The intestinal microbiota and chronic disorders of the gut

Mucosal surfaces of the gut are colonized by large numbers of heterogeneous bacteria that contribute to intestinal health and disease. In genetically susceptible individuals, a 'pathogenic community' may arise, whereby abnormal gut flora contributes to alterations in the mucosa and local immune system leading to gastrointestinal disease. These diseases include enteric infections, such as Clostridium difficile infection, small intestinal bacterial overgrowth, functional gastrointestinal disorders (including IBS), IBD and colorectal cancer. Prebiotics, probiotics and synbiotics (a combination of prebiotics and probiotics) have the capacity to reverse pathologic changes in gut flora and local immunity. Intestinal health and disease need to be thoroughly characterized to understand the interplay between the indigenous microbiota, the immune system and genetic host factors. This Review provides a broad overview of the importance of the intestinal microbiota in chronic disorders of the gut.     

Starring role of toll-like receptor-4 activation in the gut-liver axis

Since the introduction of the term “gut-liver axis”, many studies have focused on the functional links of intestinal microbiota, barrier function and immune responses to liver physiology. Intestinal and extra-intestinal diseases alter microbiota composition and lead to dysbiosis, which aggravates impaired intestinal barrier function via increased lipopolysaccharide translocation. The subsequent increased passage of gut-derived product from the intestinal lumen to the organ wall and bloodstream affects gut motility and liver biology. The activation of the toll-like receptor 4 (TLR-4) likely plays a key role in both cases. This review analyzed the most recent literature on the gut-liver axis, with a particular focus on the role of TLR-4 activation. Findings that linked liver disease with dysbiosis are evaluated, and links between dysbiosis and alterations of intestinal permeability and motility are discussed. We also examine the mechanisms of translocated gut bacteria and/or the bacterial product activation of liver inflammation and fibrogenesis via activity on different hepatic cell types.     

Microbiota alterations in acute and chronic gastrointestinal inflammation of cats and dogs

The intestinal microbiota is the collection of the living microorganisms(bacteria, fungi, protozoa, and viruses) inhabiting the gastrointestinal tract. Novel bacterial identification approaches have revealed that the gastrointestinal microbiota of dogs and cats is, similarly to humans, a highly complex ecosystem. Studies in dogs and cats have demonstrated that acute and chronic gastrointestinal diseases, including inflammatory bowel disease(IBD), are associated with alterations in the small intestinal and fecal microbial communities. Of interest is that these alterations are generally similar to the dysbiosis observed in humans with IBD or animal models of intestinal inflammation, suggesting that microbial responses to inflammatory conditions of the gut are conserved across mammalian host types. Studies have also revealed possible underlying susceptibilities in the innate immune system of dogs and cats with IBD, which further demonstrate the intricate relationship between gut microbiota and host health. Commonly identified microbiome changes in IBD are decreases in bacterial groups within the phyla Firmicutes and Bacteroidetes, and increases within Proteobacteia. Furthermore, a reduction in the diversity of Clostridium clusters XIVa and IV(i.e., Lachnospiraceae and Clostridium coccoides subgroups) are associated with IBD, suggesting that these bacterial groups may play an important role in maintenance of gastrointestinal health. Future studies are warranted to evaluate the functional changes associated with intestinal dysbiosis in dogs and cats.     

Gastrointestinal neuromuscular apparatus: An underestimated target of gut microbiota

Over the last few years, the importance of the resident intestinal microbiota in the pathogenesis of several gastrointestinal diseases has been largely investigated. Growing evidence suggest that microbiota can influence gastrointestinal motility. The current working hypothesis is that dysbiosis-driven mucosal alterations induce the production of several inflammatory/immune mediators which affect gut neuro-muscular functions. Besides these indirect mucosal-mediated effects, the present review highlights that recent evidence suggests that microbiota can directly affect enteric nerves and smooth muscle cells functions through its metabolic products or bacterial molecular components translocated from the intestinal lumen. Tolllike receptors, the bacterial recognition receptors, are expressed both on enteric nerves and smooth muscle and are emerging as potential mediators between microbiota and the enteric neuromuscular apparatus. Furthermore, the ongoing studies on probiotics support the hypothesis that the neuromuscular apparatus may represent a target of intervention, thus opening new physiopathological and therapeutic scenarios.     

Antibiotics,gut microbiota,and irritable bowel syndrome: What are the relations?

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder in which recurrent abdominal pain is associated with defecation or a change in bowel habits (constipation, diarrhea, or both), and it is often accompanied by symptoms of abdominal bloating and distension. IBS is an important health care issue because it negatively affects the quality of life of patients and places a considerable financial burden on health care systems. Despite extensive research, the etiology and underlying pathophysiology of IBS remain incompletely understood. Proposed mechanisms involved in its pathogenesis include increased intestinal permeability, changes in the immune system, visceral hypersensitivity, impaired gut motility, and emotional disorders. Recently, accumulating evidence has highlighted the important role of the gut microbiota in the development of IBS. Microbial dysbiosis within the gut is thought to contribute to all aspects of its multifactorial pathogenesis. The last few decades have also seen an increasing interest in the impact of antibiotics on the gut microbiota. Moreover, antibiotics have been suggested to play a role in the development of IBS. Extensive research has established that antibacterial therapy induces remarkable shifts in the bacterial community composition that are quite similar to those observed in IBS. This suggestion is further supported by data from cohort and case-control studies, indicating that antibiotic treatment is associated with an increased risk of IBS. This paper summarizes the main findings on this issue and contributes to a deeper understanding of the link between antibiotic use and the development of IBS.     

The intestinal microbiome,probiotics and prebiotics in neurogastroenterology

The brain-gut axis allows bidirectional communication between the central nervous system (CNS) and the enteric nervous system (ENS), linking emotional and cognitive centers of the brain with peripheral intestinal functions. Recent experimental work suggests that the gut microbiota have an impact on the brain-gut axis. A group of experts convened by the International Scientific Association for Probiotics and Prebiotics (ISAPP) discussed the role of gut bacteria on brain functions and the implications for probiotic and prebiotic science. The experts reviewed and discussed current available data on the role of gut microbiota on epithelial cell function, gastrointestinal motility, visceral sensitivity, perception and behavior. Data, mostly gathered from animal studies, suggest interactions of gut microbiota not only with the enteric nervous system but also with the central nervous system via neural, neuroendocrine, neuroimmune and humoral links. Microbial colonization impacts mammalian brain development in early life and subsequent adult behavior. These findings provide novel insights for improved understanding of the potential role of gut microbial communities on psychological disorders, most particularly in the field of psychological comorbidities associated with functional bowel disorders like irritable bowel syndrome (IBS) and should present new opportunity for interventions with pro- and prebiotics.     

Recent developments in the pathophysiology of irritable bowel syndrome

Irritable bowel syndrome(IBS) is a common gastrointestinal disorder, the pathophysiology of which is not completely known, although it has been shown that genetic/social learning factors, diet, intestinal microbiota, intestinal low-grade inflammation, and abnormal gastrointestinal endocrine cells play a major role. Studies of familial aggregation and on twins have confirmed the heritability of IBS. However, the proposed IBS risk genes are thus far nonvalidated hits rather than true predisposing factors. There is no convincing evidence that IBS patients suffer from food allergy/intolerance, with the effect exerted by diet seemingly caused by intake of poorly absorbed carbohydrates and fiber. Obesity is a possible comorbidity of IBS. Differences in the microbiota between IBS patients and healthy controls have been reported, but the association between IBS symptoms and specific bacterial species is uncertain. Low-grade inflammation appears to play a role in the pathophysiology of a major subset of IBS, namely postinfectious IBS. The density of intestinal endocrine cells is reduced in patients with IBS, possibly as a result of genetic factors, diet, intestinal microbiota, and low-grade inflammation interfering with the regulatory signals controlling the intestinal stem-cell clonogenic and differentiation activities. Furthermore, there is speculation that this decreased number of endocrine cells is responsible for the visceral hypersensitivity, disturbed gastrointestinal motility, and abnormal gut secretion seen in IBS patients.     

Microbial and metabolic interactions between the gastrointestinal tract and Clostridium difficile infection

Antibiotics disturb the gastrointestinal tract microbiota and in turn reduce colonization resistance against Clostridium difficile. The mechanism for this loss of colonization resistance is still unknown but likely reflects structural (microbial) and functional (metabolic) changes to the gastrointestinal tract. Members of the gut microbial community shape intestinal metabolism that provides nutrients and ultimately supports host immunity. This review will discuss how antibiotics alter the structure of the gut microbiota and how this impacts bacterial metabolism in the gut. It will also explore the chemical requirements for C. difficile germination, growth, toxin production and sporulation. Many of the metabolites that influence C. difficile physiology are products of gut microbial metabolism including bile acids, carbohydrates and amino acids. To restore colonization resistance against C. difficile after antibiotics a targeted approach restoring both the structure and function of the gastrointestinal tract is needed.     

Effect of commensals and probiotics on visceral sensitivity and pain in irritable bowel syndrome

The last ten years’ wide progress in the gut microbiota phylogenetic and functional characterization has been made evidencing dysbiosis in several gastrointestinal diseases including inflammatory bowel diseases and irritable bowel syndrome (IBS). IBS is a functional gut disease with high prevalence and negative impact on patient’s quality of life characterized mainly by visceral pain and/or discomfort, representing a good paradigm of chronic gut hypersensitivity. The IBS features are strongly regulated by bidirectional gut-brain interactions and there is increasing evidence for the involvement of gut bacteria and/or their metabolites in these features, including visceral pain. Further, gut microbiota modulation by antibiotics or probiotics has been promising in IBS. Mechanistic data provided mainly by animal studies highlight that commensals or probiotics may exert a direct action through bacterial metabolites on sensitive nerve endings in the gut mucosa, or indirect pathways targeting the intestinal epithelial barrier, the mucosal and/or systemic immune activation, and subsequent neuronal sensitization and/or activation.     

肠道菌群：功能性胃肠病的防治新靶点

功能性胃肠病（FGIDs）是一组无器质性改变但存在消化功能异常的疾病,是消化科门诊中常见疾病之一。在 最新的罗马Ⅳ标准中将功能性肠胃病定义为脑-肠互动异常疾病。肠道菌群在脑-肠互动中发挥重要作用,参与功 能性胃肠病发生的多种病理生理机制。肠道菌群失调主要通过增加肠道渗透及内脏高敏感性、改变肠道动力和激活 免疫反应参与FGIDs症状产生。因此,重塑肠道菌群稳态的策略在治疗FGIDs中显示出一定的前景。     

The canine gastrointestinal microbiota: early studies and research frontiers

ABSTRACT

The canine gut microbiota is a complex microbial population that is potentially related to metabolism, immunologic activity and gastrointestinal (GI) diseases. Early studies revealed that the canine gut microbiota was dynamic, and bacterial populations in the adjacent gut segments were similar, with anaerobes predominating. Metagenomics analysis revealed that nutrient contents in the diet modulated bacterial populations and metabolites in the canine gut. Further research revealed significant correlations between dietary factors and canine gut core microbiomes. Canine GI diseases are closely correlated with gut microbiota dysbiosis and metabolic disorders. Probiotic-related therapies can effectively treat canine GI diseases. Recent studies have revealed that the canine gut microbiota is similar to the human gut microbiota, and dietary factors affect both. Studying canine intestinal microorganisms enables clarifying changes in the canine intestinal bacteria under different conditions, simulating human diseases in dog models, and conducting in-depth studies of the interactions between intestinal bacteria and disease.     

Gut microbiota in autism and mood disorders

The hypothesis of an important role of gut microbiota in the maintenance of physiological state into the gastrointestinal (GI) system is supported by several studies that have shown a qualitative and quantitative alteration of the intestinal flora in a number of gastrointestinal and extra-gastrointestinal diseases. In the last few years, the importance of gut microbiota impairment in the etiopathogenesis of pathology such as autism, dementia and mood disorder, has been raised. The evidence of the inflammatory state alteration, highlighted in disorders such as schizophrenia, major depressive disorder and bipolar disorder, strongly recalls the microbiota alteration, highly suggesting an important role of the alteration of GI system also in neuropsychiatric disorders. Up to now, available evidences display that the impairment of gut microbiota plays a key role in the development of autism and mood disorders. The application of therapeutic modulators of gut microbiota to autism and mood disorders has been experienced only in experimental settings to date, with few but promising results. A deeper assessment of the role of gut microbiota in the development of autism spectrum disorder (ASD), as well as the advancement of the therapeutic armamentarium for the modulation of gut microbiota is warranted for a better management of ASD and mood disorders.     

Gut microbiota in various childhood disorders: Implication and indications

Gut microbiota has a significant role in gut development, maturation, and immune system differentiation. It exerts considerable effects on the child's physical and mental development. The gut microbiota composition and structure depend on many host and microbial factors. The host factors include age, genetic pool, general health, dietary factors, medication use, the intestine's pH, peristalsis, and transit time, mucus secretions, mucous immunoglobulin, and tissue oxidation-reduction potentials. The microbial factors include nutrient availability, bacterial cooperation or antagonism, and bacterial adhesion. Each part of the gut has its microbiota due to its specific characteristics. The gut microbiota interacts with different body parts, affecting the pathogenesis of many local and systemic diseases. Dysbiosis is a common finding in many childhood disorders such as autism, failure to thrive, nutritional disorders, coeliac disease, Necrotizing Enterocolitis, helicobacter pylori infection, functional gastrointestinal disorders of childhood, inflammatory bowel diseases, and many other gastrointestinal disorders. Dysbiosis is also observed in allergic conditions like atopic dermatitis, allergic rhinitis, and asthma. Dysbiosis can also impact the development and the progression of immune disorders and cardiac disorders, including heart failure. Probiotic supplements could provide some help in managing these disorders. However, we are still in need of more studies. In this narrative review, we will shed some light on the role of microbiota in the development and management of common childhood disorders.     

Microbiota of the gastrointestinal tract: Friend or foe?

The gut microbiota is currently considered an external organ of the human body that provides important mechanisms of metabolic regulation and protection. The gut microbiota encodes over 3 million genes, which is approximately 150 times more than the total number of genes present in the human genome. Changes in the qualitative and quantitative composition of the microbiome lead to disruption in the synthesis of key bacterial metabolites, changes in intestinal barrier function, and inflammation and can cause the development of a wide variety of diseases, such as diabetes, obesity, gastrointestinal disorders, cardiovascular issues, neurological disorders and oncological concerns. In this review, I consider issues related to the role of the microbiome in the regulation of intestinal barrier function, its influence on physiological and pathological processes occurring in the body, and potential new therapeutic strategies aimed at restoring the gut microbiome. Herewith, it is important to understand that the gut microbiota and human body should be considered as a single biological system, where change of one element will inevitably affect its other components. Thus, the study of the impact of the intestinal microbiota on health should be considered only taking into account numerous factors, the role of which has not yet been fully elucidated.     

Indoles: metabolites produced by intestinal bacteria capable of controlling liver disease manifestation

Alterations in the bacteria that reside in our gastrointestinal tract play a role in the pathogenesis and progression of many disorders including liver and gastrointestinal diseases. Both qualitative (composition) and quantitative (amount) changes in gut microbes are associated with increased susceptibility to liver disease. Importantly, the intestinal microbiota is involved in the regulation of many host signalling pathways via the generation of different metabolites. Hence, dysbiosis influences disease development and progression by directly affecting the host–bacteria metabolic interaction. Microbe‐derived harmful metabolites can translocate to distant organs due to increased intestinal permeability as observed during dysbiosis. Contrary, certain bacterial metabolites such as tryptophan metabolites contribute to intestinal and systemic homeostasis. Here, we provide an overview of current evidence describing to what extent microbial metabolites modulate the development of chronic liver diseases such as alcoholic steatohepatitis and nonalcoholic fatty liver disease with a special emphasis on indoles.     

The gut microbiome and irritable bowel syndrome: State of art review

Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal tract, the physiology of which is not very well understood. There are multiple factors and pathways involved in pathogenesis of this entity. Among all, dysmotility, dysregulation of the brain-gut axis, altered intestinal microbiota and visceral hypersensitivity play a major role. Over the last years, research has shown that the type of gut microbiome present in an individual plays a significant role in the pathophysiology of IBS. Multiple studies have consistently shown that subjects diagnosed with IBS have disruption in gut microbiota balance. It has been established that host immune system and its interaction with metabolic products of gut microbiota play an important role in the gastrointestinal tract. Therefore, probiotics, prebiotics and antibiotics have shown some promising results in managing IBS symptoms via modulating the interaction between the above. This paper discusses the various factors involved in pathophysiology of IBS, especially gut microbiota.     

肠道菌群与脑-肠轴功能相互影响的研究进展

人体肠道内的菌群参与了许多生理功能的维持和疾病的发生。作为大脑和胃肠道功能相互调节的重要桥梁,脑-肠轴功能的正常发挥是肠道菌群维持稳定的条件。脑-肠轴紊乱可激活肠黏膜免疫,对肠道菌群产生影响,使菌群结构发生改变。反之,肠道菌群结构改变亦会影响神经系统发育,导致脑-肠轴功能紊乱,其中迷走神经和血清代谢物质在脑-肠轴功能的调节中发挥重要作用。本文就肠道菌群与脑-肠轴功能相互影响的研究进展作一综述。     

Gut microbiota and irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that poses a significant health concern. Although its etiology remains unknown, there is growing evidence that gut dysbiosis is involved in the development and exacerbation of IBS. Previous studies have reported altered microbial diversity, abundance, and composition in IBS patients when compared to controls. However, whether dysbiosis or aberrant changes in the intestinal microbiota can be used as a hallmark of IBS remains inconclusive. We reviewed the literatures on changes in and roles of intestinal microbiota in relation to IBS and discussed various gut microbiota manipulation strategies. Gut microbiota may affect IBS development by regulating the mucosal immune system, brain–gut–microbiome interaction, and intestinal barrier function. The advent of high-throughput multi-omics provides important insights into the pathogenesis of IBS and promotes the development of individualized treatment for IBS. Despite advances in currently available microbiota-directed therapies, large-scale, well-organized, and long-term randomized controlled trials are highly warranted to assess their clinical effects. Overall, gut microbiota alterations play a critical role in the pathophysiology of IBS, and modulation of microbiota has a significant therapeutic potential that requires to be further verified.     

Gut microbiota and metabolic syndrome

Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome,as confirmed by studies conducted both on humans and animal models.Gut microbial composition and functions are strongly influenced by diet.This complex intestinal“superorganism”seems to affect host metabolic balance modulating energy absorption,gut motility,appetite,glucose and lipid metabolism,as well as hepatic fatty storage.An impairment of the fine balance between gut microbes and host’s immune system could culminate in the intestinal translocation of bacterial fragments and the development of“metabolic endotoxemia”,leading to systemic inflammation and insulin resistance.Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition,that seem to affect the success,or the inefficacy,of treatment strategies.Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity,thus,ameliorating metabolic balance and promoting weight loss.However,further evidence is needed to better understand their clinical impact and therapeutic use.     

Microbiota in health and irritable bowel syndrome: current knowledge,perspectives and therapeutic options

Abstract

The gastrointestinal tract is a natural reservoir of microbiota. The gut is germ-free at birth, but rapidly becomes host to various bacteria establishing a progressively mutual relationship. The composition of gut microbiota is individual-specific and depends on the genotype of the host and environmental factors. Novel techniques have been used to characterize gastrointestinal microbiota, including genomic approaches. The bacterial profile shows that dominant and minor phyla are present in the gastrointestinal tract. From the proximal to the distal segments of the gut the bacterial density gradually increases, reaching an estimated 10¹¹ to 10¹² bacteria per gram of colonic content. Dynamic interactions between gut and microbiota play a physiological role in metabolic, protective and structural functions, while dysbiosis contributes to several diseases. Microbiota appear to play a role in IBS, where qualitative and quantitative changes of bacteriaoccur in IBS subtypes. Initial therapeutic approaches in IBS have focused on microbiota. The relationship between perturbations of the microbiota, mucosal inflammation and IBS remains to be further investigated.