Microbiome-based Therapeutics Research Articles

Alteration of gut microbiome in goslings infected with goose astrovirus

Goose astrovirus (GoAstV) is an emerging avian pathogen that induces gout in goslings with a mortality of up to 50%. Organ damage caused by GoAstV infection was considered the cause of gout, but it is still unclear whether other factors are involved. Human and murine studies have linked the gut microbiome-derived urate and gout, thus we hypothesized that gut microbiome may also play an important role in gout induced by GoAstV infection. This study tested the pathogenicity of our isolated GoAstV genotype 2 strain on goslings, while the appearance of clinical signs, histopathological changes, viral distribution and the blood level of cytokines were monitored for 18 days post-infection (dpi). The dynamics in the gut microbiome were profiled by 16S sequencing and then correlated with GoAstV infection. Results showed that this study successfully developed an experimental infection model for studying the pathogenicity of the GoAstV infection which induces typical symptoms of gout. GoAstV infection significantly altered the gut microbiome of goslings with the enrichment of potential pro-inflammatory bacteria and depletion of beneficial bacteria that can produce short-chain fatty acids. More importantly, the microbial pathway involved in urate production was significantly increased in goslings infected with GoAstV, suggesting that gut microbiome-derived urate may also contribute to the gout symptoms. Overall, this study demonstrated the role of gut microbiome in the pathogenesis of GoAstV infection, highlighting the potential of gut microbiome-based therapeutics against gout symptoms.

Fecal microbiota transplantation: current challenges and future landscapes.

SUMMARYGiven the importance of gut microbial homeostasis in maintaining health, there has been considerable interest in developing innovative therapeutic strategies for restoring gut microbiota. One such approach, fecal microbiota transplantation (FMT), is the main "whole gut microbiome replacement" strategy and has been integrated into clinical practice guidelines for treating recurrent Clostridioides difficile infection (rCDI). Furthermore, the potential application of FMT in other indications such as inflammatory bowel disease (IBD), metabolic syndrome, and solid tumor malignancies is an area of intense interest and active research. However, the complex and variable nature of FMT makes it challenging to address its precise functionality and to assess clinical efficacy and safety in different disease contexts. In this review, we outline clinical applications, efficacy, durability, and safety of FMT and provide a comprehensive assessment of its procedural and administration aspects. The clinical applications of FMT in children and cancer immunotherapy are also described. We focus on data from human studies in IBD in contrast with rCDI to delineate the putative mechanisms of this treatment in IBD as a model, including colonization resistance and functional restoration through bacterial engraftment, modulating effects of virome/phageome, gut metabolome and host interactions, and immunoregulatory actions of FMT. Furthermore, we comprehensively review omics technologies, metagenomic approaches, and bioinformatics pipelines to characterize complex microbial communities and discuss their limitations. FMT regulatory challenges, ethical considerations, and pharmacomicrobiomics are also highlighted to shed light on future development of tailored microbiome-based therapeutics.

Taking Microbiome Science to the Next Level: Recommendations to Advance the Emerging Field of Microbiome-based Therapeutics and Diagnostics.

Taking Microbiome Science to the Next Level: Recommendations to Advance the Emerging Field of Microbiome-based Therapeutics and Diagnostics.

Exploiting gut microbial traits and trade-offs in microbiome-based therapeutics

Exploiting gut microbial traits and trade-offs in microbiome-based therapeutics

Faecalibacterium duncaniae as a novel next generation probiotic against influenza.

The gut-lung axis is critical during viral respiratory infections such as influenza. Gut dysbiosis during infection translates into a massive drop of microbially produced short-chain fatty acids (SCFAs). Among them, butyrate is important during influenza suggesting that microbiome-based therapeutics targeting butyrate might hold promises. The butyrate-producing bacterium Faecalibacterium duncaniae (formerly referred to as F. prausnitzii) is an emerging probiotic with several health-promoting characteristics. To investigate the potential effects of F. duncaniae on influenza outcomes, mice were gavaged with live F. duncaniae (A2-165 or I-4574 strains) five days before infection. Supplementation of F. duncaniae was associated with less severe disease, a lower pulmonary viral load, and lower levels of lung inflammation. F. duncaniae supplementation impacted on gut dysbiosis induced by infection, as assessed by 16S rRNA sequencing. Interestingly, F. duncaniae administration was associated with a recovery in levels of SCFAs (including butyrate) in infected animals. The live form of F. duncaniae was more potent that the pasteurized form in improving influenza outcomes. Lastly, F. duncaniae partially protected against secondary (systemic) bacterial infection. We conclude that F. duncaniae might serve as a novel next generation probiotic against acute viral respiratory diseases.

Probiotics in Allergy and Immunological Diseases: A Comprehensive Review.

Allergy and immunological disorders like autoimmune diseases are vastly prevalent worldwide. These conditions account for a substantial amount of personal and social burden. Such illnesses have lengthy, uncertain, and spotted courses with unpredictable exacerbations. A definite tendency for improving the overall quality of life ofindividuals suffering from such diseases is crucial to tackling these diseases, especiallythrough diet or lifestyle modification. Further, interventions like microbiome-based therapeutics such as prebiotics or probiotics were explored. Changes in the microbial population were evident during the flare-up of autoimmune and allergic conditions. The realization that the human microbiome is a central player in immunological diseases isa hallmark of its potential usefulness in therapy for such illnesses. This review focuses on the intricate symphony in the orchestra of the human microbiome and the immune system. New therapeutic strategies involving probiotics appearto be the future of personalized medicine. Through this review, we explore the narrative of probiotics and reaffirm their use as therapeutic and preventive agents in immunological disorders.

Can Therapeutic Targeting of the Human Microbiome Influence Asthma Management? A Pro/Con Debate

Asthma is a clinically heterogenous disease and despite substantial improvements in therapies, there remains an unmet need for well-tolerated, effective treatments. Observational studies have demonstrated that alterations in the respiratory and gut microbiome are associated with the development of asthma as well as its severity. These findings are supported by preclinical models demonstrating that respiratory and gut microbes can alter airway inflammation. Therapeutic approaches to target the human microbiome have been increasingly applied to a wide range of acute and chronic diseases, but there are currently no microbiome-based therapeutics approved for the treatment of asthma. This clinical commentary addresses the future role of microbiome-based therapeutics in asthma management from both a pro and con perspective. We examine (1) the prospects for clinical studies demonstrating a causal relationship between the human microbiome and the severity of asthma, (2) the challenges and potential solutions for designing, testing, and implementing a microbiome-based therapeutic, and (3) the possibility of microbiome-based therapeutics for conditions co-morbid to asthma. We conclude by identifying research priorities that will help determine the future of microbiome-based therapeutics for the management of asthma.

Targeting the Gut Microbiome to Treat Cardiometabolic Disease.

Cardiometabolic diseases, which include obesity, type 2 diabetes, and cardiovascular diseases, constitute a worldwide health crisis of unparalleled proportions. The human gut microbiota has emerged as a prominent topic of inquiry in the search for novel treatment techniques. This review summarizes current research on the potential of addressing the gut microbiota to treat cardiometabolic disease. Recent studies have highlighted a complex link between the gut microbiota and host physiology, shedding light on the several processes through which gut microorganisms impact metabolic health, inflammation, and cardiovascular function. Furthermore, a growing corpus of research is available on microbiome-based therapies such as dietary interventions, probiotics, prebiotics, synbiotics, and fecal microbiota transplantation. These therapies show promise as methods for reshaping the gut microbiota and, as a result, improving cardiometabolic outcomes. However, hurdles remain, ranging from the intricacies of microbiome research to the necessity for tailored treatments that take individual microbial variations into consideration, emphasizing the significance of furthering research to bridge the gap between microbiome science and clinical practice. The gut microbiome is a beacon of hope for improving the management of cardiometabolic disease in the age of precision medicine, since its association with their pathophysiology is constantly being unraveled and strengthened. Available studies point to the potential of gut microbiome-based therapeutics, which remains to be tested in appropriately designed clinical trials. Further preclinical research is, however, essential to provide answers to the existing obstacles, with the ultimate goal of enhancing patient care.

Pharmacomicrobiomics-Guided Precision Oncology: A New Frontier of P4 (Predictive, Personalized, Preventive, and Participatory) Medicine and Microbiome-Based Therapeutics.

Pharmacomicrobiomics is a rapidly developing field that promises to make significant contributions to predictive, personalized, preventive, and participatory (P4) medicine. This is becoming evident particularly in the field of precision (P4) oncology by taking seriously the crucial role microbiome plays in health and disease. Several studies have already shown that clinicians can harness insights from the microbiome to better predict treatment response, reduce side effects, and improve overall outcomes for cancer patients. Furthermore, pharmacomicrobiomics will undoubtedly play a crucial role in shaping the future of cancer treatment in the era of P4 oncology as we continue to unravel the intricate relationships between the microbiome and cancer. This perspective and innovation analysis discusses the emerging intersection of P4 medicine and P4 oncology, as seen through a lens of pharmacomicrobiomics. A key promise of pharmacomicrobiomics is the development of personalized microbiome-based therapeutics. In all, we suggest that optimizing cancer treatment and prevention by harnessing pharmacomicrobiomics has vast potentials for precision oncology, and personalized medicine using the right drug, at the right dose, for the right patient, and at the right time.

Should probiotics be administered as an adjunctive treatment along with antidepressants for major depressive disorder?

Madam, Major depressive disorder (MDD) is a significant factor in global disability rates and contributes significantly to the overall disease burden worldwide. According to estimates, approximately 3.8% of the global population is impacted, with a prevalence of 5.0% among adults and 5.7% among adults aged 60 years and above [1]. It is also the leading cause of suicide among individuals. While the administration of antidepressants is the widely known and successful treatment for this mental disorder, recent research and accumulating evidence have demonstrated that probiotics also function effectively in controlling anxiety and depression. Probiotics that provide psychological benefits are now referred to as psychobiotics. Psychobiotics are defined as live organisms that, when consumed in sufficient quantities, produce unexpected health benefits in individuals with psychiatric disorders [2]. Around 30% of patients with major depressive disorder (MDD) do not respond to traditional antidepressant medications targeting monoamine pathways, indicating the involvement of other biological mechanisms in the development of MDD [3]. One particularly promising hypothesis regarding the pathogenesis of MDD is the dysfunction of the gut-brain axis (GBA), with the gut microbiota playing a crucial role [4]. Numerous studies have investigated the impact of probiotics on stress resilience. The recent meta-analysis discovered a significant finding: when probiotics were combined with antidepressants, they showed a remarkable reduction in depressive symptoms. However, when used alone, probiotics exhibited a less impact on alleviating depressive symptoms. This highlights the crucial role of combining probiotics with standard treatments for a more substantial effect on managing depression [5]. These impressive results elucidate the advantages of administering probiotic strains in individuals suffering from mental health disorders, specifically MDD, by effectively addressing the imbalance within the gut-brain axis (GBA) and suppressing stress-induced activation of biological pathways involved in psychological disturbances. Recurrent evidence has proven that gut microbiota play a significant role in neuronal homeostasis and any imbalance may contribute as a factor in the underlying mechanism of the pathogenesis of MDD. Henceforth, further research should be encouraged in order to develop promising microbiome-based therapeutics for MDD, and physicians should consider administering probiotics as an adjunctive treatment for depression alongside antidepressants. Moreover, the importance of probiotics should be thoroughly studied, and medical doctors should raise awareness of the significance of the gut-brain axis and associated biological pathways, which play a major role in an individual's mental health.

Gut Microbiome-Based Therapeutics in Critically Ill Adult Patients-A Narrative Review.

The gut microbiota plays a crucial role in the human microenvironment. Dysbiosis of the gut microbiota is a common pathophysiological phenomenon in critically ill patients. Therefore, utilizing intestinal microbiota to prevent complications and improve the prognosis of critically ill patients is a possible therapeutic direction. The gut microbiome-based therapeutics approach focuses on improving intestinal microbiota homeostasis by modulating its diversity, or treating critical illness by altering the metabolites of intestinal microbiota. There is growing evidence that fecal microbiota transplantation (FMT), selective digestive decontamination (SDD), and microbiota-derived therapies are all effective treatments for critical illness. However, different treatments are appropriate for different conditions, and more evidence is needed to support the selection of optimal gut microbiota-related treatments for different diseases. This narrative review summarizes the curative effects and limitations of microbiome-based therapeutics in different critically ill adult patients, aiming to provide possible directions for gut microbiome-based therapeutics for critically ill patients such as ventilator-associated pneumonia, sepsis, acute respiratory distress syndrome, and COVID-19, etc.

Role of the Human Microbiome in Health and Disease in United Kingdom

Purpose: The aim of the study was to investigate the role of the human microbiome in health and disease in United Kingdom.
 Methodology: The study adopted a desktop methodology. Desk research refers to secondary data or that which can be collected without fieldwork. Desk research is basically involved in collecting data from existing resources hence it is often considered a low cost technique as compared to field research, as the main cost is involved in executive’s time, telephone charges and directories. Thus, the study relied on already published studies, reports and statistics. This secondary data was easily accessed through the online journals and library
 Findings: The microbiome influences human health and disease by providing essential functions, such as nutrient metabolism, immune regulation, and protection against pathogens. However, the microbiome can also be disrupted by various factors, such as diet, lifestyle, age, genetics, and infections, leading to dysbiosis and increased risk of diseases. In the United Kingdom, research on the microbiome has been conducted to understand its role in various conditions, such as obesity, diabetes, inflammatory bowel disease, cancer, and mental health. The findings suggest that modulating the microbiome through dietary interventions, probiotics, prebiotics, or fecal microbiota transplantation may offer novel strategies for preventing or treating these diseases.
 Unique Contribution to Theory, Practice and Policy: Microbiome Dysbiosis Theory, Hygiene Hypothesis Theory and Microbiota-Brain-Gut Axis Theory may be used to anchor future studies on role of the human microbiome in health and disease in United Kingdom. Findings can invest in the development of microbiome-based therapeutics, including fecal microbiota transplantation (FMT), engineered probiotics, and microbial-derived products. Policymakers should establish a regulatory framework for microbiome-based interventions, ensuring their safety, efficacy, and accessibility.

Microbiome-Based Therapeutics in Digestive Diseases: What They Are and How Are They Regulated.

Microbiome-Based Therapeutics in Digestive Diseases: What They Are and How Are They Regulated.

Importanţa microbiomului în obezitatea pediatrică

Childhood involves aspects for interventions that con­fi­gure the microbiome to alleviate obesity-related dis­tur­bances. Children with obesity have gut microbiota com­po­si­tio­nal and functional differences, including in­creased pro­in­flam­matory bacterial characteristics. Re­sto­ra­tion of the gut microbiota to a healthy state may ame­lio­rate conditions associated with obesity and help main­tain a healthy weight. This review brings to the fore the consequences and aspects of childhood obesity, the im­por­tance of the developing microbiome in establishing meta­bolic path­ways, and the therapeutic attitude. It contributes basically to denote future research directions for the potential develop­ment of microbiome-based therapeutics to treat obesity.

Host microbiome in tuberculosis: disease, treatment, and immunity perspectives.

Tuberculosis (TB), an airborne pulmonary disease caused by Mycobacterium tuberculosis (M. tb), poses an unprecedented health and economic burden to most of the developing countries. Treatment of TB requires prolonged use of a cocktail of antibiotics, which often manifest several side effects, including stomach upset, nausea, and loss of appetite spurring on treatment non-compliance and the emergence of antibiotic resistant M. tb. The anti-TB treatment regimen causes imbalances in the composition of autochthonous microbiota associated with the human body, which also contributes to major side effects. The microbiota residing in the gastrointestinal tract play an important role in various physiological processes, including resistance against colonization by pathogens, boosting host immunity, and providing key metabolic functions. In TB patients, due to prolonged exposure to anti-tuberculosis drugs, the gut microbiota significantly loses its diversity and several keystone bacterial taxa. This loss may result in a significant reduction in the functional potency of the microbiota, which is a probable reason for poor treatment outcomes. In this review, we discuss the structural and functional changes of the gut microbiota during TB and its treatment. A major focus of the review is oriented to the gut microbial association with micronutrient profiles and immune cell dynamics during TB infection. Furthermore, we summarize the acquisition of anti-microbial resistance in M. tb along with the microbiome-based therapeutics to cure the infections. Understanding the relationship between these components and host susceptibility to TB disease is important to finding potential targets that may be used in TB prevention, progression, and cure.

The human microbiome: A critical player in health and disease

The human microbiome is a remarkable and sophisticated ecology made up of billions of bacteria that live in various regions of the human body, and its importance in supporting human health cannot be understated. The gut microbiome, in particular, has been widely studied and determined to have an important role in immune system regulation, digestion and absorption of nutrients, and the creation of numerous metabolites. Gut microbiome dysbiosis has been related to a variety of conditions and diseases, including metabolic disorders and inflammatory bowel disease. However, the encouraging outcomes of microbiome-based therapeutics like fecal microbiota transplantation and probiotics have given fresh hope for the treatment and prevention of many disorders. Similarly, the skin microbiome and oral microbiome have been discovered to play significant roles in pathogen protection, inflammatory regulation, and general health. Skin and mouth microbiome dysbiosis have been linked to a variety of dermatological and dental illnesses, respectively. Microbiome-based treatments, such as topical probiotics, oral probiotics, and prebiotics, have shown success in the treatment and prevention of various disorders.The human microbiome is an intriguing and promising field of research that might lead to new ways of preserving and improving human health. We can create novel ways for preventing and treating a variety of illnesses and diseases by better understanding the intricate connections between the microbiome and the host. It is imperative to continue exploring the microbiome to discover novel and effective therapeutics to battle the increase in chronic illnesses and enhance the general health of our communities.

Microbiome-based therapeutics for Clostridioides difficile infection: helpful solutions or unclear cocktails?

Microbiome-based therapeutics for Clostridioides difficile infection: helpful solutions or unclear cocktails?

Immunological consequences of microbiome-based therapeutics.

The complex network of microscopic organisms living on and within humans, collectively referred to as the microbiome, produce wide array of biologically active molecules that shape our health. Disruption of the microbiome is associated with susceptibility to a range of diseases such as cancer, diabetes, allergy, obesity, and infection. A new series of next-generation microbiome-based therapies are being developed to treat these diseases by transplanting bacteria or bacterial-derived byproducts into a diseased individual to reset the recipient's microbiome and restore health. Microbiome transplantation therapy is still in its early stages of being a routine treatment option and, with a few notable exceptions, has had limited success in clinical trials. In this review, we highlight the successes and challenges of implementing these therapies to treat disease with a focus on interactions between the immune system and microbiome-based therapeutics. The immune activation status of the microbiome transplant recipient prior to transplantation has an important role in supporting bacterial engraftment. Following engraftment, microbiome transplant derived signals can modulate immune function to ameliorate disease. As novel microbiome-based therapeutics are developed, consideration of how the transplants will interact with the immune system will be a key factor in determining whether the microbiome-based transplant elicits its intended therapeutic effect.

Understanding respiratory microbiome-immune system interactions in health and disease.

Interactions between the developing microbiome and maturing immune system in early life are critical for establishment of a homeostasis beneficial to both host and commensals. The lung harbors a diverse community of microbes associated with health and local or systemic disease. We discuss how early life colonization and community changes correlate with immune development and health and disease throughout infancy, childhood, and adult life. We highlight key advances in microbiology, immunology, and computational biology that allow investigation of the functional relevance of interactions between the respiratory microbiome and host immune system, which may unlock the potential for microbiome-based therapeutics.

Human Fecal Bile Acid Analysis after Investigational Microbiota-Based Live Biotherapeutic Delivery for Recurrent Clostridioides difficile Infection

Microbiome-based therapeutics are increasingly evaluated as a strategy to reduce recurrent Clostridioides difficile infection (rCDI), with proposed mechanisms including restoration of the microbiota and microbiota-mediated functions, such as bile acid (BA) metabolism. This study reports a quantitative and sensitive assay for targeted metabolomic assessment, and the application of the assay to profile BA composition in a Phase 2 trial of the investigational microbiota-based live biotherapeutic RBX2660 for reduction of rCDI. A liquid chromatography tandem mass spectrometry method was developed to extract and quantify 35 BAs from 113 participant stool samples from 27 RBX2660-treated rCDI participants in the double-blinded, placebo-controlled clinical trial. The results demonstrate a high-confidence assay as represented by sensitivity, linearity, accuracy, and precision. Furthermore, the assay enabled the observation of primary BAs as the dominant BA species at baseline in stool samples from clinical trial participants, consistent with the expected loss of commensals after broad-spectrum antibiotic treatment. After RBX2660 administration, there was a significant drop in primary BAs concurrent with increased secondary BAs that sustained through 24 months post-RBX2660. Taken together, we describe a robust assay that demonstrates altered BA metabolism in rCDI patients treated with RBX2660 administration.