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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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Efficacy of mindfulness-based intervention for the treatment of chronic headaches: A systematic review and meta-analysis.
Aemaz Ur Rehman, M, Waseem, R, Habiba, U, Fahad Wasim, M, Alam Rehmani, S, Alam Rehmani, M, Abdullah, M, Khabir, Y, Rehan Hashmi, M, Almas, T, et al
Annals of medicine and surgery (2012). 2022;78:103862
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The International Headache Society defines chronic daily headache (CDH) as headaches occurring on 15 or more days in a month for at least three months. Many pharmacological treatments are available to minimize the functional disability caused by headaches. However, meditation-based mindfulness techniques have gained popularity in recent years. The main aim of this study was to determine the efficacy of mindfulness-based cognitive therapy (MBCT) and mindfulness-based stress reduction (MBSR) in improving headache frequency, duration, and intensity in patients suffering from chronic headaches. This study is an updated systematic review and meta-analysis which included 10 full-text articles (4 from previous meta-analysis and 6 recently published). Results provide limited evidence that MBSR/MBCT intervention may be effective in reducing the frequency, duration, and pain intensity of headaches, in patients with chronic headaches including tension-type and migraine compared with the usual care but it demonstrated a significant difference between groups in achieving mindfulness. Authors conclude that since their findings are inconclusive, MBSR/MBCT interventions for the treatment of migraine and/or tension-type headaches cannot be recommended.
Abstract
Background: Mindfulness-based stress reduction/cognitive therapy has attained popularity as an adjunctive treatment for a plethora of medical and psychiatric conditions, however, its impact on chronic headaches is inconclusive. This review aims to assess the impact of MBSR/MBCT in alleviating the symptoms of chronic headaches. Data sources and data selection: PubMed and Cochrane CENTRAL were searched from inception till 1st May 2021. Randomized Control Trials evaluating mindfulness-based stress reduction/cognitive therapy with either passive comparators (usual care) or active comparators (e.g., Health education or cognitive behavioral therapy) for chronic headaches (Migraine, Tension-type, or cluster headaches), which evaluated either headache frequency, pain intensity or headache duration as primary outcome were eligible for inclusion. The Risk of Bias was evaluated using the Cochrane Collaboration's Risk of Bias Tool. Results: A total of ten Randomized Controlled Trials (five on migraine; three on tension-type; two with mixed samples) were evaluated. In comparison to usual care, mindfulness-based stress reduction/cognitive therapy did not illustrate significant changes in headache frequency (MD = -0.14; 95% CI -1.26 to 0.97; P = 0.80; Moderate Certainty), headache duration (MD = -0.27; 95% CI -3.51 to 2.97, P = 0.87; Low Certainty) or pain intensity (MD = -0.19; 95% CI -0.46 to 0.07; P = 0.15; Moderate Certainty). Conclusion: The results found are insignificant for the three primary outcomes, which may be due to the low number of participants and often a high or unclear risk of bias in the randomized control trials included. Perhaps more aggressive clinical trials with a larger sample size effectively demonstrate differences in outcomes before and after therapy for MBSR/MBCT could provide a more significant change.
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Practitioner review: health anxiety in children and young people in the context of the COVID-19 pandemic.
Haig-Ferguson, A, Cooper, K, Cartwright, E, Loades, ME, Daniels, J
Behavioural and cognitive psychotherapy. 2021;49(2):129-143
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In response to the Covid-19 pandemic, many individuals have health-related fear of contracting the disease. In some, this has developed into health anxiety (HA) whereby the sufferer is obsessed with contracting or developing a serious illness, impairing their day-to-day functioning. HA is commonplace in adulthood and most research is in adults; however, it is now thought that it can develop in children. This review on HA in adults aimed to identify adaptations needed to ensure diagnosis and interventions are appropriate for children. The review discussed that children may not be diagnosed with HA, as the criteria used for diagnosis may not be age appropriate; HA symptoms in adults may not be the same in children and adolescents. Health-related worries are relatively common in children but may not be diagnosed as HA. The authors then went on to discuss HA in children in the context of Covid-19 and outlined that limited brain development, pre-existing mental health or physical problems and the influence of parent or carer mental health may contribute to its development. Finally, the paper discussed how diagnosis and treatment in adults could be adapted for children, with a strong focus on cognitive behavioural therapy. It was concluded that HA can develop in children and for those individuals an adapted multi-pronged approach to diagnosis and treatment may be of benefit, however more research is needed. This study could be used by healthcare professionals to understand that children can suffer from HA, how it presents itself and possible treatments for children.
Abstract
Health-related fear is a normal and common response in the face of the global pandemic of COVID-19. Children and young people are frequently being exposed to messages about the threat to health, including from the media and authorities. Whilst for most, their anxiety will be proportionate to the threat, for some, existing pre-occupation with physical symptoms and illness will become more problematic. There is a growing body of evidence that health anxiety may occur in childhood, however much of the literature is taken from research using adult samples. This practitioner review aims to give an overview of the assessment and treatment of health-related worries in children and young people in the context of the COVID-19 pandemic. This review is based on the limited existing evidence in this population and the more substantial evidence base for treating health anxiety in adults. We consider the adaptations needed to ensure such interventions are developmentally appropriate.
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Brain Neurotransmitter Modulation by Gut Microbiota in Anxiety and Depression.
Huang, F, Wu, X
Frontiers in cell and developmental biology. 2021;9:649103
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The causes of anxiety and depression are unclear, but growing evidence points to a role of the gut microbiota. One possible way that the gut microbiota may have an influence on mental health is through a group of chemical messengers in the brain, known as neurotransmitters. This review summarised the research surrounding neurotransmitters and gut microbiota. The review began by looking at research in animal models and the roles of various neurotransmitters and how they may be influenced by the gut microbiota. The neurotransmitters outlined were serotonin, dopamine, and noradrenaline and it was stated that there is evidence that gut microbiota may be able to influence them alleviating anxiety and/or depression, however there was limited evidence with noradrenaline. It was concluded that there is a close connection between the gut microbiota and anxiety and depression. There is more research needed in humans, as most work has been completed in animal models. This paper could be used by healthcare professionals to understand the role of the gut microbiota in mental health disorders and the importance of gut health in individuals suffering from these.
Abstract
Anxiety and depression are highly prevalent mental illnesses worldwide and have long been thought to be closely associated to neurotransmitter modulation. There is growing evidence indicating that changes in the composition of the gut microbiota are related to mental health including anxiety and depression. In this review, we focus on combining the intestinal microbiota with serotonergic, dopaminergic, and noradrenergic neurotransmission in brain, with special emphasis on the anxiety- and depression-like behaviors in stress-related rodent models. Therefore, we reviewed studies conducted on germ-free rodents, or in animals subjected to microbiota absence using antibiotics, as well as via the usage of probiotics. All the results strongly support that the brain neurotransmitter modulation by gut microbiota is indispensable to the physiopathology of anxiety and depression. However, a lot of work is needed to determine how gut microbiota mediated neurotransmission in human brain has any physiological significance and, if any, how it can be used in therapy. Overall, the gut microbiota provides a novel way to alter neurotransmitter modulation in the brain and treat gut-brain axis diseases, such as anxiety and depression.
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The Impact of Nutrients on Mental Health and Well-Being: Insights From the Literature.
Muscaritoli, M
Frontiers in nutrition. 2021;8:656290
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Diet, mental health, and well-being are linked through several biological pathways. In addition to a healthy diet, nutrient supplements may be of benefit due to their ability to influence these pathways. This review aimed to outline the relationship between specific nutrients and their beneficial effect on mental health. The review outlined the various benefits of polyunsaturated fats, vitamin E, magnesium and folic acid on stress, anxiety, sleep disorders, mild cognitive impairment, depression, bipolar disorders, and obsessive-compulsive disorder. With regards to stress, it was outlined that insufficient vitamins, excessive fat and nutritional imbalance can be contributory. Human research exists to support the benefits of magnesium and polyunsaturated fat for stress and these plus vitamin E for anxiety, however it appears that evidence is lacking for vitamin E and stress and the authors did not comment on folic acid for either condition. Extensive research exists for the use of polyunsaturated fats in mild cognitive impairment, and it was stated that high doses for long periods of time may be needed to show any benefits. The use of vitamin E in cognitive impairment is controversial and more studies may be needed. The authors did not comment on magnesium or folic acid supplementation. It was concluded that an unhealthy diet and lifestyle may be associated with poor mental health and well-being and the importance of a balanced, varied diet for normal brain function. This study could be used by healthcare professionals to understand the importance of recommending a healthy diet for mental well-being in individuals who are suffering from mental health disorders.
Abstract
A good nutritional status is important for maintaining normal body function and preventing or mitigating the dysfunction induced by internal or external factors. Nutritional deficiencies often result in impaired function, and, conversely, intakes at recommended levels can resume or further enhance body functions. An increasing number of studies are revealing that diet and nutrition are critical not only for physiology and body composition, but also have significant effects on mood and mental well-being. In particular, Western dietary habits have been the object of several research studies focusing on the relationship between nutrition and mental health. This review aims to summarize the current knowledge about the relationship between the intake of specific micro- and macronutrients, including eicosapentaenoic acid, docosahexaenoic acid, alpha-tocopherol, magnesium and folic acid, and mental health, with particular reference to their beneficial effect on stress, sleep disorders, anxiety, mild cognitive impairment, as well as on neuropsychiatric disorders, all significantly affecting the quality of life of an increasing number of people. Overall data support a positive role for the nutrients mentioned above in the preservation of normal brain function and mental well-being, also through the control of neuroinflammation, and encourage their integration in a well-balanced and varied diet, accompanied by a healthy lifestyle. This strategy is of particular importance when considering the global human aging and that the brain suffers significantly from the life-long impact of stress factors.
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Using psychoneuroimmunity against COVID-19.
Kim, SW, Su, KP
Brain, behavior, and immunity. 2020;87:4-5
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This viewpoint article raises awareness of the threat of COVID-19 poses to psychiatric patients who are in mental health hospitals. Those patients appear to have a much elevated mortality rate and are potentially more vulnerable to the effects of panic/anxiety due to the pandemic. Their lifestyle choices, influenced by fears about the virus, may also have a negative effect on their immunity. The article also raises the issue of the effects the pandemic and associated changes to day-to-day life can have on the mental and general health of the rest of the population, and in particular to mental health professionals, whose ability to care for their psychiatric patients may be impaired. The authors also briefly discuss the psychological and immunological mechanisms that connect our mental state to the ability of our immune system to fight infections, and the impact of our lifestyles and environments. To summarise they state that infected patients, uninfected quarantined individuals and medical professionals all require mental health supporting strategies, and that epidemiological studies of potential long-term psychiatric consequences are essential.
Abstract
The worldwide outbreak of coronavirus disease 2019 (COVID-19) raises concerns of widespread panic and anxiety in individuals subjected to the real or perceived threat of the virus. Compared to general populations, patients who are institutionalized in a closed unit are also very vulnerable to COVID-19 infection and complications. This crisis touched on difficult issues of not only psychiatric care and ethics, but also psychological impacts to psychiatric care givers. In this Viewpoint, we address both physical and biopsychosocial aspects of this infection, as well as the psychoneuroimmunity of preventive strategies of healthy lifestyle, regular exercise, balanced nutrition, quality sleep and a strong connection with people. Social distancing and wearing masks might help us from pathogen exposure, yet such these measures also prevent us from expressing compassion and friendliness. Therefore, all forms of psychological support should be routinely implemented not only to consider psychological resilience but also to enhance psychoneuroimmunity against COVID-19.
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How Does the Brain Implement Adaptive Decision Making to Eat?
Compan, V, Walsh, BT, Kaye, W, Geliebter, A
The Journal of neuroscience : the official journal of the Society for Neuroscience. 2015;35(41):13868-78
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While food intake is critical for survival, adaptive decision-making can be altered through various mechanisms and eventually lead to disordered eating patterns. Feeding behaviour is dependent on homeostatic rules, motivational drives, biological predispositions and external stressors. This complex web elucidates how humans can decide to satisfy or abstain from hunger cues, and the underlying mechanisms of this behaviour have been increasingly explored. This review summarises the overall neural circuitry in restrictive food choice and binge eating. Serotonergic systems play a key role in eating disorders because they are involved in responses to stress, emotions and feeding behaviour. The decision to overeat or abstain from eating is a reward, and this goal-directed and persistent behaviour mirror some aspects of drug dependence. This review found that voluntary processes in the nervous system could be modified to predominate over homeostatic control of hunger. Eating disorders may emerge when serotonin neurons reach their limit of adaptive capacities, potentially to the extent of compromised survival. This study provides a basis for developing more effective interventions for this population.
Abstract
Adaptive decision making to eat is crucial for survival, but in anorexia nervosa, the brain persistently supports reduced food intake despite a growing need for energy. How the brain persists in reducing food intake, sometimes even to the point of death and despite the evolution of multiple mechanisms to ensure survival by governing adaptive eating behaviors, remains mysterious. Neural substrates belong to the reward-habit system, which could differ among the eating disorders. The present review provides an overview of neural circuitry of restrictive food choice, binge eating, and the contribution of specific serotonin receptors. One possibility is that restrictive food intake critically engages goal-directed (decision making) systems and "habit," supporting the view that persistent caloric restriction mimics some aspects of addiction to drugs of abuse. SIGNIFICANCE STATEMENT An improved understanding of the neural basis of eating disorders is a timely challenge because these disorders can be deadly. Up to 70 million of people in the world suffer from eating disorders. Anorexia nervosa affects 1-4% of women in United States and is the first cause of death among adolescents in Europe. Studies relying on animal models suggest that decision making to eat (or not) can prevail over actual energy requirements due to emotional disturbances resulting in abnormal habitual behavior, mimicking dependence. These recent studies provide a foundation for developing more specific and effective interventions for these disorders.
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Locus of control and obesity.
Neymotin, F, Nemzer, LR
Frontiers in endocrinology. 2014;5:159
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Obesity is a multifactorial disease, which makes it a complicated issue to address. In particular psychology and a concept know as locus of control plays a huge role. Locus of control refers to an individual’s ability to acknowledge that their environment and choices are under their control. However, whether this is a cause of obesity or mutually occurring is unclear. This review of 49 papers aimed to determine the relationship between obesity and locus of control. The authors discussed that the majority of literature agrees on a correlation between locus of control and obesity, however it is not straight forward as there is no set definition for locus of control. Whether locus of control causes obesity or obesity causes locus of control was also difficult to determine, but it was stated that locus of control is difficult to change. The mechanisms behind causation were discussed and stress hormones and hormones which make you feel full or hungry were implicated. It was concluded that there is a correlation between locus of control and obesity, however which one is causal, still needs more research. This paper could be used by healthcare practitioners to understand the important role that psychology plays in the development of obesity.
Abstract
In the developed world, the hazards associated with obesity have largely outstripped the risk of starvation. Obesity remains a difficult public health issue to address, due in large part to the many disciplines involved. A full understanding requires knowledge in the fields of genetics, endocrinology, psychology, sociology, economics, and public policy - among others. In this short review, which serves as an introduction to the Frontiers in Endocrinology research topic, we address one cross-disciplinary relationship: the interaction between the hunger/satiation neural circuitry, an individual's perceived locus of control, and the risk for obesity. Mammals have evolved a complex system for modulating energy intake. Overlaid on this, in humans, there exists a wide variation in "perceived locus of control" - that is, the extent to which an individual believes to be in charge of the events that affect them. Whether one has primarily an internal or external locus of control itself affects, and is affected by, external and physiological factors and has been correlated with the risk for obesity. Thus, the path from hunger and satiation to an individual's actual behavior may often be moderated by psychological factors, included among which is locus of control.