&lt;p&gt;Fecal microbiota profiles in treatment-na&amp;iuml;ve pediatric inflammatory bowel disease &amp;ndash; associations with disease phenotype, treatment, and outcome&lt;/p&gt;

Olbjørn, Christine; Småstuen, Milada Cvancarova; Thiis‐Evensen, Espen; Nakstad, Britt; Vatn, Morten H.; Jahnsen, Jørgen; Ricanek, Petr; Vatn, Simen; Moen, Aina Elisabeth Fossum; Tannæs, Tone M.; Lindstrøm, Jonas Christoffer; Söderholm, Johan D.; Halfvarson, Jonas; Gomollón, Fernando; Casèn, Christina; Karlsson, M. K.; Kalla, Rahul; Adams, Alexander T.; Satsangi, Jack; Perminow, Gøri

doi:10.2147/ceg.s186235

Cited by 69 publications

(83 citation statements)

References 50 publications

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“…Changes in Prevotella spp. were reported previously, with conflicting results in multiple studies [26,28,31,46]. Our results showed a relatively weak negative association between Prevotella spp.…”

Section: Discussioncontrasting

confidence: 70%

“…Supporting that hypothesis, most of our results were consistent with published studies with IBD patients. For example, reduced abundance of F. prausnitzii was reported in many studies [22][23][24][25][26][27][28][29]. We found that F. prausnitzii was negatively associated with fecal calprotectin, EPX, and IgA in the current study.…”

Section: Discussionsupporting

confidence: 67%

“…Additionally, fecal levels of several commensal bacteria, including Veillonella spp., E. coli, and Fusobacterium spp., were positively associated with inflammation biomarkers in the current study. All of those bacteria were considered as invasive [38][39][40], and high levels were reported previously in IBD patients [23,28,31,33,[41][42][43][44][45]. Changes in Prevotella spp.…”

Section: Discussionmentioning

confidence: 97%

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Development of an Index Score for Intestinal Inflammation-Associated Dysbiosis Using Real-World Stool Test Results

et al. 2019

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Background Gut microbiota play an important role in human health. However, the application of gut microbiome in regular clinical practice is limited by interindividual variations and complexity of test results. Hypothesis It is possible to address interindividual variation by using large data-based exploratory-pattern analysis. Methods The current study was conducted using a large data set (n = 173,221) of nonselective incoming patients' test results from a stool test. The data set included assays for the detection of 24 selected commensal microorganisms and multiple biomarkers in feces. Patients were grouped based on their levels of inflammation biomarkers such as calprotectin, eosinophil protein X, and IgA. Group mean values of biomarkers and commensal microbes were used in an exploratory-pattern analysis for association from which an index score for intestinal inflammation-associated dysbiosis (IAD) was developed. The IAD score was evaluated in one questionnaire-based study (n = 7263) and one prospective case series study (n = 122) with patients of inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and celiac disease. Results We identified a microbial profile strongly associated with fecal inflammation biomarkers. Developed on the pattern of the microbial profile, the IAD score demonstrated a strong association with fecal inflammation biomarkers and was significantly different between patients with IBD and those with IBS or celiac disease. Conclusion Using real-world data, we have developed a method to predict gut dysbiosis associated with different GI disease conditions. It may help clinicians simplify the process of interpreting gut microbial status and provide gut health assessment and treatment evaluation.

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Section: Discussioncontrasting

confidence: 70%

Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 97%

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Development of an Index Score for Intestinal Inflammation-Associated Dysbiosis Using Real-World Stool Test Results

et al. 2019

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“…Oligofructoseenriched inulin in overweight children has been shown to increase satiety, reduce energy intake as well as BMI and body fat mass over 16 weeks (body weight decrease of 3.1%, percent body fat decrease of 2.4% compared with children given placebo (increase of 0.5%, increase of 0.05% respectively). There is now some evidence that the stool microbiota profiles of patients with inflammatory conditions, such as inflammatory bowel disease, differs from those who are heathy, 166 understand the extent to which clinical success depends on these factors. 167 Indeed, some clinical trials have noted the importance of baseline microbiota composition among responders.…”

Section: [H1] Translation To the Clinicmentioning

confidence: 99%

Probiotics and prebiotics in intestinal health and disease: from biology to the clinic

Sanders¹,

Merenstein

Reid

et al. 2019

Nat Rev Gastroenterol Hepatol

1,273

740

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Probiotics and prebiotics are microbiota management tools for improved host health. They target gastrointestinal effects via the gut, although direct application to other sites such as the oral cavity, vaginal tract and skin are being explored. Here, we describe gut-derived effects in humans. In the past decade, research on the gut microbiome has rapidly accumulated, accompanied by increased interest in probiotics and prebiotics as a means to modulate the gut microbiota. Given the importance of these approaches for public health, it is timely to reiterate factual and supporting information on their clinical application and use. In this Review, we discuss scientific evidence on probiotics and prebiotics, including mechanistic insights into health effects. Strains of Lactobacillus, Bifidobacterium, and Saccharomyces have a long history of safe and effective use as probiotics, but Roseburia spp., Akkermansia spp., Propionibacterium spp. and Faecalibacterium spp. show promise. For prebiotics, glucans and fructans are well proven with evidence building on prebiotic effects of other substances (e.g. oligomers of mannose, glucose, xylose, pectin, starches, human milk; and polyphenols). 2 Key Points  The human gut microbiota is integral to health and is associated with a variety of diseases  Therapeutic and prophylactic effects of some probiotics and prebiotics for a variety of gut-related disorders might be, at least in part, mediated through modification of the microbiota and/or its function  Probiotic microorganisms act via a variety of means, including modulation of immune function, production of organic acids and antimicrobial compounds, interaction with resident microbiota, interfacing with the host, improving gut barrier integrity and enzyme formation  Prebiotics are substrates that are selectively utilized by host microorganisms conferring a health benefit; prebiotic effects include defence against pathogens, immune modulation, mineral absorption, bowel function, metabolic effects and satiety  Use of some probiotics and prebiotics is justified by robust assessments of efficacy, but not all products have been validated; the goal is evidence-based use by healthcare professionals

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“…The absence of PXR and CAR also led to an increase in the Lactobacillus genus, corresponding to reduced taurine-conjugated BAs. Lastly, species differences in PXR (mPXR vs. hPXR) also profoundly altered the gut microbiome, including higher Prevotella as well as lower A. muciniphila, both of which are hallmarks of in ammatory bowel disease [73,74], thus caution is warranted when using WT mouse models to study PXR and in ammation, as mPXR carriers may be more resistant to GI in ammation than hPXR carriers.…”

Section: Discussionmentioning

confidence: 99%

Understanding the Physiological Functions of the Host Xenobiotic-sensing Nuclear Receptors PXR and CAR on the Gut Microbiome using Genetically Modified Mice

Little

Dutta

et al. 2020

Preprint

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Background: Pharmacological activation of the host xenobiotic-sensing nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) is well-known to increase drug metabolism and reduce inflammation. Little is known regarding the physiological functions of PXR and CAR on the gut microbiome, which is an important regulator for the host immune surveillance and bile acid (BA) metabolism. We examined the gut microbiome composition and BA metabolites in high vs. low PXR/CAR-expressing mice, and in mice that are deficient in PXR, CAR, or both, at two developmental ages. We also utilized humanized PXR transgenic (hPXR-TG) mice to compare the species-specific effect of PXR on the gut microbiome. Results: We discovered bivalent hormetic functions of PXR and CAR in modulating the richness of the gut microbiome and inflammatory biomarkers: the high PXR/CAR expressers had higher microbial richness, pro-inflammatory bacteria (distinct taxa in Helicobacteraceae and Helicobacter), and fecal pro-inflammatory cytokines, suggesting higher immune surveillance to prevent the colonization of harmful bacteria. Interestingly, the absence of PXR or CAR also increased the microbial richness, and absence of both receptors synergistically increased the microbial richness. PXR and CAR deficiency increased the pro-inflammatory bacteria (Helicobacteraceae and Helicobacter). Most notably, deficiency in both PXR and CAR markedly increased the relative abundance of Lactobacillus, which is capable of bile salt hydrolase (BSH) activity. This corresponded to a decrease in major primary taurine-conjugated bile acids (BAs) in feces, which may lead to higher internal burden of taurine and unconjugated BAs, both of which are linked to inflammation, oxidative stress, and cytotoxicity. hPXR-TG mice had a distinct microbial profile as compared to wild-type mice, including a higher representation of Prevotella. hPXR-TG mice also had higher 12-OH BAs but lower 6-OH BAs, suggesting PXR’s species-specific role in modulating host hepatic BA synthesis. Conclusions: This study is the first to show that the host PXR and CAR profoundly influence the composition of the gut microbiome and its BA metabolites, with a bivalent hormetic relationship between PXR/CAR levels and microbial richness, unveiling the involvement of PXR/CAR-microbiome interactions in host immune surveillance and BA metabolism.

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<p>Fecal microbiota profiles in treatment-naïve pediatric inflammatory bowel disease – associations with disease phenotype, treatment, and outcome</p>

Cited by 69 publications

References 50 publications

Development of an Index Score for Intestinal Inflammation-Associated Dysbiosis Using Real-World Stool Test Results

Development of an Index Score for Intestinal Inflammation-Associated Dysbiosis Using Real-World Stool Test Results

Probiotics and prebiotics in intestinal health and disease: from biology to the clinic

Understanding the Physiological Functions of the Host Xenobiotic-sensing Nuclear Receptors PXR and CAR on the Gut Microbiome using Genetically Modified Mice

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