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Modulating the Gut Microbiome in Multiple Sclerosis Management: A Systematic Review of Current Interventions.
Tsogka, A, Kitsos, DK, Stavrogianni, K, Giannopapas, V, Chasiotis, A, Christouli, N, Tsivgoulis, G, Tzartos, JS, Giannopoulos, S
Journal of clinical medicine. 2023;12(24)
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Multiple sclerosis (MS) is an autoimmune disease caused by the altered immune system mistakenly attacking the central nervous system. While genetics play a leading causative role in the manifestation of this disease, other contributing environmental factors can also exist, such as a disruption in the intestinal microbial composition. Previous research has shown that the bidirectional communication between the brain's and gut's health, also known as the gut-brain axis, may contribute to the prognosis of MS. Modulating gut microbial composition can be a therapeutic strategy in MS patients to manage symptoms and prevent disease progression. This systematic review assessed different protocols for modulating gut microbial composition, including dietary modifications, probiotic use, intermittent fasting, and faecal microbial transplantation. The review included thirteen studies that compared the effects of the above gut microbial modulation intervention protocols in MS patients with healthy participants. While different dietary modification strategies improved MS symptoms, probiotic supplementations and intermittent fasting reduced inflammation, and faecal microbial transplantation showed promising positive effects in a few reports. Due to the methodological limitations of the included studies, further robust studies are required to evaluate the beneficial effects of gut microbial modulation strategies in reducing the symptoms of MS patients. However, healthcare professionals can use the results of this study to understand the benefits of gut microbial modulation in MS patients.
Abstract
This review attempted to explore all recent clinical studies that have investigated the clinical and autoimmune impact of gut microbiota interventions in multiple sclerosis (MS), including dietary protocols, probiotics, fecal microbiota transplantation (FMT), and intermittent fasting (IF). Methods: Thirteen studies were held between 2011 and 2023 this demonstrated interventions in gut microbiome among patients with MS and their impact the clinical parameters of the disease. These included specialized dietary interventions, the supply of probiotic mixtures, FMT, and IF. Results: Dietary interventions positively affected various aspects of MS, including relapse rates, EDSS disability scores, MS-related fatigue, and metabolic features. Probiotic mixtures showed promising results on MS-related fatigue, EDSS parameters, inflammation; meanwhile, FMT-though a limited number of studies was included-indicated some clinical improvement in similar variables. IF showed reductions in EDSS scores and significant improvement in patients' emotional statuses. Conclusions: In dietary protocols, clinical MS parameters, including relapse rate, EDSS, MFIS, FSS, and MSQoL54 scales, were significantly improved through the application of a specific diet each time. Probiotic nutritional mixtures promote a shift in inflammation towards an anti-inflammatory cytokine profile in patients with MS. The administration of such mixtures affected disability, mood levels, and quality of life among patients with MS. FMT protocols possibly demonstrate a therapeutic effect in some case reports. IF protocols were found to ameliorate EDSS and FAMS scores. All interventional means of gut microbiome modulation provided significant conclusions on several clinical aspects of MS and highlight the complexity in the relationship between MS and the gut microbiome.
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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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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.
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Microbiome-Gut-Brain Axis and Toll-Like Receptors in Parkinson's Disease.
Caputi, V, Giron, MC
International journal of molecular sciences. 2018;19(6)
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Parkinson’s disease (PD) is a progressively debilitating neurodegenerative disease and recently the role of the microbiota-gut-brain axis has gained attention in patients with PD. Research shows that an altered gut microbiota can activate Toll-like receptors (TLRs), receptors involved in the innate immune response, causing an inflammatory cascade in the gut and brain. Based on this knowledge, gut microbiota and TLRs may be potential therapeutic targets for PD. This review sheds light on the current knowledge regarding the association between the microbiota-gut-brain axis and innate immunity via TLR signalling in PD. Increased understanding of this relationship should lead to insights on the pathophysiology of PD, as well as improved dietary and pharmaceutical therapeutic approaches in PD patients. Based on the existing evidence, the authors conclude that through modulating the gut, thus balancing the immune response in PD patients, it may be possible to influence early phases of the neurodegenerative cascade.
Abstract
Parkinson’s disease (PD) is a progressively debilitating neurodegenerative disease characterized by α-synucleinopathy, which involves all districts of the brain-gut axis, including the central, autonomic and enteric nervous systems. The highly bidirectional communication between the brain and the gut is markedly influenced by the microbiome through integrated immunological, neuroendocrine and neurological processes. The gut microbiota and its relevant metabolites interact with the host via a series of biochemical and functional inputs, thereby affecting host homeostasis and health. Indeed, a dysregulated microbiota-gut-brain axis in PD might lie at the basis of gastrointestinal dysfunctions which predominantly emerge many years prior to the diagnosis, corroborating the theory that the pathological process is spread from the gut to the brain. Toll-like receptors (TLRs) play a crucial role in innate immunity by recognizing conserved motifs primarily found in microorganisms and a dysregulation in their signaling may be implicated in α-synucleinopathy, such as PD. An overstimulation of the innate immune system due to gut dysbiosis and/or small intestinal bacterial overgrowth, together with higher intestinal barrier permeability, may provoke local and systemic inflammation as well as enteric neuroglial activation, ultimately triggering the development of alpha-synuclein pathology. In this review, we provide the current knowledge regarding the relationship between the microbiota-gut⁻brain axis and TLRs in PD. A better understanding of the dialogue sustained by the microbiota-gut-brain axis and innate immunity via TLR signaling should bring interesting insights in the pathophysiology of PD and provide novel dietary and/or therapeutic measures aimed at shaping the gut microbiota composition, improving the intestinal epithelial barrier function and balancing the innate immune response in PD patients, in order to influence the early phases of the following neurodegenerative cascade.
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Harnessing the Power of Microbiome Assessment Tools as Part of Neuroprotective Nutrition and Lifestyle Medicine Interventions.
Toribio-Mateas, M
Microorganisms. 2018;6(2)
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This is a practical review written by a clinician for other clinicians. It draws from an extensive body of evidence on the links between the gut microbes (bacteria amongst them), called the microbiota, both in health and in a variety of human diseases. The author, who is also a researcher in the communication between the gut and the brain (the gut-brain axis), focuses on the translation of science into simple clinical applications that result in measurable health outcomes, and in particular in neurodegenerative conditions such as Alzheimer's and Parkinson's, but also other less well studied such as Chronic Fatigue Syndrome (CFS). The paper also covers mental health / mood conditions such as anxiety, and depression. Practitioners who work in the area of gut health and use stool tests to assess various imbalances their patients may be experiencing will get the most out this paper. The author takes a look at the physiological processes that influence gastrointestinal as well as brain health and discusses how tools such as the characterisation or "mapping" of commensal bacteria (the bacteria that lives inside our guts normally), along with the identification of potential opportunistic and pathogenic bacteria and parasites, together with knowledge of molecules such as short chain fatty acids or zonulin can enable better clinical decision making by nutrition and lifestyle medicine practitioners. The paper also includes a valuable discussion on patient-reported outcome measures (PROMs), and particularly on the use of MYMOP by practitioners as a validated tool to collect insight from exposure to real world data in clinical practice.
Abstract
An extensive body of evidence documents the importance of the gut microbiome both in health and in a variety of human diseases. Cell and animal studies describing this relationship abound, whilst clinical studies exploring the associations between changes in gut microbiota and the corresponding metabolites with neurodegeneration in the human brain have only begun to emerge more recently. Further, the findings of such studies are often difficult to translate into simple clinical applications that result in measurable health outcomes. The purpose of this paper is to appraise the literature on a select set of faecal biomarkers from a clinician’s perspective. This practical review aims to examine key physiological processes that influence both gastrointestinal, as well as brain health, and to discuss how tools such as the characterisation of commensal bacteria, the identification of potential opportunistic, pathogenic and parasitic organisms and the quantification of gut microbiome biomarkers and metabolites can help inform clinical decisions of nutrition and lifestyle medicine practitioners.
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The Gut-Brain Axis and the Microbiome: Clues to Pathophysiology and Opportunities for Novel Management Strategies in Irritable Bowel Syndrome (IBS).
Quigley, EMM
Journal of clinical medicine. 2018;7(1)
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Irritable bowel syndrome (IBS) is a common functional gut disorder that is seen to have a number of causes. Given the widespread interest in the gut microbiome in health and disease, the role of microbiota has now been explored in the gut-brain axis paradigm. This review explores the novel addition of microbiota to the gut-brain axis and its implications to the assessment and management of IBS. Current literature suggests that a disturbed microbiome or an aberrant immune response to the disturbed microbiome may impact the central nervous system. These findings have confirmed the microbiota is useful in understanding the development of symptoms in IBS. Based on the existing literature, the author concludes there is new insight for diagnostic and therapeutic approaches to IBS.
Abstract
Irritable bowel syndrome (IBS) is one of the most common of all medical disorders worldwide and, while for some it represents no more than a nuisance, for others it imposes significant negative impacts on daily life and activities. IBS is a heterogeneous disorder and may well have a number of causes which may lie anywhere from the external environment to the contents of the gut lumen and from the enteric neuromuscular apparatus and the gut immune system to the central nervous system. Consequently, the paradigm of the gut-brain axis, which includes the participation of these various factors, has proven a useful model to assist clinicians and patients alike in understanding the genesis of symptoms in IBS. Now, given the widespread interest in the gut microbiome in health and disease, in general, reports of disordered enteric bacterial communities in IBS, and experimental data to indicate that components of the gut microbiota can influence brain morphology and function, as well as behavior and cognition, this concept has been extended to encompass the microbiota-gut-brain axis. The implications of this novel concept to the assessment and management of IBS will be explored in this review.
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Intestinal microbiome-gut-brain axis and irritable bowel syndrome.
Moser, G, Fournier, C, Peter, J
Wiener medizinische Wochenschrift (1946). 2018;168(3-4):62-66
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The gut-brain-microbiota axis connects the nervous system with the metabolic, hormonal and immune functions of the intestines. Irritable bowel syndrome (IBS) is a functional gut disorder that commonly presents with psychological co-morbidities, and while animal studies show strong associations between stress and gut microbiota, studies in humans are rare. This review assesses the current literature on intestinal microbiome and its association with stress, anxiety and depression in patients with IBS. Based on existing studies, the authors found the gut microbiota forms a crucial link between the intestine and nervous system. Therapies targeted at both modulating the gut microbiome and psychological interventions are recommended. The authors conclude further randomised clinical trials are needed to better understand which therapies work best for patients with IBS.
Abstract
Psychological comorbidity is highly present in irritable bowel syndrome (IBS). Recent research points to a role of intestinal microbiota in visceral hypersensitivity, anxiety, and depression. Increased disease reactivity to psychological stress has been described too. A few clinical studies have attempted to identify features of dysbiosis in IBS. While animal studies revealed strong associations between stress and gut microbiota, studies in humans are rare. This review covers the most important studies on intestinal microbial correlates of psychological and clinical features in IBS, including stress, anxiety, and depression.