Microbes Microbial Metabolism And Mucosal Immunity

The study of microbiome and microbial metabolites and their roles in host mucosal immunology is a rapidly developing area of research. One major way in which the microbiome influences the host is through altered metabolism. Metabolites, readily available to the host, engender significant consequences. Microbial metabolites have been shown to impact the disease processes in both proximal and distal organs, including the brain in several neurocognitive disorders. Microbes, Microbial Metabolism and Mucosal Immunity: An Overview presents a concise and well-vetted treatise on the study of microbiome and microbial metabolites. This volume is up-to-date with the most recent developments from the last decade. It encompasses the interaction of immunity and microbes - and their metabolites - from different mucosal organs including eye, skin, gastrointestinal system, lung, intestine and cervix. Along with the efficiency of the immune system in inhibiting the growth and proliferation of microbes, the volume discusses how the mediators of the immune system can be targeted to develop therapies. This book presents the latest methods, gives broad and systematic coverage of most mucosal systems and diseases, and takes a fresh perspective that looks at the functional aspects of change in the microbiome.

This work sheds new light on the interplay between the gut, gut microbiota, and host physiological processes in production animals. The gut microbiome shapes health and susceptibility to disease and has become a leading area of research in the animal sciences. Gut health encompasses a number of physiological and functional features. Nutrient digestion and absorption, host metabolism and energy generation, a stable microbiome, mucus layer development, barrier function, and mucosal immune responses; all of which are required to interact to make an animal perform physiologically and according to its greatest genetic potential. This carefully presented book broadens our vision, approach and results on gut health and the ability to regulate animal production. Understanding the chemistry of microbiomes has broad implications, including providing functional annotations for the microbial genomes, insights into the chemical languages that link microbes to each other and to their host, and translational implications for precision veterinary medicine, environmental health, and sustainable animal agriculture and welfare. Experts working in microbiome research, host immunity, and animal production, veterinarians and researchers in livestock science will understand the great importance of this volume.

Background: Human body surfaces are lined by mucosal membranes composed of epithelial cells which serve as the primary barrier for protection against pathogens. These mucous membranes function in a shared environment with resident microbes, creating a complex ecosystem with communal sources of nutrients for the host as well as its microbes. Encounters with viral, fungal, and bacterial pathogens can directly or indirectly damage epithelial cells, disrupting tight junctions that keep mucosal barriers intact. Disruption of epithelial barriers lead to downstream inflammation, translocation of microbial products into the bloodstream, and exacerbation of disease. For example, Human immunodeficiency virus-1 (HIV) proteins can target zonula occludens for viral entry and dissemination, Clostridium perfringens utilizes claudin proteins as receptors for entry, and candidalysin toxin from Candida albicans targets junctional complexes for translocation, all of which induce permeability in epithelial barriers. Furthermore, autoimmune diseases such as inflammatory bowel disease and diabetes exhibit similar pathologies in intestinal barrier disruption and microbial dysbiosis. While these barrier defects have been observed across a broad range of diseases, there is a lack of understanding in how tight junctions are regulated by epithelial cells and which therapeutic targets will be effective. My dissertation takes two approaches to address this issue: 1) mucosal repair in chronic inflammation and 2) mucosal protection against pathogens. I hypothesized that strategies targeting entry of pathogens and cellular metabolism at mucosal sites will be fundamental for effective prevention and treatment of chronic diseases. This dissertation presents three studies that advance our knowledge about mucosal repair/protection by leveraging host-microbial metabolic pathways and mucoadhesive drug delivery systems. 1: Repair of gut epithelial barriers during SIV-induced chronic gut inflammation through the mitochondria-microbiota crosstalk. Chronic gut inflammatory diseases are associated with disruption of intestinal epithelial barriers and impaired mucosal immunity. HIV causes depletion of mucosal CD4+ T cells early in infection and disruption of gut epithelium, resulting in chronic inflammation and immunodeficiency. Although antiretroviral therapy is effective in suppressing viral replication, it is incapable of restoring the "leaky gut," which poses an impediment for HIV cure efforts. Using the intestinal loop model in SIV-infected rhesus macaques, we found rapid repair of gut epithelial barriers within five hours of administering Lactobacillus plantarum into virally inflamed gut. The rapid recovery was driven by peroxisome proliferator-activated receptor (PPAR[alpha]) activation and occurred independent of mucosal CD4+ T cell recovery, highlighting a metabolic repair pathway in mitochondrial [beta]-oxidation that can be targeted for epithelial repair prior to complete immune recovery. These findings highlight the critical role of PPAR[alpha] at the intersection between microbial metabolism and epithelial repair in virally inflamed gut and as a potential mitochondrial target for restoring gut barriers in infectious or inflammatory diseases. Study 2: Renewal of gut epithelial barriers in metabolic disease through PPAR[alpha] signaling at the host-microbe interface in metabolic disease. Metabolic disease affects approximately one-third of the US adult population, and is defined by pathological conditions associated with obesity, insulin resistance, hypertension, and hyperlipidemia. Metabolic disease is concomitant to dysfunctions in the intestinal barrier and an increased risk for mucosal infection and systemic inflammation, all of which are poorly understood. Using a canine model of diabetes mellitus (DM), we translated our findings in Study 1 and tested the clinical translation of PPAR[alpha] activation on gut epithelial barriers using fenofibrate, a known PPAR[alpha] agonist. We found that a 3-week oral dosage of fenofibrate alleviates small intestinal barrier disruption and improves lipid metabolism in dogs with DM. Reduction of plasma triglycerides after 3 weeks correlated with lower immune activation and reduction of intraepithelial T lymphocytes in the duodenum. The gut microbial composition remained stable after fenofibrate administration, suggesting that repair of intestinal barriers can be achieved independent of surrounding microbiota. These findings indicate that lipid metabolism is essential to functionality of the gut epithelium, which can be rescued by PPAR[alpha] activation in DM. Study 3: Protection of genital mucosal surfaces against HIV and SHIV viruses using Silk fibroin mucoadhesive delivery platform. Efforts to end the AIDS epidemic using anti-retroviral therapy have been widely successful in reducing HIV-related deaths. However, challenges for the prevention of new HIV infections have not been fully resolved. Most new HIV infections occur through mucosal transmission, so it is imperative that HIV prevention platforms are effective at mucosal sites, can be produced inexpensively, and are accessible to vulnerable populations. In these cases, protection against HIV transmission must overcome individual-to-individual variation in the context of mucosal microbiota composition, host metabolic status, and immune response. In this study, we developed a silk fibroin (SF)-based drug delivery platform that encapsulates a potent HIV entry inhibitor Griffithsin (Grft) that can be readily administered into genital mucosal sites for HIV prevention. The SF formulation, capable of holding several anti-HIV proteins, is thermodynamically stable for over one year, can be released over the course of one month, and provides an innovative platform that is safe and effective against transmission of HIV. We demonstrate the safety and efficacy of SF-Grft in both vaginal and rectal compartments using a non-human primate model in vivo and human explant cultures ex vivo. Effective release and mucosal adherence of SF-Grft protected against HIV and SHIV challenge with negligible changes in local microbiota or inflammatory responses. These findings provide support for the development of SF as an effective HIV prevention modality at mucosal sites to help address the global disparity in HIV infection. Conclusion: These studies provide novel insights into new metabolic targets to repair inflamed gut mucosa and impart protection against pathogens at mucosal surfaces through innovative mucoadhesive technology. This dissertation deciphers the molecular, cellular, and microbial components involved in chronic gut inflammatory diseases, identifies molecular mechanisms of reversing mucosal damage, and defines the significance of addressing this complexity to bolster systemic and mucosal health.

"Infectious Microecology: Theory and Applications" firstly introduces microecology in the study of infection and proposes new anti-infection methods and strategies and then provides a comprehensive and up-to-date overview of research on infectious microecology. It concludes with a new theory for studying infectious diseases. This book presents the basic theories and fundamentals of infectious microecology, covering all the microecological systems relevant to clinical work. It also describes a new strategy and method to combat infectious diseases and provides detailed descriptions of studies and techniques in infectious microecology. The book discusses utilizing 10 years’ worth of research and clinical practice, referring to recent literature on the relationship between infection and microecology and combined with the latest research findings on liver microecology. In addition, it outlines the latest advances in the theory and techniques in the field of infectious microecology. It is intended for doctors, researchers and graduate students in the fields of infectious disease and microecology. Dr. Lanjuan Li is member of the Chinese Academy of Engineering, she is also a Professor and Chief Physician at Zhejiang University, China.

Transport of molecules across the cell membrane is a fundamental process of all living organisms. It is essential for understanding growth, development, nutrition as well as uptake and excretion of exogenous or synthesized molecules. Microbes respresent general and basic functional systems where many transport processes have been studied on a molecular basis. Knowledge of the microbial transport processes will provide new perspectives to treatments by inhibitors, drugs, antibiotics, vitamins, growth promotion compounds, activators and toxic compunds of various kinds.

This title represents a broad review of current research on LAB and their novel applications with contributions from a number of well-known leading scientists. The book encompasses a wide range of topics including both traditional and novel developing fields, and provides unparalleled, comprehensive information on new advances of genomics, proteomics, metabolism and biodiversity of LAB. Chapters contain state-of-the-art discussions of specific LAB applications such as their use as probiotics, live vaccines and starter cultures in old and new fermented products. The safety of these microorganisms and their interactions with diverse ecosystems natural biota are also covered as well as the new applications of well-known (bacteriocins) and novel (vitamins, low-calorie sugars, etc.) metabolites produced by LAB. This book is an essential reference for established researchers and scientists, doctoral and post-doctoral students, university professors and instructors, and food technologists working on food microbiology, physiology and biotechnology of lactic acid bacteria.

This is the first comprehensive volume to look at the importance of short-chain fatty acids in digestion, the function of the large intestine and their role in human health. Short-chain fatty acids are the major product of bacterial fermentation of dietary carbohydrates in the human and animal large intestine. They represent the major end products of digestive processes occurring in the caecum and large intestine. As such, they form an important dietary component and it is increasingly recognised that they may have a significant role in protecting against large bowel cancer and in metabolism. Prepared by an international team of contributors who are at the forefront of this area of research, this volume will be an essential source of reference for gastroenterologists, nutritionists and others active in this area.