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.

The effects of dairy and dairy-derived products on the human gut microbiota remains understudied. A systematic literature search was conducted using Medline, CINAHL, Embase, Scopus, and PubMed databases with the aim of collating evidence on the intakes of all types of dairy and their effects on the gut microbiota in adults. Risk of bias was assessed using the Cochrane risk-of-bias tool.The search resulted in 6,592 studies, of which eight randomized controlled trials (RCTs) met pre-determined eligibility criteria for inclusion, consisting of a total of 468 participants. Seven studies assessed the effect of type of dairy (milk, yogurt, and kefir) and dairy derivatives (whey and casein) on the gut microbiota, and one study assessed the effect of the quantity of dairy (high dairy vs low dairy). Three studies showed that dairy types consumed (milk, yogurt, and kefir) increased the abundance of beneficial genera Lactobacillus and Bifidobacterium. One study showed that yogurt reduced the abundance of Bacteroides fragilis, a pathogenic strain. Whey and casein isolates and the quantity of dairy consumed did not prompt changes to the gut microbiota composition. All but one study reported no changes to bacterial diversity in response to dairy interventions and one study reported reduction in bacterial diversity in response to milk intake.In conclusion, the results of this review suggest that dairy products such as milk, yogurt, and kefir may modulate the gut microbiota composition in favor to the host. However, the broader health implications of these findings remain unclear and warrant further studies.

Mental disorders including depression and anxiety are often comorbid with gut problems, suggesting a bidirectional relationship between mental health and gut function. Several mechanisms might explain this comorbidity, such as inflammation and immune activation; intestinal permeability; perturbations in the hypothalamic–pituitary–adrenal axis; neurotransmitter/neuropeptide dysregulation; dietary deficiencies; and disturbed gut microbiome composition. The potential of modulating the microbiome–gut–brain axis, and subsequently mental health, through the use of functional foods, is an emerging and novel topic of interest. Fermented foods are considered functional foods due to their putative health benefits. The process of microbial fermentation converts food substrates into more nutritionally and functionally rich products, resulting in functional microorganisms (probiotics), substrates that enhance proliferation of beneficial bacteria in the gut (prebiotics), and bioactive components (biogenics). These functional ingredients act biologically in the gastrointestinal tract and have the ability to modify the gut microbiota, influence translocation of endotoxins and subsequent immune activation, and promote host nutrition. This narrative review explores the theoretical potential of the functional components present in fermented foods to alter gut physiology and to impact the biological mechanisms thought to underpin depression and anxiety. Pre-clinical studies indicate the benefits of fermented foods in relieving perturbed gut function and for animal models of depression and anxiety. However, in humans, the literature relating to the relevance of fermented food for treating or preventing depression and anxiety is sparse, heterogeneous and has significant limitations. This review identifies a critical research gap for further evaluation of fermented foods in the management of depression anxiety in humans.

In mice, the maternal microbiome influences fetal immune development and postnatal allergic outcomes. Westernized populations have high rates of allergic disease and low rates of gastrointestinal carriage of Prevotella, a commensal bacterial genus that produces short chain fatty acids and endotoxins, each of which may promote the development of fetal immune tolerance. In this study, we use a prebirth cohort (n = 1064 mothers) to conduct a nested case-cohort study comparing 58 mothers of babies with clinically proven food IgE mediated food allergy with 258 randomly selected mothers. Analysis of the V4 region of the 16S rRNA gene in fecal samples shows maternal carriage of Prevotella copri during pregnancy strongly predicts the absence of food allergy in the offspring. This association was confirmed using targeted qPCR and was independent of infant carriage of P. copri. Larger household size, which is a well-established protective factor for allergic disease, strongly predicts maternal carriage of P. copri.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is globally increasing in prevalence. The rise of ASD can be partially attributed to diagnostic expansion and advocacy efforts; however, the interplay between genetic predisposition and modern environmental exposures is likely driving a true increase in incidence. A range of evidence indicates that prenatal exposures are critical. Infection during pregnancy, gestational diabetes, and maternal obesity are established risk factors for ASD. Emerging areas of research include the effects of maternal use of selective serotonin reuptake inhibitors, antibiotics, and exposure to toxicants during pregnancy on brain development and subsequent ASD. The underlying pathways of these risk factors remain uncertain, with varying levels of evidence implicating immune dysregulation, mitochondrial dysfunction, oxidative stress, gut microbiome alterations, and hormonal disruptions. This narrative review assesses the evidence of contributing prenatal environmental factors for ASD and associated mechanisms as potential targets for novel prevention strategies.

Murine studies demonstrate that maternal prenatal gut microbiota influences brain development and behaviour of offspring. No human study has related maternal gut microbiota to behavioural outcomes during early life. This study aimed to evaluate relationships between the prenatal faecal microbiota, prenatal diet and childhood behaviour. A sub-cohort of 213 mothers and 215 children were selected from a longitudinal pre-birth cohort. Maternal prenatal exposure measures collected during the third trimester included the faecal microbiota (generated using 16S rRNA amplicon sequencing), and dietary intake. The behavioural outcome used the Childhood Behaviour Checklist at age two. Models were adjusted for prenatal diet, smoking, perceived stress, maternal age and sample batch. We found evidence that the alpha diversity of the maternal faecal microbiota during the third trimester of pregnancy predicts child internalising behaviour at two years of age (-2·74, (-4·71, -0·78), p = 0·01 (Wald test), R2=0·07). Taxa from butyrate-producing families, Lachnospiraceae and Ruminococcaceae, were more abundant in mothers of children with normative behaviour. A healthy prenatal diet indirectly related to decreased child internalising behaviours via higher alpha diversity of maternal faecal microbiota. These findings support animal studies showing that the composition of maternal prenatal gut microbiota is related to offspring brain development and behaviour. Our findings highlight the need to evaluate potential impacts of the prenatal gut microbiota on early life brain development. This study was funded by the National Health and Medical Research Council of Australia (1082307, 1147980), Murdoch Children's Research Institute, Barwon Health and Deakin University.