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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.
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Limosilactobacillus fermentum WIS32 alleviates LPS-induced depression-like behavior via the microbiota-gut-brain axis.
INTRODUCTION: In recent years, the global incidence of depression has continued to rise, posing a severe threat to physical and mental health as well as overall quality of life. While Lactobacillus, as a significant probiotic, has demonstrated remarkable potential in alleviating depressive symptoms, the specific mechanisms of Limosilactobacillus fermentum in depression have not been fully elucidated. This study aimed to evaluate the antidepressant effects of L. fermentum WIS32 and explore its underlying mechanisms via the microbiota-gut-brain axis (MGBA). METHODS: A cross-cohort meta-analysis was initially conducted to assess the abundance of L. fermentum in the gut microbiota of patients with depression. Subsequently, in vitro experiments were performed to evaluate the gastrointestinal tolerance, antioxidant capacity, and antibacterial properties of WIS32 compared to a control strain, LFG89. In vivo, a lipopolysaccharide (LPS)-induced mouse model of depression was established to assess the effects of WIS32 intervention on behavioral phenotypes, hippocampal neurochemicals (5-HT and BDNF), and serum pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). Finally, full-length 16S rRNA sequencing and correlation analyses were utilized to examine the remodeling of the gut microbiota structure. RESULTS: The meta-analysis revealed a significant reduction in the abundance of L. fermentum in patients with depression. In vitro assessments demonstrated that WIS32 exhibited superior gastrointestinal tolerance, antioxidant capacity, and antibacterial properties compared to LFG89. In vivo, WIS32 intervention significantly ameliorated LPS-induced depressive-like behaviors, upregulated 5-HT and BDNF levels in the hippocampus, and inhibited serum pro-inflammatory cytokines. Furthermore, 16S rRNA sequencing indicated that WIS32 significantly remodeled the gut microbiota by promoting beneficial taxa, such as Bacteroides stercorirosoris and Massilimaliae timonensis, while inhibiting pro-inflammatory pathogens like Streptococcus-effects that were more pronounced than those of LFG89. Correlation analysis confirmed that these microbial shifts were strongly associated with reduced inflammation and enhanced neuroplasticity. DISCUSSION: These findings demonstrate that L. fermentum WIS32 effectively alleviates depressive symptoms by modulating key taxa within the gut microbiota to suppress inflammation and promote neuroplasticity. Therefore, L. fermentum WIS32 holds significant promise as a potential psychobiotic for the treatment and management of depression.
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Adolescent Dietary Supplementation of Omega-3 Polyunsaturated Fatty Acids Alleviates PTSD-Like Fear Memory and Affective Dysregulation in Rats.
Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder affecting approximately 3.9% of individuals worldwide over their lifetimes. Since adolescence is characterized by ongoing brain maturation and increased responsiveness to environmental stressors, this developmental stage may provide an important window for PTSD intervention. Growing evidence supports an association between ω-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and the restoration of stress-induced neural damage. However, how ω-3 PUFA supplementation during adolescence affects adult susceptibility to PTSD remains poorly understood. Here, we observed significantly reduced DHA and EPA concentrations in the prefrontal cortex (PFC) and serum of PTSD-susceptible rats. Providing 1.2% DHA and EPA in the adolescent diet significantly reduced PTSD-like phenotypes in adulthood, including excessive fear memory retention, depressive-like and anxiety-like behaviors, while also reducing serum levels of proinflammatory cytokines. These phenotypic and inflammatory improvements were associated with changes in the gut microbiome, including its composition and diversity. DHA/EPA supplementation was also linked to alterations in multiple lipid species, with serum phosphatidylcholine levels showing a significant correlation with fear memory expression. Moreover, we observed dysregulation of the PI3K/AKT/mTOR pathway in the PFC of PTSD-like rats, which was less pronounced in DHA/EPA-supplemented animals. Collectively, these findings provide the first evidence relating adolescent ω-3 PUFA status to PTSD-like phenotypes in adulthood. It further identifies that gut microbiota composition, lipid metabolic profiles (notably phosphatidylcholine), and prefrontal PI3K/AKT/mTOR signaling are correlated with these behavioral outcomes, suggesting that these systems may collectively contribute to trauma resilience.
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Improvements of Age-Related Cognitive Decline in Mice by Lactobacillus helveticus WHH1889, a Novel Strain with Psychobiotic Properties.
A gradual decline in cognitive function occurs with age. Accumulating evidence suggests that certain probiotic strains exert beneficial effects on age-related cognitive decline. Our previous study revealed that Lactobacillus helveticus WHH1889 attenuated symptoms of anxiety and depression in depressed mice via shaping the 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan (5-HTP) metabolism and gut microbial community, indicating the psychobiotic potential of WHH1889. In the present study, the effects of WHH1889 on age-related cognitive decline were investigated. WHH1889 was orally administrated (1 × 109 CFU/day) for twelve weeks in aged mice, and their cognitive behaviors, neurochemical factors, cognitive-related gene expressions, neuroinflammation, and serum tryptophan pathway-targeted metabolic profiling, as well as gut microbiome composition were assessed. WHH1889 demonstrated improvement of the cognitive behaviors via the novel object recognition test (NORT), the active shuttle avoidance test (ASAT), the Y-maze test, and the passive avoidance test (PAT). The hippocampal neuronal loss; the declined concentrations of BDNF, 5-HT, and 5-HTP; the decreased gene expressions of neurodegeneration biomarkers; and the increased production of hippocampal inflammatory cytokines in aged mice were restored by WHH1889. In addition, WHH1889 increased the 5-HT/5HTP levels and decreased the serum levels of tryptophan-derived metabolites (e.g., kynurenine, xanthurenic acid, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid). Furthermore, WHH1889 was revealed to shape the gut microbiota community by reversing the relative abundances of Bacteroidota and Firmicutes. The present findings suggest that L. helveticus WHH1889 exerted cognitive improving effects on aged mice, which was associated with the modulation of 5-HT and 5-HTP metabolism and gut microbial composition. The supplementation of WHH1889 may therefore be a promising therapeutic agent for age-related cognitive deficits.
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The Role of the Gut Microbiome in Psychiatric Disorders.
The role of the gut microbiome in mental health has been of great interest in the past years, with several breakthroughs happening in the last decade. Its implications in several psychiatric disorders, namely anxiety, depression, autism and schizophrenia, are highlighted. In this review were included relevant studies on rodents, as well as human studies. There seems to be a connection between the gut microbiome and these pathologies, the link being emphasized both in rodents and humans. The results obtained in murine models align with the results acquired from patients; however, fewer studies regarding anxiety were conducted on humans. The process of sequencing and analyzing the microbiome has been conducted in humans for several other pathologies mentioned above. Additionally, the possible beneficial role of probiotics and postbiotics administered as an aid to the psychiatric medication was analyzed.
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Potential Role of the Microbiome in Acne: A Comprehensive Review.
Acne is a highly prevalent inflammatory skin condition involving sebaceous sties. Although it clearly develops from an interplay of multiple factors, the exact cause of acne remains elusive. It is increasingly believed that the interaction between skin microbes and host immunity plays an important role in this disease, with perturbed microbial composition and activity found in acne patients. Cutibacterium acnes (C. acnes; formerly called Propionibacterium acnes) is commonly found in sebum-rich areas and its over-proliferation has long been thought to contribute to the disease. However, information provided by advanced metagenomic sequencing has indicated that the cutaneous microbiota in acne patients and acne-free individuals differ at the virulent-specific lineage level. Acne also has close connections with the gastrointestinal tract, and many argue that the gut microbiota could be involved in the pathogenic process of acne. The emotions of stress (e.g., depression and anxiety), for instance, have been hypothesized to aggravate acne by altering the gut microbiota and increasing intestinal permeability, potentially contributing to skin inflammation. Over the years, an expanding body of research has highlighted the presence of a gut-brain-skin axis that connects gut microbes, oral probiotics, and diet, currently an area of intense scrutiny, to acne severity. This review concentrates on the skin and gut microbes in acne, the role that the gut-brain-skin axis plays in the immunobiology of acne, and newly emerging microbiome-based therapies that can be applied to treat acne.
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Assessing the effect of interaction between gut microbiome and inflammatory bowel disease on the risks of depression.
BACKGROUND: Gut microbiome and inflammatory bowel disease (IBD) are implicated in the development of depression, but the effect of their interactions on the risk of depression remains unclear. We aim to analyze the effect of interactions between gut microbiome and IBD on the risk of depression, and explore candidate genes involving the interactions. METHODS: Using the individual genotype and depression traits data from the UK Biobank, we calculated the polygenetic risk scores (PRS) of 114 gut microbiome, ulcerative colitis (UC), Crohn's disease (CD), and total IBD (CD + UC) respectively. The effects of interactions between gut microbiome and IBD on depression were assessed through a linear regression model. Moreover, for observed significant interactions between gut microbiome PRS and IBD PRS, PLINK software was used to test pair-wise single nucleotide polymorphisms (SNPs) interaction of corresponding gut microbiome PRS and IBD PRS on depression. RESULTS: We found 64 candidate interactions between gut microbiome and IBD on four phenotypes of depression, such as F_Lachnospiraceae (RNT) × (CD + UC) for patient health questionnaire-9 (PHQ-9) score (P = 1.48 × 10-3), F_Veillonellaceae (HB) × UC for self-reported depression (P = 2.83 × 10-3) and P_Firmicutes (RNT) × CD for age at first episode of depression (P = 8.50 × 10-3). We observed interactions of gut-microbiome-associated SNPs × IBD-associated SNPs, such as G_Alloprevotella (HB)-associated rs147650986 (GPM6A) × IBD-associated rs114471990 (QRICH1) (P = 2.26 × 10-4). CONCLUSION: Our results support the effects of interactions between gut microbiome and IBD on depression risk, and reported several novel candidate genes for depression.
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The Role of Diet on the Gut Microbiome, Mood and Happiness.
The gut microbiome may be both helpful and harmful, and not only is it affected by diet, it has also been shown to affect mental health including personality, mood, anxiety and depression. In this clinical study we assessed dietary nutrient composition, mood, happiness, and the gut microbiome in order to understand the role of diet in the gut microbiome and how that affects mood and happiness. For this pilot study, we enrolled 20 adults to follow this protocol: recording a 2-day food log, sampling their gut microbiome, and completing five validated surveys of mental health, mood, happiness and well-being, followed by a minimum 1 week diet change and repeating the food log, microbiome sampling and the 5 surveys. The change from a predominantly Western diet to vegetarian, Mediterranean and ketogenic diets led to changes in calorie and fiber intake. After the diet change, we observed significant changes in measures of anxiety, well-being and happiness, and without changes in gut microbiome diversity. We found strong correlations between greater consumption of fat and protein to lower anxiety and depression, while consuming higher percentages of carbohydrates was associated with increased stress, anxiety, and depression. We also found strong negative correlations between total calories and total fiber intake with gut microbiome diversity without correlations to measures of mental health, mood or happiness. We have shown that changing diet affects mood and happiness, that greater fat and carbohydrate intake is directly associated with anxiety and depression and inversely correlated with gut microbiome diversity. This study is an important step towards understanding how our diet affects the gut microbiome and in turn our mood, happiness and mental health.
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The Future Potential of Biosensors to Investigate the Gut-Brain Axis.
The multifaceted and heterogeneous nature of depression presents challenges in pinpointing treatments. Among these contributions are the interconnections between the gut microbiome and neurological function termed the gut-brain axis. A diverse range of microbiome-produced metabolites interact with host signaling and metabolic pathways through this gut-brain axis relationship. Therefore, biosensor detection of gut metabolites offers the potential to quantify the microbiome's contributions to depression. Herein we review synthetic biology strategies to detect signals that indicate gut-brain axis dysregulation that may contribute to depression. We also highlight future challenges in developing living diagnostics of microbiome conditions influencing depression.