Pathobionts in Inflammatory Bowel Disease: Origins, Underlying Mechanisms, and Implications for Clinical Care.

The gut microbiota plays a significant role in the pathogenesis of both forms of inflammatory bowel disease (IBD), namely, Crohn's disease (CD) and ulcerative colitis (UC). Although evidence suggests dysbiosis and loss of beneficial microbial species can exacerbate IBD, many new studies have identified microbes with pathogenic qualities, termed "pathobionts," within the intestines of patients with IBD. The concept of pathobionts initiating or driving the chronicity of IBD has largely focused on the putative aggravating role that adherent invasive Escherichia coli may play in CD. However, recent studies have identified additional bacterial and fungal pathobionts in patients with CD and UC. This review will highlight the characteristics of these pathobionts and their implications for IBD treatment. Beyond exploring the origins of pathobionts, we discuss those associated with specific clinical features and the potential mechanisms involved, such as creeping fat (Clostridium innocuum) and impaired wound healing (Debaryomyces hansenii) in patients with CD as well as the increased fecal proteolytic activity (Bacteroides vulgatus) seen as a biomarker for UC severity. Finally, we examine the potential impact of pathobionts on current IBD therapies, and several new approaches to target pathobionts currently in the early stages of development. Despite recognizing that pathobionts likely contribute to the pathogenesis of IBD, more work is needed to define their modes of action. Determining whether causal relationships exist between pathobionts and specific disease characteristics could pave the way for improved care for patients, particularly for those not responding to current IBD therapies.

Microbiome composition recovery after liver transplantation correlates with initial liver disease severity and antibiotics treatment.

Liver transplantation (LT) is crucial for end-stage liver disease, but it is linked to infection risks. Pathobionts, microorganisms potentially harmful under specific conditions, can cause complications posttransplant. Monitoring such pathogens in fecal samples can be challenging and therefore remains underexplored post-LT. This study aimed to analyze the gut microbiome before and after LT, tracking pathobionts and correlating clinical data. The study involved 17 liver transplant recipients, 17 healthy relatives (spouses), and 13 donors. Gut samples collected pretranplantation and posttransplantation underwent bacterial and fungal profiling through DNA sequencing. Quantitative polymerase chain reaction was used to assess microbial load. Statistical analyses included alpha and beta diversity measures, differential abundance analysis, and correlation tests between microbiome and clinical parameters. Microbiome analysis revealed dynamic changes in diversity posttransplant. Notably, high-severity patients showed persistent and greater dysbiosis during the first months post-LT compared with low-severity patients, partly due to an antibiotic treatment pre-LT. The analysis identified a higher proportion of pathogens such as Escherichia coli/Shigella flexneri in high-severity cases posttransplant. Furthermore, butyrate producers including Roseburia intestinalis, Anaerostipes hadrus, and Eubacterium coprostanoligenes were positively correlated with levels of albumin. This study offers valuable insights into post-LT microbiome changes, shedding light on the need for tailored prophylactic treatment post-LT.

The Gut Microbiome and Inflammatory Bowel Diseases.

Inflammatory bowel diseases (IBD) arise from a convergence of genetic risk, environmental factors, and gut microbiota, where each is necessary but not sufficient to cause disease. Emerging evidence supports a bidirectional relationship between disease progression and changes in microbiota membership and function. Thus, the study of the gut microbiome and host-microbe interactions should provide critical insights into disease pathogenesis as well as leads for developing microbiome-based diagnostics and interventions for IBD. In this article, we review the most recent advances in understanding the relationship between the gut microbiota and IBD and highlight the importance of going beyond establishing description and association to gain mechanistic insights into causes and consequences of IBD. The review aims to contextualize recent findings to form conceptional frameworks for understanding the etiopathogenesis of IBD and for the future development of microbiome-based diagnostics and interventions.

Intestinal homeostasis and inflammation: Gut microbiota at the crossroads of pancreas-intestinal barrier axis.

The pancreas contains exocrine glands, which release enzymes (e.g., amylase, trypsin, and lipase) that are important for digestion and islets, which produce hormones. Digestive enzymes and hormones are secreted from the pancreas into the duodenum and bloodstream, respectively. Growing evidence suggests that the roles of the pancreas extend to not only the secretion of digestive enzymes and hormones but also to the regulation of intestinal homeostasis and inflammation (e.g., mucosal defense to pathogens and pathobionts). Organ crosstalk between the pancreas and intestine is linked to a range of physiological, immunological, and pathological activities, such as the regulation of the gut microbiota by the pancreatic proteins and lipids, the retroaction of the gut microbiota on the pancreas, the relationship between inflammatory bowel disease, and pancreatic diseases. We herein discuss the current understanding of the pancreas-intestinal barrier axis and the control of commensal bacteria in intestinal inflammation.

Microbiota-Liver Diseases Interactions.

Gut microbiota regulates essential processes of host metabolism and physiology: synthesis of vitamins, digestion of foods non-digestible by the host (such as fibers), and-most important-protects the digestive tract from pathogens. In this study, we focus on the CRISPR/Cas9 technology, which is extensively used to correct multiple diseases, including liver diseases. Then, we discuss the non-alcoholic fatty liver disease (NAFLD), affecting more than 25% of the global population; colorectal cancer (CRC) is second in mortality. We give space to rarely discussed topics, such as pathobionts and multiple mutations. Pathobionts help to understand the origin and complexity of the microbiota. Since several types of cancers have as target the gut, it is vital extending the research of multiple mutations to the type of cancers affecting the gut-liver axis.

Microbe-Driven Genotoxicity in Gastrointestinal Carcinogenesis.

The intestinal epithelium serves as a barrier to discriminate the outside from the inside and is in constant exchange with the luminal contents, including nutrients and the microbiota. Pathogens have evolved mechanisms to overcome the multiple ways of defense in the mucosa, while several members of the microbiota can exhibit pathogenic features once the healthy barrier integrity of the epithelium is disrupted. This not only leads to symptoms accompanying the acute infection but may also contribute to long-term injuries such as genomic instability, which is linked to mutations and cancer. While for Helicobacter pylori a link between infection and cancer is well established, many other bacteria and their virulence factors have only recently been linked to gastrointestinal malignancies through epidemiological as well as mechanistic studies. This review will focus on those pathogens and members of the microbiota that have been linked to genotoxicity in the context of gastric or colorectal cancer. We will address the mechanisms by which such bacteria establish contact with the gastrointestinal epithelium-either via an existing breach in the barrier or via their own virulence factors as well as the mechanisms by which they interfere with host genomic integrity.

Interplay of Human Gut Microbiome in Health and Wellness.

The gut microbiome analysis, with specific interest on their direct impact towards the human health, is currently revolutionizing the unexplored frontiers of the pathogenesis and wellness. Although in-depth investigations of gut microbiome, 'the Black Boxes', complexities and functionalities are yet at its infancy, profound evidences are being reported for their concurrent involvement in disease etiology and its treatment. Interestingly, studies from the 'minimal murine' (Oligo-MM12), 'humanized' microbiota gnotobiotic mice models and patient samples, combined with multi-omics and cell biology approaches, have been revealing the implications of these findings in the treatment of gut dysbiosis associated diseases. Nonetheless, due to the inherent heterogeneity of the gut commensals and their unified co-existence with opportunistic pathobionts, it is utmost essential to highlight their functionalities in 'good or bad' gut in human wellness. We have specifically reviewed dietary lifestyle and infectious diseases linked with the gut bacterial consortia to delineate the ecobiotic approaches towards their treatment. This notably includes gut mucosal immunity mediated diseases such as Tuberculosis, IBD, CDI, Type 2 Diabetes, etc. Alongside of each dysbiosis, we have described the current therapeutic advancements of the pre- and probiotics derived from human microbiome studies to restore gut microbial homeostasis. With a continuous running debate on the role of microbiota in above mentioned diseases, we have collected numerous scientific evidences highlighting a previously unanticipated complex involvement of gut microbiome in the potential of human health.

Pathobiont release from dysbiotic gut microbiota biofilms in intestinal inflammatory diseases: a role for iron?

Gut microbiota interacting with an intact mucosal surface are key to the maintenance of homeostasis and health. This review discusses the current state of knowledge of the biofilm mode of growth of these microbiota communities, and how in turn their disruptions may cause disease. Beyond alterations of relative microbial abundance and diversity, the aim of the review is to focus on the disruptions of the microbiota biofilm structure and function, the dispersion of commensal bacteria, and the mechanisms whereby these dispersed commensals may become pathobionts. Recent findings have linked iron acquisition to the expression of virulence factors in gut commensals that have become pathobionts. Causal studies are emerging, and mechanisms common to enteropathogen-induced disruptions, as well as those reported for Inflammatory Bowel Disease and colo-rectal cancer are used as examples to illustrate the great translational potential of such research. These new observations shed new light on our attempts to develop new therapies that are able to protect and restore gut microbiota homeostasis in the many disease conditions that have been linked to microbiota dysbiosis.

Mucosal microbial parasites/symbionts in health and disease: an integrative overview.

Microbial parasites adapted to thrive at mammalian mucosal surfaces have evolved multiple times from phylogenetically distant lineages into various extracellular and intracellular life styles. Their symbiotic relationships can range from commensalism to parasitism and more recently some host-parasites interactions are thought to have evolved into mutualistic associations too. It is increasingly appreciated that this diversity of symbiotic outcomes is the product of a complex network of parasites-microbiota-host interactions. Refinement and broader use of DNA based detection techniques are providing increasing evidence of how common some mucosal microbial parasites are and their host range, with some species being able to swap hosts, including from farm and pet animals to humans. A selection of examples will illustrate the zoonotic potential for a number of microbial parasites and how some species can be either disruptive or beneficial nodes in the complex networks of host-microbe interactions disrupting or maintaining mucosal homoeostasis. It will be argued that mucosal microbial parasitic diversity will represent an important resource to help us dissect through comparative studies the role of host-microbe interactions in both human health and disease.

Individual differences in stress vulnerability: The role of gut pathobionts in stress-induced colitis.

Chronic subordinate colony housing (CSC), an established mouse model for chronic psychosocial stress, promotes a microbial signature of gut inflammation, characterized by expansion of Proteobacteria, specifically Helicobacter spp., in association with colitis development. However, whether the presence of Helicobacter spp. during CSC is critically required for colitis development is unknown. Notably, during previous CSC studies performed at Regensburg University (University 1), male specific-pathogen-free (SPF) CSC mice lived in continuous subordination to a physically present and Helicobacter spp.-positive resident. Therefore, it is likely that CSC mice were colonized, during the CSC procedure, with Helicobacter spp. originating from the dominant resident. In the present study we show that employing SPF CSC mice and Helicobacter spp.-free SPF residents at Ulm University (University 2), results in physiological responses that are typical of chronic psychosocial stress, including increased adrenal and decreased thymus weights, decreased adrenal in vitro adrenocorticotropic hormone (ACTH) responsiveness, and increased anxiety-related behavior. However, in contrast to previous studies that used Helicobacter spp.-positive resident mice, use of Helicobacter spp.-negative resident mice failed to induce spontaneous colitis in SPF CSC mice. Consistent with the hypothesis that the latter is due to a lack of Helicobacter spp. transmission from dominant residents to subordinate mice during the CSC procedure, colonization of SPF residents with Helicobacter typhlonius at University 2, prior to the start of the CSC model, rescued the colitis-inducing potential of CSC exposure. Furthermore, using SPF CSC mice and H. typhlonius-free SPF residents at University 1 prevented CSC-induced colitis. In summary, our data support the hypothesis that the presence or absence of exposure to certain pathobionts contributes to individual variability in susceptibility to stress-/trauma-associated pathologies and to reproducibility of stress-related outcomes between laboratories.

Effects of a 217-km mountain ultramarathon on the gut microbiota of an obese runner: A case report.

Obesity is characterized by specific changes in the composition of the gut microbiota (GM). Exercise can contribute to the modulation of GM. This is the first case study to analyze the composition and metabolism of the GM of an obese runner in a single-stage mountain ultramarathon (MUM) with a mileage of 217 km. Fecal samples were collected 7 days before the race (T0), 15 min after the end of the race (T1), and 7 days after the end of the race (T2). GM composition was analyzed by real-time PCR and shotgun sequencing. We observed a decrease in Bacillota/Bacteroidota ratio and α-diversity after the race. After the 217-km MUM, we observed a decrease in symbiont microorganisms and a notable increase in harmful bacteria. In conclusion, we found that the 217-km MUM may have contributed to the intestinal dysbiosis of the obese runner.

Gut bacteriome in inflammatory bowel disease: An update on recent advances.

Inflammatory bowel diseases (IBD) are chronic inflammatory gut disorders, majorly classified as ulcerative colitis and Crohn's disease. The complex, multifactorial etiopathogenesis of IBD involves genetic predisposition, environmental cues, aberrant mucosal immune response and a disturbed gut microbiota. Epidemiological trends, studies in gnotobiotic mice models and genome-wide association studies, identifying genes involved in microbial handling, together mount evidence in support of the gut microbiota playing a pivotal role in IBD pathogenesis. Both Crohn's disease and ulcerative colitis are characterized by severe dysbiosis of the gut microbiome, marked by an expansion of detrimental taxa and concomitant depletion of beneficial members. IBD is characterized by reduction in abundances of bacterial genera involved in production of short-chain fatty acids, bio-transformations of bile acids and synthesis of indole-based tryptophan compounds such as Faecalibacterium, Ruminococcus, Coprococcus, Dorea, Parabacteroides, Eubacterium, Oscillibacter and Prevotella and elevation in members of phyla Proteobacteria and Actinobacteria. This imbalance not only results in exaggerated immune signaling towards the microbial antigens, but also results in an altered metabolomic milieu that triggers additional inflammatory cascades. The present review provides insights into the bacterial dysbiosis observed across different intestinal sites and their metabolomic imprints participating in IBD.

An inflammatory paradox: strategies inflammophilic oral pathobionts employ to exploit innate immunity via neutrophil manipulation.

Inflammatory dysbiotic diseases present an intriguing biological paradox. Like most other infectious disease processes, the alarm bells of the host are potently activated by tissue-destructive pathobionts, triggering a cascade of physiological responses that ultimately mobilize immune cells like neutrophils to sites of active infection. Typically, these inflammatory host responses are critical to inhibit and/or eradicate infecting microbes. However, for many inflammatory dysbiotic diseases, inflammophilic pathobiont-enriched communities not only survive the inflammatory response, but they actually obtain a growth advantage when challenged with an inflammatory environment. This is especially true for those organisms that have evolved various strategies to resist and/or manipulate components of innate immunity. In contrast, members of the commensal microbiome typically experience a competitive growth disadvantage under inflammatory selective pressure, hindering their critical ability to restrict pathobiont proliferation. Here, we examine examples of bacteria-neutrophil interactions from both conventional pathogens and inflammophiles. We discuss some of the strategies utilized by them to illustrate how inflammophilic microbes can play a central role in the positive feedback cycle that exemplifies dysbiotic chronic inflammatory diseases.

Gut Colonization With Antibiotic-Resistant Escherichia coli Pathobionts Leads to Disease Severity in Ulcerative Colitis.

BACKGROUND: Escherichia coli is a Gram-negative commensal of human gut. Surprisingly, the role of E. coli in the pathogenesis of ulcerative colitis (UC) has not been explored until now. METHODS: Human gut microbiota composition and meta-gut resistome were evaluated using metagenomics. Antibiotic susceptibility of E. coli isolates against different class of antibiotics was investigated. Further, the genome sequence analysis of E. coli isolates was performed to gain insight into the antimicrobial resistance (AMR) mechanism and virulence factors. Gut proteome of UC and non-UC was examined to understand the effect of resistant bacteria on host physiology. RESULTS: In UC patients, meta-gut resistome was found to be dominated by AMR genes (829) compared to healthy controls (HC) [518]. The metagenome study revealed a higher prevalence of AMR genes in the rural population (378 in HC; 607 in UC) compared to the urban (340 in HC; 578 in UC). Approximately, 40% of all E. coli isolates were multi-drug resistant (MDR), with higher prevalence in UC (43.75%) compared to HC (33.33%). Up-regulated expression of antimicrobial human proteins (lactotransferrin, azurocidin, cathepsin G, neutrophil elastase, and neutrophil defensin 3) and inflammatory mediator (Protein S100-A9 and Protein S100-A8) suggest microbial infection in UC gut. CONCLUSIONS: In addition to the conventional culturomics method, a multi-omics strategy provides deeper insights into the disease etiology, emergence of MDR pathobionts, and their roles in the disruption of the healthy gut environment in UC patients.

Changes in the pharyngeal and nasal microbiota in pediatric patients with adenotonsillar hypertrophy.

The present study aimed to investigate the pharyngeal and nasal microbiota composition in children with adenotonsillar hypertrophy (AH) and assess longitudinal alterations in both microbiota after a probiotic oral spray treatment. A cohort of 57 AH patients were enrolled and randomly assigned to the probiotic and placebo groups for a 5-month treatment course. Pharyngeal and nasal swabs were collected before and after treatment and analyzed by 16S rRNA-based metataxonomics and axenic cultures for pathobiont identification. 16S rRNA sequences from pharyngeal and nasal swabs of 65 healthy children (HC) were used as microbiota reference profiles. We found that the pharyngeal and nasal microbiota of AH children were similar. When compared to HC, we observed an increase of the genera Rothia, Granulicatella, Streptococcus, Neisseria, and Haemophilus, as well as a reduction of Corynebacterium, Pseudomonas, Acinetobacter, and Moraxella in both microbiota of AH patients. After probiotic treatment, we confirmed the absence of adverse effects and a reduction of upper respiratory tract infections (URTI). Moreover, the composition of pharyngeal microbiota was positively influenced by the reduction of potential pathobionts, like Haemophilus spp., with an increase of beneficial microbial metabolic pathways. Finally, the probiotic reduced the abundance of the pathobionts Streptococcus mitis and Gemella haemolysans in relation to AH severity. In conclusion, our results highlight the alterations of the pharyngeal and nasal microbiota associated with AH. Moreover, probiotic administration conferred protection against URTI and reduced the presence of potential pathobionts in patients with AH. IMPORTANCE: Adenotonsillar hypertrophy (AH) is considered the main cause of breathing disorders during sleep in children. AH patients, after significant morbidity and often multiple courses of antibiotics, often proceed to tonsillectomy and/or adenoidectomy. Given the potential risks associated with these procedures, there is a growing interest in the use of nonsurgical adjuvant therapies, such as probiotics, that could potentially reduce their need for surgical intervention. In this study, we investigated the pharyngeal and nasal microbiota in patients with AH compared with healthy children. Furthermore, we tested the effects of probiotic spray administration on both disease symptoms and microbiota profiles, to evaluate the possible use of this microbial therapy as an adjuvant for AH patients.

Update on the reciprocal interference between immunosuppressive therapy and gut microbiota after kidney transplantation.

Gut microbiota is often modified after kidney transplantation. This principally happens in the first period after transplantation. Antibiotics and, most of all, immunosuppressive drugs are the main responsible. The relationship between immunosuppressive drugs and the gut microbiota is bilateral. From one side immunosuppressive drugs modify the gut microbiota, often generating dysbiosis; from the other side microbiota may interfere with the immunosuppressant pharmacokinetics, producing products more or less active with respect to the original drug. These phenomena have influence over the graft outcomes and clinical consequences as rejections, infections, diarrhea may be caused by the dysbiotic condition. Corticosteroids, calcineurin inhibitors such as tacrolimus and cyclosporine, mycophenolate mofetil and mTOR inhibitors are the immunosuppressive drugs whose effect on the gut microbiota is better known. In contrast is well known how the gut microbiota may interfere with glucocorticoids, which may be transformed into androgens. Tacrolimus may be transformed by micro biota into a product called M1 that is 15-fold less active with respect to tacrolimus. The pro-drug mycophenolate mofetil is normally transformed in mycophenolic acid that according the presence or not of microbes producing the enzyme glu curonidase, may be transformed into the inactive product.

Bile acid-gut microbiota imbalance in cholestasis and its long-term effect in mice.

Cholestasis is a common morbid state that may occur in different phases; however, a comprehensive evaluation of the long-term effect post-recovery is still lacking. In the hepatic cholestasis mouse model, which was induced by a temporary complete blockage of the bile duct, the stasis of bile acids and liver damage typically recovered within a short period. However, we found that the temporary hepatic cholestasis had a long-term effect on gut microbiota dysbiosis, including overgrowth of small intestinal bacteria, decreased diversity of the gut microbiota, and an overall imbalance in its composition accompanied by an elevated inflammation level. Additionally, we observed an increase in Escherichia-Shigella (represented by ASV136078), rich in virulence factors, in both small and large intestines following cholestasis. To confirm the causal role of dysregulated gut microbiota in promoting hepatic inflammation and injury, we conducted gut microbiota transplantation into germ-free mice. We found that recipient mice transplanted with feces from cholestasis mice exhibited liver inflammation, damage, and accumulation of hepatic bile acids. In conclusion, our study demonstrates that cholestasis disrupts the overall load and structural composition of the gut microbiota in mice, and these adverse effects persist after recovery from cholestatic liver injury. This finding suggests the importance of monitoring the structural composition of the gut microbiota in patients with cholestasis and during their recovery. IMPORTANCE: Our pre-clinical study using a mouse model of cholestasis underscores that cholestasis not only disrupts the equilibrium and structural configuration of the gut microbiota but also emphasizes the persistence of these adverse effects even after bile stasis restoration. This suggests the need of monitoring and initiating interventions for gut microbiota structural restoration in patients with cholestasis during and after recovery. We believe that our study contributes to novel and better understanding of the intricate interplay among bile acid homeostasis, gut microbiota, and cholestasis-associated complications. Our pre-clinical findings may provide implications for the clinical management of patients with cholestasis.

Linking preterm infant gut microbiota to nasograstric enteral feeding tubes: exploring potential interactions and microbial strain transmission.

Introduction: Preterm birth is a growing problem worldwide. Staying at a neonatal intensive care unit (NICU) after birth is critical for the survival of preterm infants whose feeding often requires the use of nasogastric enteral feeding tubes (NEFT). These can be colonized by hospital-associated pathobionts that can access the gut of the preterm infants through this route. Since the gut microbiota is the most impactful factor on maturation of the immune system, any disturbance in this may condition their health. Therefore, the aim of this study is to assess the impact of NEFT-associated microbial communities on the establishment of the gut microbiota in preterm infants. Material and methods: A metataxonomic analysis of fecal and NEFT-related samples obtained during the first 2 weeks of life of preterm infants was performed. The potential sharing of strains isolated from the same set of samples of bacterial species involved in NICU's outbreaks, was assessed by Random Amplification of Polymorphic DNA (RAPD) genotyping. Results: In the samples taken 48 h after birth (NEFT-1 and Me/F1), Staphylococcus spp. was the most abundant genera (62% and 14%, respectively) and it was latter displaced to 5.5% and 0.45%, respectively by Enterobacteriaceae. Significant differences in beta diversity were detected in NEFT and fecal samples taken at day 17 after birth (NEFT-3 and F3) (p = 0.003 and p = 0.024, respectively). Significant positive correlations were found between the most relevant genera detected in NEFT-3 and F3. 28% of the patients shared at least one RAPD-PCR profile in fecal and NEFT samples and 11% of the total profiles were found at least once simultaneously in NEFT and fecal samples from the same patient. Conclusion: The results indicate a parallel bacterial colonization of the gut of preterm neonates and the NEFTs used for feeding, potentially involving strain sharing between these niches. Moreover, the same bacterial RAPD profiles were found in neonates hospitalized in different boxes, suggesting a microbial transference within the NICU environment. This study may assist clinical staff in implementing best practices to mitigate the spread of pathogens that could threaten the health of preterm infants.

Oral pathobiont Klebsiella chaperon usher pili provide site-specific adaptation for the inflamed gut mucosa.

The ectopic gut colonization by orally derived pathobionts has been implicated in the pathogenesis of various gastrointestinal diseases, including inflammatory bowel disease (IBD). For example, gut colonization by orally derived Klebsiella spp. has been linked to IBD in mice and humans. However, the mechanisms whereby oral pathobionts colonize extra-oral niches, such as the gut mucosa, remain largely unknown. Here, we performed a high-density transposon (Tn) screening to identify genes required for the adaptation of an oral Klebsiella strain to different mucosal sites - the oral and gut mucosae - at the steady state and during inflammation. We find that K. aerogenes, an oral pathobiont associated with both oral and gut inflammation in mice, harbors a newly identified genomic locus named "locus of colonization in the inflamed gut (LIG)" that encodes genes related to iron acquisition (Sit and Chu) and host adhesion (chaperon usher pili [CUP] system). The LIG locus is highly conserved among K. aerogenes strains, and these genes are also present in several other Klebsiella species. The Tn screening revealed that the LIG locus is required for the adaptation of K. aerogenes in its ectopic niche. In particular, we determined K. aerogenes employs a CUP system (CUP1) present in the LIG locus for colonization in the inflamed gut, but not in the oral mucosa. Thus, oral pathobionts likely exploit distinct adaptation mechanisms in their ectopically colonized intestinal niche compared to their native niche.

Update on the gut microbiome in health and diseases.

The Human Microbiome Project, Earth Microbiome Project, and next-generation sequencing have advanced novel genome association, host genetic linkages, and pathogen identification. The microbiome is the sum of the microbes, their genetic information, and their ecological niche. This study will describe how millions of bacteria in the gut affect the human body in health and disease. The gut microbiome changes in relation with age, with an increase in Bacteroidetes and Firmicutes. Host and environmental factors affecting the gut microbiome are diet, drugs, age, smoking, exercise, and host genetics. In addition, changes in the gut microbiome may affect the local gut immune system and systemic immune system. In this study, we discuss how the microbiome may affect the metabolism of healthy subjects or may affect the pathogenesis of metabolism-generating metabolic diseases. Due to the high number of publications on the argument, from a methodologically point of view, we decided to select the best papers published in referred journals in the last 3 years. Then we selected the previously published papers. The major goals of our study were to elucidate which microbiome and by which pathways are related to healthy and disease conditions.