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Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders.
The emerging links between our gut microbiome and the central nervous system (CNS) are regarded as a paradigm shift in neuroscience with possible implications for not only understanding the pathophysiology of stress-related psychiatric disorders, but also their treatment. Thus the gut microbiome and its influence on host barrier function is positioned to be a critical node within the brain-gut axis. Mounting preclinical evidence broadly suggests that the gut microbiota can modulate brain development, function and behavior by immune, endocrine and neural pathways of the brain-gut-microbiota axis. Detailed mechanistic insights explaining these specific interactions are currently underdeveloped. However, the concept that a "leaky gut" may facilitate communication between the microbiota and these key signaling pathways has gained traction. Deficits in intestinal permeability may underpin the chronic low-grade inflammation observed in disorders such as depression and the gut microbiome plays a critical role in regulating intestinal permeability. In this review we will discuss the possible role played by the gut microbiota in maintaining intestinal barrier function and the CNS consequences when it becomes disrupted. We will draw on both clinical and preclinical evidence to support this concept as well as the key features of the gut microbiota which are necessary for normal intestinal barrier function.
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Association of Gut-Microbiome and mental health and effects of probiotics on psychiatric disorders: A Meta-analysis and systematic review.
BACKGROUND: A correlation between gut microbiome and mental health has drawn significant attention lately. The effects of microbiome microorganisms and their byproducts on disease states represent a complex and dynamic field of study. The objective of this article is to review the association of gut microbes and mental health and the effects of probiotics on psychiatric disorders, if any. METHODOLOGY: This meta-analysis was conducted using the PRISMA standards. We have compiled the most recent advancements in the field according to human research published in this Systematic review and meta-analysis. RESULTS: The forest plot analysis revealed that probiotics or probiotics combined with other intervention modalities did significantly reduce some extent of mental disorders in comparison to the control group (Standardized mean difference) SMD = 0.95, 95% Confidence Interval (CI): -6.52 to 8.42, P value< 0.01. CONCLUSION: Overall, the reviewed literature supports the importance of gut microbiota-brain interaction in human mental illnesses, including the impact of probiotics on mental health outcomes and brain connection.
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Sugary Drinks May Influence Depression Through Gut Microbiome.
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The Ruminal Microbiome and Metabolome Alterations Associated with Diet-Induced Milk Fat Depression in Dairy Cows.
Milk fat depression (MFD) syndrome represents a significant drawback to the dairy industry. The aim of this study was to unravel the ruminal metabolome-microbiome interaction in response to diet-induced MFD in dairy cows. Twelve healthy second parity Holstein dairy cows (days in milk (DIM) = 119 ± 14) were randomly assigned into control (CON, n = 6) group and treatment (TR, n = 6) group. Cows in TR group received a high-starch total mixed ration (TMR) designed to induce an MFD syndrome. Decreased milk fat yield and concentration in TR cows displayed the successful development of MFD syndrome. TR diet increased the relative abundance of Prevotella and decreased the relative abundance of unclassified Lachnospiraceae, Oribacterium, unclassified Veillonellaceae and Pseudobutyrivibrio in ruminal fluid. Metabolomics analysis revealed that the ruminal fluid content of glucose, amino acids and amines were significantly increased in TR cows compared with CON cows. Correlation analysis revealed that the concentration of amines and amino acids were highly correlated with the abundance of Oribacterium, Pseudobutyrivibrio, RC9_gut_group, unclassified BS11_gut_group and Selenomonas. In general, these findings revealed that TR diet reduced the rumination time and altered rumen fermentation type, which led to changes in the composition of ruminal microbiota and metabolites, and caused MFD.
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The gut microbiome in children with mood, anxiety, and neurodevelopmental disorders: An umbrella review.
Research on the gut microbiome and mental health among children and adolescents is growing. This umbrella review provides a high-level overview of current evidence syntheses to amalgamate current research and inform future directions. Searches were conducted across seven databases for peer-reviewed pediatric (<18 years) review literature. Studies reporting gut microbiome composition and/or biotic supplementation on depression, bipolar disorder, anxiety, attention deficit hyperactivity disorder, autism spectrum disorder (ASD), or obsessive-compulsive disorder (OCD) were included. Deduplication and screening took place in Covidence. A sensitivity analysis was conducted to assess the degree of primary study overlap. Among the 39 included review studies, 23 (59%) were observational and 16 (41%) were interventional. Most reviews (92%) focused on ASD. Over half (56%) of the observational and interventional reviews scored low or critically low for methodological quality. A higher abundance of Clostridium clusters and a lower abundance of Bifidobacterium were consistently observed in ASD studies. Biotic supplementation was associated with ASD symptom improvement. Gut microbiome-mental health evidence syntheses in child and youth depression, anxiety, bipolar disorder, and OCD are lacking. Preliminary evidence suggests an association between specific microbiota and ASD symptoms, with some evidence supporting a role for probiotic supplementation ASD therapy.
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Gut Microbiota and Depressive Symptoms at the End of CRT for Rectal Cancer: A Cross-Sectional Pilot Study.
BACKGROUND: The role of alterations in gut microbiota composition (termed dysbiosis) has been implicated in the pathobiology of depressive symptoms; however, evidence remains limited. This cross-sectional pilot study is aimed at exploring whether depressive symptom scores changed during neoadjuvant chemotherapy and radiation therapy to treat rectal cancer, and if gut microbial taxa abundances and predicted functional pathways correlate with depressive symptoms at the end of chemotherapy and radiation therapy. METHODS: 40 newly diagnosed rectal cancer patients (ages 28-81; 23 males) were assessed for depressive symptoms using the Hamilton Rating Scale for Depression (HAM-D) and provided stool samples for 16S rRNA sequencing. Gut microbiome data were analyzed using QIIME2, and correlations and regression analyses were performed in R. RESULTS: Participants had significantly higher depressive symptoms at the end as compared to before CRT. The relative abundances of Gemella, Bacillales Family XI, Actinomyces, Streptococcus, Lactococcus, Weissella, and Leuconostocaceae were positively correlated (Spearman's rho = 0.42 to 0.32), while Coprobacter, Intestinibacter, Intestimonas, Lachnospiraceae, Phascolarctobacterium, Ruminiclostridium, Ruminococcaceae (UCG-005 and uncultured), Tyzzerella, and Parasutterella (Spearman's rho = -0.43 to - 0.31) were negatively correlated with HAM-D scores. Of the 14 predicted MetaCyc pathways that correlated with depressive symptom scores at the end of CRT, 11 (79%) were associated with biosynthetic pathways. CONCLUSIONS: Significant bacterial taxa and predicted functional pathways correlated with depressive symptoms at the end of chemotherapy and radiation therapy for rectal cancer which warrants further examination and replication of our findings.
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Antidepressant effects of coumarins and their derivatives: A critical analysis of research advances.
Coumarins and their derivatives are non-flavonoids polyphenols with diverse pharmacological activities including anti-depressant effects. This study systematically examines the antidepressant effects of coumarins and their derivatives in relation to time series of research progress in the pharmacological pathways, association with other diseases, toxicity and bibliometric analysis. The review was approached using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) coupled with R package involving Biblioshiny, a web interface for Bibliometrix analysis and VOSviewer software analytic tools. Literature searches were conducted in Scopus, Web of Science, and PubMed from the inception through January 21, 2023. Coumarins, depression, coumarin derivatives and treatment were the main search terms used which resulted in the inclusion of 46 eligible publications. Scopoletin, psoralen, 7-hydroxycoumarin, meranzin hydrate, osthole, esculetin/umbelliferone were the most studied coumarins with antidepressant effects. Coumarins and their derivatives exerted antidepressant effects with a stronger affinity for monoamine oxidase-B (MAO-B) inhibition and, their inhibitory effect via neurotransmitter pathway on MAO is well-studied. However, epigenetic modification, neuroendocrine, neurotrophic pathways are understudied. Recent research focuses on their antidepressant effects which targeted cytokines and fibromyalgia. There is a link between the gut microbiome, the brain, and depression; meranzin hydrate exerts an antidepressant activity by remodelling the gastrointestinal system. We established that empirical data on some coumarins and their derivatives to support their antidepressant effects are limited. Likewise, the safe dose range for several coumarins and their derivatives is yet to be fully determined.
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Changes in the rodent gut microbiome following chronic restraint stress and low-intensity rTMS.
Gut microbiome composition is associated with mood-relating behaviours, including those reflecting depression-like phenotypes. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, is an effective treatment for depression, but its effects on the gut microbiome remain largely unknown. This study assessed microbial changes from rat faecal samples longitudinally following chronic restraint stress (CRS) and 10 Hz low-intensity rTMS treatment. CRS increased abundance within the Proteobacteria (Deltaproteobacteria, Desulfovibrionales) and Firmicutes (Anaerostipes, Frinsingococcus), with decreases in Firmicutes family (Acidaminococcaceae) and genera (Roseburia, Phascolarctobacterium and Fusicatenibacter) persisting for up to 4 weeks post CRS. The decrease in Firmicutes was not observed in the handling control and LI-rTMS groups, suggesting that handling alone may have sustained changes in gut microbiome associated with CRS. Nonetheless, LI-rTMS was specifically associated with an increase in Roseburia genus that developed 2 weeks after treatment, and the abundance of both Roseburia and Fusicatenibacter genera was significantly correlated with rTMS behavioural and MRI outcomes. In addition, LI-rTMS treated rats had a reduction in apoptosis pathways and several indicators of reduced inflammatory processes. These findings provide evidence that the brain can influence the gut microbiome in a "top-down" manner, presumably via stimulation of descending pathways, and/or indirectly via behavioural modification.
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Antidepressant Effects of Rosemary Extracts Associate With Anti-inflammatory Effect and Rebalance of Gut Microbiota.
It is currently believed that inflammation acts as a central part in the pathophysiology of depression. Rosemary extracts (RE), the crucial active constituents extracted from Rosmarinus officinalis Linn, have drawn wide concerns because of their potential for anti-inflammatory effects. However, no study has highlighted the antidepressant effects of RE on chronic restraint stress (CRS) mice, and the inflammatory mechanisms related to gut microbiome have not yet been elucidated. This study showed that depressive-like behaviors, gut microbiota dysbiosis, and activation of inflammatory reactions in the hippocampus and serum of CRS mice, as well as activation of inflammatory reactions in BV-2 microglia cells induced by lipopolysaccharide (LPS), could be attenuated by RE. We found that the pretreatment with RE increased the time in the center of open field test (OFT), and decreased immobility duration in tail suspension test (TST) as well as forced swimming test (FST). Furthermore, RE enhanced the sequences proportion of Lactobacillus and Firmicutes, and reduced the sequences proportion of Bacteroidetes and Proteobacteria in feces. Moreover, RE obviously suppressed protein expression of IL-1β, TNF-α, p-NF-κ B p65 and Iba1 in hippocampus, and elevated BDNF as well as p-AKT/AKT expression. Importantly, pre-incubation with RE protected microglia by alleviating protein expression of IL-1β, TNF-α and p-NF-κ B p65 induced by LPS. Additionally, RE downregulated the level of IL-1β and TNF-α in serum. In conclusion, this study showed the antidepressant effects of RE are mediated by anti-inflammatory effects in hippocampus, serum and BV-2 microglia as well as rebalancing gut microbiota.
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Lacticaseibacillus rhamnosus HN001 alters the microbiota composition in the cecum but not the feces in a piglet model.
The probiotic Lacticaseibacillus rhamnosus strain HN001 has been shown to have several beneficial health effects for both pediatric and maternal groups, including reduced risk of eczema in infants and gestational diabetes and postnatal depression in mothers. While L. rhamnosus HN001 appears to modify immune and gut barrier biomarkers, its mode of action remains to be fully elucidated. To gain insights into the role of HN001 on the infant microbiome, the impacts of L. rhamnosus HN001 supplementation was studied in 10-day old male piglets that were fed either infant formula, or infant formula with L. rhamnosus HN001 at a low (1.3 × 105 CFU/ml) or high dose (7.9 × 106 CFU/ml) daily for 24 days. The cecal and fecal microbial communities were assessed by shotgun metagenome sequencing and host gene expression in the cecum and colon tissue was assessed by RNA-seq. Piglet fecal samples showed only modest differences between controls and those receiving dietary L. rhamnosus HN001. However, striking differences between the three groups were observed for cecal samples. While total lactobacilli were significantly increased only in the high dose L. rhamnosus HN001 group, both high and low dose groups showed an up to twofold reduction across the Firmicutes phylum and up to fourfold increase in Prevotella compared to controls. Methanobrevibacter was also decreased in HN001 fed piglets. Microbial genes involved in carbohydrate and vitamin metabolism were among those that differed in relative abundance between those with and without L. rhamnosus HN001. Changes in the cecal microbiome were accompanied by increased expression of tight junction pathway genes and decreased autophagy pathway genes in the cecal tissue of piglets fed the higher dose of L. rhamnosus HN001. Our findings showed supplementation with L. rhamnosus HN001 caused substantial changes in the cecal microbiome with likely consequences for key microbial metabolic pathways. Host gene expression changes in the cecum support previous research showing L. rhamnosus HN001 beneficially impacts intestinal barrier function. We show that fecal samples may not adequately reflect microbiome composition higher in the gastrointestinal tract, with the implication that effects of probiotic consumption may be missed by examining only the fecal microbiome.