Patient Perceptions of Microbiome-Based Therapies as Novel Treatments for Mood Disorders: A Mixed Methods Study: Perceptions des patients sur les thérapies basées sur le microbiome pour les troubles de l'humeur : une étude à méthodes mixtes.

OBJECTIVE: Medications are critical for treating major depressive disorder (MDD) and bipolar disorder (BD). Unfortunately, 30% to 40% of individuals do not respond well to current pharmacotherapy. Given the compelling growing body of research on the gut-brain axis, this study aims to assess patient perspectives regarding microbiome-based therapies (MBT) such as probiotics, prebiotics, dietary changes, or fecal microbiota transplantation (FMT) in the management of MDD and BD. METHODS: This single-centred observational study used quantitative and qualitative assessments to examine patient perceptions of MBT. Participants diagnosed with MDD or BD completed an anonymous questionnaire obtaining demographics, prior medication history, and symptom burden. Self-assessment questionnaires specific to each diagnosis were also used: Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR), Altman Self-Rating Mania Scale (ASRM), and General Anxiety Disorder Questionnaire (GAD-7). A logistic regression model analysed the association of MBT acceptance with disorder type, QIDS-SR, and GAD-7 scores. A bootstrap method assessed the proportion of MBT acceptance. The qualitative assessment consisted of 30-minute interviews to elicit perceptions and attitudes towards MBT. RESULTS: The qualitative assessment achieved information power with n = 20. Results from the 63-item MBT questionnaire (n = 43) showed probiotics (37.2%) as the top choice, followed by FMT (32.6%), dietary change (25.6%), and prebiotics (4.6%). A majority of participants (72.1%) expressed willingness to try MBT for their mood disorder, however, logistic regression analysis did not identify statistically significant predictors for MBT acceptance among disorder type, QIDS-SR, and GAD-7. CONCLUSION: There is an increased focus on the gut microbiota's role in mood disorders' etiology and treatment. Promising research and patient interest underscore the necessity for exploring and educating on patient perspectives and the factors influencing attitudes towards MBT.

Potential in vivo delivery routes of postbiotics.

Bioactive micro- and macro-molecules (postbiotics) derived from gut beneficial microbes are among natural chemical compounds with medical significance. Currently, a unique therapeutic strategy has been developed with an emphasis on the small molecular weight biomolecules that are made by the microbiome, which endow the host with several physiological health benefits. A large number of postbiotics have been characterized, which due to their unique pharmacokinetic properties in terms of controllable aspects of the dosage and various delivery routes, could be employed as promising medical tools since they exert both prevention and treatment strategies in the host. Nevertheless, there are still main challenges for the in vivo delivery of postbiotics. Currently, scientific literature confirms that targeted delivery systems based on nanoparticles, due to their appealing properties in terms of high biocompatibility, biodegradability, low toxicity, and significant capability to carry both hydrophobic and hydrophilic postbiotics, can be used as a novel and safe strategy for targeted delivery or/and release of postbiotics in various (oral, intradermal, and intravenous) in vivo models. The in vivo delivery of postbiotics are in their emerging phase and require massive investigation and randomized double-blind clinical trials if they are to be applied extensively as treatment strategies. This manuscript provides an overview of the various postbiotic metabolites derived from the gut beneficial microbes, their potential therapeutic activities, and recent progressions in the drug delivery field, as well as concisely giving an insight on the main in vivo delivery routes of postbiotics.

Past, present, and future of microbiome-based therapies.

Technological advances in studying the human microbiome in depth have enabled the identification of microbial signatures associated with health and disease. This confirms the crucial role of microbiota in maintaining homeostasis and the host health status. Nowadays, there are several ways to modulate the microbiota composition to effectively improve host health; therefore, the development of therapeutic treatments based on the gut microbiota is experiencing rapid growth. In this review, we summarize the influence of the gut microbiota on the development of infectious disease and cancer, which are two of the main targets of microbiome-based therapies currently being developed. We analyze the two-way interaction between the gut microbiota and traditional drugs in order to emphasize the influence of gut microbial composition on drug effectivity and treatment response. We explore the different strategies currently available for modulating this ecosystem to our benefit, ranging from 1st generation intervention strategies to more complex 2nd generation microbiome-based therapies and their regulatory framework. Lastly, we finish with a quick overview of what we believe is the future of these strategies, that is 3rd generation microbiome-based therapies developed with the use of artificial intelligence (AI) algorithms.

Is there a role for microbiome-based approach in common variable immunodeficiency?

Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by low levels of serum immunoglobulins and increased susceptibility to infections, autoimmune disorders and cancer. CVID embraces a plethora of heterogeneous manifestations linked to complex immune dysregulation. While CVID is thought to be due to genetic defects, the exact cause of this immune disorder is unknown in the large majority of cases. Compelling evidences support a linkage between the gut microbiome and the CVID pathogenesis, therefore a potential for microbiome-based treatments to be a therapeutic pathway for this disorder. Here we discuss the potential of treating CVID patients by developing a gut microbiome-based personalized approach, including diet, prebiotics, probiotics, postbiotics and fecal microbiota transplantation. We also highlight the need for a better understanding of microbiota-host interactions in CVID patients to prime the development of improved preventive strategies and specific therapeutic targets.

Age-related diseases, therapies and gut microbiome: A new frontier for healthy aging.

The gut microbiome is undoubtedly a key modulator of human health, which can promote or impair homeostasis throughout life. This is even more relevant in old age, when there is a gradual loss of function in multiple organ systems, related to growth, metabolism, and immunity. Several studies have described changes in the gut microbiome across age groups up to the extreme limits of lifespan, including maladaptations that occur in the context of age-related conditions, such as frailty, neurodegenerative diseases, and cardiometabolic diseases. The gut microbiome can also interact bi-directionally with anti-age-related disease therapies, being affected and in turn influencing their efficacy. In this framework, the development of integrated microbiome-based intervention strategies, aimed at favoring a eubiotic configuration and trajectory, could therefore represent an innovative approach for the promotion of healthy aging and the achievement of longevity.

The Relationship Between the Gut Microbiome and Neurodegenerative Diseases.

Many recent studies have shown that the gut microbiome plays important roles in human physiology and pathology. Also, microbiome-based therapies have been used to improve health status and treat diseases. In addition, aging and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, have become topics of intense interest in biomedical research. Several researchers have explored the links between these topics to study the potential pathogenic or therapeutic effects of intestinal microbiota in disease. But the exact relationship between neurodegenerative diseases and gut microbiota remains unclear. As technology advances, new techniques for studying the microbiome will be developed and refined, and the relationship between diseases and gut microbiota will be revealed. This article summarizes the known interactions between the gut microbiome and neurodegenerative diseases, highlighting assay techniques for the gut microbiome, and we also discuss the potential therapeutic role of microbiome-based therapies in diseases.

New Approaches to Microbiome-Based Therapies.

Over the last decade, our understanding of the composition and functions of the gut microbiota has greatly increased. To a large extent, this has been due to the development of high-throughput genomic analyses of microbial communities, which have identified the critical contributions of the microbiome to human health. Consequently, the intestinal microbiota has emerged as an attractive therapeutic target. The large majority of microbiota-targeted therapies aim at engineering the intestinal ecosystem by means of probiotics or prebiotics. Recently, a novel therapeutic approach has emerged which focuses on molecules that are secreted, modulated, or degraded by the microbiome and act directly on the host. Here, we discuss the advantages and challenges associated with the metabolite-based "postbiotic" approach, highlighting recent progress and the areas that need intensive attention and investigation over the next 5 years. The time is ripe for postbiotic therapies to be developed in the near future.

The Relationship Between the Gut Microbiome and Neurodegenerative Diseases / 神经科学通报·英文版

Many recent studies have shown that the gut microbiome plays important roles in human physiology and pathology. Also, microbiome-based therapies have been used to improve health status and treat diseases. In addition, aging and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, have become topics of intense interest in biomedical research. Several researchers have explored the links between these topics to study the potential pathogenic or therapeutic effects of intestinal microbiota in disease. But the exact relationship between neurodegenerative diseases and gut microbiota remains unclear. As technology advances, new techniques for studying the microbiome will be developed and refined, and the relationship between diseases and gut microbiota will be revealed. This article summarizes the known interactions between the gut microbiome and neurodegenerative diseases, highlighting assay techniques for the gut microbiome, and we also discuss the potential therapeutic role of microbiome-based therapies in diseases.

The Relationship Between the Gut Microbiome and Neurodegenerative Diseases / 神经科学通报·英文版

Many recent studies have shown that the gut microbiome plays important roles in human physiology and pathology. Also, microbiome-based therapies have been used to improve health status and treat diseases. In addition, aging and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, have become topics of intense interest in biomedical research. Several researchers have explored the links between these topics to study the potential pathogenic or therapeutic effects of intestinal microbiota in disease. But the exact relationship between neurodegenerative diseases and gut microbiota remains unclear. As technology advances, new techniques for studying the microbiome will be developed and refined, and the relationship between diseases and gut microbiota will be revealed. This article summarizes the known interactions between the gut microbiome and neurodegenerative diseases, highlighting assay techniques for the gut microbiome, and we also discuss the potential therapeutic role of microbiome-based therapies in diseases.