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Effect of prebiotics, probiotics, synbiotics on depression: results from a meta-analysis.
Zhang, Q, Chen, B, Zhang, J, Dong, J, Ma, J, Zhang, Y, Jin, K, Lu, J
BMC psychiatry. 2023;23(1):477
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Major depressive disorder (MDD) is a mood disorder that impairs psychosocial function and quality of life. Recent studies show that prebiotics, probiotics, and synbiotics reveal a novel way to treat psychiatric disorders such as depression through the microbiota-gut-brain axis. The aim of this study was to evaluate the effectiveness of prebiotics, probiotics and synbiotics in alleviating depressive symptoms. This study was a meta-analysis of thirteen studies with a total of 786 participants who were allocated to the intervention group (n=427) and the placebo group (n=359). Results showed that the overall effects of probiotics, prebiotics and synbiotics on depressive symptoms were significantly superior to those of placebo. Additionally, biological sex was a vital factor that influenced patients’ responses to the treatment. Authors concluded that agents that manipulate gut microbiota might become a novel approach to treat patients with mild-to-moderate depression.
Abstract
Accumulating studies have shown the effects of gut microbiota management tools in improving depression. We conducted a meta-analysis to evaluate the effects of prebiotics, probiotics, and synbiotics on patients with depression. We searched six databases up to July 2022. In total, 13 randomized controlled trials (RCTs) with 786 participants were included. The overall results demonstrated that patients who received prebiotics, probiotics or synbiotics had significantly improved symptoms of depression compared with those in the placebo group. However, subgroup analysis only confirmed the significant antidepressant effects of agents that contained probiotics. In addition, patients with mild or moderate depression could both benefit from the treatment. Studies with a lower proportion of females reported stronger effects for alleviating depressive symptoms. In conclusion, agents that manipulate gut microbiota might improve mild-to-moderate depression. It is necessary to further investigate the benefits of prebiotic, probiotic and synbiotic treatments relative to antidepressants and follow up with individuals over a longer time before these therapies are implemented in clinical practice.
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Effects of probiotics on neurocognitive outcomes in infants and young children: a meta-analysis.
Lin, FL, Chen, CM, Sun, CK, Cheng, YS, Tzang, RF, Chiu, HJ, Wang, MY, Cheng, YC, Hung, KC
Frontiers in public health. 2023;11:1323511
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There have been increasing investigations into the use of probiotics for treating a variety of neurodevelopmental disorders and also for improvement of neurocognitive outcomes in preterm infants or children. The aim of this study was to provide updated evidence of the therapeutic effects of probiotics on enhancing different neurocognitive functions in infants and children as well as to identify important factors that may influence their treatment efficacies. This study was a meta-analysis of nine randomised controlled studies with 3,026 participants. Results did not show significantly better neurocognitive outcomes in those receiving probiotic treatments than those in the placebo group. However, significantly better neurocognitive development was noted in the probiotic group when focusing on studies that used probiotics for more than six months. Authors concluded that further investigations into the enhancement of therapeutic effects of probiotics on neurocognitive development is required since current evidence is still not strong enough to rule out the beneficial effects of probiotics on neurocognitive development.
Abstract
BACKGROUND Therapeutic efficacies of probiotics in improving neurocognitive functions in infants and young children remained unclear. This meta-analysis focused on different cognitive outcomes in this population. METHODS Major databases were searched electronically from inception to October 2023 to identify randomized controlled trials (RCTs) that investigated the therapeutic efficacy of probiotics in enhancing cognitive functions assessed by standardized tasks. The overall effect size was calculated as standardized mean difference (SMD) based on a random effects model. RESULTS Nine RCTs with 3,026 participants were identified. Both our primary and secondary results demonstrated no significant difference in neurocognitive outcomes between infants/children treated with probiotics and those receiving placebos. However, our subgroup analysis of studies that offered a probiotics treatment course of over six months demonstrated a significantly better neurocognitive outcome than placebos (SMD = 0.21, p = 0.03, two studies with 451 participants), but this finding was based on only two RCTs. CONCLUSION Despite lack of significant therapeutic effects of probiotics on neurocognitive outcomes, our finding of a positive impact of probiotics on neurocognitive development in those undergoing treatment for over six months may provide an important direction for further investigations into the enhancement of therapeutic effects of probiotics on neurocognitive development in infants and young children. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42023463412.
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Meta-Analysis Reveals Compositional and Functional Microbial Changes Associated with Osteoporosis.
Akinsuyi, OS, Roesch, LFW
Microbiology spectrum. 2023;11(3):e0032223
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Osteoporosis (OP) is the most common metabolic bone disease associated with aging. Microbiome dysbiosis leading to impaired intestinal immune responses and subsequent production of osteoclastogenic cytokines has been proposed as the mechanism by which gut microbes are associated with osteoporosis. The aim of this study was to identify gut bacteria consistently associated with osteoporosis across different cohorts. This study was a meta-analysis of five studies. Results showed that gut microbial dysbiosis in osteoporosis patients is associated with functional changes, which result in significant changes in metabolites that play a key role in bone metabolism. Authors concluded that their findings set the stage for future studies to provide more comprehensive knowledge on how dysbiosis in the gut microbiome contributes to osteoporosis.
Abstract
Over the past decade, the role of the gut microbiota in many disease states has gained a great deal of attention. Mounting evidence from case-control and observational studies has linked changes in the gut microbiota to the pathophysiology of osteoporosis (OP). Nonetheless, the results of these studies contain discrepancies, leaving the literature without a consensus on osteoporosis-associated microbial signatures. Here, we conducted a comprehensive meta-analysis combining and reexamining five publicly available 16S rRNA partial sequence data sets to identify gut bacteria consistently associated with osteoporosis across different cohorts. After adjusting for the batch effect associated with technical variation and heterogeneity of studies, we observed a significant shift in the microbiota composition in the osteoporosis group. An increase in the relative abundance of opportunistic pathogens Clostridium sensu stricto, Bacteroides, and Intestinibacter was observed in the OP group. Moreover, short-chain-fatty-acid (SCFA) producers, including members of the genera Collinsella, Megasphaera, Agathobaculum, Mediterraneibacter, Clostridium XIV, and Dorea, were depleted in the OP group relative to the healthy control (HC) group. Lactic acid-producing bacteria, including Limosilactobacillus, were significantly increased in the OP group. The random forest algorithm further confirmed that these bacteria differentiate the two groups. Furthermore, functional prediction revealed depletion of the SCFA biosynthesis pathway (glycolysis, tricarboxylic acid [TCA] cycle, and Wood-Ljungdahl pathway) and amino acid biosynthesis pathway (methionine, histidine, and arginine) in the OP group relative to the HC group. This study uncovered OP-associated compositional and functional microbial alterations, providing robust insight into OP pathogenesis and aiding the possible development of a therapeutic intervention to manage the disease. IMPORTANCE Osteoporosis is the most common metabolic bone disease associated with aging. Mounting evidence has linked changes in the gut microbiota to the pathophysiology of osteoporosis. However, which microbes are associated with dysbiosis and their impact on bone density and inflammation remain largely unknown due to inconsistent results in the literature. Here, we present a meta-analysis with a standard workflow, robust statistical approaches, and machine learning algorithms to identify notable microbial compositional changes influencing osteoporosis.
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Evolution of the Human Diet and Its Impact on Gut Microbiota, Immune Responses, and Brain Health.
González Olmo, BM, Butler, MJ, Barrientos, RM
Nutrients. 2021;13(1)
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One explanation for the increased prevalence in chronic disease and mental illness is from the evolutionary perspective. This suggests the rapid shift in diet towards processed foods in the past 200 years has not allowed for sufficient adaptation of the gut microbiome. The gut microbiome plays an important role in the digestive, immune and nervous systems via the gut-brain axis, and may be a key factor in modulating inflammation and disease. The aim of this review is to discuss how what we eat affects the immune system and impacts our brain health. The literature currently shows significant associations between the Western diet and its impact on the health of the gut microbiome and the brain. Increased intake of saturated fats, refined carbohydrates and sugar, coupled with a reduction in fiber, negatively impacts the digestive system and elicits an immune response. This response can lead to neuroinflammation, which is now found to be associated with deficits in learning and memory, as well as increased rates of neurodegenerative disease and depression. Based on the existing literature, the authors conclude the human gut microbiome has not had sufficient time to adapt to many modern foods, thus leading to inflammation and disease. The authors recommend that a diet composed of natural whole foods with minimal processing can help prevent and alleviate some of the burden caused by chronic disease, and suggest future studies focus on improving techniques to evaluate neuroinflammation in humans.
Abstract
The relatively rapid shift from consuming preagricultural wild foods for thousands of years, to consuming postindustrial semi-processed and ultra-processed foods endemic of the Western world less than 200 years ago did not allow for evolutionary adaptation of the commensal microbial species that inhabit the human gastrointestinal (GI) tract, and this has significantly impacted gut health. The human gut microbiota, the diverse and dynamic population of microbes, has been demonstrated to have extensive and important interactions with the digestive, immune, and nervous systems. Western diet-induced dysbiosis of the gut microbiota has been shown to negatively impact human digestive physiology, to have pathogenic effects on the immune system, and, in turn, cause exaggerated neuroinflammation. Given the tremendous amount of evidence linking neuroinflammation with neural dysfunction, it is no surprise that the Western diet has been implicated in the development of many diseases and disorders of the brain, including memory impairments, neurodegenerative disorders, and depression. In this review, we discuss each of these concepts to understand how what we eat can lead to cognitive and psychiatric diseases.
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Exploring the Role and Potential of Probiotics in the Field of Mental Health: Major Depressive Disorder.
Johnson, D, Thurairajasingam, S, Letchumanan, V, Chan, KG, Lee, LH
Nutrients. 2021;13(5)
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A bi-directional communication between the brain and the microbiome of the gut may exist, known as the microbiome-gut-brain axis (MGBA). The role of this and the use of probiotics in relation to many psychiatric and neurological disorders is being increasingly researched. This review aimed to summarise the research on the use of probiotics for the treatment of mental health disorders and major depressive disorder (MDD). Probiotics and their use were summarised concluding that they have a diverse range of health benefits due to their anti-inflammatory, antipathogenic and antimicrobial actions. Imbalances in the four major phyla of gut bacteria; Bacteroidetes, Firmicutes, Proteobacteria and Actinobacteria may have a major role in the development of MDD. Probiotics may have several mechanisms through which they benefit MDD and decreased inflammation in the brain, increased production of chemicals involved in brain signalling and decreased stress hormones, were all implicated. It was concluded that probiotics have mental health benefits, however gaps in the evidence from studies needs to be addressed. This study could be used by healthcare professionals to understand the role of probiotics in the treatment of mental health disorders and in particular MDD.
Abstract
The field of probiotic has been exponentially expanding over the recent decades with a more therapeutic-centered research. Probiotics mediated microbiota modulation within the microbiota-gut-brain axis (MGBA) have been proven to be beneficial in various health domains through pre-clinical and clinical studies. In the context of mental health, although probiotic research is still in its infancy stage, the promising role and potential of probiotics in various mental disorders demonstrated via in-vivo and in-vitro studies have laid a strong foundation for translating preclinical models to humans. The exploration of the therapeutic role and potential of probiotics in major depressive disorder (MDD) is an extremely noteworthy field of research. The possible etio-pathological mechanisms of depression involving inflammation, neurotransmitters, the hypothalamic-pituitary-adrenal (HPA) axis and epigenetic mechanisms potentially benefit from probiotic intervention. Probiotics, both as an adjunct to antidepressants or a stand-alone intervention, have a beneficial role and potential in mitigating anti-depressive effects, and confers some advantages compared to conventional treatments of depression using anti-depressants.
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Gut Microbiota and Pathophysiology of Depressive Disorder.
Kunugi, H
Annals of nutrition & metabolism. 2021;77 Suppl 2:11-20
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Bidirectional communication between the brain and gastrointestinal tract has been established and evidence suggests the microbiota-gut-brain axis may play a role in many psychiatric diseases, including major depression disorder (MDD). Although there is currently no established biochemical marker used in the clinical setting, recent findings have identified four potential mechanisms underlying MDD. The aim of this review is to outline these mechanisms and summarise the current evidence related to the pathophysiology of MDD. The literature suggests the gut microbiota impacts each of the potential mechanisms in the pathophysiology of MDD, and recent clinical trials on probiotics indicate beneficial effects on depression symptoms. Based on these results, the author concludes that practices leading to a healthier gut microbiota may aid in the reduction of depression symptoms. Future research on the microbiota-gut-brain axis in MDD is a promising avenue for better understanding the pathophysiology of disease and developing improved treatments for MDD.
Abstract
BACKGROUND Accumulating evidence has suggested that the bi-directional communication pathway, the microbiota-gut-brain axis, plays an important role in the pathophysiology of many neuropsychiatric diseases including major depressive disorder (MDD). This review outlines current evidence and promising findings related to the pathophysiology and treatment of MDD. SUMMARY There are at least 4 key biological molecules/systems underlying the pathophysiology of MDD: central dopamine, stress responses by the hypothalamic-pituitary-adrenal axis and autonomic nervous system, inflammation, and brain-derived neurotrophic factor. Animal experiments in several depression models have clearly indicated that gut microbiota is closely related to these molecules/systems and administration of probiotics and prebitotics may have beneficial effects on them. Although the results of microbiota profile of MDD patients varied from a study to another, multiple studies reported that bacteria which produce short-chain fatty acids such as butyrate and those protective against metabolic diseases (e.g., Bacteroidetes) were reduced. Clinical trials of probiotics have emerged, and the majority of the studies have reported beneficial effects on depression symptoms and related biological markers. Key Messages: The accumulating evidence suggests that research on the microbiota-gut-brain axis in major depressive disorder (MDD) is promising to elucidate the pathophysiology and to develop novel treatment of MDD, although there is still a long distance yet to reach the goals.
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Effects of Probiotics on Anxiety, Stress, Mood and Fitness of Badminton Players.
Salleh, RM, Kuan, G, Aziz, MNA, Rahim, MRA, Rahayu, T, Sulaiman, S, Kusuma, DWY, Adikari, AMGCP, Razam, MSM, Radhakrishnan, AK, et al
Nutrients. 2021;13(6)
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Exercise has been shown to improve fitness, wellbeing, and health. However, strenuous exercise may be detrimental physiologically, as well as affecting psychological health. The aim of this study was to determine the effects of daily probiotic supplementation on anxiety, stress, mood and fitness levels among competitive badminton players. This study was a randomised, placebo-controlled study. Recruited participants (n=30) were randomly divided into the probiotic group and the control group. The participants were given treatments for six weeks without altering the training schedule of the athletes. Results showed that stress and anxiety in badminton players could be alleviated with the daily consumption of probiotics for six weeks. Additionally, probiotics supplementation increased aerobic capacity. Authors conclude that probiotic supplements could be beneficial for athletes to enhance their mental state and physical performance. Thus, probiotic supplementation that may influence the regulation of pathways (neuro-endocrine) and mechanism of action in response to physical and psychological stressors encountered by badminton players should further studied.
Abstract
BACKGROUND Reports of probiotic consumption on athletes' performance are debatable due to their equivocal results. There is a need for more evidence on the effects of probiotic intake on psychological state and fitness level. Thus, this study determined the effects of daily probiotic consumption on competitive anxiety, perceived stress and mood among university badminton players, besides their fitness like aerobic capacity, strength, speed, leg power and agility. METHODS Thirty university badminton players aged from 19 to 22 years old were randomly divided equally into two groups, where the probiotic group (PG; n = 15) received a drink that contained Lactobacillus casei Shirota (3 × 1010 CFU) and placebo group (CG; n = 15) a placebo drink for six weeks. Anxiety, stress and mood levels were determined using the CSAI-2R, PSS and BRUMS questionnaires, respectively. Fitness levels were measured using by subjecting the players to 20-m shuttle runs (aerobic capacity), handgrips (muscular strength), vertical jumps (leg power), 40-m dash (speed) and T-test (agility). The Student's t-test (p < 0.05) was used to determine the differences between PG and CG players. RESULTS After six weeks, the anxiety and stress levels of PG players significantly decreased by 16% (p < 0.001) and 20% (p < 0.001), respectively, but there were no significant changes detected in CG players. Supplementation of probiotics also improved aerobic capacity in PG players by 5.9% (p < 0.001) but did not influence the speed, strength, leg power and agility. CONCLUSIONS Probiotics supplementation showed improved aerobic capacity and relieve anxiety and stress. However, further studies need to be carried out to determine the mechanisms through which probiotic intake produces these effects.
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Differential Health Effects on Inflammatory, Immunological and Stress Parameters in Professional Soccer Players and Sedentary Individuals after Consuming a Synbiotic. A Triple-Blinded, Randomized, Placebo-Controlled Pilot Study.
Quero, CD, Manonelles, P, Fernández, M, Abellán-Aynés, O, López-Plaza, D, Andreu-Caravaca, L, Hinchado, MD, Gálvez, I, Ortega, E
Nutrients. 2021;13(4)
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Synbiotic, a mixture of prebiotics and probiotics, is known to improve neurotransmitter interactions, immune, inflammatory, and stress responses by modulating the gut microbial composition. It is also believed that physical activity plays an important role in the modulation of immune function and stress response. The purpose of this triple-blinded, randomized, placebo-controlled pilot study was to evaluate the health benefits of symbiotic intervention in fourteen sedentary students and thirteen soccer players, especially in terms of improving immunophysiological and metabolic parameters. The 300mg of symbiotic intervention contained Bifidobacterium lactis CBP-001010, Lactobacillus rhamnosus CNCM I-4036, Bifidobacterium longum ES1(109 colony-forming unit), and fructooligosaccharides (200 mg) plus 1.5 mg of zinc, 8.25 µg of selenium, 0.75 µg of vitamin, and maltodextrin. Following a one-month intervention with synbiotic formulation, soccer players showed improvements in anxiety, sleep quality and stress, a slight reduction in proinflammatory cytokine IL-1β, an exercise-induced significant increase in dopamine and a slight elevation of corticotropin-releasing hormone. For confirmation of results of this pilot study and to assess more significant effects of symbiotic intervention in athletes as well as in the general population, longer-term robust studies are required. The findings of this study can help healthcare professionals understand the extensive health benefits of synbiotic intervention and its relationship to physical activity.
Abstract
The main objective of this research was to carry out an experimental study, triple-blind, on the possible immunophysiological effects of a nutritional supplement (synbiotic, Gasteel Plus®, Heel España S.A.U.), containing a mixture of probiotic strains, such as Bifidobacterium lactis CBP-001010, Lactobacillus rhamnosus CNCM I-4036, and Bifidobacterium longum ES1, as well as the prebiotic fructooligosaccharides, on both professional athletes and sedentary people. The effects on some inflammatory/immune (IL-1β, IL-10, and immunoglobulin A) and stress (epinephrine, norepinephrine, dopamine, serotonin, corticotropin-releasing hormone (CRH), Adrenocorticotropic hormone (ACTH), and cortisol) biomarkers were evaluated, determined by flow cytometer and ELISA. The effects on metabolic profile and physical activity, as well as on various parameters that could affect physical and mental health, were also evaluated via the use of accelerometry and validated questionnaires. The participants were professional soccer players in the Second Division B of the Spanish League and sedentary students of the same sex and age range. Both study groups were randomly divided into two groups: a control group-administered with placebo, and an experimental group-administered with the synbiotic. Each participant was evaluated at baseline, as well as after the intervention, which lasted one month. Only in the athlete group did the synbiotic intervention clearly improve objective physical activity and sleep quality, as well as perceived general health, stress, and anxiety levels. Furthermore, the synbiotic induced an immunophysiological bioregulatory effect, depending on the basal situation of each experimental group, particularly in the systemic levels of IL-1β (increased significantly only in the sedentary group), CRH (decreased significantly only in the sedentary group), and dopamine (increased significantly only in the athlete group). There were no significant differences between groups in the levels of immunoglobulin A or in the metabolic profile as a result of the intervention. It is concluded that synbiotic nutritional supplements can improve anxiety, stress, and sleep quality, particularly in sportspeople, which appears to be linked to an improved immuno-neuroendocrine response in which IL-1β, CRH, and dopamine are clearly involved.
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Gut Microbiome and Depression: How Microbes Affect the Way We Think.
Limbana, T, Khan, F, Eskander, N
Cureus. 2020;12(8):e9966
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Recent findings have shown that a healthy gut microflora transmits signals to the brain through various pathways, namely the gut-brain axis. With the gut and brain working in a bidirectional relationship, emerging research suggests this could potentially impact stress, anxiety, depression and cognition. Therefore the aim of this review was to determine the role of the gut microbiome in mental health and depression. A total of 26 articles were reviewed and based on these articles, a strong link exists between the gut microbiome and its impact on mental health. Additionally, the literature supports the notion that the gut-brain axis serves as an essential pathway. Based on these findings, the authors agree there is a strong association between the gut microbiome and mental health, while also acknowledging the need to establish a causal link between these two entities. The authors conclude that the microbiome is a promising approach when considering the prevention, treatment and management of mental health diseases in the future.
Abstract
The gut microbiome serves an important role in the human body. Reportedly, one of the benefits of these microflora is on mental health. Once established, food and other dietary sources that enhance quality microbiome content in our gastrointestinal system will be a significant consideration in individuals' day to day lives. This literature review conducted a PubMed search for studies about the gut microbiome and its relation to depression. In using several Medical Subject Heading (MeSH) keywords, relevant literature was selected. A total of 26 articles were selected after applying the inclusion and exclusion criteria, and after checking the articles' accessibility. This literature would like to establish the role of the gut microbiome in depression. This study's findings showed that there is a strong association of microbiome function to mental well-being.
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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.