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Assessing the long-term effects of microbial therapeutics as treatment within psychiatry: a systematic review.
BACKGROUND: The management and treatment of psychiatric disorders by manipulating the gut microbiome and utilizing microbial therapeutics, via modulation of the gut-brain-axis, has been a rapidly growing field of research. Given the novelty of using microbial therapeutics within psychiatry, a growing number of studies have investigated their use as treatment for various psychiatric disorders and symptoms. However, few studies have explored the longitudinal efficacy of these treatments. This review aims to summarize the findings of any studies assessing the long-term effects of gut-related interventions on mood and psychiatric symptoms. METHODS: A systematic search of 4 databases (Embase, PsycINFO, Medline, Web of Science) from inception to May 28, 2025, informed by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and using key words relating to microbial therapeutics, psychiatric disorders, and long-term effects was conducted. Findings were included or excluded using pre-determined eligibility criteria such as being been written in English and published by a peer-reviewed journal, assessed for quality using the Cochrane Handbook for Systematic Reviews of Interventions Risk of Bias tool, and qualitatively evaluated. RESULTS: The search yielded 4175 studies, of which 1274 duplicates were removed. All remaining studies underwent abstract screening, from which 70 records were full-text screened and a total of ten clinical studies (n = 10) met eligibility criteria and were included in the review. The majority of studies explored the effects of microbial therapeutics such as fecal microbiota transplant and probiotics, as treatment for disorders of the gastrointestinal tract as the primary scope, with additional outcome measures assessing psychiatric well-being. The review presented with mixed findings: many studies reported a sustained improvement in symptoms of depression and anxiety ranging from 3- to 18-months post-treatment, while others reported the opposite with no sustained long-term improvement in mood-related symptoms. There was also a lack of consistency across follow-up duration between studies, making it difficult to compare findings. CONCLUSIONS: Overall, this review highlighted the need for more placebo-controlled studies with larger sample sizes to effectively evaluate the longitudinal potential of microbial therapeutics as treatment for mood-disturbances and psychiatric symptoms. With consideration for the limitations of this field, these results provide evidence that there may be long-term benefits of targeting the gut microbiome as treatment for mood-related disturbances.
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Prenatal Depression, Breastfeeding, and Infant Gut Microbiota.
Depressive symptoms are common during pregnancy and are estimated to affect 7-20% of pregnant women, with higher prevalence found in those with a prior history of depression, in ethnic minorities, and those with increased exposure to stressful life events. Maternal depression often remains undiagnosed, and its symptoms can increase adverse health risks to the infant, including impaired cognitive development, behavioral problems, and higher susceptibility to physical illnesses. Accumulating research evidence supports the association between maternal physical health elements to infant gut health, including factors such as mode of delivery, medication, feeding status, and antibiotic use. However, specific maternal prenatal psychosocial factors and their effect on infant gut microbiota and immunity remains an area that is not well understood. This article reviews the literature and supplements it with new findings to show that prenatal depression alters: (i) gut microbial composition in partially and fully formula-fed infants at 3-4 months of age, and (ii) gut immunity (i.e., secretory Immunoglobulin A) in all infants independent of breastfeeding status. Understanding the implications of maternal depression on the infant gut microbiome is important to enhance both maternal and child health and to better inform disease outcomes and management.
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Akkermansia muciniphila improving depression-like behaviors by regulating glycerophospholipid metabolism in gut-brain axis.
BACKGROUND: Akkermansia muciniphila (AKK) is a potential probiotic. Our previous studies have shown that it could alleviate depressive-like behaviors (DLBs) in mice by inhibiting neuroinflammation in brain. To further explore its antidepressant effect, this study focused on the effects of AKK on the metabolic activities in gut-brain axis. METHODS: After chronic restraint stress (CRS) depression model was successfully built, AKK was used as intervention method for 3 weeks. The gut microbiome in feces and two intestinal permeability proteins in colon (Claudin-1, Occludin) were measured, and the metabolites in feces, colon, liver, and prefrontal cortex were also measured. In addition, two inflammation-related factors in hippocampus (Free fatty acid receptors 3 (FFAR3), phosphorylated NF-κB p65 (p-p65)) were measured. RESULTS: AKK was successfully colonized in gut of chronic restraint stress (CRS) mice. The DLBs in CRS mice receiving AKK (CRS + AKK) were significantly improved, along with the improved gut microbiome. Both Claudin-1 and Occludin in colon were significantly increased in CRS + AKK mice compared to CRS mice receiving phosphate buffer saline (PBS) (CRS + p). Metabolomics analysis indicated that AKK could significantly improve the changed lipids and lipid-like molecules in gut-brain axis of CRS mice; and function analysis using differential metabolites showed that AKK could significantly improve the disordered glycerophospholipid metabolism in feces, colon, liver, and prefrontal cortex of CRS mice. Additionally, we found that FFAR3 and phosphorylated NF-κB p65 were increased and decreased, respectively, in hippocampus of CRS + AKK mice compared to CRS + p mice. CONCLUSION: Our results suggested that AKK might improve the disturbances of gut microbiome, intestinal permeability, host's lipid metabolism and inflammation levels in hippocampus. Glycerophospholipid metabolism in gut-brain axis might be the important mediator in the process of AKK producing antidepressants effects.
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The butyrate-producing and spore-forming bacterial genus Coprococcus as a potential biomarker for neurological disorders.
The host-intestinal microbiome interaction has gained much scientific attention in the past two decades, boosted by advances in DNA sequencing and cultivation techniques. An accumulating amount of evidence shows that gut microbes play crucial roles in gut homeostasis, immune system education, and are associated with quality-of-life indicators. Beneficial health factors are associated with the digestion of dietary fibres in the colon and the subsequent production of short-chain fatty acids, including acetate, propionate, and butyrate. Coprococcus is a butyrate-producing genus in the phylum Firmicutes, and its abundance is inversely correlated with several neuropsychological and neurodegenerative disorders. Case-control studies provide strong evidence of decreased abundance of Coprococcus spp. in depressed individuals. The species Coprococcus eutactus has the unique capacity to use two separate pathways for butyrate synthesis and has been found to be depleted in children with delayed language development and adults with Parkinson's disease. The combined literature on Coprococcus and the gut microbiota-brain axis points towards enhanced butyrate production and reduced colonisation of pathogenic clades as factors explaining its association with health effects. The genus Coprococcus is a promising candidate for a mental health biomarker and an interesting lead for novel dietary-based preventive therapies for specific neurological disorders.
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Gut microbiota: emerging biomarkers and potential therapeutics for premature ovarian failure.
Premature ovarian failure is a prevalent gynecological endocrine disorder with an increasing incidence rate each year, impacting women's physical and mental health. The causes of POF are poorly understood, but genetic, immune, iatrogenic, environmental, and psychological factors are key contributors. Clinically, POF manifests as oligomenorrhea, amenorrhea, elevated follicle-stimulating hormone (FSH) levels, and decreased estrogen levels, leading to infertility in women. POF not only impacts reproductive function but also elevates the risk of cardiovascular diseases, osteoporosis, depression, anxiety, cognitive decline, and neurological disorders, thereby adversely affecting women's mental health and quality of life over the long term. The gut microbiota (GM) comprises a vast and complex microbial community within the human gastrointestinal tract. GM dysregulation is closely associated with numerous human diseases, including autoimmune diseases, allergic disorders, cardiovascular diseases, cancers, and metabolic disorders. Studies have shown that GMs play a pivotal role in female reproductive health, participating in the pathogenesis of reproductive endocrine disorders through direct or indirect involvement in sex hormone regulation, stimulation of inflammatory cytokine production, modulation of immune function, metabolic homeostasis, and regulation of neurotransmitter synthesis. Recently, advancements in human microbiology have highlighted the significant interest in the connection between POF and the gut microbiome. Researching the molecular mechanisms by which GMs and their metabolites regulate the occurrence of POF opens up a new direction for studying the pathogenesis of POF. This research aims to identify an efficient, non-invasive, and accurate diagnostic method for clinical diagnosis and treatment of POF, providing novel theoretical insights and precise intervention strategies for the clinical prevention and treatment of POF.
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Acute intake of B. longum probiotic does not reduce stress, anxiety, or depression in young adults: A pilot study.
BACKGROUND: The gut microbiome communicates bidirectionally with the brain, linking the gut to psychological phenomena such as stress, depression, and anxiety. Probiotics, or ingestible supplements containing billions of mutualistic bacteria, have demonstrated the mechanistic potential to influence mood; however, few studies have experimentally examined the acute effects of these compounds on individuals not recruited for psychopathology or gut dysfunction. The present study hypothesized reductions in stress, anxiety and depression symptoms following an acute, one week dosing period of B. longum intake. METHODS: The efficacy of a one-week period of orally administered B. longum was tested utilizing a double-blind experimental design. Participants were randomly assigned to either placebo or probiotic capsules under double blinded conditions and completed the Perceived Stress Scale (PSS), the Center for Epidemiological Studies Depression scale (CES-D), and the State-Trait Anxiety Inventory (STAI Y2 form) to assess for differences before and after one-week intervention. RESULTS: No significant reduction in symptoms between groups over the one-week period was found. CONCLUSIONS: These findings suggest that 7-days of B. longum does not reduce stress, depressive symptoms, or anxiety in generally healthy young adults.
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Seasonal dynamics and starvation impact on the gut microbiome of urochordate ascidian Halocynthia roretzi.
BACKGROUND: Gut microbiota plays important roles in host animal metabolism, homeostasis and environmental adaptation. However, the interplay between the gut microbiome and urochordate ascidian, the most closet relative of vertebrate, remains less explored. In this study, we characterized the gut microbial communities of urochordate ascidian (Halocynthia roretzi) across the changes of season and starvation stress using a comprehensive set of omic approaches including 16S rRNA gene amplicon sequencing, shotgun metagenomics, metabolomic profiling, and transcriptome sequencing. RESULTS: The 16S rRNA gene amplicon profiling revealed that ascidians harbor indigenous gut microbiota distinctly different to the marine microbial community and significant variations in composition and abundance of gut bacteria, with predominant bacterial orders representing each season. Depressed alpha-diversities of gut microbiota were observed across starvation stress when compared to the communities in aquafarm condition. Synechococcales involving photosynthesis and its related biosynthesis was reduced in abundance while the enrichments of Xanthomonadales and Legionellales may facilitate bile acid biosynthesis during starvation. Metabolomics analysis found that long chain fatty acids, linolenic acid, cyanoamino acid, and pigments derived from gut bacteria were upregulated, suggesting a beneficial contribution of the gut microbiome to the ascidian under starvation stress. CONCLUSIONS: Our findings revealed seasonal variation of ascidian gut microbiota. Defense and energy-associated metabolites derived from gut microbiome may provide an adaptive interplay between gut microbiome and ascidian host that maintains a beneficial metabolic system across season and starvation stress. The diversity-generating metabolisms from both microbiota and host might lead to the co-evolution and environmental adaptation.
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Gut thinking: the gut microbiome and mental health beyond the head.
Background: In recent decades, dominant models of mental illness have become increasingly focused on the head, with mental disorders being figured as brain disorders. However, research into the active role that the microbiome-gut-brain axis plays in affecting mood and behaviour may lead to the conclusion that mental health is more than an internalised problem of individual brains. Objective: This article explores the implications of shifting understandings about mental health that have come about through research into links between the gut microbiome and mental health problems such as depression and anxiety. It aims to analyse the different ways that the lines between mind and body and mental and physical health are re-shaped by this research, which is starting to inform clinical and public understanding. Design: As mental health has become a pressing issue of political and public concern it has become increasingly constructed in socio-cultural and personal terms beyond clinical spaces, requiring a conceptual response that exceeds biomedical inquiry. This article argues that an interdisciplinary critical medical humanities approach is well positioned to analyse the impact of microbiome-gut-brain research on conceptions of mind. Results: The entanglement of mind and matter evinced by microbiome-gut-brain axis research potentially provides a different way to conceptualise the physical and social concomitants of mental distress. Conclusion: Mental health is not narrowly located in the head but is assimilated by the physical body and intermingled with the natural world, requiring different methods of research to unfold the meanings and implications of gut thinking for conceptions of human selfhood.
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Stress and depression-associated shifts in gut microbiota: A pilot study of human pregnancy.
BACKGROUND: Psychosocial stress and mood-related disorders, such as depression, are prevalent and vulnerability to these conditions is heightened during pregnancy. Psychosocial stress induces consequences via several mechanisms including the gut microbiota-brain axis and associated signaling pathways. Previous preclinical work indicates that prenatal stress alters maternal gut microbial composition and impairs offspring development. Importantly, although the fecal and vaginal microenvironments undergo alterations across pregnancy, we lack consensus regarding which shifts are adaptive or maladaptive in the presence of prenatal stress and depression. Clinical studies interrogating these relationships have identified unique taxa but have been limited in study design. METHODS: We conducted a prospective cohort study of pregnant individuals consisting of repeated administration of psychometrics (Perceived Stress Scale (PSS) and Center for Epidemiological Studies Depression Scale (CES-D)) and collection of fecal and vaginal microbiome samples. Fecal and vaginal microbial community composition across psychometric responses were interrogated using full-length 16S rRNA sequencing followed by α and β-diversity metrics and taxonomic abundance. RESULTS: Early pregnancy stress was associated with increased abundance of fecal taxa not previously identified in related studies, and stress from late pregnancy through postpartum was associated with increased abundance of typical vaginal taxa and opportunistic pathogens in the fecal microenvironment. Additionally, in late pregnancy, maternal stress and depression scores were associated with each other and with elevated maternal C-C motif chemokine ligand 2 (CCL2) concentrations. At delivery, concordant with previous literature, umbilical CCL2 concentration was negatively correlated with relative abundance of maternal fecal Lactobacilli. Lastly, participants with more severe depressive symptoms experienced steeper decreases in prenatal vaginal α-diversity. CONCLUSION: These findings a) underscore previous preclinical and clinical research demonstrating the effects of prenatal stress on maternal microbiome composition, b) suggest distinct biological pathways for the consequences of stress versus depression and c) extend the literature by identifying several taxa which may serve critical roles in mediating this relationship. Thus, further interrogation of the role of specific maternal microbial taxa in relation to psychosocial stress and its sequelae is warranted.
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Vitamin-mediated interaction between the gut microbiome and mitochondria in depression: A systematic review-based integrated perspective.
Depression is one of the world's most prevalent mental disorders and its treatment remains suboptimal. Depression is a systemic disease with highly complex biological mechanisms. Emerging evidence points towards the involvement of mitochondria, microbiome and vitamins in its pathophysiology. Mitochondrial energy production was shown to be lowered in patients with depression. Mitochondrial energy production depends on vitamins, which are available from food, but are also synthesized by the gut microbiota. Several studies reported altered vitamin levels as well as changes in the gut microbiome composition and its vitamin metabolism in patients with depression. Therefore, the question of a connection between mitochondria and gut microbiome and vitamins influencing the mental health arises. This review aims to systematically investigate a combination of the topics - depression, mitochondria, microbiome, and vitamins - to generate an overview of a novel yet extremely complex and interconnected research field. A systematic literature search yielded 34 articles, and the results were summarized and bundled to develop this new integrative perspective on mitochondrial function mediated by the microbiome and microbiome-derived vitamins in depression. Furthermore, by discussing the research gaps this review aims to encourage innovative research approaches to better understand the biology of depression, which could result in optimized therapeutic approaches.