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Probiotics in pregnancy: protocol of a double-blind randomized controlled pilot trial for pregnant women with depression and anxiety (PIP pilot trial).
BACKGROUND: Maternal prenatal depressive or anxiety symptoms are associated with adverse maternal and infant health outcomes. With prevalence rates of maternal prenatal depression and anxiety ranging between 10 and 20%, attempts to identify effective interventions to reduce symptoms are priority. There are indications that probiotics can reduce symptoms of maternal depression or anxiety. Probiotics ingested by the mother may thus offer a promising and accessible intervention to complement existing treatments. METHODS: The Probiotics in Pregnancy (PIP) pilot trial is a double-blind, placebo-controlled, randomized pilot trial. While one group orally consumes a probiotic mixture (Ecologic® Barrier; 2,5 × 109 colony forming units/g; 2 g; daily), the other group consumes a placebo, from between 26 and 30 weeks gestation until delivery. Subjects are randomly allocated (1:1) to the intervention or placebo group. Forty healthy pregnant women with symptoms of depression or anxiety and uncomplicated pregnancies at randomization will be included. The primary aim is to determine the feasibility and acceptability of a probiotic trial to reduce symptoms of maternal depression or anxiety in pregnancy. The secondary aim is to exploratorily compare the potential effect of probiotics, compared to placebo, on depressive and/or anxiety symptoms, maternal stress (i.e. reported/hair cortisol), maternal vaginal and intestinal microbiota, and by possibly affecting maternal mood and microbiota, maternal bonding to offspring, infant microbiota and infant crying. DISCUSSION: Results of this pilot trial will help determine whether or not to proceed with a full trial after the pilot trial, and if so, whether revisions should be made to the study protocol and procedures before conducting a full randomized controlled trial. Additionally, they are expected to provide insights into whether changes in psychological, behavioral and biological parameters can be attributed to the probiotic intervention. TRIAL REGISTRATION: Netherlands Trial Register, NTR6219 . Registered on 28 February 2017.
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Valeriana jatamansi jones improves depressive behavior in CUMS mice by modulating vitamin B12-related ileal homeostasis.
ETHNOPHARMACOLOGICAL RELEVANCE: Valeriana jatamansi Jones (V. jatamansi) is a traditional Chinese medicine (TCM). It was recorded in Diannan Bencao, Compendium of Materia Medica and some local medical books and was described as useful in treating insomnia, distraction, poor mental health, vomiting and diarrhea. AIM OF THE STUDY: To investigate whether the antidepressant effect of V. jatamansi may operate through modulating vitamin B12-related ileal homeostasis using a chronic unpredictable mild stress (CUMS) mouse model. MATERIALS AND METHODS: A CUMS-induced depression model was established in mice for five weeks, after which V. jatamansi extracts were administered for three weeks. At week eight, the forced swimming test and novelty-suppressed feeding test were conducted. H&E staining assessed ileal pathology, while 16S rDNA sequencing analyzed changes in ileal microbiota. Additionally, B12 in serum, cubilin (CUBN) and amnionless (AMN) in ileal tissue, methionine synthase (MS) and homocysteine (Hcy) in the hippocampus were measured using ELISA, and the correlations between them and ileal microbiota were explored. RESULTS: Mice in the model group exhibited significant depressive behavior. However, after treatment with V. jatamansi, immobility time and feeding latency were improved. H&E staining demonstrated the repairing effect of V. jatamansi on the ileum regarding tissue damage. The alpha and beta diversity of the ileal microbiota were regulated and converged to the normal group. Additionally, V. jatamansi modulated B12, CUBN, AMN, MS, and Hcy levels. Correlation analysis showed that there are certain correlations between a variety of microorganisms and B12-related factors. CONCLUSION: These findings suggest that the mechanism of V. jatamansi in treating depression may be through repairing depression-associated intestinal damage. This repair process may affect the intestinal absorption and microbial production of B12. By reversing the reduction of serum B12, V. jatamansi ultimately reduces the infiltration of Hcy into the CNS.
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A diet-induced gut microbiota component and related plasma metabolites are associated with depressive-like behaviour in rats.
It is well-established in preclinical studies that various probiotics may improve behaviours related to psychiatric disease. We have previously shown that probiotics protected against high-fat diet (HFD)-induced depressive-like behaviour in Flinders Sensitive Line (FSL) rats, whereas FSL rats on control (CON) diet were unaffected. Therefore, we hypothesised that a dysmetabolic component of depression may exist that involves the gut microbiota and that such component may be reflected in the plasma metabolome. The aims of the present study post hoc analyses were 1) to study the effect of probiotics on gut microbiota composition and its association with depressive-like behaviour in FSL rats, and 2) to identify plasma metabolites associated with gut microbiota and depressive-like behaviour. Forty-six FSL rats were fed CON or HFD and treated with multi-species probiotics (nine Bifidobacterium, Lactococcus and Lactobacillus species) for 12 weeks. Faecal samples were collected for 16S rRNA (VR4) gene amplicon sequencing (Illumina MiSeq), and an untargeted plasma metabolomics was performed. We found that probiotics increased the relative faecal abundance of the Bifidobacterium, Lactococcus and Lactobacillus genera in HFD-fed rats only. Also, a HFD-induced microbiota component associated with depressive-like behaviour was identified, and probiotics improved the component score. Finally, the plasma levels of 44 metabolites correlated with the depression-related microbiota component, and three such metabolites had good predictive ability for depressive-like behaviour. Potentially, our findings imply that a subtype of depression characterised by a diet-induced, pro-depressant gut microbiota may exist and that analysis of related plasma metabolites may reveal aberrant microbiota functioning related to depression.
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Gut microbiome profiles may be related to atypical antipsychotic associated overweight in Asian children with psychiatric disorder: a preliminary study.
OBJECTIVE: Atypical antipsychotics (APs) modify the gut microbiome, and weight gain in response to AP could be mediated by the gut microbiome. Thus, the present study aimed to explore the changes in the gut bacterial microbiome in AP-exposed children with obesity. METHODS: To rule out the confounder of AP indication, the gut bacterial microbiome was compared between healthy controls (Con) and AP-exposed individuals with overweight (APO) or normal weight (APN). Fifty-seven AP-treated outpatients (21 APO and 36 APN) and 25 Con were included in this cross-sectional microbiota study. RESULTS: AP users, regardless of body mass index, exhibited decreased microbial richness and diversity and a distinct metagenomic composition compared to the Con. Although no differences in the microbiota structure were observed between APO and APN groups, the APO group was characterised by a higher abundance of Megamonas and Lachnospira. Additionally, the differences in the microbial functions were observed between APO and APN groups. CONCLUSIONS: The gut bacterial microbiota of APO children revealed taxonomic and functional differences compared to Con and APN. Further studies are needed to verify these findings and to explore the temporal and causal relationships between these variables.
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Kynurenines: Tryptophan's metabolites in exercise, inflammation, and mental health.
Kynurenine metabolites are generated by tryptophan catabolism and regulate biological processes that include host-microbiome signaling, immune cell response, and neuronal excitability. Enzymes of the kynurenine pathway are expressed in different tissues and cell types throughout the body and are regulated by cues, including nutritional and inflammatory signals. As a consequence of this systemic metabolic integration, peripheral inflammation can contribute to accumulation of kynurenine in the brain, which has been associated with depression and schizophrenia. Conversely, kynurenine accumulation can be suppressed by activating kynurenine clearance in exercised skeletal muscle. The effect of exercise training on depression through modulation of the kynurenine pathway highlights an important mechanism of interorgan cross-talk mediated by these metabolites. Here, we discuss peripheral mechanisms of tryptophan-kynurenine metabolism and their effects on inflammatory, metabolic, oncologic, and psychiatric disorders.
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[Psychoneuroimmunology in irritable bowel syndrome].
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[Diversity of intestinal microflora in patients with depression after stroke].
OBJECTIVE: To investigate the changes in the population and distribution intestinal microflora and their relationship with depression in post-stroke patients. METHODS: Fecal specimens were obtained from 32 patients with post-stroke depression and 30 healthy adults for gene sequencing of 16S RNA V3 region of the intestinal microorganism using Roche/45 high-throughput sequencing platform. RESULTS: The genus and species of intestinal bacteria showed significant differences between the post-stroke patients and health adults. CONCLUSION: Significant changes in the structure of intestinal flora occur in patients with post-stroke depression.
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Association Between Gastrointestinal Symptoms and Depression in a Representative Sample of Adults in the United States: Findings From National Health and Nutrition Examination Survey (2005-2016).
BACKGROUND: The microbiome's role in the etiology of depression has been a topic of many recent investigations. Findings suggest that dysbiosis, which describes a general disturbance in the gut microbiome, underlies negative gastrointestinal symptoms and is implicated in depression. We studied associations between gastrointestinal symptoms and depressive symptoms at a population level using cross-sectional data from the National Health and Nutrition Examination Survey (2005-2016, n = 36,287). We hypothesized that the odds of depressive symptoms would be significantly higher in those showing signs of gastrointestinal distress. METHODS: We analyzed 31,191 adults participating in the National Health and Nutrition Examination Survey from 2005-2016. Outcomes included presence of mucus or liquid in bowel leakage and stomach illness in the past month, diarrhea in the past year, and number of weekly bowel movements. The survey (and thus, our analyses) does not include microbiome samples, only self-reported gastrointestinal symptoms. Depressive symptoms were measured using the Patient Health Questionnaire. Moderate, moderately severe, and severe scores were coded as a positive outcome. RESULTS: Compared to those without depressive symptoms, those with moderate-to-severe depressive symptoms had elevated odds of bowel mucus (odds ratio = 2.78; 95% confidence interval = 1.82-4.24), bowel liquid (odds ratio = 2.16; 95% confidence interval = 1.63-2.86), stomach illness (odds ratio = 1.82; 95% confidence interval = 1.31-2.53), diarrhea (sometimes vs. never odds ratio = 1.72; 95% confidence interval = 1.30-2.29), and constipation (sometimes vs. never odds ratio = 2.76; 95% confidence interval = 2.11-3.62). Overall, those with gastrointestinal symptoms were significantly more likely to have depressive symptoms. CONCLUSIONS: While the intricacies of the brain-gut axis are being investigated at the molecular level, these population data provide further evidence for the association between depressive symptoms and signs of dysbiosis, which may inform health care providers' patient interactions.
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A systematic review on gut-brain axis aberrations in bipolar disorder and methods of balancing the gut microbiota.
BACKGROUND: Bipolar disorder (BD) is a mood disorder that affects millions worldwide. Up to half of the diagnosed patients are reported to not receive adequate treatment. This study aims to assess the relationship between the gut-brain axis and BD and to discuss and compare the efficacy of varying methods of balancing gut microbiotas in BD. METHODS: Using PubMed, Embase, and Google Scholar from November 2021 to February 2022, we found 5310 studies on gut microbiota and its relation to BD. Using our inclusion criteria, 5283 studies were excluded. A total of 27 full-text articles were assessed for eligibility. Also, 12 articles that met our criteria and eligibility criteria reported on 613 BD patients. RESULTS: Most studies analyzed found an overall difference in gut microbiota composition in bipolar patients compared to healthy controls, though the alterations found were not consistent. Differences in Lactobacillus, Faecalibacterium, and Ruminococcus abundance in BD compared to controls were found to be the most consistent across a few of the studies, but their effects on the gut-brain axis conflicted. Probiotic supplementation was found to lower patient rehospitalizations and significantly improve depressive symptoms and cognitive impairments among patients with BD. CONCLUSIONS: Multiple studies included in this review point toward a possible link between BD and the gut microbiota. Probiotic supplements and other gut-balancing therapies could serve as effective adjunctive methods for the treatment of BD. Notable limitations of the studies included for analysis were small sample sizes and majority observational study designs. Furthermore, the microbiota aberrations found in patients with BD were not consistent across multiple studies. Despite these limitations, our findings demonstrate the need for further research regarding the relationship between aberrant gut microbiota profiles and BD, as well as the effectiveness of gut balancing methods as adjunctive treatments.
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Faecal microbiota transplants for depression - Who gives a crapsule?