High-throughput diversity and functionality analysis of the gastrointestinal tract microbiota

The human gastrointestinal (GI) tract microbiota plays a pivotal role in our health. For more than a decade a major input for describing the diversity of the GI tract microbiota has been derived from the application of small subunit ribosomal RNA (SSU rRNA)-based technologies. These not only provided a phylogenetic framework of the GI tract microbiota, the majority of which has not yet been cultured, but also advanced insights into the impact of host and environmental factors on the microbiota community structure and dynamics. In addition, it emerged that GI tract microbial communities are host and GI tract location-specific. This complicates establishing relevant links between the host's health and the presence or abundance of specific microbial populations and argues for the implementation of novel high-throughput technologies in studying the diversity and functionality of the GI tract microbiota. Here, we focus on the recent developments and applications of phylogenetic microarrays based on SSU rRNA sequences and metagenomics approaches exploiting rapid sequencing technologies in unravelling the secrets of our GI tract microbiota.     

The Microbiota and Microbiome in Aging: Potential Implications in Health and Age‐Related Diseases

Advances in bacterial deoxyribonucleic acid sequencing allow for characterization of the human commensal bacterial community (microbiota) and its corresponding genome (microbiome). Surveys of healthy adults reveal that a signature composite of bacteria characterizes each unique body habitat (e.g., gut, skin, oral cavity, vagina). A myriad of clinical changes, including a basal proinflammatory state (inflamm‐aging), that directly interface with the microbiota of older adults and enhance susceptibility to disease accompany aging. Studies in older adults demonstrate that the gut microbiota correlates with diet, location of residence (e.g., community dwelling, long‐term care settings), and basal level of inflammation. Links exist between the microbiota and a variety of clinical problems plaguing older adults, including physical frailty, Clostridium difficile colitis, vulvovaginal atrophy, colorectal carcinoma, and atherosclerotic disease. Manipulation of the microbiota and microbiome of older adults holds promise as an innovative strategy to influence the development of comorbidities associated with aging.     

Long-term maintenance of species-specific bacterial microbiota in the basal metazoan Hydra

Epithelia in animals are colonized by complex communities of microbes. Although a topic of long-standing interest, understanding the evolution of the microbial communities and their role in triggering innate immune responses has resisted analysis. Cnidaria are among the simplest animals at the tissue grade of organization. To obtain a better understanding of the microbiota associated with phylogenetically ancient epithelia, we have identified the epibiotic and endosymbiotic bacteria of two species of the cnidarian Hydra on the basis of rRNA comparisons. We analyzed individuals of Hydra oligactis and Hydra vulgaris from both laboratory cultures and the wild. We discovered that individuals from both species differ greatly in their bacterial microbiota. Although H. vulgaris polyps have a quite diverse microbiota, H. oligactis appears to be associated with only a limited number of microbes; some of them were found, unexpectedly, to be endosymbionts. Surprisingly, the microfauna showed similar characteristics in individuals of cultures maintained in the laboratory for >30 years and polyps directly isolated from the wild. The significant differences in the microbial communities between the two species and the maintenance of specific microbial communities over long periods of time strongly indicate distinct selective pressures imposed on and within the epithelium. Our analysis suggests that the Hydra epithelium actively selects and shapes its microbial community.     

Factors associated with the diversification of the gut microbial communities within chimpanzees from Gombe National Park

The gastrointestinal tract harbors large and diverse populations of bacteria that vary among individuals and within individuals over time. Numerous internal and external factors can influence the contents of these microbial communities, including diet, geography, physiology, and the extent of contact among hosts. To investigate the contributions of such factors to the variation and changes in gut microbial communities, we analyzed the distal gut microbiota of individual chimpanzees from two communities in Gombe National Park, Tanzania. These samples, which were derived from 35 chimpanzees, many of whom have been monitored for multiple years, provide an unusually comprehensive longitudinal depth for individuals of known genetic relationships. Although the composition of the great-ape microbiota has been shown to codiversify with host species, indicating that host genetics and phylogeny have played a major role in its differentiation over evolutionary timescales, the geneaological relationships of individual chimpanzees did not coincide with the similarity in their gut microbial communities. However, the inhabitants from adjacent chimpanzee communities could be distinguished based on the contents of their gut microbiota. Despite the broad similarity of community members, as would be expected from shared diet or interactions, long-term immigrants to a community often harbored the most distinctive gut microbiota, suggesting that individuals retain hallmarks of their previous gut microbial communities for extended periods. This pattern was reinforced in several chimpanzees sampled over long temporal scales, in which the major constituents of the gut microbiota were maintained for nearly a decade.     

Gastrointestinal involvement in systemic sclerosis: An updated review

The gastrointestinal tract (GI) is the second most affected organ system in individuals suffering from systemic/localized scleroderma (SSc) or localized scleroderma. SSc can affect any part of the GI, between the oral cavity and anorectum. The annual incidence of SSc in the United States is estimated to be 19.3 cases per million adults, with the highest incidence reported in people aged 44 to 55. Females are 5 times more likely than males to suffer from SSc. Morbidity and mortality rates associated with SSc are predominantly elevated among patients with GI manifestations. Esophageal and intestinal manifestations impact 90% and 40% to 70% of patients with systemic scleroderma, respectively. SSc patients are known to suffer from small bowel hypomotility and small intestinal bacterial overgrowth, which cause malabsorption and malnutrition, ultimately contributing to the 50% mortality rate. Fecal incontinence is a common symptom of SSc that can lead to depression. SSc patients may suffer from gastrointestinal complications that can negatively impact their quality of life on a daily basis. Multidisciplinary approaches are necessary for systematically managing gastrointestinal complications associated with SSc. A prospective study should focus on developing targeted therapies to improve recovery patterns and prognosis in cases of SSc. This article summarizes the epidemiology, commonly reported clinical manifestations, complications, and available treatments for treating GI pathology in SSc patients.     

Intestinal microbiota are transiently altered during Salmonella-induced gastroenteritis

Evaluation of: Barman M, Unold D, Shifl ey K et al. Enteric salmonellosis disrupts the microbialecology of the murine gastrointestinal tract. Infect. Immun. 76(3), 907-915 (2008).

The mammalian GI tract contains a large and diverse ecosystem of microorganisms that play a profound role in our development and physiology. Interestingly, the microbial make-up within the intestine has been found to be altered in many clinically important diseases, including inflammatory bowel disease, irritable bowel syndrome, Types 1 and 2 diabetes, and obesity. Barman et al. used a Salmonella-induced murine model of gastroenteritis to show that the intestinal microbiota are transiently altered during the host inflammatory response to infection. These findings are of interest as understanding how the microbiota are altered during disease states may offer insight into which microbial populations are important in maintaining intestinal homeostasis. Recently, probiotics have been shown to modulate the mucosal immune system and improve intestinal barrier function, validating their potential as therapeutics for gastrointestinal-associated diseases. As we begin to understand the benefits conferred to the intestine by microbiota, the use of probiotics to modify its composition is an attractive option to improve human health.     

Microbial perturbations and modulation in conditions associated with malnutrition and malabsorption

The intestinal microbiota is a complex ecosystem, which can be considered an accessory organ. It involves complex microbe–microbe and host–microbe interactions with indispensable functions for the human host with regard to the intestinal epithelium and barrier function, the innate and adaptive immune system, and its large metabolic capacity. Saccharolytic fermentation results in the production of short chain fatty acids, which exert an array of beneficial effects, while proteolytic fermentation leads to an increase in potentially harmful metabolites. In addition, numerous other microbial metabolites are being produced with various intestinal as well as extra-intestinal effects. Their generation depends on the composition of the microbiota as well as the availability of substrates, which both vary along the GI tract.Diet impacts the intestinal microbiota composition and activity in early infancy as well as in adults. Microbial perturbations have been demonstrated in subjects with under-nutrition and/or malabsorption. The bidirectional interactions between the microbiome, nutrient availability and GI function, can contribute to a vicious circle, further impairing health outcome in conditions associated with malnutrition and/or malabsorption. Integrated multivariate approaches are needed to further unravel the complex interaction between microbiome, diet and host factors, as well as possible modulation thereof by prebiotics or probiotics.The present overview will briefly outline the composition and function of the intestinal microbiota, its association with nutrient intake and availability, and will address the role of the intestinal microbiota in malnutrition and malabsorption.     

Amelioration of DSS-induced murine colitis by VSL#3 supplementation is primarily associated with changes in ileal microbiota composition.

Inflammatory bowel diseases encompass gastrointestinal illnesses typified by chronic inflammation, loss of epithelial integrity and gastrointestinal microbiota dysbiosis. In an effort to counteract these characteristic perturbations, we used stem cells and/or a probiotic therapy in a murine model of Dextran Sodium Sulfate induced colitis to examine both their efficacy in ameliorating disease and impact on niche-specific microbial communities of the lower GI tract. Colitis was induced in C57BL/6 mice by administering 3% DSS in drinking water for 10 days prior to administering one of three treatment plans: daily probiotic (VSL#3) supplementation for 3 days, a single tail vein injection of 1x10⁶ murine mesenchymal stem cells, or both. Ileal, cecal and colonic sections were collected for microbiota and histological analyses. Microbiota profiling revealed distinct bacterial community compositions in the ileum, cecum and colon of control untreated animals, all of which were predicted in silico to be enriched for a number of discrete KEGG pathways, indicating compositional and functional niche specificity in healthy animals. DSS-treatment perturbed community composition in all three niches with ileal communities exhibiting the greatest change relative to control animals. Each treatment group exhibited treatment-specific alterations in microbiota composition in the lower GI tract, though disease scores were only improved in VSL#3-treated animals. The ileal microbiota were most profoundly altered in composition in this group of animals and characterized by significant Enterobacteriaceae enrichment compared with colitic mice (P < 0.05).     

Microbial modulation of the gut microbiome for treating autoimmune diseases

ABSTRACT

Introduction: Many studies have shown the relationship between autoimmune diseases and the gut microbiome in humans: those with autoimmune conditions display gut microbiome dysbiosis. The big question that needs to be addressed is if restoring eubiosis of the gut microbiota can help suppress the autoimmune condition by activating various immune regulatory mechanisms. Inducing these self-healing mechanisms should prolong good health in affected individuals.

Area covered: Here, we review the available clinical and preclinical studies that have used selective bacteria for modulating gut microbiota for treating autoimmune diseases. The potential bacterial candidates and their mechanism of action in treating autoimmune diseases will be discussed. We searched for genetically modified and potential probiotics for diseases and discuss the most likely candidates.

Expert commentary: To achieve eubiosis, manipulation of the gut microbiota must occur in some form. Several approaches for modulating gut microbiota include prebiotic diets, antimicrobial interventions, fecal microbiota transplants, and selective probiotics. One novel approach showing promising results is the use of selective bacterial candidates to modulate microbial composition. Use of single microbe for treatment has an advantage as compared to multi-species as microbes grow at different rates and if needed, a single microbe is easy to target.     

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.     

“Urinary Tract Infection”—Requiem for a Heavyweight

“Urinary tract infection” (“UTI”) is an ambiguous, expansive, overused diagnosis that can lead to marked, harmful antibiotic overtreatment. “Significant bacteriuria,” central to most definitions of “UTI,” has little significance in identifying individuals who will benefit from treatment. “Urinary symptoms” are similarly uninformative. Neither criterion is well defined. Bacteriuria and symptoms remit and recur spontaneously. Treatment is standard for acute uncomplicated cystitis and common for asymptomatic bacteriuria, but definite benefits are few. Treatment for “UTI” in older adults with delirium and bacteriuria is widespread but no evidence supports the practice, and expert opinion opposes it. Sensitive diagnostic tests now demonstrate that healthy urinary tracts host a ubiquitous, complex microbial community. Recognition of this microbiome, largely undetectable using standard agar‐based cultures, offers a new perspective on “UTI.” Everyone is bacteriuric. From this perspective, most people who are treated for a “UTI” would probably be better off without treatment. Elderly adults, little studied in this regard, face particular risk. Invasive bacterial diseases such as pyelonephritis and bacteremic bacteriuria are also “UTIs.” Mindful decisions about antibiotic use will require a far better understanding of how pathogenicity arises within microbial communities. It is likely that public education and meaningful informed‐consent discussions about antibiotic treatment of bacteriuria, emphasizing potential harms and uncertain benefits, would reduce overtreatment. Emphasizing the microbiome's significance and using the term “urinary tract dysbiosis” instead of “UTI” might also help and might encourage mindful study of the relationships among host, aging, microbiome, disease, and antibiotic treatment.     

Inflammatory effect on the gastrointestinal system associated with COVID-19

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) that causes coronavirus disease-2019 (COVID-19) has provoked a global pandemic, mainly affecting the respiratory tract; however, a percentage of infected individuals can develop gastrointestinal (GI) symptoms. Some studies describe the development of GI symptoms and how they affect the progression of COVID-19. In this review, we summarize the main mechanisms associated with gut damage during infection by SARS-CoV-2 as well as other organs such as the liver and pancreas. Not only are host factors associated with severe COVID-19 but intestinal microbiota dysbiosis is also observed in patients with severe disease.     

Probiotics in functional bowel disorders

Functional bowel disorders (FBDs) are the most common gastrointestinal (GI) disorders seen by gastroenterologists and primary care physicians. The disorders affect patients functioning and quality of life (QOL) and are associated with significant healthcare burden. The current theory regarding the development of FBDs suggests brain-gut axis dysfunctions associated abnormal GI motility and sensation. Recent data suggest that alterations in the intestinal microbiota may have a role in the pathogenesis of FBDs; or at least have the potential to affect intestinal functions that are thought to be relevant to the development of functional GI symptoms. This has led to growing interest of healthcare providers and patients in targeting the intestinal microbiota for the treatment of FBDs. In this article we discuss the potential role probiotic interventions in the treatment of FBDs. We review the evidence from pre-clinical and clinical studies and discuss the current recommendations for the use of probiotics for FBDs in clinical practice.     

Prevention of respiratory infections in the elderly

The risk of nosocomial infections is 3–5-fold higher among older patients than among younger adults. Both the increased incidence of respiratory infections and the high mortality among older people are a consequence of a number of age-related factors, including coexisting illnesses, therapeutic interventions, and the aging process itself. Risk factors for the development of respiratory infections in older people can be broadly classified into factors that alter host defenses and factors that increase exposure to bacteria. These factors combine to adversely affect the person's capacity to defend against pathogens of the upper and lower respiratory tract. Despite the availability of potent new antimicrobials, the increasingly limited treatment efficacy of these antimicrobials is related to emerging microbial resistance. Recently, new methods of treating respiratory infections according to the mechanisms of infection have been introduced. Effective methods of preventing respiratory infections in older people were reviewed.     

Proton pump inhibitors and dysbiosis: Current knowledge and aspects to be clarified

Proton pump inhibitors (PPIs) are common medications within the practice of gastroenterology. These drugs, which act through the irreversible inhibition of the hydrogen/potassium pump (H+/K+-ATPase pump) in the gastric parietal cells, are used in the treatment of several acid-related disorders. PPIs are generally well tolerated but, through the long-term reduction of gastric acid secretion, can increase the risk of an imbalance in gut microbiota composition (i.e., dysbiosis). The gut microbiota is a complex ecosystem in which microbes coexist and interact with the human host. Indeed, the resident gut bacteria are needed for multiple vital functions, such as nutrient and drug metabolism, the production of energy, defense against pathogens, the modulation of the immune system and support of the integrity of the gut mucosal barrier. The bacteria are collected in communities that vary in density and composition within each segment of the gastrointestinal (GI) tract. Therefore, every change in the gut ecosystem has been connected to an increased susceptibility or exacerbation of various GI disorders. The aim of this review is to summarize the recently available data on PPI-related microbiota alterations in each segment of the GI tract and to analyze the possible involvement of PPIs in the pathogenesis of several specific GI diseases.     

The mycobiome: Role in health and disease,and as a potential probiotic target in gastrointestinal disease

The human gastrointestinal (GI) tract is home to trillions of microorganisms, some beneficial and others potentially harmful. Recent advances in science have allowed us to identify the multitude of organisms inhabiting the GI tract and parse out those that play a role in inflammatory bowel disease (IBD). Unfortunately, most research has focused on studying only the bacteria while ,overlooking a key player, fungus. In order to address this issue, we have focused our efforts on studying the fungal community in the GI tract known as the mycobiome. We found that patients with Crohn’s disease (CD) tend to have much higher levels of the fungus Candida tropicalis compared to their healthy family members, as well as two bacteria, Escherichia coli and Serratia marcescens. Furthermore, we showed that these three organisms worked together to form robust biofilms capable of exacerbating intestinal inflammation. Herein, we discuss the role of the mycobiome in health and disease, and highlight the importance of maintaining balance of the GI microbiota. Additionally, taking into consideration recent next generation sequencing data, we provide insight into potentially new therapeutic approaches in the treatment of IBD through the use of antifungals and/or probiotics aimed at establishing and maintaining a healthy balance of the GI total microbial community including fungi and bacteria.     

Early life establishment of site-specific microbial communities in the gut

Fecal sampling is widely utilized to define small intestinal tissue-level microbial communities in healthy and diseased newborns. However, this approach may lead to inaccurate assessments of disease or therapeutics in newborns because of the assumption that the taxa in the fecal microbiota are representative of the taxa present throughout the gastrointestinal tract. To assess the stratification of microbes in the newborn gut and to evaluate the probable shortcoming of fecal sampling in place of tissue sampling, we simultaneously compared intestinal mucosa and fecal microbial communities in 15 neonates undergoing intestinal resections. We report three key results. First, when the site of fecal and mucosal samples are further apart, their microbial communities are more distinct, as indicated by low mean Sørensen similarity indices for each patient's fecal and tissue microbiota. Second, two distinct niches (intestinal mucosa and fecal microbiota) are evident by principal component analyses, demonstrating the critical role of sample source in defining microbial composition. Finally, in contrast to adult studies, intestinal bacterial diversity was higher in tissue than in fecal samples. This study represents an unprecedented map of the infant microbiota from intestinal mucosa and establishes discernable biogeography throughout the neonatal gastrointestinal tract. Our results question the reliance on fecal microbiota as a proxy for the developing intestinal microbiota. Additionally, the robust intestinal tissue-level bacterial diversity we detected at these early ages may contribute to the maturation of mucosal immunity.     

The gastrointestinal microbiome – Functional interference between stomach and intestine

The gastrointestinal (GI) tract is a complex and dynamic network with interplay between various gut mucosal cells and their defence molecules, the immune system, food particles, and the resident microbiota. This ecosystem acts as a functional unit organized as a semipermeable multi-layer system that allows the absorption of nutrients and macromolecules required for human metabolic processes and, on the other hand, protects the individual from potentially invasive microorganisms. Commensal microbiota and the host are a unique entity in a continuum along the GI tract, every change in one of these players is able to modify the whole homeostasis. In the stomach, Helicobacter pylori is a gram-negative pathogen that is widespread all over the world, infecting more than 50% of the world's population. In this scenario, H. pylori infection is associated with changes in the gastric microenvironment, which in turn affects the gastric microbiota composition, but also might trigger large intestinal microbiota changes. It is able to influence all the vital pathways of human system and also to influence microbiota composition along the GI tract. This can cause a change in the normal functions exerted by intestinal commensal microorganisms leading to a new gastrointestinal physiological balance. This review focuses and speculates on the possible interactions between gastric microorganisms and intestinal microbiota and on the consequences of this interplay in modulating gut health.     

Probiotics against neoplastic transformation of gastric mucosa: Effects on cell proliferation and polyamine metabolism

Gastric cancer is still the second leading cause of cancer death worldwide, accounting for about 10% of newly diagnosed neoplasms. In the last decades, an emerging role has been attributed to the relations between the intestinal microbiota and the onset of both gastrointestinal and non-gastrointestinal neoplasms. Thus, exogenous microbial administration of peculiar bacterial strains (probiotics) has been suggested as having a profound influence on multiple processes associated with a change in cancer risk. The internationally accepted definition of probiotics is live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. The possible effects on the gastrointestinal tract following probiotic administration have been investigated in vitro and in animal models, as well as in healthy volunteers and in patients suffering from different human gastrointestinal diseases. Although several evidences are available on the use of probiotics against the carcinogen Helicobacter pylori, little is still known about the potential cross-interactions among probiotics, the composition and quality of intestinal flora and the neoplastic transformation of gastric mucosa. In this connection, a significant role in cell proliferation is played by polyamines (putrescine, spermidine, and spermine). These small amines are required in both pre-neoplastic and neoplastic tissue to sustain the cell growth and the evidences here provided suggest that probiotics may act as antineoplastic agents in the stomach by affecting also the polyamine content and functions. This review will summarize data on the most widely recognized effects of probiotics against neoplastic transformation of gastric mucosa and in particular on their ability in modulating cell proliferation, paying attention to the polyamine metabolism.     

Change in gut microbiota for eczema: Implications for novel therapeutic strategies

Eczema is one of the most common inflammatory diseases, often constituting a lifelong burden for afflicted individuals. The complex interaction of host genetic and multiple environmental factors contribute to its pathogenesis. A relationship between maladjustment of gut microbiota and eczema has been brought into the light of day in most previous studies. In eczema preclinical models, specific intestinal microbial species have been demonstrated to prohibit or dwindle immune responsiveness, indicating that these strains among commensal gut bacteria may exert either a morbific or phylactic function in eczema progression. As such, oral probiotics can serve as a medicinal approach for eczema therapy. Given that relative scientific work is still at the early stage, only limited data are available in the field. New sequencing techniques have been fortunately performed to gain access to an extended research on the relationship between gut bacterial flora and human diseases. In the current review, we identified the role of intestinal microbiota in the development of eczema and how specific bacterial strains adjust the immune responsiveness in the midst of disease progression. Probiotics as an applicable treatment for eczema were evaluated in other threads as well.