New insights into the interactions between Blastocystis,the gut microbiota,and host immunity

The human gut microbiota is a diverse and complex ecosystem that is involved in beneficial physiological functions as well as disease pathogenesis. Blastocystis is a common protistan parasite and is increasingly recognized as an important component of the gut microbiota. The correlations between Blastocystis and other communities of intestinal microbiota have been investigated, and, to a lesser extent, the role of this parasite in maintaining the host immunological homeostasis. Despite recent studies suggesting that Blastocystis decreases the abundance of beneficial bacteria, most reports indicate that Blastocystis is a common component of the healthy gut microbiome. This review covers recent finding on the potential interactions between Blastocystis and the gut microbiota communities and its roles in regulating host immune responses.     

The role of the gut microbiome and its metabolites in metabolic diseases

It is well known that an unhealthy lifestyle is a major risk factor for metabolic diseases,while in recent years,accumulating evidence has demonstrated that the gut microbiome and its metabolites also play a crucial role in the onset and development of many metabolic dis-eases,including obesity,type 2 diabetes,nonalcoholic fatty liver disease,cardiovascular disease and so on.Numerous microorganisms dwell in the gastrointestinal tract,which is a key interface for energy acquisition and can metabolize dietary nutrients into many bioactive substances,thus acting as a link between the gut microbiome and its host.The gut microbiome is shaped by host genetics,immune responses and dietary fac-tors.The metabolic and immune potential of the gut microbiome determines its significance in host health and diseases.Therefore,targeting the gut microbiome and relevant metabolic pathways would be effective therapeutic treatments for many metabolic diseases in the near future.This review will summarize information about the role of the gut microbiome in organism metabolism and the relationship between gut micro-biome-derived metabolites and the pathogenesis of many metabolic diseases.Furthermore,recent advan-ces in improving metabolic diseases by regulating the gut microbiome will be discussed.     

Gut microbes as future therapeutics in treating inflammatory and infectious diseases: Lessons from recent findings

The human gut microbiota has been the interest of extensive research in recent years and our knowledge on using the potential capacity of these microbes are growing rapidly. Microorganisms colonized throughout the gastrointestinal tract of human are coevolved through symbiotic relationship and can influence physiology, metabolism, nutrition and immune functions of an individual. The gut microbes are directly involved in conferring protection against pathogen colonization by inducing direct killing, competing with nutrients and enhancing the response of the gut-associated immune repertoire. Damage in the microbiome (dysbiosis) is linked with several life-threatening outcomes viz. inflammatory bowel disease, cancer, obesity, allergy, and auto-immune disorders. Therefore, the manipulation of human gut microbiota came out as a potential choice for therapeutic intervention of the several human diseases. Herein, we review significant studies emphasizing the influence of the gut microbiota on the regulation of host responses in combating infectious and inflammatory diseases alongside describing the promises of gut microbes as future therapeutics.     

Role of the enteric microbiota in intestinal homeostasis and inflammation

The mammalian intestine encounters many more microorganisms than any other tissue in the body thus making it the largest and most complex component of the immune system. Indeed, there are greater than 100 trillion (10¹⁴) microbes within the healthy human intestine, and the total number of genes derived from this diverse microbiome exceeds that of the entire human genome by at least 100-fold. Our coexistence with the gut microbiota represents a dynamic and mutually beneficial relationship that is thought to be a major determinant of health and disease. Because of the potential for intestinal microorganisms to induce local and/or systemic inflammation, the intestinal immune system has developed a number of immune mechanisms to protect the host from pathogenic infections while limiting the inflammatory tissue injury that accompanies these immune responses. Failure to properly regulate intestinal mucosal immunity is thought to be responsible for the inflammatory tissue injury observed in the inflammatory bowel diseases (IBD; Crohn disease, ulcerative colitis). An accumulating body of experimental and clinical evidence strongly suggests that IBD results from a dysregulated immune response to components of the normal gut flora in genetically susceptible individuals. The objective of this review is to present our current understanding of the role that enteric microbiota play in intestinal homeostasis and pathogenesis of chronic intestinal inflammation.     

Nutritional modulation of the intestinal microbiota; future opportunities for the prevention and treatment of neuroimmune and neuroinflammatory disease

The gut–brain axis refers to the bidirectional communication between the enteric nervous system and the central nervous system. Mounting evidence supports the premise that the intestinal microbiota plays a pivotal role in its function and has led to the more common and perhaps more accurate term gut–microbiota–brain axis. Numerous studies have identified associations between an altered microbiome and neuroimmune and neuroinflammatory diseases. In most cases, it is unknown if these associations are cause or effect; notwithstanding, maintaining or restoring homeostasis of the microbiota may represent future opportunities when treating or preventing these diseases. In recent years, several studies have identified the diet as a primary contributing factor in shaping the composition of the gut microbiota and, in turn, the mucosal and systemic immune systems. In this review, we will discuss the potential opportunities and challenges with respect to modifying and shaping the microbiota through diet and nutrition in order to treat or prevent neuroimmune and neuroinflammatory disease.     

Iron in infectious diseases friend or foe?: The role of gut microbiota

Iron is a trace element involved in metabolic functions for all organisms, from microorganisms to mammalians. Iron deficiency is a prevalent health problem that affects billions of people worldwide, and iron overload could have some hazardous effect. The complex microbial community in the human body, also called microbiota, influences the host immune defence against infections. An imbalance in gut microbiota, dysbiosis, changes the host's susceptibility to infections by regulating the immune system. In recent years, the number of studies on the relationship between infectious diseases and microbiota has increased. Gut microbiota is affected by different parameters, including mode of delivery, hygiene habits, diet, drugs, and plasma iron levels during the lifetime. Gut microbiota may influence iron levels in the body, and iron overload and deficiency can also affect gut microbiota composition. Novel researches on microbiota shed light on the fact that the bidirectional interactions between gut microbiota and iron play a role in the pathogenesis of many diseases, especially infections. A better understanding of these interactions may help us to comprehend the pathogenesis of many infectious and metabolic diseases affecting people worldwide and following the development of more effective preventive and/or therapeutic strategies. In this review, we aimed to present the iron-mediated host-gut microbiota interactions, susceptibility to bacterial infections, and iron-targeted therapy approaches for infections.     

Neuropathy in COVID-19 associated with dysbiosis-related inflammation

Although COVID-19 affects mainly lungs with a hyperactive and imbalanced immune response, gastrointestinal and neurological symptoms such as diarrhea and neuropathic pains have been described as well in patients with COVID-19. Studies indicate that gut–lung axis maintains host homeostasis and disease development with the association of immune system, and gut microbiota is involved in the COVID-19 severity in patients with extrapulmonary conditions. Gut microbiota dysbiosis impairs the gut permeability resulting in translocation of gut microbes and their metabolites into the circulatory system and induce systemic inflammation which, in turn, can affect distal organs such as the brain. Moreover, gut microbiota maintains the availability of tryptophan for kynurenine pathway, which is important for both central nervous and gastrointestinal system in regulating inflammation. SARS-CoV-2 infection disturbs the gut microbiota and leads to immune dysfunction with generalized inflammation. It has been known that cytokines and microbial products crossing the blood-brain barrier induce the neuroinflammation, which contributes to the pathophysiology of neurodegenerative diseases including neuropathies. Therefore, we believe that both gut–lung and gut–brain axes are involved in COVID-19 severity and extrapulmonary complications. Furthermore, gut microbial dysbiosis could be the reason of the neurologic complications seen in severe COVID-19 patients with the association of dysbiosis-related neuroinflammation. This review will provide valuable insights into the role of gut microbiota dysbiosis and dysbiosis-related inflammation on the neuropathy in COVID-19 patients and the disease severity.     

The microbiome: stress,health and disease

Bacterial colonisation of the gut plays a major role in postnatal development and maturation of key systems that have the capacity to influence central nervous system (CNS) programming and signaling, including the immune and endocrine systems. Individually, these systems have been implicated in the neuropathology of many CNS disorders and collectively they form an important bidirectional pathway of communication between the microbiota and the brain in health and disease. Regulation of the microbiome–brain–gut axis is essential for maintaining homeostasis, including that of the CNS. Moreover, there is now expanding evidence for the view that commensal organisms within the gut play a role in early programming and later responsivity of the stress system. Research has focused on how the microbiota communicates with the CNS and thereby influences brain function. The routes of this communication are not fully elucidated but include neural, humoral, immune and metabolic pathways. This view is underpinned by studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic agents or antibiotics which indicate a role for the gut microbiota in the regulation of mood, cognition, pain and obesity. Thus, the concept of a microbiome–brain–gut axis is emerging which suggests that modulation of the gut microflora may be a tractable strategy for developing novel therapeutics for complex stress-related CNS disorders where there is a huge unmet medical need.     

Balancing reactive oxygen species generation by rebooting gut microbiota

Reactive oxygen species (ROS; free radical form O₂^•−, superoxide radical; OH^•, hydroxyl radical; ROO^•, peroxyl; RO^•, alkoxyl and non-radical form ¹O₂, singlet oxygen; H₂O₂, hydrogen peroxide) are inevitable companions of aerobic life with crucial role in gut health. But, overwhelming production of ROS can cause serious damage to biomolecules. In this review, we have discussed several sources of ROS production that can be beneficial or dangerous to the human gut. Micro-organisms, organelles and enzymes play crucial role in ROS generation, where NOX1 is the main intestinal enzyme, which produce ROS in the intestine epithelial cells. Previous studies have reported that probiotics play significant role in gut homeostasis by checking the ROS generation, maintaining the antioxidant level, immune system and barrier protection. With current knowledge, we have critically analysed the available literature and presented the outcome in the form of bubble maps to suggest that the probiotics help in controlling the ROS-specific intestinal diseases, such as inflammatory bowel disease (IBD) and colon cancer. Finally, it has been concluded that rebooting of the gut microbiota with probiotics, postbiotics or faecal microbiota transplantation (FMT) can have crucial implications in the structuring of gut communities for the personalized management of the gastrointestinal (GI) diseases.     

Arthritis susceptibility and the gut microbiome

Rheumatoid arthritis (RA) is an autoimmune disease with unknown etiology though both genetic and environmental factors have been suggested to be involved in its pathogenesis. While infections and other environmental factors (e.g. smoking) have been studied extensively and show some association, a direct link between all the factors has been difficult to prove. With the recent advances in technology, it has become possible to sequence the commensals that are residing in our gut. The gut microbiome may provide the missing link to this puzzle and help solve the mystery of many leaky gut syndromes. The gut commensals are involved in maintaining host immune homeostasis and function suggesting that they might be critical in altering the immune system, which leads to autoimmune diseases like RA. Mouse models support the role of the gut microbiota in predisposition to RA. If that is true, the power of gut-derived commensal can be harnessed to our benefit by generating a biomarker profile along with genetic factors to define individuals at risk and by altering the gut microbial composition using various means.     

Importance of microbial colonization of the gut in early life to the development of immunity

The mammalian gastrointestinal tract harbors a complex microbiota consisting of between 500 and 1000 distinct microbial species. Comparative studies based on the germ-free gut have provided clear evidence that the gut microbiota is instrumental in promoting the development of both the gut and systemic immune systems. Early microbial exposure of the gut is thought to dramatically reduce the incidence of inflammatory, autoimmune and atopic diseases further fuelling the scientific viewpoint, that microbial colonization plays an important role in regulating and fine-tuning the immune system throughout life. Recent molecular diversity studies have provided additional evidence that the human gut microbiota is compositionally altered in individuals suffering from inflammatory bowel disorders, suggesting that specific bacterial species are important to maintaining immunological balance and health. New and exciting insights into how gut bacteria modulate the mammalian immune system are emerging. However, much remains to be elucidated about how commensal bacteria influence the function of cells of both the innate and adaptive immune systems in health and disease.     

Metaproteomic and Metabolomic Approaches for Characterizing the Gut Microbiome

The gut microbiome has been shown to play a significant role in human healthy and diseased states. The dynamic signaling that occurs between the host and microbiome is critical for the maintenance of host homeostasis. Analyzing the human microbiome with metaproteomics, metabolomics, and integrative multi‐omics analyses can provide significant information on markers for healthy and diseased states, allowing for the eventual creation of microbiome‐targeted treatments for diseases associated with dysbiosis. Metaproteomics enables functional activity information to be gained from the microbiome samples, while metabolomics provides insight into the overall metabolic states affecting/representing the host–microbiome interactions. Combining these functional ‐omic platforms together with microbiome composition profiling allows for a holistic overview on the functional and metabolic state of the microbiome and its influence on human health. Here the benefits of metaproteomics, metabolomics, and the integrative multi‐omic approaches to investigating the gut microbiome in the context of human health and diseases are reviewed.     

蜜蜂肠道菌群定殖研究进展

肠道菌群在其宿主健康中发挥着各种各样的重要功能。蜜蜂是高度社会化的昆虫,其肠道菌群与大多数昆虫明显不同,由兼性厌氧和微好氧的细菌组成,具有高度保守性和专门的核心肠道微生物群。近年来的研究表明,蜜蜂肠道微生物群在代谢、免疫功能、生长发育以及保护机体免受病原体侵袭等方面起着重要作用,并已证实肠道微生物在蜜蜂健康和疾病中起着重要作用,肠道微生物群的破坏对蜜蜂健康会产生不利影响。本文综述了蜜蜂肠道菌群的特征及菌群定殖研究进展,介绍了蜜蜂的日龄、群体、季节等对蜜蜂肠道菌群定殖的影响,探讨了宿主的功能和新陈代谢对肠道菌群的影响。     

益生菌促进胃肠道健康的机制及应用

人体胃肠道内生活着大量微生物,它们影响着宿主的健康.益生菌是一种活的微生物,对维持肠黏膜屏障功能、调节免疫功能和促进营养物质的代谢吸收等具有重要作用;对肠道菌群紊乱、功能性消化不良、肠胃炎、腹泻、便秘、肠绞痛、肠易激综合征、炎症性肠病以及幽门螺杆菌感染等胃肠道疾病具有良好的应用.本文对益生菌与胃肠道健康的影响作简要概述...     

Gut microbiome and cancer immunotherapy

Gut microbiome has received significant attention for its influences on a variety of host functions, especially immune modulation. With the next-generation sequencing methodologies, more knowledge is gathered about gut microbiome and its irreplaceable role in keeping the balance between human health and diseases is figured out. Immune checkpoint inhibitors (ICIs) are one of the most innovational cancer immunotherapies across cancer types and significantly expand the therapeutic options of cancer patients. However, a proportion of patients show no effective responses or develop immune-related adverse events when responses do occur. More important, it is demonstrated that the therapeutic response or treatment-limiting toxicity of cancer immunotherapy can be ameliorated or diminished by gut microbiome modulation. In this review, we first introduce the relationship between gut microbiome and cancer immunotherapy. And then, we expound the impact of gut microbiome on efficacy and toxicity of cancer immunotherapy. Further, we review approaches to manipulating gut microbiome to regulate response to ICIs. Finally, we discuss the current challenges and propose future directions to improve cancer immunotherapy via gut microbiome manipulation.     

Removal of adult cyathostomins alters faecal microbiota and promotes an inflammatory phenotype in horses

The interactions between parasitic helminths and gut microbiota are considered to be an important, although as yet incompletely understood, factor in the regulation of immunity, inflammation and a range of diseases. Infection with intestinal helminths is ubiquitous in grazing horses, with cyathostomins (about 50 species of which are recorded) predominating. Consequences of infection include both chronic effects, and an acute inflammatory syndrome, acute larval cyathostominosis, which sometimes follows removal of adult helminths by administration of anthelmintic drugs. The presence of cyathostomins as a resident helminth population of the equine gut (the “helminthome”) provides an opportunity to investigate the effect helminth infection, and its perturbation, has on both the immune system and bacterial microbiome of the gut, as well as to determine the specific mechanisms of pathophysiology involved in equine acute larval cyathostominosis. We studied changes in the faecal microbiota of two groups of horses following treatment with anthelmintics (fenbendazole or moxidectin). We found decreases in both alpha diversity and beta diversity of the faecal microbiota at Day 7 post-treatment, which were reversed by Day 14. These changes were accompanied by increases in inflammatory biomarkers. The general pattern of faecal microbiota detected was similar to that seen in the relatively few equine gut microbiome studies reported to date. We conclude that interplay between resident cyathostomin populations and the bacterial microbiota of the equine large intestine is important in maintaining homeostasis and that disturbance of this ecology can lead to gut dysbiosis and play a role in the aetiology of inflammatory conditions in the horse, including acute larval cyathostominosis.     

Gut microbiome and the risk factors in central nervous system autoimmunity

Humans are colonized after birth by microbial organisms that form a heterogeneous community, collectively termed microbiota. The genomic pool of this macro-community is named microbiome. The gut microbiota is essential for the complete development of the immune system, representing a binary network in which the microbiota interact with the host providing important immune and physiologic function and conversely the bacteria protect themselves from host immune defense. Alterations in the balance of the gut microbiome due to a combination of environmental and genetic factors can now be associated with detrimental or protective effects in experimental autoimmune diseases. These gut microbiome alterations can unbalance the gastrointestinal immune responses and influence distal effector sites leading to CNS disease including both demyelination and affective disorders. The current range of risk factors for MS includes genetic makeup and environmental elements. Of interest to this review is the consistency between this range of MS risk factors and the gut microbiome. We postulate that the gut microbiome serves as the niche where different MS risk factors merge, thereby influencing the disease process.     

Amino acid supplements and metabolic health: a potential interplay between intestinal microbiota and systems control

Dietary supplementation of essential amino acids (EAAs) has been shown to promote healthspan. EAAs regulate, in fact, glucose and lipid metabolism and energy balance, increase mitochondrial biogenesis, and maintain immune homeostasis. Basic science and epidemiological results indicate that dietary macronutrient composition affects healthspan through multiple and integrated mechanisms, and their effects are closely related to the metabolic status to which they act. In particular, EAA supplementation can trigger different and even opposite effects depending on the catabolic and anabolic states of the organisms. Among others, gut-associated microbial communities (referred to as gut microbiota) emerged as a major regulator of the host metabolism. Diet and host health influence gut microbiota, and composition of gut microbiota, in turn, controls many aspects of host health, including nutrient metabolism, resistance to infection, and immune signals. Altered communication between the innate immune system and the gut microbiota might contribute to complex diseases. Furthermore, gut microbiota and its impact to host health change largely during different life phases such as lactation, weaning, and aging. Here we will review the accumulating body of knowledge on the impact of dietary EAA supplementation on the host metabolic health and healthspan from a holistic perspective. Moreover, we will focus on the current efforts to establish causal relationships among dietary EAAs, gut microbiota, and health during human development.     

A role for IL-22 in the relationship between intestinal helminths,gut microbiota and mucosal immunity

The intestinal tract is home to nematodes as well as commensal bacteria (microbiota), which have coevolved with the mammalian host. The mucosal immune system must balance between an appropriate response to dangerous pathogens and an inappropriate response to commensal microbiota that may breach the epithelial barrier, in order to maintain intestinal homeostasis. IL-22 has been shown to play a critical role in maintaining barrier homeostasis against intestinal pathogens and commensal bacteria. Here we review the advances in our understanding of the role of IL-22 in helminth infections, as well as in response to commensal and pathogenic bacteria of the intestinal tract. We then consider the relationship between intestinal helminths and gut microbiota and hypothesize that this relationship may explain how helminths may improve symptoms of inflammatory bowel diseases. We propose that by inducing an immune response that includes IL-22, intestinal helminths may enhance the mucosal barrier function of the intestinal epithelium. This may restore the mucosal microbiota populations from dysbiosis associated with colitis and improve intestinal homeostasis.     

The journey of gut microbiome – An introduction and its influence on metabolic disorders

Background

Metabolic disorders such as Obesity, Diabetes Type 2 (T2DM) and Inflammatory Bowel Diseases (IBD) are the most prevalent globally. Recently, there has been a surge in the evidence indicating the correlation between the intestinal microbiota and development of these metabolic conditions apart from predisposing genetic and epigenetic factors. Gut microbiome is pivotal in controlling the host metabolism and physiology. But imbalances in the microbiota patterns lead to these disorders via several pathways. Animal and human studies so far have concentrated mostly on metagenomics for the whole microbiome characterization to understand how microbiome supports health in general. However, the accurate mechanisms connecting the metabolic disorders and alterations in gut microbial composition in host and the metabolites employed by the microorganisms in regulating the metabolic disorders is still vague.

Objective

The review delineates the latest findings about the role of gut microbiome to the pathophysiology of Obesity, IBD and Diabetes Mellitus. Here, we provide a brief introduction to the gut microbiome followed by the current therapeutic interventions in restoration of the disrupted intestinal microbiota.

Methods

A methodical PubMed search was performed using keywords like “gut microbiome,” “obesity,” “diabetes,” “IBD,” and “metabolic syndromes.” All significant and latest publications up to January 2018 were accounted for the review.

Results

Out of the 93 articles cited, 63 articles focused on the gut microbiota association to these disorders. The rest 18 literature outlines the therapeutic approaches in maintaining the gut homeostasis using probiotics, prebiotics and faecal microbial transplant (FMT).

Conclusion

Metabolic disorders have intricate etiology and thus a lucid understanding of the complex host-microbiome inter-relationships will open avenues to novel therapeutics for the diagnosis, prevention and treatment of the metabolic diseases.