Diet, Microbiome & Gut-Brain Axis

An imbalance in the "microbiota-gut-brain axis", which reflects the constant bidirectional communication between the central nervous system and the gastrointestinal tract, has long been used as a hypothesis to interpret the pathogenesis of depression, but this 2020 review outlines the changes observed in the gut microbiota in these depressive states and assesses the association between these alterations with depression-like behavior, demonstrating possible mechanisms involved in this link. Du et al. (2020) proposed the concept that the gut barrier may increase in permeability following gut microbiota changes, leading to activation of systemic inflammation and immune responses, regulation of monoamine neurotransmitter release, disturbance of the hypothalamic-pituitary-adrenal (HPA) axis, and perturbation of the brain-derived neurotrophic factor (BDNF) concentrations, and ultimately depression. The review did realise that a more detailed mechanistic understanding is required to fully realize the importance of the microbiota-gut-brain axis in depression, and thus encouraged further animal and clinical research to explore these potential causative mechanisms.

Association of Loneliness and Wisdom With Gut Microbial Diversity and Composition: An Exploratory Study

Liu et al. (2019) recognised that the mechanisms underlying the association between the alterations in gut microbiota (GM) with neurodevelopmental, neurodegenerative, and psychiatric disorders were mainly based on parallel CNS, endocrine, and immune-related molecular pathways that interact with each other. Due to the scarcity of data on how structural and functional changes in the brain correspond with gut microbiotic states in vivo, this review inspected the recent studies that employed advanced neuroimaging techniques and gut microbiome analyses to study the structure, function, and molecular aspects of brain activity in living healthy human and patient populations. The imaging modalities are discussed before the researchers provide evidence of the human GM profile’s significant association with brain microstructure, intrinsic activities, functional connectivity (FC), cognitive function and mood.

Since the prevalence of psychological disorders are not decreasing despite the rise in pharmacological treatments, Ganci et al. (2019) aimed to enhance their understanding of the precise role of gut microbiota (GM) in psychological illness (since it represents an attractive target for novel interventions) by closely examining the relevant literature. This paper found that gut microbiota may directly and indirectly influence mood, cognition, and behavior, which are key components of mental health, and outlined how GM may be implicated in psychological disorders from etiology through to treatment and prevention using the Four P model of case formulation. The writers believed a significant paradigm shift in the whole discipline of psychology would be needed to integrate GM into the conceptualization and treatment of psychological illness. While its importance in psychological well-being must be respected, GM is by no means a route to panacea but an additional arm to a multidisciplinary approach to treatment and prevention.

Allen et al. (2017) point out that research may have indicated the connection between the gut microbiota and cognition as well as various other stress-related behaviours, but the underlying mechanisms are not yet known. This review outlines the role psychology has to play in understanding the brain-gut-microbiome axis, with a focus on human psychology and the use of research in laboratory animals to model human psychology. For instance, it was mentioned that interventions aimed at ameliorating disorders in one part of the brain-gut-microbiome axis (e.g. psychotherapy for depression) may affect other parts of the axis (e.g. microbiome composition and function), and functional gastrointestinal disorders such as irritable bowel syndrome represent a disorder of the axis, rather than an isolated problem either of psychology or of gastrointestinal function. Greater understanding of how psychological development (and even social and cultural factors) impact upon the brain-gut-microbiome axis could inform psychological interventions that promote health.

Novotny et al. (2019) performed a literature review to summarize human intestinal microbiome’s impact on cognitive impairments and the influences of diet and eating habits on learning processes, since greater knowledge in these areas would revolutionize the possibilities of therapy for many diseases. The review learnt that the digestive tube is inhabited by billions of living microorganisms (viruses, bacteria, protozoa, helminths, microscopic fungi) and that the microbiome in the intestines remain relatively steady in adulthood under physiological conditions. The maintenance of a steady microbiome relies on genetics, lifestyle, diet and eating habits, geography, and age, the reviewers found. The gastrointestinal tract and the brain communicate with each other through several pathways, and specific diets and eating habits can have a positive effect on a balanced microbiota composition and thus contribute to the enhancement of cognitive functions, which are important for any learning process. The review also highlights that new pieces of evidence appear on an annual basis on the association between intestinal dysbiosis and neurological/psychiatric diseases.

This 2015 article reviewed the bidirectional relationship between the gut microbiota and the brain [also termed the microbiota-gut-brain (MGB) axis] using articles taken from the Medline database, and discussed how it contributes to the pathogenesis of certain disorders that may involve brain inflammation. Various afferent or efferent pathways were discovered to be involved in the MGB axis: information about the intestinal state is conveyed to the central nervous system by triggers from antibiotics, environmental and infectious agents, intestinal neurotransmitters/neuromodulators, sensory vagal fibers, cytokines, and essential metabolites. Moreover, the hypothalamic-pituitary-adrenal axis, the central nervous system regulatory areas of satiety, and neuropeptides released from sensory nerve fibers all affect the gut microbiota composition directly or through nutrient availability. These interactions listed earlier appear to influence the pathogenesis of numerous disorders in which inflammation is implicated, such as mood disorder, autism-spectrum disorders, attention-deficit hypersensitivity disorder, multiple sclerosis, and obesity. This article proceeds to discuss appropriate early-life preventive measures or corrective measures such as using psychobiotics, fecal microbiota transplantation, and flavonoids. Ultimately, the recognition of the relationship between the MGB axis and the neuroimmune systems would provide a novel approach for improving our understanding of and managing these disorders.

Bailey et al. (2011) acknowledges that there are studies already that have demonstrated the influential role of stressor exposures in the stability of microbiota and that they predispose bacterial translocation, but the biological importance of this was not well understood. This animal-model study on mice aimed to determine whether the microbiome contributes to stressor-induced immunoenhancement, by exposing the mice to a social stressor called social disruption (SDR) and characterizing the bacterial populations in the cecum using bacterial tag-encoded FLX amplicon pyrosequencing. SDR is known to increase circulating cytokines and to prime the innate immune system for enhanced reactivity. The stressor exposure significantly changed the community structure of the microbiota, especially immediately after the exposure. The relative abundance of bacteria in the genus Bacteroides decreased while the relative abundance of bacteria in the genus Clostridium rose upon stressor exposure. In addition, elevated levels of IL-6 and MCP-1 were observed, which were significantly correlated with stressor-induced changes to three bacterial genera (i.e., Coprococcus, Pseudobutyrivibrio, and Dorea). Finally, to determine whether reducing the microbiota would block the stress-induced rise in circulating cytokines, the mice were treated with an antibiotic cocktail before exposure to SDR. The concentrations of IL-6 and MCP-1 did not increase in the antibiotic treated mice, suggesting that the microbiota are necessary for these stress-induced increases in circulating cytokines to occur. Additionally, the results showed that exposure to SDR significantly affects bacterial populations in the intestines.

The objective of this 2018 narrative review was to summarize the evidence for the effects of psychological, environmental, and physical stressors on gut microbiota composition and function, since many studies have implicated the gut microbiota as an important mediator of host health. The stressors investigated were: psychological stress, circadian disruption, sleep deprivation, environmental extremes (high altitude, heat, and cold), environmental pathogens, toxicants, pollutants, and noise, physical activity, and diet (nutrient composition and food restriction). These were selected for their relevance to military personnel who commonly experience these stressors, often at extremes, and some in combination, although they are common in civilian populations also. A number of preclinical studies observed alterations in composition, function and metabolic activity of the gut microbiota induced by stressors, but the effects varied among stressors and could be deemed either beneficial or detrimental to host health. Since it cannot be confirmed with certainty that transient or cumulative exposures to psychological, environmental, and physical stressors have any consistent, meaningful impact on the human gut microbiota, Karl et al. (2018) highlighted the necessity of translational research that can elucidate the impact of stressors on the human gut microbiota, and determine how the gut microbiota can be manipulated, for example by using nutrition, to mitigate adverse stress responses.

Given the emerging role of the gut-brain axis in a variety of brain disorders, such as anxiety and depression, Lach et al. (2018) regard it important to understand the contribution of bidirectional interactions between peptide hormones released from the gut and intestinal bacteria in the context of this axis. Peptides secreted by the gastrointestinal tract into the systemic circulation can bind cognate receptors on immune cells and vagus nerve terminals and thereby enable indirect gut-brain communication. The concentrations of these gut peptides are influenced by enteric microbiota signals in addition to the composition of the intestinal microbiota. This review discusses the gut microbiota’ function as a regulator of anxiety and depression, and explores the role of gut-derived peptides as signaling molecules in microbiome-gut-brain communication. Also presented here are the potential interactions of the microbiota with gut hormones and endocrine peptides such as neuropeptide Y, peptide YY, pancreatic polypeptide, cholecystokinin, glucagon-like peptide, corticotropin-releasing factor, oxytocin, and ghrelin in microbiome-to-brain signaling. Finally it was concluded that gut peptides are important regulators of microbiota-gut-brain signaling in health and stress-related psychiatric illnesses.

While the world is becoming increasingly reliant on highly processed, poor quality foods with links to increased mental disorder risk, Dawson et al. (2016) point out there is evidence that nutrient-rich diet provides protection for mental health, and that the microbiota in the gut is believed to be the key mediator of this relationship. This review discusses specific, targeted dietary and gut focused strategies for the prevention and treatment of mental disorders. Early life and adolescence have been identified as the critical time periods of rapid development and transition in which strategies for prevention and interventions can be implemented. Strategies that promote overall diet quality, high in fiber and nutrients, have been associated with increased microbial diversity and gut health, which may benefit the mental health of current and future generations.

Niccolai et al. (2019) writes about the multifactorial disorder that is obesity, in which various elements (including genetic, host, and environment) play a definite role, although the etiology has not been fully understood yet. It is hypothesized that the brain could be the seat of the initial malfunction leading to obesity, since neurological comorbidities such as anxiety and depression charge the global obesity burden, but the gut microbiome may also play an influential function in energy homeostasis regulating energy harvesting, fat deposition, as well as feeding behavior and appetite. This review focused on the microbiome’s role in the development of obesity, including its interaction with hosts’ behaviors through the nervous system, and mutual crosstalk with the immune and the endocrine systems. The gut-brain axis is discussed as well as dietary patterns, some of which (Western diet) are known to be major causes of obesity and probably promote a dysbiotic drift in the gut microbiota.

This 2018 review explored the role of gut microbiota in bidirectional interactions between the gut and the brain, including neural, immune-mediated, and metabolic mechanisms. Recent preclinical and clinical trials revealed that gut microbiota plays an important role in the bidirectional interactions between the gastrointestinal tract, the enteric nervous system, and the central nervous system, which is alarming since alterations in gut microbiota composition may be associated with pathogenesis of various neurological disorders, including stress, autism, depression, Parkinson's disease, and Alzheimer's disease. Kim et al. (2018) also highlighted recent advances in the understanding of probiotic modulation of neurological and neuropsychiatric disorders.

Clapp et al. (2017) describe the increasing evidence showing bidirectional communication between the central nervous system and gut microbiota (referred to as the gut-brain-axis), and associating these microbiota in the gut with gastrointestinal and extragastrointestinal diseases. Since dysbiosis and inflammation of the gut has been linked to the predisposition of several mental illnesses including anxiety and depression, probiotics have been proposed to potentially treat or prevent anxiety and depression due to its ability to restore normal microbial balance. The aim of this review was to discuss the development of the gut microbiota, the connection between dysbiosis with anxiety and depression, and the possible clinical applications of probiotics.

This 2018 Polish article, translated into English, explains the phenomenon known as the “gut-brain axis” and mentions the growing knowledge on the links that exist between the gut microbiome with the development and functioning of the central nervous system. The strongest evidence for the role of microbes in the gut-brain axis comes from animal studies, with even recent research associating the composition of gut microbiota with mental disorders (response to depression and chronic stress). The gut brain crosstalk is a bidirectional communication system that not only provides gastrointestinal homeostasis, but can also affect motivation and higher cognitive functions. Gut microbiome may be related with obesity and inflammatory gastrointestinal disorders, but further investigations into the gut-brain axis are warranted, particularly in the aspect of discovering potential therapeutic options.

According to this 2017 article, there is considerable evidence mainly from rodent studies, that microbiota in the gut play a role in the development of the central nervous system, are linked to the brain through a bidirectional system involving the vagus nerve, the immune system, and various neurotransmitters, plus they modulate stress response, memory functions, social behavior, and mood. With microbiota also affecting exaggerated responses to stress and inflammatory features commonly observed in depression, this has led to hypotheses about the role of microbiota in human psychiatric disorders. Some have suggested its role in autism spectrum disorder and in schizophrenia due to the data on microbiota’s role in neurodevelopment and in the modulation of social behavior. Future research should test such hypotheses in translational human studies since alterations in gut microbiota of individuals with psychiatric disorders would mean the ingestion of probiotics could have antidepressant or antipsychotic effects.

While it is becoming well established that the gut microbiome has a profound impact on human health and disease, this 2018 review explores how steroids can affect gut microbiota, and how the gut microbiota can influence hormone levels, while also examining human studies on the possible role of gut microbiota in depression and anxiety. Within the context of the gut microbiome-brain axis, Tetel et al. (2018) discusses how gut microbiota disturbances can alter the stress axis and behavior. Lastly, the authors present the challenges and the important questions that future studies must address, concerning steroids, stress, gut-brain axis and human health.

This 2019 paper briefly reviewed the connection of the intestinal microbiome to the rise in non-communicable conditions related to atopic disease, obesity and mental health. Following their analysis, Jheeta & Smith (2019) suggested that components of the microbiome assess microbial antigens in food and pass this information back to the immune system via chemical messengers that are not yet described (authors called them kairomones), and thus atopic disease arises partly due to the insufficient antigens present on the processed foods consumed failing to activate this kairomone feedback mechanism, which atrophies as a result. This paper also proposed the idea that obesity is a consequence of the decreasing production of allomone-like psychotropic compounds (including the known microbial metabolites dopamine and serotonin), is induced by dysbiosis, and the weakening of the gut-brain axis and the negative effect on mental health that follows. Dysbiosis can occur through other ways including antibiotic use and sterile caesarian section, but Jheeta & Smith (2019) are hopeful that these problems can be overcome and the future can be free of these non-communicable diseases.

While uncertainty remains regarding the generalizability of findings from controlled animal studies on microorganisms inhabiting the gastrointestinal tract (gut microbiota) and their impact on host health and physiology, to the more multifaceted pattern of human pathophysiology, this 2018 narrative review summarizes the current knowledge on gut microbial influence over physiological function, with an emphasis on neurobehavioral and neurological impairment based on growing understanding of the gut-brain axis. Altered communication between gut microbiota and host systems have been associated with disorders such as obesity, diabetes mellitus, and autoimmune disorders as well as neuropsychiatric disorders, including autism, anxiety, and major depressive disorders. The suggested communication pathways between gut microbiota and the central nervous system include autonomic, neuroendocrine, enteric, and immune systems, with pathology resulting in disruption to neurotransmitter balance, increases in chronic inflammation, or exacerbated hypothalamic-pituitary-adrenal axis activity. This review also describes experimental and clinical data regarding means of therapeutic manipulation of gut microbiota as a novel treatment option for mental health, and discusses the important knowledge gaps in this area of research.

With neuroscience researchers suggesting over the past few years that the gut microbiota is essential for the development and maturation of brain systems associated with stress responses, Kim & Shin (2018) decided to provide an overview of the communication that takes place between microbiota, the gut and the brain, while also summarizing the results of preclinical and clinical studies on gut microbiota used in treatments for neuropsychiatric disorders. This review found numerous recent studies reporting that several neuropsychiatric disorders, including autism, depression, anxiety, and schizophrenia, were associated with or modulated by diversity in the microbiome, microbial substrates, exogenous prebiotics, antibiotics, and probiotics. The conclusion was that the microbiota-gut-brain axis has the potential to provide us with novel targets for prevention and treatment of neuropsychiatric disorders, although further studies are required to substantiate the clinical use of probiotics, prebiotics and fecal microbiota transplant (FMT).

While the complex interaction of multiple mechanisms underlying depression still needs to be elucidated despite its high prevalence, this 2017 review provides a comprehensive overview of the multifaceted links between the microbiota, diet, and depression. In addition, Koopman & El AIdy (2017) summarized the existing literature on gut microbiota, inflammation and diet within the context of depression. Inflammation appeared to be linked with both biological factors such as excessive neurotransmitter concentrations as well as psychological processes such as adult stress reactivity and a history of childhood trauma, while a balanced microbiota community, modulated by diet, has been found to be a key modulator of host physiology. This review describes several pathways relating early life trauma, pharmacological treatment effects, and nutrition to the microbiome in depression, hopefully fostering novel interventions targeting the microbiota and aiming to treat depressed patients.

This introductory paper published in 2018 by the European project MyNewGut briefly summarizes the past research on the role of dietary patterns and food components in metabolic and mental health, and on several microbiome-mediating mechanisms. The authors state that since diet is a key modifiable environmental factor that modulates the gut microbiota and its metabolic actions, the two can act synergistically and provide resilience against disease. This hypothesis can be used to explain the associations between unhealthy dietary patterns, non-communicable diseases and intestinal dysbiosis. This paper discusses how the growing knowledge of the microbiome's role in dietary health benefits could potentially provide the base from which sound dietary advice arise and start to promote healthy living.

This 2016 review examined the influence gut microbiomes have on brain development and neurological function, and the mechanism in which this can lead to mental illnesses. Evidence has emerged that the gut microbiome can have an impact on neural development, cognition and behaviour through gut-brain axis (the bidirectional communication system between the central nervous system and the gastrointestinal tract), and also that gut microbiota composition can be altered by behavior changes, while diversifying the microbiome can induce depressive-like behaviours. Rogers et al. (2016) go on to discuss how the increasing number of studies in this area of research can form a platform on which novel effective therapies can be designed.

As public interest in the potential of microbiome-based therapies in the treatment of mental illnesses rises, Butler et al. (2019) regards it crucial that those taking care of and working with individuals with mental illness are informed on the rationale and current evidence base for such treatment strategies. This review explains the gut microbiome, and how it relates to the gut-brain communication and psychological function. These microbiota have been seen to influence the gut-brain communication through the neural, immune, and endocrine pathways, and the populations of these trillions of bacteria are distinctly different in people with psychiatric disorders such as depression, bipolar disorder, schizophrenia, and autism spectrum disorder. This review also describes the fundamental principles and basic techniques used in microbiome-gut-brain axis research, and summarizes the current evidence of microbiome-based strategies for various psychiatric disorders. Since the use of probiotics, prebiotics, or dietary change have been identified as having potential in alleviating anxiety and improving mood, this article provides practical advice for patients seeking to try these options to better their mental health.

This 2019 review provides a summary of the current data on the influencing power of nutrition in the immune system and on the development of neuroinflammation and neurological disease. Evidence has been accumulating indicating that dietary patterns can modulate the development of metabolic alterations and inflammation through a variety of methods but many involve the nutrients obtained from the diet affecting microbiome composition, release of microbial products, gastrointestinal signaling molecules, and neurotransmitters. It is these signal molecules that can either promote or inhibit the production of pro-inflammatory cytokines and also the growth of certain leukocyte subpopulations, such as Th17 and Treg cells, which are relevant in the development of neuroinflammatory and neurodegenerative conditions. Estrada & Contreras (2019) support the implementation and maintenance of adequate dietary habits as a strategy to prevent neurological pathologies.

This 2020 review discusses the gut microbiota and major depressive disorder (MDD) - the psychological disorder gut microbiome has been implicated in influencing. Firstly Bastiaanssen et al. (2020) report on the impactful factors on the onset/development of MDD that also involve the composition of the gut microbiota (e.g. diet and stressful life events). The relationship between the microbiome and MDD is also analyzed, examining evidence suggesting the alteration of microbiota in MDD patients. This review then takes a look at the reasons why the microbiota should be taken into account in the treatment of MDD, and how it can become an effective therapeutic target in the future. This area of research is still at an early stage, but the authors express their optimism for microbiome creating new avenues for developing potential strategies for managing MDD.

Here is a 2018 systematic review analyzing peer review articles on the relationship between human brain function and the gut-brain axis (a critical bidirectional link and communication between the brain and the gut). Arneth (2018) found that the gut-brain axis links various intestinal functions to brain centres through a wide selection of processes and pathways, such as endocrine signalling and immune system activation. Other findings included the bidirectional communication between different systems in the gut-brain axis were driven by the vagus nerve, and these signals are transmitted from the luminal environment to the central nervous system in humans. The researcher believes it is paramount to fully understand this gut-brain axis since this communication can influence brain function and trigger several psychiatric conditions for instance, such as schizophrenia and depression.

Ipci et al. (2017) explain that exposure to microbes at an early stage of life appears to be crucial for the development of a strong immune system, with chronic inflammation found to be triggered by disturbances in either the microbiota or host immune response. This systematic review discusses the importance of microbiome in allergic disease by searching Medline (PubMed) and the search engine of Kirikkale University for all relevant articles containing the keywords "microbiome", "dysbiosis", "allergy", "allergic rhinitis", "allergic disease", "mechanisms" or "treatment". Microbial dysbiosis, which is defined as qualitative and quantitative changes of microbes in the intestinal flora, was also reviewed.

This 2019 review summarizes the function of gut microbiota in neurological disorders including neurotoxicity induced by environmental stressors such as drugs, environmental contaminants, and dietary factors. Dempsey et al. (2019) offer several mechanisms by which gut microbiome remotely senses and regulates CNS signaling, including: mediating the biotransformation of neurotoxicants which effectively alters the neuro-reactivity of the parent compounds; exposure to certain environmental stressors disturbing the production of neuro-reactive microbial metabolites; altering of intestinal barrier permeability through bi-directional communication within the gut-brain axis; and the regulation of mucosal immune function. It is also explained how specific metabolites from the microbes could potentially regulate neuroinflammation, cell survival or even cell death, through entering systemic circulation and reprogramming the expression of host genes in the CNS. This review additionally looks at how the gut-brain axis is being studied currently, and offers suggestions in order to make advancements in this area.

This 2017 review breaks down the studies supporting gut microbiota’s role in neuropsychiatric disorders and also takes a look at the possible mechanisms in which it contributes to mental health and illness. Cenit et al. (2017) highlighted the fact that it was not yet known whether or not the alterations in the gut microbiota composition (that are associated with numerous neuropsychiatric conditions, including depression, autism and Parkinson's disease) are the causal factors or are simply its secondary effects. Gut microbiota has been suggested to be capable of influencing the development or pathogenesis of neuropsychiatric conditions following a few animal studies showing the transfer of a behavioral phenotype after gut microbiota transplantation. The review recognises the importance of elucidating all the underlying mechanisms by which the microbiota in the gut and the brain communicate with one another, in the quest for novel strategies to regulate the gut microbiota and improve mental health. The possible microbiota-targeted intervention strategies are discussed here, taking into consideration the stages of life where the gut microbiota is more susceptible to the effects of environmental stressors.

This 2020 review explains the influential role of gut microbiota in the gut-brain axis, focusing on the regulation of physiological functions by the microbiota-related gut hormones. These gut hormones are signalling molecules released by enteroendocrine cells present all over the gastrointestinal tract, and can play a crucial part in maintaining health. The gut microbiota itself are essential in the modulation of several gut-brain axis-related diseases, ranging from gastrointestinal disorders to psychiatric diseases. Sun et al. (2020) encouraged future studies to utilize this microbiota-hormones-gut brain axis in the development of novel therapeutics for psychiatric and gastrointestinal disorders, such as obesity, anxiety, and depression.

Mohajeri et al. (2018) evaluated the evidence showing how brain function may be affected by gut microbiome in adults, highlighting in vitro, in vivo and human studies that have related functional changes observed in the brain with gut microbiome alteration, and those studies that explain the exact mechanism by which the brain affects the microbiome and the gastrointestinal tract. Gut microbiome’s effect on brain function would suggest it would also alter levels of stress, anxiety, depression, and cognition. This review proposes various possible modalities in which the gut microbiome and the brain functionally affect each other, including the administration of probiotic supplements which has already demonstrated its promise but requires the confirmation of its mechanism of action and safety profile. Interventions using prebiotics and probiotics will need to be researched further too; they can potentially equilibrate brain function in both healthy individuals and those with illnesses/diseases.

Rinninella et al. (2019) state that the effects of these modern dietary habits and diets have on the microbiota in the gut are not fully understood yet, and it is possible that the intestinal barrier and the immune system can become compromised as a result. The aim of this review was to examine the impact of various components of foods (such as salt and food additives) and of a variety of dietary habits (vegan and vegetarian, gluten-free, ketogenic, high sugar, low FODMAP, Western-type, and Mediterranean diets) on gut microbiota composition, in the hopes of determining the optimal diet for a healthy assortment of gut microbiota.

The objective of this 2019 review was to showcase the most recent evidence utilizing diet as a tool to exert positive effects, both directly and indirectly, on human health, via gut microbiota activity. It is the metabolites, formed by the breakdown of dietary components by intestinal microbes, that can be either harmful or beneficial and can play a part in the incidence and progression of several intestinal-related and non-related diseases. De Angelis et al. (2019) explain that the main initiators of the gut microbiota-induced metabolic pathways are polymers including fibers, proteins, fat and polyphenols. It appears that fibers improve the synthesis of short-chain fatty acids, decrease the levels of molecules that are involved in disease state such as p-cresyl sulfate, indoxyl sulfate and trimethylamine N-oxide, and therefore are proposed to be the most beneficial dietary treatment.

Carlessi et al. (2019) explain that since treatments used for major depressive disorder (MDD) are not universally effective, some of the attention has shifted to associating different systems/pathways with MDD pathogenesis. Some studies have indicated elevated levels of inflammatory mediators (such as cytokines and chemokines) in both peripheral and central nervous systems (CNS). This review focuses on the research conducted on the relationship between inflammation with the gut microbiota-brain axis and with MDD. There is evidence linking microglial activation with triggering signaling cascades and gene expression that would be indicative of the onset of depressive symptoms. It has also been proposed that responses to treatments can be dictated by the microglia, which is reactive to the systemic inflammation induced by alterations in the gut microbiota. Finally, prebiotics and probiotics have shown promise in this area of research, exhibiting antidepressant responses and anti-inflammatory effects.

Lima-Ojeda et al. (2017) describe the past research demonstrating the influential role of gut microbiota in human immunology, nutrition, digestion, energy homeostasis, and the central nervous system. Alterations in the gut microbiome have been associated with the pathophysiology of various diseases including neuropsychiatric disorders while disruption of the microbiome-gut-brain axis has additionally been linked with elevated risk of developing depression. This is why this review aimed to investigate the gut microbiome’s function in neurodevelopment and in the etiology of the depressive syndrome, including nutritional, immunological, and energy homeostasis approaches.

Palacios-Garcia & Parada (2020) provide their thoughts on the body signals that affect mood and behavior, as well as the possible influences of gut microbiota and its suggested mechanisms. The review discusses the potential therapeutic use of probiotics for regulating behaviors and the evidence behind it. The authors also reveal the areas that remain unknown and require further research, while also leaving their opinions on how they see what the future holds.

Since there has been studies emerging showing the beneficial effects of probiotics and prebiotics by changing the gut microbiome, translating to its potential in treating many diseases, this 2018 review analyzed the current literature on the impact that probiotics and prebiotics can have on irritable bowel syndrome (IBS) and on mood disorders such as anxiety and depression. Through a search of MEDLINE via Pubmed, Pusceddu et al. (2018) were able to identify numerous trials demonstrating probiotics’ and prebiotics’ positive impacts on both IBS-related symptoms and emotional states. But several limitations were spotted including the scarcity of clinical studies, the study design, sample size, and placebo effect. Despite this, the findings highlighted the potential of both prebiotics and probiotics in forming a strategy to treat disorders related to the gut-brain axis such as IBS and depression.

Liang et al. (2018) express their thoughts on how the gut microbiota has experienced great change over the last centuries due to the transition movements especially in diet and lifestyle, and consider the research that investigates gut microbiota’s role in the pathophysiology of numerous mental and neurological diseases. The review takes an optimistic approach on the potential use of the microbiota–gut–brain axis and the area of gut-brain psychology, in enhancing the knowledge on psychology, neuroscience, and psychiatry. The researchers point out various methods to improve the gut microbiome, such as fecal microbiota transplantation, probiotics, prebiotics, a healthy diet, and healthy lifestyle, which can all provide hope that brain and mental health can be prevented and treated through harnessing the power of these gut microbiota.

While a gut-brain axis has been used to describe the complex networks and relationships between the microbiota and the central nervous system (CNS) via autonomic, neuroendocrine, enteric, and immune system pathways, Rieder et al. (2017) explain here that when these networks are disturbed, it could have a great impact on health and disease. It is believed that hypothalamic-pituitary-adrenal (HPA)-axis activation, and altered activity of neurotransmitter and immune systems may be involved in these effects. Perturbations of the microbial populations in the gastrointestinal tract have been implicated in various diseases such as obesity, diabetes, and inflammation, while the microbiota-gut-brain axis has been associated with neuropsychiatric disorders. The purpose of this review was to analyze the influence of the gut microbiota on the functioning of the central nervous system, while examining the link with anxiety and depressive symptoms. The reviewers discuss the involvement of stress and stress-mediated changes in autonomic, neuroendocrine, immune, and neurotransmitter systems, as well as the potential therapeutic use of the microbiota and the gastrointestinal tract in the prevention and treatment of psychological disorders such as anxiety and depression.

Since many studies examining mood’s relationship with gastrointestinal microbiota fail to control for diet (although a habitual diet affects mood and microbiota in the GI tract), Taylor et al. (2020) decided to explore the associations between diet, GI microbiota, and mood in 133 adults (aged 25-45) without mood disorders diagnosed by physicians. Fecal DNA was extracted and sequences of the 16S rRNA gene’s V4 region were analyzed using QIIME2, determining the prevalence of fecal microbial taxa, while subjective mood state was examined with the 42-item Depression, Anxiety, and Stress Scale (DASS-42) and dietary consumption was reported using the National Cancer Institute's Diet History Questionnaire II. After exploring the relationship between 21 bacterial taxa and DASS-42 scores, 2 inverse associations were found: one between anxiety scale scores and Bifidobacterium among the female participants; and another between depression scale scores and Lactobacillus in the male group. After diet quality was evaluated with the 2010 Healthy Eating Index (HEI), it was discovered that the total fruit and dairy components were negatively related with depression and stress scales. Relationships were also observed between 28 bacterial taxa and DASS-42 scores, suggesting, overall, that there are correlations between GI microbes and mood in adults without diagnosed mood disorders. These connections may differ by sex and affected by consumption of dietary fiber but these researchers encourage consideration of diet in future studies relating to the gut-microbiota-brain, in order to improve our understanding on the roles of these microbes and dietary components in mental health.

This 2019 review examines germ-free murine models that were used to reveal the gut microbiome’s role in the development and modulation of brain function and the immune system. The review also presents multiple pathways by which stress-induced inflammation damages brain activity and affects mental health. Peirce & Alviña (2019) list the gut-microbiome-derived compounds that are involved in influencing the gut microbiome’s interaction with mental health (for example, short-chain fatty acids, tryptophan catabolites, microbial pattern recognition) in addition to the related mechanisms such as vagal nerve activity and fecal microbiota transplants. It appears that the gut microbiome plays a facilitating role between stress response, inflammation, and depression, and anxiety. This review discusses the potentially positive findings observed in favour of probiotics and prebiotics, and the possible targets for future research: the elucidation of the microbiome’s causal role; the mechanisms by which gut microbes impact brain function and mental health; and the development of novel microbe-related treatments that improve mental health.

This 2016 review discusses the impact of manipulating tryptophan levels, which modifies peripheral and central serotonin levels, on mood and cognition. In addition, Jenkins et al. (2016) considers the potential influence of the gut-brain axis (bi-directional communication between the brain and gastrointestinal tract) which effectively links emotional and cognitive centres of the brain with peripheral functioning of the digestive tract. Since there is an increasing amount of data on the role of gut microbiota in altering the host’s behavior (as well as the roles of tryptophan and serotonin), it is possible that changes in the gut are responsible for human central nervous system disorders. The researchers present clinical and preclinical evidence that shows that serotonin is involved in higher order brain function, and that associates low brain serotonin levels with poor memory and depressed mood.

Montiel-Castro et al. (2013) reveals to us the increasingly likely fact that as well as protecting the host from pathogens, metabolizing complex lipids and polysaccharides and thereby making certain nutrients accessible, neutralizing drugs and carcinogens, altering intestinal motility, and making visceral perception possible, the microbiota within the gut play an influential role in various physiological processes, including cognitive functions (learning, memory and decision making). It is also becoming evident that the gastrointestinal tract and the brain communicate mainly through the vagus nerve, and this phenomenon called the "microbiota-gut-vagus-brain axis" is crucial in the maintenance of homeostasis and is implicated in the etiology of several metabolic and mental dysfunctions/disorders. The aim of this review was to examine the research conducted on gut microbiota’s ability to communicate with the brain and thus modulate behavior, and also to discuss the ethological and cultural strategies of human and non-human primates to select, transfer and eliminate microorganisms, and therefore select their commensal profile.

Limbana et al. (2020) considered the beneficial effects of the gut microbiome on mental health, and thus conducted this literature review searching the PubMed database for studies pertinent to the gut microbiome and its relationship with depression. After analyzing the 26 studies that met the inclusion criteria, this review discovered a strong association between microbiome function and mental health.

This 2020 narrative review evaluates the theoretical potential of fermented food components in manipulating gut physiology and the biological mechanisms thought to be involved in depression and anxiety. While fermented foods are considered functional because of their possible health benefits, it is the conversion of food substrates by the microbes into functional microorganisms (probiotics) and the production of growth-inducing substrates of beneficial gut bacteria (prebiotics) and of bioactive components (biogenics), that have the ability to modulate the gut microbiota and regulate translocation of endotoxins, thus leading to immune activation and promotion of host nutrition. Preclinical studies have shown the benefits of fermented foods in relieving disrupted gut function and in animal models of depression and anxiety, but human research investigating fermented foods as treatments or preventions for depression and anxiety is limited, while the few studies that do exist are heterogeneous and with significant limitations. It is critical that this gap in knowledge is filled and that the effectiveness of fermented foods in managing human depression and anxiety is examined.

This 2015 article reviewed the bidirectional relationship between the gut microbiota and the brain [also termed the microbiota-gut-brain (MGB) axis] using articles taken from the Medline database, and discussed how it contributes to the pathogenesis of certain disorders that may involve brain inflammation. Various afferent or efferent pathways were discovered to be involved in the MGB axis: information about the intestinal state is conveyed to the central nervous system by triggers from antibiotics, environmental and infectious agents, intestinal neurotransmitters/neuromodulators, sensory vagal fibers, cytokines, and essential metabolites. Moreover, the hypothalamic-pituitary-adrenal axis, the central nervous system regulatory areas of satiety, and neuropeptides released from sensory nerve fibers all affect the gut microbiota composition directly or through nutrient availability. These interactions listed earlier appear to influence the pathogenesis of numerous disorders in which inflammation is implicated, such as mood disorder, autism-spectrum disorders, attention-deficit hypersensitivity disorder, multiple sclerosis, and obesity. This article proceeds to discuss appropriate early-life preventive measures or corrective measures such as using psychobiotics, fecal microbiota transplantation, and flavonoids. Ultimately, the recognition of the relationship between the MGB axis and the neuroimmune systems would provide a novel approach for improving our understanding of and managing these disorders.

Claesson et al. (2012) state that there is greater inter-individual variation in intestinal microbiota among older people than younger adults. Among an elderly population (n = 178), this study found a correlation between faecal microbiota composition and residence location, no matter whether it was in the community, day-hospital, rehabilitation or in long-term residential care. And when the sample was grouped by diet, participants were separated by the same residence location and microbiota groupings. When the subjects were separated by microbiota composition, significant associations with measures of frailty, comorbidity, nutritional status, markers of inflammation and with metabolites in faecal water were discovered. Absence of community-associated microbiota was related to increased frailty. There was also less diversity in the microbiota of those in long-stay care, compared with community dwellers. Diet, microbiota, and health status seem to be connected, which could signify the alteration of microbiota through diet may be relevant in the rate of declining health that accompanies aging.

The purpose of this 2015 review was to report the recent advances in the area of microbiome, considering studies across both Western and non-Western populations, and involving samples of various age groups. The human gut microbiome was found to be diverse and variable, with long-term diet reported to be the largest external influence. Although diet can dramatically alter the gut microbiome, short-term dietary intervention was often unsuccessful in treating obesity and malnutrition. We will need to increase our knowledge and understanding of the gut microbiome under many different conditions in order to be able to diagnose and treat many diseases associated with certain microbial communities.

Since diet is heavily connected with gut microbiota, with past studies reporting links between long-term dietary patterns and short-term dietary interventions with the composition and diversity of gut microbiome, this 2017 article reviewed the role of diet in modulating the composition and function of the gut microbiota across the lifespan. In addition to dietary habits, Donovan (2017) discussed conditions such as obesity and undernutrition, and the impact of prebiotics, dietary fiber, and fat composition.

Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals

Requena et al. (2018) discusses the variation in gut microbiota profiles in our society, with the microbial community of urban-industrial guts lower in richness compared with individuals from rural areas. This review highlights the strong influence of dietary components (e.g. fibers, fats, proteins, polyphenols) in altering the gut microbiota communities and modulating the decline in fiber consumption related to the rise in chronic non-transmissible diseases. Diet and derived microbial metabolites have strong implications with the development of food associated diseases such as obesity and metabolic syndrome, malnutrition and eating disorders, intestinal inflammatory diseases and colorectal cancer, and more. These researchers emphasized the need to determine the microbiota-related biomarkers of risk for these disorders. Even so, it could prove valuable to increase dietary fiber and promote probiotic and prebiotic consumption to restore beneficial bacteria and overall diversity again, which may change the tide from disease to health promoting states.

Long-term dietary patterns are associated with pro-inflammatory and anti-inflammatory features of the gut microbiome

The role of inflammation and the gut microbiome in depression and anxiety

This 2020 review evaluated the current evidence on the impact of gut microbes on cerebral blood-brain barrier (BBB) integrity. Upon describing the destruction of the BBB through the influences of microbiota and its metabolites on the nervous, endocrine, and immune systems and signaling pathways, Tang et al. (2020) suggests ways in which the BBB can be protected: through regulation and supplementation of the gut microbiota, and the targeting of immune cells and inflammatory mediators.

This 2019 review discusses the overall importance of the interactions between the microbiota in the gut and on the body, the gut, and the brain (the microbiota-gut-brain axis). Since there has been considerable research on this axis’ biological and physiological implications in psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders, it has been explained that the microbiota and the brain communicate with each other through many routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, many of these processes involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Cryan et al. (2019) also describes how the microbiota composition can be influenced from early on in life by infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. And the diversity of microbiota declines with aging, while the microbiota-brain-axis can be affected at all stages of life, especially by stress which has a significant effect. Following the numerous recent studies exploring the gut microbiota in autism, anxiety, obesity, schizophrenia, Parkinson’s disease, and Alzheimer’s disease to name a few, this review predicts the future research to focus on elucidating the mechanism underlying the microbiota-gut-brain axis, and discovering novel microbial-based interventions and therapeutic strategies for neuropsychiatric disorders.

Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms

Influence of diet on the gut microbiome and implications for human health

Long-term dietary patterns are associated with pro-inflammatory and anti-inflammatory features of the gut microbiome