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The Gut Microbiome in Early Life Stress: A Systematic Review.
Agusti, A, Lamers, F, Tamayo, M, Benito-Amat, C, Molina-Mendoza, GV, Penninx, BWJH, Sanz, Y
Nutrients. 2023;15(11)
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Children exposed to early life stress (ELS) show alterations in brain development and are at increased risk of developing mental illness. This study aims to clarify whether ELS influences the gut microbiome and whether this can be a predictor for the development of mental disorders. 13 articles were included in this systemic review. 4 looked at pre-natal stress and 9 at post-natal stress. Prenatal stress (via maternal stress) may be associated with an increase in Proteobacteria phylum and with a lower abundance of Bifidobacterium and lactic acid bacteria. In the postnatal group, greater microbiome diversity was related to lower depression and anxiety. In boys scores for adaptive skills were higher in those with good levels of Bifidobacterium. A positive association was found between EA (early adversity) experiences and gastrointestinal symptoms and anxiety. This review demonstrates links between ELS and gut microbiome changes. Further research will be necessary to draw more robust conclusions.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This systematic review consolidated and discussed existing evidence on the link between early life stress (ELS) and changes to the human microbiome
- Exposure to ELS, prenatal or postnatal during childhood and adolescence, may impact mental and physical health.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
A systematic review was conducted to consolidate clinical evidence examining the impact of early life stress (ELS) on the human intestinal microbiome.
Method
Thirteen observational studies were included in the review, sourced from Pubmed, Scopus, Web of Science, and EMBASE. Methodological quality was assessed using the Newcastle-Ottawa Assessment Scale (NOS), with most studies scoring seven or eight out of nine stars.
Study designs varied, including prospective prenatal studies, postnatal longitudinal studies, case-control studies, and cross-sectional studies. Four prenatal studies were prospective in design. The other nine postnatal studies included one longitudinal study, five case-control studies, and three cross-sectional studies. All 13 studies were published between 2015 and 2022. Because study designs and outcome assessments varied, the results were presented in a narrative form. Data was extracted by 2 independent authors.
Results
The primary findings from the review were as follows:
- Four longitudinal stress studies indicated that pregnant mothers experiencing psychological stress, increased cortisol levels, HIV, and lack of social support exhibited a lower abundance of beneficial Bifidobacterium and an increased abundance of Enterobacter genus.
- One postnatal stress longitudinal study (n=260) demonstrated lower depression and anxiety and improved internalising behaviour in patients with high microbiome diversity.
- . One postnatal stress case-control study (n=344) showed changes in the microbiome and an abundance of several bacterial taxa in stressed groups, including genera Prevotella, Bacteroides (Bacteroidetes), Coprococcus, Streptococcus, and Escherichia.
- One cross-sectional study of 128 adults without psychiatric conditions revealed that higher stress correlated with increased levels of Bacteroides, Parabacteroides, Rhodococcus, Methanobrevibacter, and Roseburia at the genus level, as well as lower Phascolarcto bacterium and Firmicutes at the phylum level.
- One large prospective study (n=446) found infants exposed to higher cumulative stress exhibited an increased relative abundance of Proteobacteria groups and lower Bifidobacterium.
Conclusion:
Due to the inconsistency of study designs and their results this review failed to find consensus microbiome signatures associated with pre- or postnatal stress, or both.
Clinical practice applications:
- Early life stress, and alterations in the gut microbiome, have been linked to mental health conditions
- Maternal prenatal stress may be linked to emotional, behavioural, and cognitive outcomes in infants.
Considerations for future research:
- Future research should standardise questionnaires, to ensure consistency and comparability across studies
- Additionally, future studies should consider using standard procedures and specific species and strain resolution shotgun metagenomics sequencing
- Consideration should be given to the influence of environmental variables (diet, physical activity, etc.) and sex in gut microbiome analysis.
Abstract
Exposure to early life stress (ELS), prenatal or postnatal during childhood and adolescence, can significantly impact mental and physical health. The role of the intestinal microbiome in human health, and particularly mental health, is becoming increasingly evident. This systematic review aims to summarize the clinical data evaluating the effect of ELS on the human intestinal microbiome. The systematic review (CRD42022351092) was performed following PRISMA guidelines, with ELS considered as exposure to psychological stressors prenatally and during early life (childhood and adolescence). Thirteen articles met all inclusion criteria, and all studies reviewed found a link between ELS and the gut microbiome in both prenatal and postnatal periods. However, we failed to find consensus microbiome signatures associated with pre- or postnatal stress, or both. The inconsistency of results is likely attributed to various factors such as different experimental designs, ages examined, questionnaires, timing of sample collection and analysis methods, small population sizes, and the type of stressors. Additional studies using similar stressors and validated stress measures, as well as higher-resolution microbiome analytical approaches, are needed to draw definitive conclusions about the links between stress and the human gut microbiome.
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Effectiveness of Probiotic, Prebiotic, and Synbiotic Supplementation to Improve Perinatal Mental Health in Mothers: A Systematic Review and Meta-Analysis.
Desai, V, Kozyrskyj, AL, Lau, S, Sanni, O, Dennett, L, Walter, J, Ospina, MB
Frontiers in psychiatry. 2021;12:622181
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Maternal mental health problems in the perinatal period are a global public health challenge. As many as one in five women develop depression and/or anxiety in the postpartum period, making them the most common complications of pregnancy and delivery. The aim of this study was to evaluate the evidence on the administration of prebiotic, probiotic, and/or synbiotic supplements during pregnancy to reduce the risk of mental health problems in the perinatal period. This study is a systemic review and meta-analysis of four studies of which three where included in the qualitative and quantitative synthesis. Results indicate limited evidence about the effectiveness of probiotics administered during pregnancy to reduce the risk of maternal mental health disorders and highlighted the lack of evidence on prebiotics and synbiotics supplementation to inform their use for similar purposes. Authors conclude that there is the need for future trials targeting microbiota interventions that test probiotic/prebiotic/synbiotic interventions that redress specific dysbioses in pregnancy gut microbiota that arise from poor mental health.
Abstract
Introduction: There is an emerging interest in modulating the gut microbiota to target the gut-brain axis and improve maternal mental health in the perinatal period. This systematic review evaluated the effectiveness of prebiotics, probiotics, and synbiotics supplementation during pregnancy to reduce the risk of maternal mental health problems in the perinatal period. Methods: Electronic biomedical databases and clinical trial registries were searched from database inception through August 2020 to identify randomized controlled clinical trials (RCTs) evaluating the effect of probiotic, prebiotic, or synbiotic supplements administered to women during pregnancy on measures of perinatal depression, anxiety, and other mental health outcomes. Study selection, risk of bias appraisal, and data extraction were independently performed by two reviewers. Pooled mean differences (MD) and odds ratios (pOR) with 95% confidence intervals (CI) were calculated in random-effects meta-analyses for the outcomes of interest in the review. Results: From 3,868 studies identified through the search strategy, three RCTs of low risk of bias involving 713 participants were included, all three testing probiotics. There were no differences between probiotics and control groups in the mean depression scores (MD -0.46; 95% CI -2.16, 1.25) at end of follow-up. Although statistical significance was not achieved, probiotics showed an advantage in the proportion of participants scoring below an established cut-off for depression (pOR 0.68; 95% CI 0.43, 1.07). Compared to placebo, probiotics in pregnancy reduced anxiety symptoms (MD -0.99; 95% CI -1.80, -0.18); however, this advantage was not translated in a reduction in the proportion of participants scoring above an established cut-off for anxiety (pOR 0.65; 95% CI 0.23, 1.85). There were no differences between probiotics and control groups in global mental health scores at end of follow-up (MD 1.09; 95% CI -2.04, 4.22). Conclusion: There is limited but promising evidence about the effectiveness of probiotics during pregnancy to reduce anxiety symptoms and reduce the proportion of women scoring ABOVE a cut-off depression score. There is a lack of RCT evidence supporting prebiotics and synbiotics supplementation for similar purposes in the perinatal period. More research is needed before prebiotics, probiotics, and synbiotics are recommended to support maternal mental health and well-being in the perinatal period. Systematic Review Registration: PROSPERO, CRD42019137158.
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Gluten and FODMAPs Relationship with Mental Disorders: Systematic Review.
Aranburu, E, Matias, S, Simón, E, Larretxi, I, Martínez, O, Bustamante, MÁ, Fernández-Gil, MDP, Miranda, J
Nutrients. 2021;13(6)
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There is growing evidence that gluten and FODMAPs, such as fermentable oligosaccharides, disaccharides, monosaccharides and polyols, can cause gastrointestinal symptoms, inflammation, and immune responses in patients with celiac disease and irritable bowel syndrome. In addition, a high intake of gluten and FODMAPs may also be associated with neurological and psychiatric disorders. Thirteen studies were included in this systematic review to examine the relationship between gluten and FODMAP consumption and illnesses affecting the central nervous system. In addition, the studies examined the effects of potential dietary strategies that consider gluten and FODMAP intake on mental disorders, anxiety, depression, schizophrenia, Alzheimer’s disease, and autism spectrum disorders. Several possible mechanisms identified in this systematic review could contribute to neurological and psychiatric disorders, including the release of proinflammatory cytokines, immune responses, gut dysbiosis, intestinal permeability, and interactions between the gut-brain axis. In patients with fibromyalgia, celiac disease, and irritable bowel syndrome, avoiding or limiting gluten may reduce depression, anxiety, and cognitive impairment. However, the effects of a low-FODMAP diet on the central nervous system are inconclusive. There is some evidence that gluten-free diets can improve cognition in schizophrenia patients. In addition, those with autism spectrum disorders may benefit from a gluten-free diet and a low-FODMAP diet. Further robust research is required to evaluate the beneficial effects of interventions that avoid or restrict the consumption of foods high in FODMAPs and gluten. However, healthcare professionals can use the results of this systematic review to understand the potential benefits of therapeutic interventions that consider the intake of FODMAPs and gluten on illnesses affecting the central nervous system and their possible mechanisms of action.
Abstract
Nowadays, gluten and FODMAP food components (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) are increasingly studied due to their possible relation with extraintestinal-associated conditions. In recent years, gluten-free diets (GFD) and low-FODMAP diets (LFD) are becoming more popular not only in order to avoid the food components that cause intolerances or allergies in some people, but also due to the direct influence of marketing movements or diet trends on feeding habits. Likewise, neurological and psychiatric diseases are currently of increasing importance in developed countries. For this reason, a bibliographic systematic review has been carried out to analyse whether there is a pathophysiological relationship between the dietary intake of gluten or FODMAPs with mental disorders. This review collects 13 clinical and randomized controlled trials, based on the PRISMA statement, which have been published in the last ten years. Based on these results, limiting or ruling out gluten or FODMAPs in the diet might be beneficial for symptoms such as depression, anxiety (7 out of 7 articles found any positive effect), or cognition deficiency (improvements in several cognition test measurements in one trial), and to a lesser extent for schizophrenia and the autism spectrum. Nevertheless, further studies are needed to obtain completely reliable conclusions.
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The Role of Diet, Eating Behavior, and Nutrition Intervention in Seasonal Affective Disorder: A Systematic Review.
Yang, Y, Zhang, S, Zhang, X, Xu, Y, Cheng, J, Yang, X
Frontiers in psychology. 2020;11:1451
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Seasonal affective disorder (SAD) is a mood disorder characterised by annual depression or bipolar disorder in a seasonal pattern. Recent evidence suggests dietary intervention and nutrition status can affect the symptoms in depressed patients, but none have specifically considered depression among SAD patients. The aim of this review was to assess the associations between diet, eating behaviour and nutrition intervention in SAD patients. Eleven studies were included and found vegetarian diet patterns and alcoholism to be associated with higher SAD prevalence. Additionally, SAD patients tend to consume larger dinners, more snacks, and show more cravings for starch-rich foods. Despite these patterns, dietary supplementation or nutrition intervention did not show benefit for SAD symptoms. Overall, the authors conclude there is a lack of evidence to draw conclusions on dietary pattern and nutritional interventions for preventing and managing SAD. The authors suggest further evidence is needed from larger controlled trials and encourage investigation of the role of the B vitamin group, rather than an isolated B12 supplementation.
Abstract
Background: Seasonal affective disorder (SAD) is a biological and mood disorder with a seasonal pattern. Dietary intervention and nutritional status have been reported to affect SAD severity. The objective of this study was to systematically review the evidence of associations between SAD and diet, eating behavior, and nutrition intervention. Methods: We performed a comprehensive search of MEDLINE, EMBASE, Web of Science, and Google Scholar from inception up to July 1, 2019. Studies that examined diet and eating behaviors in SAD patients and tests of nutrition interventions for SAD were included. Two independent investigators extracted data based on study designs, participants, outcomes, exposures, and association measures. Results: Eleven studies were included: six studies examined distinctive dietary patterns and eating behaviors in SAD patients and five studies explored the efficacy of nutrition interventions for SAD. Vegetarianism and alcoholism were associated with higher SAD prevalence, but normal alcohol intake was not correlated with SAD severity. Compared with non-clinical subjects, SAD patients tended to consume significantly larger dinners and more evening snacks during weekdays and weekends and exhibit a higher frequency of binge eating, external eating, and emotional eating. Additionally, compared to healthy controls, SAD patients presented more cravings for starch-rich food and food with high fiber. However, neither the ingestion of carbohydrate-loaded meals nor Vitamin D/B12 supplementation showed benefit for SAD. Conclusion: Studies suggest that SAD patients may exhibit distinctive diet preferences and eating behaviors, but no current nutrition intervention has demonstrated efficacy for ameliorating SAD symptoms. Further evidence is needed from randomized controlled trials with larger sample sizes and longer durations.
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The Role of Bacteria and Its Derived Metabolites in Chronic Pain and Depression: Recent Findings and Research Progress.
Li, S, Hua, D, Wang, Q, Yang, L, Wang, X, Luo, A, Yang, C
The international journal of neuropsychopharmacology. 2020;23(1):26-41
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Depression is closely associated with chronic pain yet the connection between these comorbidities is ambiguous. Recent studies have shown alterations in the gut microbiome may contribute to cognitive dysfunction via the microbiota-gut-brain axis. The aim of this systematic review is to summarize the existing evidence of the role of the gut microbiome in chronic pain and depression and explore potential mechanisms of gut dysbiosis in the development of these conditions. This review found metabolic products from the gut microbiota can mediate neuro-inflammation and neuro-immunity pathways in pain and depression, and that dysbiosis in the gut may contribute to the cause of chronic pain and depression. The authors conclude the metabolic products from the gut bacteria offer new insights to the connection between the gut microbiota and mechanisms of pain and depression, while showing potential as a therapeutic target.
Abstract
BACKGROUND Chronic pain is frequently comorbid with depression in clinical practice. Recently, alterations in gut microbiota and metabolites derived therefrom have been found to potentially contribute to abnormal behaviors and cognitive dysfunction via the "microbiota-gut-brain" axis. METHODS PubMed was searched and we selected relevant studies before October 1, 2019. The search keyword string included "pain OR chronic pain" AND "gut microbiota OR metabolites"; "depression OR depressive disorder" AND "gut microbiota OR metabolites". We also searched the reference lists of key articles manually. RESULTS This review systematically summarized the recent evidence of gut microbiota and metabolites in chronic pain and depression in animal and human studies. The results showed the pathogenesis and therapeutics of chronic pain and depression might be partially due to gut microbiota dysbiosis. Importantly, bacteria-derived metabolites, including short-chain fatty acids, tryptophan-derived metabolites, and secondary bile acids, offer new insights into the potential linkage between key triggers in gut microbiota and potential mechanisms of depression. CONCLUSION Studying gut microbiota and its metabolites has contributed to the understanding of comorbidity of chronic pain and depression. Consequently, modulating dietary structures or supplementation of specific bacteria may be an available strategy for treating chronic pain and depression.
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Altered Composition of Gut Microbiota in Depression: A Systematic Review.
Barandouzi, ZA, Starkweather, AR, Henderson, WA, Gyamfi, A, Cong, XS
Frontiers in psychiatry. 2020;11:541
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The brain-gut microbiome axis has emerged to be a link between gut microbiota pattern and depression, however the mechanism by which gut microbiota modulate depression-like behaviors remains inconclusive. While studies have observed differences in the diversity and abundance of different bacteria taxa, no definitive classifications have been confirmed. The aim of this systematic review was to identify gut microbiota patterns in people with depression compared with healthy controls. According to the nine articles included in this review, conflicting results were found on characteristics of gut microbiota in people with depression compared to healthy controls. Based on these findings, the authors conclude the role of the microbiota in the development or maintenance of depression remains limited, suggesting the likelihood of confounding factors. Further research is recommended to better understand the relationship between gut microbiota pattern and treatment outcomes for people with depression.
Abstract
Cumulative evidence shows a linkage between gut microbiota pattern and depression through the brain-gut microbiome axis. The aim of this systematic review was to identify the alterations of the gut microbiota patterns in people with depression compared to healthy controls. A comprehensive literature search of human studies, published between January 2000 and June 2019, was reviewed. The key words included gastrointestinal microbiome, gut microbiome, microbiota, depression, depressive symptoms, and depressive disorder. The systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Nine articles met the eligibility criteria. Disparities in α-diversity and β-diversity of the microbiota existed in people with depression compared to healthy controls. At the phylum level, there were inconsistencies in the abundance of Firmicutes, Bacteroidetes, and Proteobacteria. However, high abundance in Actinobacteria and Fusobacteria phyla were observed in people with depression. On the family level, high abundance of Actinomycineae, Coriobacterineae, Bifidobacteriaceae, Clostridiales incertae sedis XI, Porphyromonadaceae, Clostridiaceae, Lactobacillaceae, Streptococcaceae, Eubacteriaceae, Thermoanaerobacteriaceae, Fusobacteriaceae, Nocardiaceae, Streptomycetaceae, and low abundance of Veillonellaceae, Prevotellaceae, Bacteroidaceae, Sutterellaceae, Oscillospiraceae, Marniabilaceae, and Chitinophagaceae were observed in people with depression. On the genus level, high abundance of Oscillibacter, Blautia, Holdemania, Clostridium XIX, Anaerostipes, Anaerofilum, Streptococcus, Gelria, Turicibacter, Parabacteroides, Eggerthella, Klebsiella, Paraprevotella, Veillonella, Clostridium IV, Erysipelotrichaceae incertae sedis, Eubacterium, Parvimonas, Desulfovibrio, Parasutterella, Actinomyces, Asaccharobacter, Atopobium, Olsenella and low abundance of Coprococcus, Lactobacillus, Escherichia/Shigella, Clostridium XlVa, Dialister, Howardella, Pyramidobacter, and Sutterella were found in people with depression. Alteration of gut microbiome patterns was evident in people with depression. Further evidence is warranted to allow for the translation of microbiome findings toward innovative clinical strategies that may improve treatment outcomes in people with depression.