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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.
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The gut microbiome and child and adolescent depression and anxiety: a systematic review and meta-analysis with youth consultation.
Decreased gut microbial diversity is associated with greater depression symptoms in adults. Findings on the relationship between the gut microbiome and depression or anxiety in children and adolescents are mixed, and evidence syntheses are needed. Seven databases were searched for peer-reviewed studies on the gut microbiome and internalizing symptoms, depression, or anxiety, in children and adolescents (<19 years). Random-effects meta-analyses of alpha diversity indices were performed. Youth advisors validated the research findings' relevance to their experiences and contributed to dissemination planning. Eight studies were included, representing 2,865 participants (mean age = 11.4 years, SD = 4.3). Study designs were cross-sectional (n = 5), longitudinal (n = 2), and interventional (n = 1). No association was found between alpha or beta diversity and internalizing problems, depression, or anxiety. Increased abundance of genera within phyla Bacillota (e.g., Fusicatenibacter) and Pseudomonadota (e.g., Escherichia), along with decreased abundance of other Bacillota genera (e.g., Faecalibacterium), were associated with depression and anxiety symptoms. This review identified preliminary associations between specific bacterial taxa and depression and anxiety in children and adolescents. Larger studies using comprehensive analytical approaches are needed to explore the role of the gut microbiome in the genesis and treatment of internalizing disorders.
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Reproducible microbiome composition signatures of anxiety and depressive symptoms.
The gut microbiome is a significant contributor to mental health, with growing evidence linking its composition to anxiety and depressive disorders. Gut microbiome composition is associated with signs of anxiety and depression both in clinically diagnosed mood disorders and subclinically in the general population and may be influenced by dietary fibre intake and the presence of chronic pain. We provide an update of current evidence on the role of gut microbiome composition in depressive and anxiety disorders or symptoms by reviewing available studies. Analysing data from three independent cohorts (osteoarthritis 1 (OA1); n = 46, osteoarthritis 2 (OA2); n = 58, and healthy controls (CON); n = 67), we identified microbial composition signatures of anxiety and depressive symptoms at genus level and cross-validated our findings performing meta-analyses of our results with results from previously published studies. The genera Bifidobacterium (fixed-effect beta (95% CI) = -0.22 (-0.34, -0.10), p = 3.90e-04) and Lachnospiraceae NK4A136 group (fixed-effect beta (95% CI) = -0.09 (-0.13, -0.05), p = 2.53e-06) were found to be the best predictors of anxiety and depressive symptoms, respectively, across our three cohorts and published literature taking into account demographic and lifestyle covariates, such as fibre intake. The association with anxiety was robust in accounting for heterogeneity between cohorts and supports previous observations of the potential prophylactic effect of Bifidobacterium against anxiety symptoms.