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Summary: This systematic review and meta‐analysis investigated the association between consumption of ultraprocessed food and noncommunicable disease risk, morbidity and mortality. Forty‐three observational studies were included (N = 891,723): 21 cross‐sectional, 19 prospective, two case‐control and one conducted both a prospective and cross‐sectional analysis. Meta‐analysis demonstrated consumption of ultraprocessed food was associated with increased risk of overweight (odds ratio: 1.36; 95% confidence interval [CI], 1.23‐1.51; P < 0.001), obesity (odds ratio: 1.51; 95% CI, 1.34‐1.70; P < 0.001), abdominal obesity (odds ratio: 1.49; 95% CI, 1.34‐1.66; P < 0.0001), all‐cause mortality (hazard ratio: 1.28; 95% CI, 1.11‐1.48; P = 0.001), metabolic syndrome (odds ratio: 1.81; 95% CI, 1.12‐2.93; P = 0.015) and depression in adults (hazard ratio: 1.22; 95% CI, 1.16‐1.28, P < 0.001) as well as wheezing (odds ratio: 1.40; 95% CI, 1.27‐1.55; P < 0.001) but not asthma in adolescents (odds ratio: 1.20; 95% CI, 0.99‐1.46; P = 0.065). In addition, consumption of ultraprocessed food was associated with cardiometabolic diseases, frailty, irritable bowel syndrome, functional dyspepsia and cancer (breast and overall) in adults while also being associated with metabolic syndrome in adolescents and dyslipidaemia in children. Although links between ultraprocessed food consumption and some intermediate risk factors in adults were also highlighted, further studies are required to more clearly define associations in children and adolescents. Study registration: Prospero ID: CRD42020176752. [ABSTRACT FROM AUTHOR]

Objectives: Excessive consumption of high fat and high sugar (HFHS) diets alters reward processing, behaviour, and changes gut microbiota profiles. Previous studies in gnotobiotic mice also provide evidence that these gut microorganisms may influence social behaviour. To further investigate these interactions, we examined the impact of the intermittent access to a HFHS diet on social behaviour, gene expression and microbiota composition in adolescent rats. Methods: Male rats were permitted intermittent daily access (2 h / day) to a palatable HFHS chow diet for 28 days across adolescence. Social interaction, social memory and novel object recognition were assessed during this period. Following testing, RT-PCR was conducted on hippocampal and prefrontal cortex (PFC) samples. 16S ribosomal RNA amplicon sequencing was used for identification and relative quantification of bacterial taxa in faecal samples. Results: We observed reduced social interaction behaviours, impaired social memory and novel object recognition in HFHS diet rats compared to chow controls. RT-PCR revealed reduced levels of monoamine oxidase A (Maoa), catechol-O-methyltransferase (Comt) and brain derived neurotrophic factor (Bdnf) mRNA in the PFC of HFHS diet rats. Faecal microbiota analysis demonstrated that the relative abundance of a number of specific bacterial taxa differed significantly between the two diet groups, in particular, Lachnospiraceae and Ruminoccoceae bacteria. Discussion: Intermittent HFHS diet consumption evoked physiological changes to the brain, particularly expression of mRNA associated with reward and neuroplasticity, and gut microbiome. These changes may underpin the observed alterations to social behaviours. [ABSTRACT FROM AUTHOR]

Beyond being a source of key nutrients, bovine milk influences physiological functions by synthesising bioactive peptides during the process of digestion. Some of the claimed negative health outcomes associated with milk consumption, such as cardiovascular diseases and type 1 diabetes may be attributed to an opioid peptide, beta-casomorphin-7 (BCM-7), derived from A1 beta-casein. BCM-7 exerts its function by binding to the μ-opioid receptors in the body. It is hypothesised that activation of the μ-opioid receptors in the gut can alter gut microbial composition, impair gut barrier integrity and bile acid metabolism, in addition to increasing gastrointestinal transit time and gut inflammation. Further, it is hypothesised that BCM-7 may influence fractures and obesity via μ-opioid receptor pathways. In conclusion, it appears that BCM-7 might have multiple functions pertinent to human health; however, the evidence is limited and warrants further pre-clinical and clinical studies for hypothesis confirmation. [ABSTRACT FROM AUTHOR]

Background: Externalising 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 determine 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). Methods/design: Three 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 were families of eight month old children from nine participating local government areas. Randomised to one of three groups: Combined, Targeted or Usual care. The interventions comprises (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. 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. Discussion: This 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. Trial registration: ISRCTN61137690 [ABSTRACT FROM AUTHOR]

Objectives:Methods:Results:Discussion:In experimental models, the prenatal diet influences gut microbiota composition in mothers and offspring; however, it is unclear whether this occurs in humans. We investigated the effects of a gut-focused perinatal dietary intervention on maternal and infant gut microbiota composition four weeks after birth.This randomised controlled trial randomised pregnant women to receive dietary advice as part of standard care, or additionally receive a dietary intervention focused on the Australian Dietary Guidelines and increasing prebiotic and probiotic/fermented food intakes (ACTRN12616000936426). Study assessments occurred from gestation week 26 (baseline) to four weeks postpartum (follow-up). Faecal samples, collected at baseline for mothers, and follow-up for mothers and infants, underwent 16SrRNA sequencing. The primary outcome was a between-group mean difference in infant faecal Shannon index. Secondary outcomes included between-group differences in other microbiota measures, including maternal change from baseline CLR-transformed Prevotella abundance.Forty-four women and 45 infants completed the study. The mean Shannon index of infants in the intervention group was −0.35 (95% CI: −0.64, −0.06, SD: 0.52) units lower than control group infants, corresponding to a medium effect size (Cohen’s D: −0.74, 95% CI: −1.34, −0.13). The findings were similar using other metrics of α-diversity. There were no between-group differences in β-diversity, nor any differentially abundant taxa in infants. The intervention increased abundances of the genus Prevotella in mothers compared to controls.This gut-focused perinatal dietary intervention was associated with differences in the maternal and infant gut microbiota composition. Larger studies are required to replicate and extend these findings. [ABSTRACT FROM AUTHOR]

The microbiota-gut-brain axis' role in Parkinson's disease (PD) pathophysiology, and how this differs from typical ageing, is poorly understood. Presently, gut-bacterial diversity, taxonomic abundance and metabolic bacterial pathways were compared across healthy young (n = 22, 18–35 years), healthy older (n = 33, 50–80 years), and PD groups (n = 18, 50–80 years) using shotgun sequencing and compositional data analysis. Associations between the gut-microbiome and PD symptoms, and between lifestyle factors (fibre intake, physical activity, and sleep) and the gut-microbiome were conducted. Alpha-diversity did not differ between PD participants and older adults, whilst beta-diversity differed between these groups. Lower abundance of Butyricimonas synergistica , a butyrate-producer, was associated with worse PD non-motor symptoms in the PD group. Regarding typical ageing, Bifidobacterium bifidum , was greater in the younger compared to older group, with no difference between the older and PD group. Abundance of metabolic pathways related to butyrate production did not differ among the groups, while other metabolic pathways differed among the three groups. Sleep efficiency was positively associated with Roseburia inulinivorans in the older group. These results highlight the relevance of gut-microbiota to PD and that reduced butyrate-production may be involved with PD pathophysiology. Future studies should account for lifestyle factors when investigating gut-microbiomes across ageing and in PD. This article is part of the Special Issue on "Microbiome & the Brain: Mechanisms & Maladies". • Shotgun sequencing and compositional data analysis of gut bacteria data. • Butyrate producer, B. synergistica, associated with worse PD non-motor symptoms. • Lifestyle factors were differently related to gut bacteria across groups. • Bacterial metabolic functions differed across healthy ageing and in PD groups. [ABSTRACT FROM AUTHOR]

Knowledge of the microbiome-gut-brain axis has revolutionized the field of psychiatry. It is now well recognized that the gut bacteriome is associated with, and likely influences, the pathogenesis of mental disorders, including major depressive disorder and bipolar disorder. However, while substantial advances in the field of microbiome science have been made, we have likely only scratched the surface in our understanding of how these ecosystems might contribute to mental disorder pathophysiology. Beyond the gut bacteriome, research into lesser explored components of the gut microbiome, including the gut virome, mycobiome, archaeome, and parasitome, is increasingly suggesting relevance in psychiatry. The contribution of microbiomes beyond the gut, including the oral, lung, and small intestinal microbiomes, to human health and pathology should not be overlooked. Increasing both our awareness and understanding of these less traversed fields of research are critical to improving the therapeutic benefits of treatments targeting the gut microbiome, including fecal microbiome transplantation, postbiotics and biogenics, and dietary intervention. Interdisciplinary collaborations integrating systems biology approaches are required to fully elucidate how these different microbial components and distinct microbial niches interact with each other and their human hosts. Excitingly, we may be at the start of the next microbiome revolution and thus one step closer to informing the field of precision psychiatry to improve outcomes for those living with mental illness., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: An increasing body of evidence supports associations between inflammation and mental health difficulties, but the onset and directionality of these relationships are unclear., Methods: Data sources: Barwon Infant Study (BIS; n = 500 4-year-olds) and Longitudinal Study of Australian Children (LSAC; n = 1099 10-13-year-olds)., Measures: Strengths and Difficulties Questionnaire emotional symptoms at 4, 10-11 and 12-13 years, and circulating levels of two inflammatory biomarkers, high-sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls (GlycA), at 4 and 11-12 years., Analysis: Adjusted quantile regression models examining cross-sectional associations between emotional symptoms and inflammation in 4-year-olds (BIS), and cross-lagged associations in 10-13-year-olds (LSAC)., Results: We identified a small association between higher emotional symptoms at 10-11 years and higher GlycA levels a year later (standardised coefficient β = 0.09; 95%CI: 0.02 to 0.15). Sex-stratified analyses revealed this association was stronger for boys (β = 0.13; 95%CI: 0.04 to 0.21) than girls (β = 0.01; 95%CI: -0.09 to 0.11). These associations were not observed for hsCRP. There was little evidence of an association between higher GlycA or hsCRP at 11-12 years and emotional symptoms a year later, or cross-sectional associations between emotional symptoms and hsCRP or GlycA at 4 years., Limitations: A single time-point of biomarker collection in late childhood precluded adjustment for baseline inflammatory biomarkers., Conclusions: Our results support the direction of association from emotional symptoms to inflammation in late childhood, with potential sex differences. This adds to the body of evidence that addressing emotional symptoms in childhood is a major priority in optimising overall health throughout the life course., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Pre-pregnancy obesity is an emerging risk factor for perinatal depression. However, the underlying mechanisms remain unclear. We investigated the association between pre-pregnancy body mass index (BMI) and perinatal depressive symptoms in a large population-based pre-birth cohort, the Barwon Infant Study. We also assessed whether the levels of circulating inflammatory markers during pregnancy mediated this relationship., Methods: Depressive symptoms were assessed in 883 women using the Edinburgh Postnatal Depression Scale (EPDS) and psychological stress using the Perceived Stress Scale (PSS) at 28 weeks gestation and 4 weeks postpartum. Glycoprotein acetyls (GlycA), high-sensitivity C-reactive protein (hsCRP) and cytokines were assessed at 28 weeks gestation. We performed regression analyses, adjusted for potential confounders, and investigated mediation using nested counterfactual models., Results: The estimated effect of pre-pregnancy obesity (BMI ≥ 30 kg/m 2 ) on antenatal EPDS scores was 1.05 points per kg/m 2 increase in BMI (95% CI: 0.20, 1.90; p = 0.02). GlycA, hsCRP, interleukin (IL) -1ra and IL-6 were higher in women with obesity, compared to healthy weight women, while eotaxin and IL-4 were lower. Higher GlycA was associated with higher EPDS and PSS scores and partially mediated the association between pre-pregnancy obesity and EPDS/PSS scores in unadjusted models, but this association attenuated upon adjustment for socioeconomic adversity. IL-6 and eotaxin were negatively associated with EPDS/PSS scores, however there was no evidence for mediation., Conclusions: Pre-pregnancy obesity increases the risk of antenatal depressive symptoms and is also associated with systemic inflammation during pregnancy. While discrete inflammatory markers are associated with antenatal depressive symptoms and perceived stress, their role in mediating the effects of pre-pregnancy obesity on antenatal depression requires further investigation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Mental disorders, including major depressive disorder (MDD), are a leading cause of non-fatal burden of disease globally. Current conventional treatments for depression have significant limitations, and there have been few new treatments in decades. The microbiota-gut-brain-axis is now recognised as playing a role in mental and brain health, and promising preclinical and clinical data suggest Faecal Microbiota Transplants (FMT) may be efficacious for treating a range of mental illnesses. However, there are no existing published studies in humans evaluating the efficacy of FMT for MDD., Methods and Design: This protocol describes an 8-week, triple-blind, 2:1 parallel group, randomised controlled pilot trial (n = 15), of enema-delivered FMT treatment (n = 10) compared with a placebo enema (n = 5) in adults with moderate-to-severe MDD. There will be a further 26-week follow-up to monitor longer-term safety. Participants will receive four FMT or placebo enemas over four consecutive days. The primary aims of the study are to evaluate feasibility and safety of FMT as an adjunctive treatment for MDD in adults. Changes in gut microbiota will be assessed as a secondary outcome. Other data will be collected, including changes in depression and anxiety symptoms, and safety parameters., Discussion: Modification of the microbiota-gut-brain axis via FMT is a promising potential treatment for MDD, but there are no published rigorous clinical trials evaluating its use. If this study finds that our FMT strategy is safe and feasible, a larger fully powered RCT is planned. Further high-quality research in this field is urgently needed to address unmet need., Trial Registration: Australian and New Zealand Clinical Trials Registry: ACTRN12621000932864., (© 2023. The Author(s).)

Background: A low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet is increasingly used to manage symptoms in irritable bowel syndrome (IBS). Although this approach may alter the colonic microbiome, the nature of these changes has not been comprehensively synthesized., Objectives: The aim of this study was to conduct a systematic review with meta-analysis of randomized controlled trials examining the impact of a low FODMAP diet on the composition and function of the microbiome in patients with IBS., Methods: A systematic search was conducted for randomized controlled trials evaluating the effects of a low FODMAP diet on the colonic microbiome in patients with IBS in MEDLINE, EMBASE, CENTRAL, and Web of Science from inception to April 2022. Outcomes included diversity of the microbiome, specific bacterial abundances, fecal SCFA concentration, and fecal pH. For fecal SCFA concentrations and pH, meta-analyses were performed via a random-effects model., Results: Nine trials involving 403 patients were included. There were no clear effects of the low FODMAP diet on diversity of the microbiome. A low FODMAP diet consistently led to lower abundance of Bifidobacteria, but there were no clear effects on diversity of the microbiome or abundances of other specific taxa. There were no differences in total fecal SCFA concentration between the low FODMAP diet and control diets (standardized mean difference: -0.25; 95% CI: -0.63, 0.13; P = 0.20), nor were there differences for fecal concentrations of specific SCFAs or fecal pH., Conclusions: In patients with IBS, the effects of a low FODMAP diet on the colonic microbiome appear to be specific to Bifidobacteria with no consistent impacts on other microbiome metrics, including diversity, fecal SCFA concentrations, and fecal pH. Further, adequately powered trials are needed to confirm these findings.This review was registered at https://www.crd.york.ac.uk/prospero/ as CRD42020192243., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Poor cognitive outcomes in early childhood predict poor educational outcomes and diminished health over the life course. We sought to investigate (i) whether maternal metabolites predict child cognition, and (ii) if maternal metabolomic profile mediates the relationship between environmental exposures and child cognition. Metabolites were measured using nuclear magnetic resonance-based metabolomics in pregnant women from a population-derived birth cohort. Child cognition was measured at age 2 years. In 662 mother-child pairs, elevated inflammatory markers (β = -2.62; 95% CI -4.10, -1.15; P = 0.0005) and lower omega-3 fatty acid-related metabolites (β = 0.49; 95% CI 0.09, 0.88; P = 0.02) in the mother were associated with lower child cognition and partially mediated the association between lower child cognition and multiple risk factors common to socioeconomic disadvantage. Modifying maternal prenatal metabolic pathways related to inflammation and omega-3 fatty acids may offset the adverse associations between prenatal risk factors related to socioeconomic disadvantage and low child cognition., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: At a population level, the relation between dairy consumption and gut microbiome composition is poorly understood., Objectives: We sought to study the cross-sectional associations between individual dairy foods (i.e., milk, yogurt, and cheese), as well as total dairy intake, and the gut microbiome composition in a large, representative sample of men living in south-eastern Australia., Methods: Data on 474 men (mean ± SD: 64.5 ± 13.5 y old) from the Geelong Osteoporosis Study were used to assess the cross-sectional association between dairy consumption and gut microbiome. Information on dairy intake was self-reported. Men were categorized as consumers and nonconsumers of milk, yogurt, cheese, and high- and low-fat milk. Milk, yogurt, and cheese intakes were summed to calculate the total dairy consumed per day and categorized into either low (<2.5 servings/d) or high (≥2.5 servings/d) total dairy groups. Fecal samples were analyzed using bacterial 16S ribosomal RNA (rRNA) gene sequencing. After assessment of α and β diversity, differential abundance analysis was performed to identify bacterial taxa associated with each of milk, yogurt, and cheese consumption compared with nonconsumption, low compared with high total dairy, and low- compared with high-fat milk consumption. All analyses were adjusted for potential confounders., Results: α Diversity was not associated with consumption of any of the dairy groups. Differences in β diversity were observed between milk and yogurt consumption compared with nonconsumption. Taxa belonging to the genera Ruminococcaceae UCG-010 and Bifidobacterium showed negative and weak positive associations with milk consumption, respectively. A taxon from the genus Streptococcus was positively associated with yogurt consumption, whereas a taxon from the genus Eisenbergiella was negatively associated with cheese consumption. No specific taxa were associated with low- compared with high-fat milk nor low compared with high total dairy consumption., Conclusions: In men, community-level microbiome differences were observed between consumers and nonconsumers of milk and yogurt. Bacterial taxon-level associations were detected with milk, yogurt, and cheese consumption. Total dairy consumption was not associated with any microbiome measures, suggesting that individual dairy foods may have differential roles in shaping the gut microbiome in men., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

There is accumulating evidence from observational and intervention studies in nutritional psychiatry regarding the importance of diet for mental health outcomes across the lifespan. Here, we synthesise this evidence, including findings from large meta-analyses showing cross-sectional and prospective associations between diet quality and mental health, even following adjustment for relevant confounding factors. Potential mechanistic pathways underpinning these associations include those of the gut-brain axis, demonstrated mostly in animal models. Dietary fibre is an important component of healthy diet and may be relevant for common mental disorders, with some studies showing a dose-dependent relationship between fibre intake and risk of depression. The potential contribution of nutraceuticals is also discussed, such as omega-3 fatty acids, vitamins, minerals, and psychobiotics. We consider the relevance of special diets such as the ketogenic diet and food sensitivities in the management of severe mental illness (e.g., anorexia nervosa) and brain disease (e.g., Alzheimer's disease). Given the relatively early nature of research in nutritional psychiatry, there remain a number of challenges to its translation into clinical practice. These span individual, clinical, and societal domains. We conclude with a discussion of micro- and macroeconomic factors which may be considered in the successful application of nutritional psychiatry research to improve public health., (© 2021 S. Karger AG, Basel.)