Dysbiosis In Inflammatory Bowel Disease Research Articles

Fecal microbiota profiles in treatment-naïve pediatric inflammatory bowel disease - associations with disease phenotype, treatment, and outcome.

PurposeImbalance in the microbiota, dysbiosis, has been identified in inflammatory bowel disease (IBD). We explored the fecal microbiota in pediatric patients with treatment-naïve IBD, non-IBD patients with gastrointestinal symptoms and healthy children, its relation to IBD subgroups, and treatment outcomes.Patients and methodsFecal samples were collected from 235 children below 18 years of age. Eighty children had Crohn’s disease (CD), 27 ulcerative colitis (UC), 3 IBD unclassified, 50 were non-IBD symptomatic patients, and 75 were healthy. The bacterial abundance of 54 predefined DNA markers was measured with a 16S rRNA DNA-based test using GA-Map™ technology at diagnosis and after therapy in IBD patients.ResultsBacterial abundance was similarly reduced in IBD and non-IBD patients in 51 of 54 markers compared to healthy patients (P<0.001). Only Prevotella was more abundant in patients (P<0.01). IBD patients with ileocolitis or total colitis had more Ruminococcus gnavus (P=0.02) than patients with colonic CD or left-sided UC. CD patients with upper gastrointestinal manifestations had higher Veillonella abundance (P<0.01). IBD patients (58%) who received biologic therapy had lower baseline Firmicutes and Mycoplasma hominis abundance (P<0.01) than conventionally treated. High Proteobacteria abundance was associated with stricturing/penetrating CD, surgery (P<0.01), and nonmucosal healing (P<0.03). Low Faecalibacterium prausnitzii abundance was associated with prior antibiotic therapy (P=0.001), surgery (P=0.02), and nonmucosal healing (P<0.03). After therapy, IBD patients had unchanged dysbiosis.ConclusionFecal microbiota profiles differentiated IBD and non-IBD symptomatic children from healthy children, but displayed similar dysbiosis in IBD and non-IBD symptomatic patients. Pretreatment fecal microbiota profiles may be of prognostic value and aid in treatment individualization in pediatric IBD as severe dysbiosis was associated with an extensive, complicated phenotype, biologic therapy, and nonmucosal healing. The dysbiosis persisted after therapy, regardless of treatments and mucosal healing.

Regulation of Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-κβ) in Inflammatory Bowel Diseases.

Inflammatory bowel diseases (IBD), encompassing both Crohn Disease (CD) and ulcerative colitis (UC) are globally prevalent diseases, impacting children of all ages. The hallmark of IBD is a perturbed immune system that leads to continuous inflammation in the gut and challenges optimal treatment. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κβ), a nuclear transcription factor, plays a major role in gut homeostasis and contributes significantly toward a balanced, homeostatic immune system. Dysregulation in the NF-κβ pathway and factors that regulate it lead to a state of uncontrolled inflammation and altered immunity, as typically observed in IBD. Levels of proinflammatory cytokines that are regulated through NF-κβ are increased in both CD and UC. Genes known to activate NF-κβ, such as, Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and Interleukin 23 (IL-23), are associated with IBD. Factors involved in inhibition of NF-κβ, such as A20 and TOLLIP, are also affected in IBD, resulting in failed inflammation suppression/regulation. NOD-2 and A20 have specifically been found to be strongly associated with pediatric IBD. Gut commensals are known to exert anti-inflammatory activities toward NF-κβ and can have a potential role in attenuating inflammation that likely occurs due to microbial dysbiosis in IBD. Failure to terminate/downregulate NF-κβ signaling results in chronic inflammation in IBD. Well-regulated control of inflammation in children with IBD can help better control the disease and suppress immune responses. Better understanding of factors that control NF-κβ can potentially lead toward discovering targeted therapeutic interventions for IBD. Suppression of NF-κβ can be achieved through many modalities including anti-sense oligonucleotides (ASOs), siRNA (small interfering RNA), factors regulating NF-κβ, and microbes. This review focuses on the role of NF-κβ, especially in pediatric IBD, and potential therapeutic venues for attenuating NF-κβ-induced inflammation.

Intestinal dysbiosis in inflammatory bowel disease associated with primary immunodeficiency

The gut microbiota plays a key role 63 in host physiology and is an actor in inflammatory bowel disease pathogenesis. Patients with primary immunodeficiency causing intestinal inflammation have disease-specific dysbiosis.

P869 Mucosa-associated dysbiosis in inflammatory bowel disease

P869 Mucosa-associated dysbiosis in inflammatory bowel disease

Microbiota dysbiosis in inflammatory bowel diseases: in silico investigation of the oxygen hypothesis

BackgroundInflammatory bowel diseases (IBD), which include ulcerative colitis and Crohn’s disease, cause chronic inflammation of the digestive tract in approximately 1.6 million Americans. A signature of IBD is dysbiosis of the gut microbiota marked by a significant reduction of obligate anaerobes and a sharp increase in facultative anaerobes. Numerous experimental studies have shown that IBD is strongly correlated with a decrease of Faecalibacterium prausnitzii and an increase of Escherichia coli. One hypothesis is that chronic inflammation induces increased oxygen levels in the gut, which in turn causes an imbalance between obligate and facultative anaerobes.ResultsTo computationally investigate the oxygen hypothesis, we developed a multispecies biofilm model based on genome-scale metabolic reconstructions of F. prausnitzii, E. coli and the common gut anaerobe Bacteroides thetaiotaomicron. Application of low bulk oxygen concentrations at the biofilm boundary reproduced experimentally observed behavior characterized by a sharp decrease of F. prausnitzii and a large increase of E. coli, demonstrating that dysbiosis consistent with IBD disease progression could be qualitatively predicted solely based on metabolic differences between the species. A diet with balanced carbohydrate and protein content was predicted to represent a metabolic “sweet spot” that increased the oxygen range over which F. prausnitzii could remain competitive and IBD could be sublimated. Host-microbiota feedback incorporated via a simple linear feedback between the average F. prausnitzii concentration and the bulk oxygen concentration did not substantially change the range of oxygen concentrations where dysbiosis was predicted, but the transition from normal species abundances to severe dysbiosis was much more dramatic and occurred over a much longer timescale. Similar predictions were obtained with sustained antibiotic treatment replacing a sustained oxygen perturbation, demonstrating how IBD might progress over several years with few noticeable effects and then suddenly produce severe disease symptoms.ConclusionsThe multispecies biofilm metabolic model predicted that oxygen concentrations of ∼1 micromolar within the gut could cause microbiota dysbiosis consistent with those observed experimentally for inflammatory bowel diseases. Our model predictions could be tested directly through the development of an appropriate in vitro system of the three species community and testing of microbiota-host interactions in gnotobiotic mice.

Analysis of endoscopic brush samples identified mucosa-associated dysbiosis in inflammatory bowel disease

BackgroundThe mucosa-associated gut microbiota directly modulates epithelial and mucosal function. In this study, we investigated the mucosa-associated microbial community in patients with inflammatory bowel disease (IBD), using endoscopic brush samples.MethodsA total of 174 mucus samples from 43 patients with ulcerative colitis (UC), 26 with Crohn’s disease (CD) and 14 non-IBD controls were obtained by gentle brushing of mucosal surfaces using endoscopic cytology brushes. The gut microbiome was analyzed using 16S rRNA gene sequencing.ResultsThere were no significant differences in microbial structure among different anatomical sites (the ileum, cecum and sigmoid colon) within individuals. There was, however, a significant difference in microbial structure between CD, UC and non-IBD controls. The difference between CD and non-IBD controls was more marked than that between UC patients and non-IBD controls. α-Diversity was significantly lower in UC and CD patients than non-IBD controls. When comparing CD patients with non-IBD controls, the phylum Proteobacteria was significantly increased and the phyla Firmicutes and Bacteroidetes were significantly reduced. These included a significant increase in the genera Escherichia, Ruminococcus (R. gnavus), Cetobacterium, Actinobacillus and Enterococcus, and a significant decrease in the genera Faecalibacterium, Coprococcus, Prevotella and Roseburia. Comparisons between CD and UC patients revealed a greater abundance of the genera Escherichia, Ruminococcus (R. gnavus), Clostridium, Cetobacterium, Peptostreptococcus in CD patients, and the genera Faecalibacterium, Blautia, Bifidobacterium, Roseburia and Citrobacter in UC patients.ConclusionsMucosa-associated dysbiosis was identified in IBD patients. CD and UC may be distinguishable from the mucosa-associated microbial community structure.

Gut microbiota and inflammatory bowel disease: so far so gut!

Major advances have occurred in the knowledge of the pathogenesis of inflammatory bowel disease (IBD) over the last decade, and perhaps the most major, and clinically advantageous of these advances has been the discovery of the microbiome as a key multifaceted component of inflammation. The gut microbiome is the largest known group of cells in the body, and is now recognized as an organ in its own right. Initial studies looking at a possible role of bacterial manipulation of the immune system in IBD, looked at identifying a specific bacterial species, and were not representative of a feasible model of inflammation in IBD overall. More recently there has been a shift towards the concept of dysbiosis, and the acceptance that a number of bacterial factors interact with the immune system in order for inflammation to occur. In the present review we will focus on past perspective of the role of microbiota in IBD, current evidences about dysbiosis in IBD and also the main therapeutic modalities to affect IBD by affecting gut microbiota: probiotics, prebiotics, fecal microbiota transplantation and emerging dietary intervention.

Understanding the Gut Microbiota in Inflammatory and Functional Gastrointestinal Diseases.

During the last decade, experimental and observational studies have shown that patients with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) may have an altered intestinal microbial composition compared with healthy individuals. However, no uniform microbial signature has as yet been detected for either IBD or IBS. This review summarizes the current knowledge of microbial dysbiosis and its potential relationship to the pathophysiology in IBD and IBS. A selective review was conducted to summarize the current knowledge of gut microbiota in the pathophysiology of IBD and IBS. Experimental and observational studies provide good evidence for intestinal microbial dysbiosis in subgroups of IBD and IBS. Still, no uniform disease pattern has been detected. This is most likely due to the heterogeneous nature of IBD and IBS, in combination with the effects of intrinsic and extrinsic factors. Such intrinsic factors include genetics, the gastrointestinal environment, and the host immune system, whereas extrinsic factors include early life diet, breastfeeding, and method of infant delivery. Recent and ongoing work to define microbial dysbiosis in IBD and IBS shows promise, but future well-designed studies with well-characterized study individuals are needed. It is likely that the microbial dysbiosis in IBD and IBS is dependent on the natural disease course of IBD and symptom pattern in IBS. Therefore, assessment of the entire microbiota along the gastrointestinal tract, in relationship to confounding factors, symptom fluctuations, and other pathophysiological factors, is needed for further understanding of the etiology of these common diseases.

Investigation of faecal volatile organic metabolites as novel diagnostic biomarkers in inflammatory bowel disease

The aetiology of inflammatory bowel disease (IBD) remains poorly understood. Recent evidence suggests an important role of gut microbial dysbiosis in IBD, and this may be associated with changes in faecal volatile organic metabolites (VOMs). To describe the changes in the faecal VOMs of patients with IBD and establish their diagnostic potential as non-invasive biomarkers. Faecal samples were obtained from 117 people with Crohn's disease (CD), 100 with ulcerative colitis (UC), and 109 healthy controls. Faecal VOMs were extracted using solid-phase micro-extraction and analysed by gas chromatography mass spectrometry. Data analysis was carried out using partial least squares-discriminate analysis (PLS-DA) to determine class membership based on distinct metabolomic profiles. The PLS-DA model showed clear separation of active CD from inactive disease and healthy controls (P < 0.001). Heptanal, 1-octen-3-ol, 2-piperidinone and 6-methyl-2-heptanone were up-regulated in the active CD group [variable important in projection (VIP) score 2.8, 2.7, 2.6 and 2.4, respectively], while methanethiol, 3-methyl-phenol, short-chain fatty acids and ester derivatives were found to be less abundant (VIP score of 3.5, 2.6, 1.5 and 1.2, respectively). The PLS-DA model also separated patients with small bowel CD from healthy controls and those with colonic CD from UC (P < 0.001). In contrast, less distinct separation was observed between active UC, inactive UC and healthy controls. Analysis of faecal volatile organic metabolites can provide an understanding of gut metabolomic changes in IBD. It has the potential to provide a non-invasive means of diagnosing IBD, and can differentiate between UC and CD.

Reduced Abundance of Butyrate-Producing Bacteria Species in the Fecal Microbial Community in Crohn's Disease

Background: The global alteration of the gut microbial community (dysbiosis) plays an important role in the pathogenesis of inflammatory bowel diseases (IBDs). However, bacterial species that characterize dysbiosis in IBD remain unclear. In this study, we assessed the alteration of the fecal microbiota profile in patients with Crohn's disease (CD) using 16S rRNA sequencing. Summary: Fecal samples from 10 inactive CD patients and 10 healthy individuals were subjected to 16S rRNA sequencing. The V3-V4 hypervariable regions of 16S rRNA were sequenced by the Illumina MiSeq™II system. The average of 62,201 reads per CD sample was significantly lower than the average of 73,716 reads per control sample. The genera Bacteroides, Eubacterium, Faecalibacterium and Ruminococcus significantly decreased in CD patients as compared to healthy controls. In contrast, the genera Actinomyces and Bifidobacterium significantly increased in CD patients. At the species level, butyrate-producing bacterial species, such as Blautia faecis, Roseburia inulinivorans, Ruminococcus torques, Clostridium lavalense, Bacteroides uniformis and Faecalibacterium prausnitzii were significantly reduced in CD patients as compared to healthy individuals (p < 0.05). These results of 16S rRNA sequencing were confirmed in additional CD patients (n = 68) and in healthy controls (n = 46) using quantitative PCR. The abundance of Roseburia inulinivorans and Ruminococcus torques was significantly lower in C-reactive protein (CRP)-positive CD patients as compared to CRP-negative CD patients (p < 0.05). Key Message: The dysbiosis of CD patients is characterized by reduced abundance of multiple butyrate-producing bacteria species.

Pathogenesis of Clostridium difficile Infection and Its Potential Role in Inflammatory Bowel Disease.

Colonization with toxigenic Clostridium difficile may be associated with a wide spectrum of clinical presentation ranging from asymptomatic carriage to mild diarrhea to life-threatening colitis. Over the last 15 years, there has been a marked increase in the incidence of C. difficile infection, which predominantly affects elderly patients on antibiotics. More recently, there has been significant interest in the association between inflammatory bowel disease (IBD) and C. difficile infection. This review article discusses in some detail current knowledge of the mechanisms by which C. difficile toxins may mediate mucosal inflammation, together with the role of cell wall components of the microorganism in disease pathogenesis. Innate and adaptive host responses to C. difficile toxins and other components are described and include consideration of the potential role of known mucosal changes in IBD that may lead to an enhanced inflammatory response in the presence of C. difficile infection. Recent studies, which have characterized resident microbiota that may mediate protection against colonization by C. difficile, including their mechanisms of action, are also discussed. This includes the role of bile acids and 7α-dehydroxylase-expressing bacteria, such as Clostridium scindens. Recent studies suggest a higher carriage rate of C. difficile in patients with IBD. It is anticipated that future studies will determine the role of dysbiosis in IBD in predisposing to colonization with C. difficile.

Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease.

To characterize the diversity and taxonomic relative abundance of the gut microbiota in patients with never-treated, recent-onset psoriatic arthritis (PsA). High-throughput 16S ribosomal RNA pyrosequencing was utilized to compare the community composition of gut microbiota in patients with PsA (n = 16), patients with psoriasis of the skin (n = 15), and healthy, matched control subjects (n = 17). Samples were further assessed for the presence and levels of fecal and serum secretory IgA (sIgA), proinflammatory proteins, and fatty acids. The gut microbiota observed in patients with PsA and patients with skin psoriasis was less diverse when compared to that in healthy controls. This could be attributed to the reduced presence of several taxa. Samples from both patient groups showed a relative decrease in abundance of Coprococcus species, while samples from PsA patients were also characterized by a significant reduction in Akkermansia, Ruminococcus, and Pseudobutyrivibrio. Supernatants of fecal samples from PsA patients revealed an increase in sIgA levels and decrease in RANKL levels. Analysis of fatty acids revealed low fecal quantities of hexanoate and heptanoate in both patients with PsA and patients with psoriasis. Patients with PsA and patients with skin psoriasis had a lower relative abundance of multiple intestinal bacteria. Although some genera were concomitantly decreased in both conditions, PsA samples had a lower abundance of reportedly beneficial taxa. This gut microbiota profile in PsA was similar to that previously described in patients with inflammatory bowel disease and was associated with changes in specific inflammatory proteins unique to this group, and distinct from that in patients with skin psoriasis and healthy controls. Thus, the role of the gut microbiome in the continuum of psoriasis-PsA pathogenesis and the associated immune response merits further study.

Dysbiotic Events in Gut Microbiota: Impact on Human Health

The human body is colonized by a large number of microbes coexisting peacefully with their host. The most colonized site is the gastrointestinal tract (GIT). More than 70% of all the microbes in the human body are in the colon. The microorganism population is 10 times larger of the total number of our somatic and germ cells. Two bacterial phyla, accounting for more than 90% of the bacterial cells, dominate the healthy adult intestine: Firmicutes and Bacteroidetes. Considerable variability in the microbiota compositions between people is found when we look at the taxonomic level of species, and strains within species. It is possible to assert that the human microbiota could be compared to a fingerprint. The microbiota acts as a barrier from pathogens, exerts important metabolic functions, and regulates inflammatory response by stimulating the immune system. Gut microbial imbalance (dysbiosis), has been linked to important human diseases such as inflammation related disorders. The present review summarizes our knowledge on the gut microbiota in a healthy context, and examines intestinal dysbiosis in inflammatory bowel disease (IBD) patients; the most frequently reported disease proven to be associated with changes in the gut microbiota.

The gut microbiota and inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gut. Although the precise cause of IBD remains unknown, the most accepted hypothesis of IBD pathogenesis to date is that an aberrant immune response against the gut microbiota is triggered by environmental factors in a genetically susceptible host. The advancement of next-generation sequencing technology has enabled identification of various alterations of the gut microbiota composition in IBD. While some results related to dysbiosis in IBD are different between studies owing to variations of sample type, method of investigation, patient profiles, and medication, the most consistent observation in IBD is reduced bacterial diversity, a decrease of Firmicutes, and an increase of Proteobacteria. It has not yet been established how dysbiosis contributes to intestinal inflammation. Many of the known IBD susceptibility genes are associated with recognition and processing of bacteria, which is consistent with a role of the gut microbiota in the pathogenesis of IBD. A number of trials have shown that therapies correcting dysbiosis, including fecal microbiota transplantation and probiotics, are promising in IBD.

Smoking cessation alters intestinal microbiota: insights from quantitative investigations on human fecal samples using FISH.

There has been a dramatic increase in investigations on the potential mechanistic role of the intestinal microbiota in various diseases and factors modulating intestinal microbial composition. We recently reported on intestinal microbial shifts after smoking cessation in humans. In this study, we aimed to conduct further microbial analyses and verify our previous results obtained by pyrosequencing using a direct quantitative microbial approach. Stool samples of healthy smoking human subjects undergoing controlled smoking cessation during a 9-week observational period were analyzed and compared with 2 control groups, ongoing smoking and nonsmoking subjects. Fluorescence in situ hybridization was applied to quantify specific bacterial groups. Intestinal microbiota composition was substantially altered after smoking cessation as characterized by an increase in key representatives from the phyla of Firmicutes (Clostridium coccoides, Eubacterium rectale, and Clostridium leptum subgroup) and Actinobacteria (HGC bacteria and Bifidobacteria) as well as a decrease in Bacteroidetes (Prevotella spp. and Bacteroides spp.) and Proteobacteria (β- and γ-subgroup of Proteobacteria). As determined by fluorescence in situ hybridization, an independent direct quantitative microbial approach, we could confirm that intestinal microbiota composition in humans is influenced by smoking. The characteristics of observed microbial shifts suggest a potential mechanistic association to alterations in body weight subsequent to smoking cessation. More importantly, regarding previously described microbial hallmarks of dysbiosis in inflammatory bowel diseases, a variety of observed microbial alterations after smoking cessation deserve further consideration in view of the divergent effect of smoking on the clinical course of Crohn's disease and ulcerative colitis.

Modulating the microbiota in inflammatory bowel diseases: prebiotics, probiotics or faecal transplantation?

Crohn's disease (CD) and ulcerative colitis (UC) are the two major phenotypes of inflammatory bowel diseases (IBD) which constitute a spectrum of chronic, debilitating diseases characterised by a relapsing inflammation of the intestinal mucosal lining. Evidence from a variety of disciplines implicates the intestinal microbiota in the pathogenesis of idiopathic IBD and their complications, including pouchitis. Many studies have reported a dysbiosis in IBD, characterised by a decrease in diversity, a decreased abundance of some dominant commensal members (such as Clostridium IV and XIVa) and an increase in detrimental bacteria (such as sulphate reducing bacteria and Escherichia coli). Therapies such as prebiotics and probiotics aim to selectively manipulate the intestinal microbiota and have been evaluated as an attractive therapeutic option with few side effects. The multispecies product VSL#3 was found effective in preventing and maintaining remission in pouchitis, whereas both VSL#3 and E. coli Nissle were effective in maintaining remission in UC. A more drastic approach to restore the composition of the microbiota and correct the underlying imbalance is a faecal microbiota transplantation (FMT). FMT has been successfully applied to treat patients with even recalcitrant Clostridium difficile infection. Particularly in UC, the majority of studies suggest that FMT may be an effective treatment option although the evidence is still limited. It is anticipated that our increasing knowledge on the composition and function of the intestinal microbiota components will allow in the future for a better selection of highly performing bacteria with specific functions required for specific benefits.

A modular organization of the human intestinal mucosal microbiota and its association with inflammatory bowel disease.

Abnormalities of the intestinal microbiota are implicated in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC), two spectra of inflammatory bowel disease (IBD). However, the high complexity and low inter-individual overlap of intestinal microbial composition are formidable barriers to identifying microbial taxa representing this dysbiosis. These difficulties might be overcome by an ecologic analytic strategy to identify modules of interacting bacteria (rather than individual bacteria) as quantitative reproducible features of microbial composition in normal and IBD mucosa. We sequenced 16S ribosomal RNA genes from 179 endoscopic lavage samples from different intestinal regions in 64 subjects (32 controls, 16 CD and 16 UC patients in clinical remission). CD and UC patients showed a reduction in phylogenetic diversity and shifts in microbial composition, comparable to previous studies using conventional mucosal biopsies. Analysis of weighted co-occurrence network revealed 5 microbial modules. These modules were unprecedented, as they were detectable in all individuals, and their composition and abundance was recapitulated in an independent, biopsy-based mucosal dataset 2 modules were associated with healthy, CD, or UC disease states. Imputed metagenome analysis indicated that these modules displayed distinct metabolic functionality, specifically the enrichment of oxidative response and glycan metabolism pathways relevant to host-pathogen interaction in the disease-associated modules. The highly preserved microbial modules accurately classified IBD status of individual patients during disease quiescence, suggesting that microbial dysbiosis in IBD may be an underlying disorder independent of disease activity. Microbial modules thus provide an integrative view of microbial ecology relevant to IBD.

A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis

ObjectiveBacteria play an important role in the onset and perpetuation of intestinal inflammation in inflammatory bowel disease (IBD). Unlike in Crohn's disease (CD), in which dysbiosis has been better characterised,...

Dysbiosis in inflammatory bowel diseases: the oxygen hypothesis.

The healthy intestine is characterized by a low level of oxygen and by the presence of large bacterial communities of obligate anaerobes. Dysbiosis of the gut microbiota has been reported in patients suffering from inflammatory bowel diseases (IBDs), but the mechanisms causing this imbalance remain unknown. Observations have included a decrease in obligate anaerobes of the phylum Firmicutes and an increase in facultative anaerobes, including members of the family Enterobacteriaceae. The shift of bacterial communities from obligate to facultative anaerobes strongly suggests a disruption in anaerobiosis and points to a role for oxygen in intestinal dysbiosis. Proposals to evaluate this hypothesis of a role for oxygen in IBD dysbiosis are provided. If this hypothesis is confirmed, decreasing oxygen in the intestine could open novel means to rebalance the microbiota and could provide novel preventative or therapeutic strategies for IBD patients in whom current treatments are ineffective.

Dysbiosis in the Pathogenesis of Pediatric Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBDs) are chronic inflammatory conditions of the gastrointestinal tract that occur in genetically susceptible individuals. Crohn's disease (CD) and ulcerative colitis (UC) are two major types of IBD. In about 20–25% of patients, disease onset is during childhood and pediatric IBD can be considered the best model for studying immunopathogentic mechanisms. The fundamentals of IBD pathogenesis are considered a defective innate immunity and bacterial killing with overaggressive adaptive immune response. A condition of “dysbiosis”, with alterations of the gut microbial composition, is regarded as the basis of IBD pathogenesis. The human gastrointestinal (GI) microbial population is a complex, dynamic ecosystem and consists of up to one thousand different bacterial species. In healthy individuals, intestinal microbiota have a symbiotic relationship with the host organism and carry out important metabolic, “barrier,” and immune functions. Microbial dysbiosis in IBD with lack of beneficial bacteria, together with genetic predisposition, is the most relevant conditions in the pathogenesis of the pediatric IBD.