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The emerging understanding of gut microbiota as ‘metabolic machinery’ influencing many aspects of physiology has gained substantial attention in the field of psychiatry. This is largely due to the many overlapping pathophysiological mechanisms associated with both the potential functionality of the gut microbiota and the biological mechanisms thought to be underpinning mental disorders. In this systematic review, we synthesised the current literature investigating differences in gut microbiota composition in people with the major psychiatric disorders, major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ), compared to ‘healthy’ controls. We also explored gut microbiota composition across disorders in an attempt to elucidate potential commonalities in the microbial signatures associated with these mental disorders. Following the PRISMA guidelines, databases were searched from inception through to December 2021. We identified 44 studies (including a total of 2510 psychiatric cases and 2407 controls) that met inclusion criteria, of which 24 investigated gut microbiota composition in MDD, seven investigated gut microbiota composition in BD, and 15 investigated gut microbiota composition in SZ. Our syntheses provide no strong evidence for a difference in the number or distribution (α-diversity) of bacteria in those with a mental disorder compared to controls. However, studies were relatively consistent in reporting differences in overall community composition (β-diversity) in people with and without mental disorders. Our syntheses also identified specific bacterial taxa commonly associated with mental disorders, including lower levels of bacterial genera that produce short-chain fatty acids (e.g. butyrate), higher levels of lactic acid-producing bacteria, and higher levels of bacteria associated with glutamate and GABA metabolism. We also observed substantial heterogeneity across studies with regards to methodologies and reporting. Further prospective and experimental research using new tools and robust guidelines hold promise for improving our understanding of the role of the gut microbiota in mental and brain health and the development of interventions based on modification of gut microbiota.

Our meta-analysis provides evidence that Hcy levels are elevated in persons with BD during mania and euthymia. Peripheral Hcy could be considered as a potential biomarker in BD, both of trait (since it is increased in euthymia), and also of state (since its increase is more accentuated in mania). Longitudinal studies are needed to clarify the relationship between bipolar disorder and Hcy, as well as the usefulness of peripheral Hcy as both a trait and state biomarker in BD.

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The field of microbiota-gut-brain axis research and medicine, including the potential and application of faecal microbiome transplants (FMT), continues to accelerate. 1 Here we update the evidence regarding the use of FMT in psychiatry, discuss the many clinical and methodological challenges, and make recommendations to guide further high-quality research.

Background: Due to the considerable burden of multiple sclerosis (MS)-related symptoms and the need to identify effective interventions to prevent disease progression, various nutraceutical interventions have been trialed as adjunctive treatments. The aim of this review was to investigate the efficacy and safety of nutraceutical interventions for clinical and biological outcomes in people with MS. Methods: In accordance with PRISMA reporting guidelines, a systematic literature search was conducted using three electronic literature databases. Risk of bias was assessed using the Jadad scale. Results: Thirty-seven randomized controlled trials, investigating fourteen nutraceuticals, were included in the review. Trials that investigated alpha lipoic acid (n = 4/6), ginkgo biloba (n = 3/5), vitamin A (n = 2/2), biotin (n = 1/2), carnitine (n = 1/2), green tea (n = 1/2), coenzyme Q10 (n = 1/1), probiotics (n = 1/1), curcumin (n = 1/1), Andrographis paniculata (n = 1/1), ginseng (n = 1/1), and lemon verbena (n = 1/1) were reported to improve biological (e.g. MRI brain volume change, antioxidant capacity) and/or clinical (e.g. fatigue, depression, Expanded Disability Status Scale) outcomes in multiple sclerosis compared to control. However, most trials were relatively small (average study sample size across included studies, n = 55) and there were few replicate studies per nutraceutical to validate the reported results. Furthermore, some nutraceuticals (e.g. green tea and inosine) should be used with caution due to reported adverse events. Risk of bias across most studies was low, with 31 studies receiving a score between 4 and 5 (out of 5) on the Jadad Scale. Conclusion:The existing literature provides preliminary support for the use of a number of nutraceutical interventions in MS. However, sufficiently powered long-term trials are required to expand the currently limited literature and to investigate unexplored nutraceuticals that may target relevant pathways involved in MS such as the gut microbiome and mitochondrial dysfunction. Prospero ID: CRD42018111736.

Background Beta-casein is a major protein in cow’s milk, of which A1 and A2 are the most frequent variants. Recent evidence implicates A1 beta-casein consumption in mechanisms that are of potential importance to mental health, yet its possible effects on psychological endpoints remains unknown. The primary aim of the study is to evaluate the comparative effects of consumption of dairy products containing A2 beta-casein versus conventional dairy (i.e. containing both A1 and A2 beta-casein) on symptoms of psychological distress in women with low mood. Methods ‘The Moo’D Study’ is a 16-week, superiority, 1:1 parallel group, triple-blinded, randomised controlled trial. Ninety women with low mood (Patient Health Questionnaire score ≥ 5) will be randomised to consume either A2 beta-casein only or conventional dairy products. The primary outcome, symptoms of psychological distress, will be measured by the 21-item Depression, Anxiety and Stress Scale. Secondary outcomes will include symptoms of depression, anxiety and stress, severity of low mood, cognition, gut microbiota composition, gut symptomatology, markers of immune function, gut inflammation, systemic metabolites, endothelial integrity and oxidative stress, body composition, perceived wellbeing, sleep, quality of life, resource use and cost-effectiveness. Discussion This study will advance our understanding of the possible impact of milk proteins on psychological distress in women as well as elucidate mechanisms underpinning any association. Given dairy products form a substantial component of traditional and Western diets, the implications of these findings are likely to be of clinical and public health importance. Trial registration The trial protocol has been prospectively registered with the Australia and New Zealand Clinical Trials Registry, ACTRN12618002023235. Registered on 17 December 2018.