Immune homeostasis, dysbiosis and therapeutic modulation of the gut microbiota (original) (raw)
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The gut microbiota and host health: a new clinical frontier
Over the last 10–15 years, our understanding of the composition and functions of the human gut microbiota has increased exponentially. To a large extent, this has been due to new 'omic' technologies that have facilitated large-scale analysis of the genetic and metabolic profile of this microbial community, revealing it to be comparable in influence to a new organ in the body and offering the possibility of a new route for therapeutic intervention. Moreover, it might be more accurate to think of it like an immune system: a collection of cells that work in unison with the host and that can promote health but sometimes initiate disease. This review gives an update on the current knowledge in the area of gut disorders, in particular metabolic syndrome and obesity-related disease, liver disease, IBD and colorectal cancer. The potential of manipulating the gut microbiota in these disorders is assessed, with an examination of the latest and most relevant evidence relating to antibiotics, probiotics, prebiotics, polyphenols and faecal microbiota transplantation.
International Journal of Experimental Research and Review, 2023
Millions of microorganisms, including bacteria, fungi, and viruses compose the human gut microbiome. There is variation in the composition of species from the moment of birth throughout the whole human lifecycle. Gut microbiome play a central role in maintaining body equilibrium, influencing a range of physiological processes including metabolism, the maintenance of barriers, inflammation, and hematopoiesis, both within and outside the intestines. An imbalanced microbial environment within the gastrointestinal tract is at the core of numerous diseases, such as inflammatory bowel disorder, obesity, diabetes, and Clostridioides difficile infection, and plays a pivotal role in their development. In this review, we discuss the therapeutic approaches of gut microbiome-related therapies including fecal microbiota transplantation, anti-microbial therapies, prebiotics, probiotics and Dietary interventions to repair the altered gut microbiome composition. The pursuit of new therapies and their subsequent improvement is propelled by an ongoing requirement for evaluation, experimentation, laboratory procedures, and the ethical and technological limitations associated with clinical translation.
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The gut microbiota provides essential signals for the development and appropriate function of the immune system. Through this critical contribution to immune fitness, the gut microbiota has a key role in health and disease. Recent advances in the technological applications to study microbial communities and their functions have contributed to a rapid increase in host-microbiota research. Although it still remains difficult to define a so-called 'normal' or 'healthy' microbial composition, alterations in the gut microbiota have been shown to influence the susceptibility of the host to different diseases. Current translational research combined with recent technological and computational advances have enabled in-depth study of the link between microbial composition and immune function, addressing the interplay between the gut microbiota and immune responses. As such, beneficial modulation of the gut microbiota is a promising clinical target for many prevalent diseases including inflammatory bowel disease, metabolic abnormalities such as obesity, reduced insulin sensitivity and low-grade inflammation, allergy and protective immunity against infections.
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Chronic inflammation is a hallmark for a variety of disorders and is at least partially responsible for disease progression and poor patient health. In recent years, the microbiota inhabiting the human gut has been associated with not only intestinal inflammatory diseases but also those that affect the brain, liver, lungs, and joints. Despite a strong correlation between specific microbial signatures and inflammation, whether or not these microbes are disease markers or disease drivers is still a matter of debate. In this review, we discuss what is known about the molecular mechanisms by which the gut microbiota can modulate inflammation, both in the intestine and beyond. We identify the current gaps in our knowledge of biological mechanisms, discuss how these gaps have likely contributed to the uncertain outcome of fecal microbiota transplantation and probiotic clinical trials, and suggest how both mechanistic insight and -omics-based approaches can better inform study design and t...
Gut Microbiota: The Next-Gen Frontier in Preventive and Therapeutic Medicine?
Frontiers in Medicine, 2014
Our gut harbors an extremely diverse collection of trillions of microbes that, besides degrading the complex dietary constituents, execute numerous activities vital for our metabolic and immune health. Although the importance of gut microbiota in maintaining digestive health has long been believed, its close correlation with numerous chronic ailments has recently been noticed, thanks to the innovative mechanistic studies on the compositional and functional aspects of gut microbial communities using germ-free or humanized animal models. Since a myriad of mysteries about the precise structures and functions of gut microbial communities in specific health situations still remains to be explicated, the emerging field of gut microbiota remains a foremost objective of research for microbiologists, immunologists, computational biologists, clinicians, food and nutrition experts, etc. Nevertheless, it is only after a comprehensive understanding of the structure, density, and function of the gut microbiota that the new therapeutic targets could be captured and utilized for a healthier gut as well as improved overall well-being.
International Journal of Research and Analytical Reviews, 2024
This review critically evaluates the role of probiotics in modulating gut microbiota composition and their potential health benefits. Probiotics are live microorganisms that confer health benefits to the host when consumed in adequate amounts. The gut microbiota plays a crucial role in maintaining gastrointestinal homeostasis, immune function, and overall health. Numerous studies have investigated the effects of probiotics on gut microbiota composition and their impact on various health outcomes. Probiotics summarize recent findings on the mechanisms by which probiotics influence gut microbiota composition, including competitive exclusion, production of antimicrobial compounds, and modulation of host immune responses. Furthermore, we discuss the clinical evidence supporting the use of probiotics in the management of gastrointestinal disorders, such as irritable bowel syndrome, inflammatory bowel disease, and antibioticassociated diarrhea. Additionally, we examine emerging research on the potential benefits of probiotics for non-gastrointestinal conditions, including allergic disorders, metabolic syndrome, and mental health disorders. Finally, we highlight gaps in current knowledge and propose future research directions to optimize the use of probiotics for promoting gut health and overall well-being.
The mutual interplay of gut microbiota, diet and human disease
The FEBS Journal, 2020
The intestinal milieu harbours the gut microbiota, consisting of a complex community of bacteria, archaea, fungi, viruses and protozoans that bring to the host organism an endowment of cells and genes more numerous than its own. In the last 10 years, mounting evidence has highlighted the prominent influence of the gut mutualistic bacterial communities on human health. Microbial colonization occurs alongside with immune system development and plays a role in intestinal physiology. The community of the gut microbiota does not undergo significant fluctuations throughout adult life. However, bacterial infections, antibiotic treatment, lifestyle, surgery and diet might profoundly affect it. Gut microbiota dysbiosis, defined as marked alterations in the amount and function of the intestinal microorganisms, is correlated with the aetiology of chronic noncommunicable diseases, ranging from cardiovascular, neurologic, respiratory and metabolic illnesses to cancer. In this review, we focus on...
The gut microbiome as therapeutic target
Pharmacology & Therapeutics, 2011
a b s t r a c t a r t i c l e i n f o Keywords: Gut microbiota LPS Obesity/type 2 diabetes Gut permeability Inflammation Endocannabinoid system Obesity, type-2 diabetes and low-grade inflammation are becoming worldwide epidemics. In this regard, the literature provides a novel concept that we call "MicrObesity" (Microbes and Obesity), which is devoted to deciphering the specific role of dysbiosis and its impact on host metabolism and energy storage. In the present review, we discuss novel findings that may partly explain how the microbial community participates in the development of the fat mass development, insulin resistance and low-grade inflammation that characterise obesity. In recent years, numerous mechanisms have been proposed and several proteins identified. Amongst the key players involved in the control of fat mass development, Fasting induced adipose factor, AMP-activated protein kinase, G-protein coupled receptor 41 and G-protein coupled receptor 43 have been linked to gut microbiota. In addition, the discovery that low-grade inflammation might be directly linked to the gut microbiota through metabolic endotoxaemia (elevated plasma lipopolysaccharide levels) has led to the identification of novel mechanisms involved in the control of the gut barrier. Amongst these, the impacts of glucagon-like peptide-2, the endocannabinoid system and specific bacteria (e.g., Bifidobacterium spp.) have been investigated. Moreover, the advent of probiotic and prebiotic treatments appears to be a promising "pharmaco-nutritional" approach to reversing the host metabolic alterations linked to the dysbiosis observed in obesity. Although novel powerful molecular system biology approaches have offered great insight into this "small world within", more studies are needed to unravel how specific changes in the gut microbial community might affect or counteract the development of obesity and related disorders.
The Central Role of the Gut Microbiota in Chronic Inflammatory Diseases
Journal of Immunology Research, 2014
The commensal microbiota is in constant interaction with the immune system, teaching immune cells to respond to antigens. Studies in mice have demonstrated that manipulation of the intestinal microbiota alters host immune cell homeostasis. Additionally, metagenomic-sequencing analysis has revealed alterations in intestinal microbiota in patients suffering from inflammatory bowel disease, asthma, and obesity. Perturbations in the microbiota composition result in a deficient immune response and impaired tolerance to commensal microorganisms. Due to altered microbiota composition which is associated to some inflammatory diseases, several strategies, such as the administration of probiotics, diet, and antibiotic usage, have been utilized to prevent or ameliorate chronic inflammatory diseases. The purpose of this review is to present and discuss recent evidence showing that the gut microbiota controls immune system function and onset, development, and resolution of some common inflammatory diseases.