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Protective Effect of Epigallocatechin-3-Gallate (EGCG) in Diseases with Uncontrolled Immune Activation: Could Such a Scenario Be Helpful to Counteract COVID-19?
Menegazzi, M, Campagnari, R, Bertoldi, M, Crupi, R, Di Paola, R, Cuzzocrea, S
International journal of molecular sciences. 2020;21(14)
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Some individuals who have contracted Covid-19 experience an extreme inflammatory reaction known as cytokine storm syndrome. This review paper of 129 studies aimed to review the use of epigallocatechin 3-gallate (EGCG), a green tea derived chemical reported to reduce inflammation with a view to be used in individuals with Covid-19. Conventional therapies used in diseases known to induce extreme inflammation were discussed focusing on steroid based drugs. However, results in Covid-19 patients have shown increased mortality and decreased viral clearance. Several other drugs are being trialled in Covid-19. The use of EGCG and green tea extract (GTE) in several diseases such as rheumatoid arthritis, Sjogrens syndrome, multiple sclerosis, human immunodeficiency virus, dengue virus and inflammatory bowel disease was discussed and beneficial effects such as being anti-inflammatory, antiviral, antimicrobial, and having anti-cancer properties were outlined. The possible mechanisms involved were extensively discussed. The use of EGCG and GTE in a clinical setting was reported to have favourable outcomes and be a potentially safe natural supplement. It was concluded that given the safety and many benefits shown by EGCG in viruses and inflammatory diseases, EGCG/GTE may be effective in Covid-19, and clinical trials are needed. This study could be used by healthcare professionals to justify the recommendation of EGCG/GTE in individuals with Covid-19 and many other inflammatory and viral diseases.
Abstract
Some coronavirus disease 2019 (COVID-19) patients develop acute pneumonia which can result in a cytokine storm syndrome in response to Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection. The most effective anti-inflammatory drugs employed so far in severe COVID-19 belong to the cytokine-directed biological agents, widely used in the management of many autoimmune diseases. In this paper we analyze the efficacy of epigallocatechin 3-gallate (EGCG), the most abundant ingredient in green tea leaves and a well-known antioxidant, in counteracting autoimmune diseases, which are dominated by a massive cytokines production. Indeed, many studies registered that EGCG inhibits signal transducer and activator of transcription (STAT)1/3 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription factors, whose activities are crucial in a multiplicity of downstream pro-inflammatory signaling pathways. Importantly, the safety of EGCG/green tea extract supplementation is well documented in many clinical trials, as discussed in this review. Since EGCG can restore the natural immunological homeostasis in many different autoimmune diseases, we propose here a supplementation therapy with EGCG in COVID-19 patients. Besides some antiviral and anti-sepsis actions, the major EGCG benefits lie in its anti-fibrotic effect and in the ability to simultaneously downregulate expression and signaling of many inflammatory mediators. In conclusion, EGCG can be considered a potential safe natural supplement to counteract hyper-inflammation growing in COVID-19.
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Can Natural Polyphenols Help in Reducing Cytokine Storm in COVID-19 Patients?
Giovinazzo, G, Gerardi, C, Uberti-Foppa, C, Lopalco, L
Molecules (Basel, Switzerland). 2020;25(24)
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During covid-19 infection the body experiences a hyper-immune reaction resulting in an extreme inflammatory response known as cytokine release syndrome (CRS), which correlates with poor prognosis and severe illness. There are no effective treatments for CRS, although there are ongoing trials. The use of natural plant chemicals known as polyphenols have been shown in previous trials to improve inflammation This review of over 90 studies aimed to summarise the use of polyphenols to fight severe covid-19 infection. The paper began by reviewing current drug therapies, which have been shown in studies to be of benefit to inflammation, with tocilizumab being heavily reviewed. The authors then reviewed several plant polyphenols and reviewed how they can modulate inflammation through inhibiting inflammatory molecules and viral activity. It was concluded that human studies are lacking data and so phytochemicals may be promising for the treatment of covid-19. This study could be used by health care professionals to understand the importance of recommending a whole food, plant rich diet with many different coloured foods for individuals who are suffering from covid-19.
Abstract
SARS-CoV-2 first emerged in China during late 2019 and rapidly spread all over the world. Alterations in the inflammatory cytokines pathway represent a strong signature during SARS-COV-2 infection and correlate with poor prognosis and severity of the illness. The hyper-activation of the immune system results in an acute severe systemic inflammatory response named cytokine release syndrome (CRS). No effective prophylactic or post-exposure treatments are available, although some anti-inflammatory compounds are currently in clinical trials. Studies of plant extracts and natural compounds show that polyphenols can play a beneficial role in the prevention and the progress of chronic diseases related to inflammation. The aim of this manuscript is to review the published background on the possible effectiveness of polyphenols to fight SARS-COV-2 infection, contributing to the reduction of inflammation. Here, some of the anti-inflammatory therapies are discussed and although great progress has been made though this year, there is no proven cytokine blocking agents for COVID currently used in clinical practice. In this regard, bioactive phytochemicals such as polyphenols may become promising tools to be used as adjuvants in the treatment of SARS-CoV-2 infection. Such nutrients, with anti-inflammatory and antioxidant properties, associated to classical anti-inflammatory drugs, could help in reducing the inflammation in patients with COVID-19.
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Thyroid-Gut-Axis: How Does the Microbiota Influence Thyroid Function?
Knezevic, J, Starchl, C, Tmava Berisha, A, Amrein, K
Nutrients. 2020;12(6)
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Thyroid and gut disease often coexist together. This literature review highlights the strong interplay between gut, microbiota and thyroid disease. In autoimmune thyroid disease (AITD) gut bacteria imbalances, bacterial overgrowth, Coeliac's disease or non-coeliacs wheat sensitivity, increased gut permeability and resulting deficiency of thyroid nutrients are not uncommon. Inflammation and intestinal wall damage that lead to increased permeability are thought to be one of the driving factors for autoimmune activity. Allergens, certain drugs, impaired gut flora and nutrient deficiencies are some of the contributors to heightened intestinal permeability. Furthermore, the gut walls host deiodinase enzymes that convert thyroid hormone to its active form. The gut microbiota however influence thyroid function in their own rights. The bacteria are crucial for nutrient synthesis, absorption and availability, including those essential for thyroid health. Gut bacteria and their metabolites also play a significant role in the regulation, development and training of immune cells, relevant to AITD. After all, the gut also houses a large proportion of the immune system known as gut-associated lymphatic tissue (GALT). Besides, some bacteria species seem to be capable of balancing fluctuating thyroid hormone levels in the blood. The writings further elaborate on thyroid-essential nutrients and the gut such as iodine, iron, zinc, selenium and Vitamin D. And the impact of bariatric surgery on thyroid function and the presence of certain gut bacteria in thyroid cancers. In summary, the authors concluded that the thyroid-gut axis seems to exhibit a strong connection. Limited evidence from human studies showed promising results of probiotics and synbiotics on thyroid function and targeting the microbiota as a novel strategies for the management of thyroid disease is encouraged to be explored further. This article may be of interest to those looking for an informative summary on the many ways in which the gut influences thyroid function in health and disease.
Abstract
A healthy gut microbiota not only has beneficial effects on the activity of the immune system, but also on thyroid function. Thyroid and intestinal diseases prevalently coexist-Hashimoto's thyroiditis (HT) and Graves' disease (GD) are the most common autoimmune thyroid diseases (AITD) and often co-occur with Celiac Disease (CD) and Non-celiac wheat sensitivity (NCWS). This can be explained by the damaged intestinal barrier and the following increase of intestinal permeability, allowing antigens to pass more easily and activate the immune system or cross-react with extraintestinal tissues, respectively. Dysbiosis has not only been found in AITDs, but has also been reported in thyroid carcinoma, in which an increased number of carcinogenic and inflammatory bacterial strains were observed. Additionally, the composition of the gut microbiota has an influence on the availability of essential micronutrients for the thyroid gland. Iodine, iron, and copper are crucial for thyroid hormone synthesis, selenium and zinc are needed for converting T4 to T3, and vitamin D assists in regulating the immune response. Those micronutrients are often found to be deficient in AITDs, resulting in malfunctioning of the thyroid. Bariatric surgery can lead to an inadequate absorption of these nutrients and further implicates changes in thyroid stimulating hormone (TSH) and T3 levels. Supplementation of probiotics showed beneficial effects on thyroid hormones and thyroid function in general. A literature research was performed to examine the interplay between gut microbiota and thyroid disorders that should be considered when treating patients suffering from thyroid diseases. Multifactorial therapeutic and preventive management strategies could be established and more specifically adjusted to patients, depending on their gut bacteria composition. Future well-powered human studies are warranted to evaluate the impact of alterations in gut microbiota on thyroid function and diseases.
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The Functional Medicine Approach to COVID-19: Nutrition and Lifestyle Practices for Strengthening Host Defense.
Minich, DM, Hanaway, PJ
Integrative medicine (Encinitas, Calif.). 2020;19(Suppl 1):54-62
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Lifestyle interventions can be an effective means to help patients regain their locus of control during times of uncertainty like those experienced in a pandemic. The study is a review about emerging research focusing on nutrition and lifestyle practices for strengthening host defense. Research indicates that there are three mechanisms that may be involved in the ability of food-derived compounds to reduce viral infection and severity: a. balancing inflammatory pathways, b. reducing oxidative stress and increasing antioxidant levels, and c. harmonizing the gut microbiome. Clinical recommendations focus mainly on nutrition, stress reduction/management, sleep quality and quantity, physical activity programme and social factors/connections. Authors conclude by emphasising that the findings of this study are only intended to identify lifestyle practices that may boost the immune system as they have not been proven effective against COVID-19.
Abstract
The developing symptoms of COVID-19, as well as the progression of illness and fatality, are a clearly a function of the overall health status of the individual. Complex, chronic diseases such as obesity, hypertension, and diabetes are directly correlated with risk of disease severity and mortality. We explore lifestyle interventions that have specifically been demonstrated to strengthen host defense, reduce the probability and mitigate the severity of viral infection. Lifestyle interventions, from a Functional Medicine perspective, include nutrition, sleep, exercise, stress reduction, and connection. These factors, when in balance, provide a foundation for optimal health and immune function.
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Nutrition, the digestive system and immunity in COVID-19 infection.
Bold, J, Harris, M, Fellows, L, Chouchane, M
Gastroenterology and hepatology from bed to bench. 2020;13(4):331-340
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Covid-19 needs both prevention and recovery strategies to reduce complications. This review study aimed to discuss the associations between nutrition, obesity, and the impact these have on stomach symptoms associated with Covid-19. Obesity has been identified as a risk factor for Covid-19 and this could be due to several factors such as impaired immune function, increased inflammation, increased susceptibility to infection and the high number of cells on fat tissue, which express the receptor known to allow Covid-19 into cells. The involvement of the gut microbiota of obese individuals was extensively reviewed and gut dysbiosis has been associated with many diseases, thus improving gut microbiota may go some way to improving Covid-19 outcomes. Nutritional interventions to reduce obesity need to be part of a multi-pronged strategy and the possible introduction of vitamin D supplements and probiotics. The paper did not draw any conclusions; however this paper could be used by healthcare professionals to understand the role of obesity in increasing the risk of Covid-19 infection, complications that may arise upon and after infection and nutritional strategies as part of a management plan.
Abstract
The current review aimed to synthesize the literature on the complex relationship between food consumption and nutritional status as well as the digestive system in order to examine the relationship between immunity and potential responses to COVID-19 infection. The goal is to help inform the many healthcare professionals working with COVID-19 patients. A literature search was performed on PubMed, Scopus, and EMBASE databases. Hand searches were also undertaken using Google and reference lists to identify recent evidence. Studies were critically appraised, and the findings were analyzed by narrative synthesis. Nutritional status can impact immunity in several ways, including affecting susceptibility to infection, severity of disease, and recovery time, and is therefore a significant consideration in the management of COVID-19. COVID-19 can also impact digestive function, which can further impact nutritional status. The role of Vitamin D deficiency in vulnerability to severe respiratory infections, including COVID-19, has been recognized, and it may have a role in treatment where deficiency is indicated. Healthcare professionals should be aware that obesity may be accompanied by micronutrient malnutrition including vitamin D deficiency and alterations in the microbiome and inflammatory responses, which can further impact immunity and disease severity. Multidisciplinary team-work is recommended in the management of patients with COVID-19, and approaches should include a consideration of nutritional status (both macronutrients and micronutrients), body weight, and gastrointestinal signs and symptom.
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The Functional Medicine Approach to COVID-19: Virus-Specific Nutraceutical and Botanical Agents.
Evans, JM, Luby, R, Lukaczer, D, Rountree, R, Stone, PM, Guilliams, TG, Yanuck, S, Messier, H, Ramsdell, K, Hanaway, PJ
Integrative medicine (Encinitas, Calif.). 2020;19(Suppl 1):34-42
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The practice of Functional Medicine, with respect to interventions, emphasizes the primacy of safety, validity, and effectiveness. Data for the effectiveness of interventions targeting the viral mechanisms of Covid-19 are nascent and rapidly emerging. The aim of this review was to assess the scientific plausibility of promising prevention approaches and therapeutic (nutraceutical and botanical) interventions and suggest clinical recommendations. A coronavirus such as SARS-CoV-2 can be deadly because of its ability to stimulate a part of the innate immune response called the inflammasome. This can cause uncontrolled release of pro-inflammatory cytokines, leading to cytokine storm and severe, sometimes irreversible, damage to respiratory epithelium. In order to prevent the activation of a particular inflammasome the following compounds are being recommended; quercetin, curcumin, epigallocatechin gallate, n-acetylcysteine, resveratrol, vitamin D, vitamin A, vitamin C, elderberry, melatonin, zinc and palmitoylethanolamide. Authors emphasise that the recommendations are meant to identify botanical and nutraceutical agents that may boost the immune system and not as a means of treatment.
Abstract
As the novel infection with SARS-CoV-2 emerges, objective assessment of the scientific plausibility of nutraceutical and botanical interventions for prevention and treatment is important. We evaluate twelve such interventions with mechanisms of action that modulate the immune system, impair viral replication, and/or have been demonstrated to reduce severity of illness. These are examples of interventions that, mechanistically, can help protect patients in the presence of the prevalent and infectious SARS-CoV-2 virus. While there are limited studies to validate these agents to specifically prevent COVID-19, they have been chosen based upon their level of evidence for effectiveness and safety profiles, in the context of other viral infections. These agents are to be used in a patient-specific manner in concert with lifestyle interventions known to strengthen immune response (see related article in this issue of IMCJ).
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Effect of ultra-processed diet on gut microbiota and thus its role in neurodegenerative diseases.
Martínez Leo, EE, Segura Campos, MR
Nutrition (Burbank, Los Angeles County, Calif.). 2020;71:110609
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The consumption of ultra-processed foods has increased dramatically in recent years, resulting in an overconsumption of foods that are nutritionally only suitable to be consumed occasionally. Prolonged and short-term dietary modifications can affect the composition and diversity of the gut microbiota and in turn, dysregulation of the gut microbiota may be associated with diseases of the brain. This systematic review study aimed to determine the relationship between diets high in ultra-processed foods, gut microbiota dysregulation and how this may influence early development of brain diseases. The authors first reviewed literature surrounding the role of gut microbiota on health owing to their ability to produce signalling molecules that have various functions around the body. An imbalance in the gut microbiota can result in an overproduction of signalling molecules that contribute to an unhealthy state. These signalling molecules can also act on the brain through several ways such as the nervous, circulatory, and immune systems. The review demonstrates that high fat, high sugar diets are related to increased risk for diseases such as Alzheimer’s disease and that diets high in fibre, are related to a low incidence of brain disorders, but as very few studies have looked at this in relation to gut microbiota relationships are only speculative. It was concluded that gut microbiota dysregulation could act as a clinical indicator between brain diseases and ultra-processed foods, however further studies are needed on the relationship between diet, gut microbiota and brain diseases.
Abstract
The current dietary pattern is characterized by high consumption of ultra-processed foods and lower consumption of fiber and vegetables, environmental factors that are associated directly with the current incidence of chronic metabolic diseases. Diet is an environmental factor that influences the diversity and functionality of the gut microbiota, where dietary changes have a direct action on their homeostasis. The environment created in the gut by ultra-processed foods, a hallmark of the Western diet that are recognized as trigger factors for low-grade systemic inflammatory and oxidative changes, favor the development of neurodegenerative diseases (NDs). From a systematic search, the present review analyzes the relationship and effect of the current feeding pattern, with the dysregulation of the microbiota and its influence on the development of cognitive decline. Because diagnosis of NDs is usually at late stages, this review highlights the importance of a search for stricter public health strategies regarding access to and development of ultra-processed foods.
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Mental Disorders Linked to Crosstalk between The Gut Microbiome and The Brain.
Choi, TY, Choi, YP, Koo, JW
Experimental neurobiology. 2020;29(6):403-416
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The gut microbiome may have a role in regular brain function and mental health and this review paper aimed to determine the mechanisms through which this may be possible. There are several mental health disorders that may be affected by the gut microbiome, major depressive disorder (MDD), anxiety disorder, autism spectrum disorder (ASD), Alzheimer’s disease (AD), and addiction. It appears that there is a correlation between a disordered gut microbiome (known as dysbiosis) and MDD, ASD and addiction. Anxiety symptoms in healthy individuals and cognitive deficits in individuals with AD have reportedly been improved with probiotics. How the gut microbiome communicates with the brain was also discussed with the enteric nervous system, vagus nerve, spinal chord, immune system and brain signalling molecules all being implicated as possible routes. Finally, the paper discussed the use of probiotics for the prevention or treatment of mental disorders, with Bifidobacteria, Lactobacillus and specifically L. reuteri, L. plantarum and L. helveticus all shown in animal models to improve aspects associated with mental disorders. Amongst the human research B. longum has been shown to relieve stress and increase cognitive function in healthy individuals. It was concluded that studies have elucidated a relationship between the gut microbiome and mental health through various routes of communication. Research should focus on how gut microbiome changes are involved in mental illness. This study could be used by healthcare professionals to further knowledge on the potential relationship between the gut microbiome and mental health.
Abstract
Often called the second brain, the gut communicates extensively with the brain and vice versa. The conversation between these two organs affects a variety of physiological mechanisms that are associated with our mental health. Over the past decade, a growing body of evidence has suggested that the gut microbiome builds a unique ecosystem inside the gastrointestinal tract to maintain the homeostasis and that compositional changes in the gut microbiome are highly correlated with several mental disorders. There are ongoing efforts to treat or prevent mental disorders by regulating the gut microbiome using probiotics. These attempts are based on the seminal findings that probiotics can control the gut microbiome and affect mental conditions. However, some issues have yet to be conclusively addressed, especially the causality between the gut microbiome and mental disorders. In this review, we focus on the mechanisms by which the gut microbiome affects mental health and diseases. Furthermore, we discuss the potential use of probiotics as therapeutic agents for psychiatric disorders.
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Bacterial Metabolites of Human Gut Microbiota Correlating with Depression.
Averina, OV, Zorkina, YA, Yunes, RA, Kovtun, AS, Ushakova, VM, Morozova, AY, Kostyuk, GP, Danilenko, VN, Chekhonin, VP
International journal of molecular sciences. 2020;21(23)
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Depression is multifactorial disease and it is the most common type of psychiatric disorder. Literature indicates that there are significant differences between the gut microbiota (GM) of patients with depression and healthy controls. The aim of this review was to examine (a) various low-molecular compounds as potential biomarkers of depression in correlation with the metabolism of the GM, and (b) ways to correct the microbiota imbalance. Results show that: - the use of the GM biomarkers, reflecting the neuromodulatory [the process by which nervous activity is regulated through classes of neurotransmitters], immunomodulatory [the process by which the body’s immune system is altered] and antioxidant statuses of the host organism, in the analysis of metagenomic [the study of a collection of genetic material (genomes) from a mixed community of organisms] data from patients with neuropsychiatric diseases, is gaining currency. - diet remains one of the most effective measures that can be taken to restore the microbial balance in the gut and alleviate the symptoms of depression. - a healthy diet during the depression therapy, along with the application of probiotics and psychobiotics, may potentially improve the course of the disease and contribute to the progress of treatment. Authors conclude that further progress in the practical understanding of the role of the GM in depression will greatly depend on correct planning of future metagenomic studies.
Abstract
Depression is a global threat to mental health that affects around 264 million people worldwide. Despite the considerable evolution in our understanding of the pathophysiology of depression, no reliable biomarkers that have contributed to objective diagnoses and clinical therapy currently exist. The discovery of the microbiota-gut-brain axis induced scientists to study the role of gut microbiota (GM) in the pathogenesis of depression. Over the last decade, many of studies were conducted in this field. The productions of metabolites and compounds with neuroactive and immunomodulatory properties among mechanisms such as the mediating effects of the GM on the brain, have been identified. This comprehensive review was focused on low molecular weight compounds implicated in depression as potential products of the GM. The other possible mechanisms of GM involvement in depression were presented, as well as changes in the composition of the microbiota of patients with depression. In conclusion, the therapeutic potential of functional foods and psychobiotics in relieving depression were considered. The described biomarkers associated with GM could potentially enhance the diagnostic criteria for depressive disorders in clinical practice and represent a potential future diagnostic tool based on metagenomic technologies for assessing the development of depressive disorders.
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Gut hormones in microbiota-gut-brain cross-talk.
Sun, LJ, Li, JN, Nie, YZ
Chinese medical journal. 2020;133(7):826-833
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The bidirectional communication between the gastrointestinal tract and the brain, termed the gut-brain axis (GBA), is evidenced to to play a role in physiological and psychological health. While precise communication pathways are not yet clear, it is hypothesised this pathway may be an important therapeutic target in complex psychiatric and gastrointestinal disorders. The aim of this review is to summarize the role of gut hormones in the GBA and focus on how the microbiota interact with these hormones in health and disease. The literature shows the gut microbiota can affect the metabolism of various gut hormones, and these hormones can influence the microbiota. Evidence suggests this cross-talk may be a key regulator in appetite, immune response, stress response, and metabolism. Based on this review, the authors conclude the gut microbiota-hormone homeostatic relationship provides insight on the complex communication between the gut and the brain. They suggest future research should target the microbiota-hormones-gut-brain axis to develop new therapeutic strategies to psychiatric disorders.
Abstract
The homeostasis of the gut-brain axis has been shown to exert several effects on physiological and psychological health. The gut hormones released by enteroendocrine cells scattered throughout the gastrointestinal tract are important signaling molecules within the gut-brain axis. The interaction between gut microbiota and gut hormones has been greatly appreciated in gut-brain cross-talk. The microbiota plays an essential role in modulating many gut-brain axis-related diseases, ranging from gastrointestinal disorders to psychiatric diseases. Similarly, gut hormones also play pleiotropic and important roles in maintaining health, and are key signals involved in gut-brain axis. More importantly, gut microbiota can affect the release and functions of gut hormones. This review highlights the role of gut microbiota in the gut-brain axis and focuses on how microbiota-related gut hormones modulate various physiological functions. Future studies could target the microbiota-hormones-gut brain axis to develop novel therapeutics for different psychiatric and gastrointestinal disorders, such as obesity, anxiety, and depression.