garnered from participants' responses will enable more personalized and effective psychosocial crisis prevention and intervention for frontline HCP in future health crises.

Possible use of fermented foods in rehabilitation of anorexia nervosa: the gut microbiota as a modulator.

Anorexia nervosa is a serious psychiatric disorder with high morbidity and mortality rate. Evidence for the optimal psychopharmacological approach to managing the disorder remains limited, with nutritional treatment, focused on weight restoration through the consumption of high energy diet, regarded as one of the fundamental steps in treatment. The human gut microbiome is increasingly recognised for its proposed role in gastrointestinal, metabolic, immune and mental health, all of which may be compromised in individuals with anorexia nervosa. Dietary intake plays an important role in shaping gut microbiota composition, whilst the use of fermented foods, foods with potential psychobiotic properties that deliver live bacteria, bacterial metabolites, prebiotics and energy, have been discussed to a lesser extent. However, fermented foods are of increasing interest due to their potential capacity to affect gut microbiota composition, provide beneficial bacterial metabolites, and confer beneficial outcomes to host health. This review provides an overview of the role of the gut microbiota in relation to the disease pathology in anorexia nervosa and especially focuses on the therapeutic potential of fermented foods, proposed here as a recommended addition to the current nutritional treatment protocols warranting further investigation.

Prebiotic and probiotic supplementation and the tryptophan-kynurenine pathway: A systematic review and meta analysis.

This systematic review aimed to synthesise the results from studies investigating the effects of prebiotics and probiotics on kynurenine pathway metabolism. Thirteen studies were identified for inclusion, comprising 12 probiotic and two prebiotic arms. Participants included healthy individuals and individuals with various clinical conditions. Twelve metabolites were examined across the studies, using a range of biological samples. Across all interventions, 11 reported an effect on ≤ metabolite. Although limited by clinical and methodological heterogeneity, pooled analysis (n = 253) found probiotics to significantly affect serum kynurenine (g = 0.315, CI = 0.070 to 0.560, p = 0.012, 4 studies, I2 = 0%) and the kynurenine:tryptophan ratio (g = 0.442, CI = 0.074 to 0.810, p = 0.018, 4 studies, I2 = 42 %). Risk of bias across the studies was generally low. The results provide preliminary evidence that probiotics can modulate kynurenine pathway metabolism, with less evidence available regarding prebiotics. Future studies which further consider methodological confounds and sample characteristics are required, to establish intervention efficacy. PROSPERO registration #CRD42019154677.

The effect of ultra-processed very low-energy diets on gut microbiota and metabolic outcomes in individuals with obesity: A systematic literature review.

This systematic review investigated the effects of ultra-processed very low-energy diets on gut microbiota and metabolic outcomes in individuals with obesity. MEDLINE complete, EMBASE, Scopus, Cochrane and CINAHL were searched between date of inception and October 2019. Seven trials were reviewed (a total of 130 participants, with 10 to 44 participants in each trial). Of these, five were single-arm interventions and included very low-energy diets adjunctive to comprehensive lifestyle interventions such as nutritional counselling, behavioural therapy and exercise programmes. Changes to taxa within the Firmicutes phylum were found, including reduced abundance of potentially beneficial butyrogenic microbes (Roseburia, Faecalbacterium prausnitzii, Lactobacillus, Bifidobacterium and Lachnospiraeceae). Conversely, increased abundance of potentially pathogenic or opportunistic microbes from the Bacteroidetes phylum was reported, including increases in Alistipes and Bacteroides taxa. However, outcomes were inconsistent, with some trials also showing decreases in Bacteroides taxa and increases in commensal microbiota, such as Lachnospiraceae and Bifidobacteriaceae. The changes in metabolic parameters observed from baseline to after the ultra-processed very low-energy diets were mostly beneficial or were not significantly altered. Although the selected articles were deemed to have satisfactory methodological quality, to understand the possible direct effects of these regimens on gut microbiota, further rigorously designed trials, with more standardised microbiological sequencing techniques and detailed reporting, are required. Study registration: Prospero ID: CRD42019124436.