Alterations In Intestinal Microbiota Composition Research Articles

Gut Microbiome and Transcriptomic Changes in Cigarette Smoke-Exposed Mice Compared to COPD and CD Patient Datasets.

Chronic obstructive pulmonary disease (COPD) patients and smokers have a higher incidence of intestinal disorders. The aim of this study was to gain insight into the transcriptomic changes in the lungs and intestines, and the fecal microbial composition after cigarette smoke exposure. Mice were exposed to cigarette smoke and their lung and ileum tissues were analyzed by RNA sequencing. The top 15 differentially expressed genes were investigated in publicly available gene expression datasets of COPD and Crohn's disease (CD) patients. The murine microbiota composition was determined by 16S rRNA sequencing. Increased expression of MMP12, GPNMB, CTSK, CD68, SPP1, CCL22, and ITGAX was found in the lungs of cigarette smoke-exposed mice and COPD patients. Changes in the intestinal expression of CD79B, PAX5, and FCRLA were observed in the ileum of cigarette smoke-exposed mice and CD patients. Furthermore, inflammatory cytokine profiles and adhesion molecules in both the lungs and intestines of cigarette smoke-exposed mice were profoundly changed. An altered intestinal microbiota composition and a reduction in bacterial diversity was observed in cigarette smoke-exposed mice. Altered gene expression in the murine lung was detected after cigarette smoke exposure, which might simulate COPD-like alterations. The transcriptomic changes in the intestine of cigarette smoke-exposed mice had some similarities with those of CD patients and were associated with changes in the intestinal microbiome. Future research could benefit from investigating the specific mechanisms underlying the observed gene expression changes due to cigarette smoke exposure, focusing on identifying potential therapeutic targets for COPD and CD.

Human metapneumovirus respiratory infection affects both innate and adaptive intestinal immunity.

Respiratory infections are one of the leading causes of morbidity and mortality worldwide, mainly in children, immunocompromised people, and the elderly. Several respiratory viruses can induce intestinal inflammation and alterations in intestinal microbiota composition. Human metapneumovirus (HMPV) is one of the major respiratory viruses contributing to infant mortality in children under 5 years of age worldwide, and the effect of this infection at the gut level has not been studied. Here, we evaluated the distal effects of HMPV infection on intestinal microbiota and inflammation in a murine model, analyzing several post-infection times (days 1, 3, and 5). Six to eight-week-old C57BL/6 mice were infected intranasally with HMPV, and mice inoculated with a non-infectious supernatant (Mock) were used as a control group. We did not detect HMPV viral load in the intestine, but we observed significant changes in the transcription of IFN-γ in the colon, analyzed by qPCR, at day 1 post-infection as compared to the control group. Furthermore, we analyzed the frequencies of different innate and adaptive immune cells in the colonic lamina propria, using flow cytometry. The frequency of monocyte populations was altered in the colon of HMPV -infected mice at days 1 and 3, with no significant difference from control mice at day 5 post-infection. Moreover, colonic CD8+ T cells and memory precursor effector CD8+ T cells were significantly increased in HMPV-infected mice at day 5, suggesting that HMPV may also alter intestinal adaptive immunity. Additionally, we did not find alterations in antimicrobial peptide expression, the frequency of colonic IgA+ plasma cells, and levels of fecal IgA. Some minor alterations in the fecal microbiota composition of HMPV -infected mice were detected using 16s rRNA sequencing. However, no significant differences were found in β-diversity and relative abundance at the genus level. To our knowledge, this is the first report describing the alterations in intestinal immunity following respiratory infection with HMPV infection. These effects do not seem to be mediated by direct viral infection in the intestinal tract. Our results indicate that HMPV can affect colonic innate and adaptive immunity but does not significantly alter the microbiota composition, and further research is required to understand the mechanisms inducing these distal effects in the intestine.

Preparation, Structural Analysis, and Intestinal Probiotic Properties of a Novel Oligosaccharide from Enzymatic Degradation of Huangshui Polysaccharide.

Huangshui polysaccharide (HSP) has attracted more and more interest due to its potential health benefits. Despite being an excellent source for the preparation of oligosaccharides, there are currently no relevant research reports on HSP. In the present study, a novel oligosaccharide (HSO) with a molecular weight of 1791 Da and a degree of polymerization of 11 was prepared through enzymatic degradation of crude HSP (cHSP). Methylation and NMR analyses revealed that the main chain of HSO was (1 → 4)-α-d-glucose with two O-6-linked branched chains. Morphological observations indicated that HSO exhibited smooth surface with lamellar and filamentary structure, and the glycan size ranged from 0.03 to 0.20 μm. Notably, HSO significantly promoted the proliferation of Bifidobacterium, Bacteroides, and Phascolarctobacterium, thereby making positive alterations in intestinal microbiota composition. Moreover, HSO markedly increased the content of short-chain fatty acids during in vitro fermentation. Metabolomics analysis illustrated the important metabolic pathways primarily involving glucose metabolism, amino acid metabolism, and fatty acid metabolism.

Microbiome-Metabolomic Analysis Reveals Beneficial Effects of Dietary Kelp Resistant Starch on Intestinal Functions of Hybrid Snakeheads (Channa maculata ♀ × Channa argus ♂).

The benefits of resistant starch on hypoglycemia, obesity prevention, antioxidant status and the alleviation of metabolic syndrome have received considerable attention. In this study, we explored how dietary kelp resistant starch (KRS) enhances intestinal morphology and function through a microbiome-metabolomic analysis. Hybrid snakeheads (initial weight: 11.4 ± 0.15 g) were fed experimental diets for 60 days. Fish were fed a basic wheat starch diet and the KRS diet. Dietary KRS improved intestinal morphology and enhanced intestinal antioxidant and digestive capabilities, as evidenced by decreased intestinal damage and upregulated intestinal biochemical markers. The microbiome analysis showed that KRS administration elevated the proportion of butyrate-producing bacteria and the abundance of beneficial bacteria that increases insulin sensitivity. Furthermore, significant alterations in metabolic profiles were observed to mainly associate with the amino acid metabolism (particularly arginine production), the metabolism of cofactors and vitamins, fat metabolism, glutathione metabolism, and the biosynthesis of other secondary metabolites. Additionally, alterations in intestinal microbiota composition were significantly associated with metabolites. Collectively, changes in intestinal microbiota and metabolite profiles produced by the replacement of common starch with dietary KRS appears to play an important role in the development of intestinal metabolism, thus leading to improved intestinal function and homeostasis.

Global trends in research related to the links between microbiota and antibiotics: a visualization study

The scientific community widely acknowledges that the gut microbiota plays a critical role in maintaining host health and can be altered by a range of factors, such as antibiotic use, diet, stress, and infections. Therefore, this study utilized bibliometric analysis to thoroughly investigate research trends in the microbiota and antibiotics. Scopus was used to extract papers linked to microbiota and antibiotics published between 2002 and 2021, and both Microsoft Excel and VOSviewer were used to conduct the analysis of the data. A total of 2,816 publications discussed the connection between the microbiota and antibiotics. Growth occurred in two stages: the first (2002–2015) was characterized by fairly slow publication production, while the second (2016–2021) saw a rapid increase in publishing progress. The United States has the most publications, 654, representing 23.22% of the total. China came second with 372 publications (13.21%), followed by the United Kingdom with 161 publications (5.72%) and India with 157 publications (5.58%). In addition, publications on ‘altered intestinal microbiota composition with antibiotic treatment’ were introduced after 2017, while ‘gut microbiota and antimicrobial resistance’ and ‘probiotics as an alternative antimicrobial therapy’ were introduced before 2017. Based on these results, this study provides an in-depth look at key moments in the history of microbiota and antibiotic research, as well as possible directions for future research in different areas of microbiota and antibiotic research. Therefore, it is suggested that more attention should be given to the latest promising hotspots, such as how antibiotic treatment changes the composition of the gut microbiota.

Bifidobacteria modulate immune response in pediatric patients with cow's milk protein allergy.

In children with an allergy to cow's milk proteins (CMA), the altered composition of intestinal microbiota influences the immune tolerance to milk proteins (CMP). This study aims to investigate the effect of probiotics on the phenotype and activation status of peripheral basophils and lymphocytes in a pediatric CMA cohort. CMA children underwent 45 days of treatment with Bifidobacteria. The basophil degranulation and the immune phenotype of B cells, T helper cells, and regulatory T cells were analyzed in peripheral blood at diagnosis (T0), after a 45-day probiotic treatment (T1), and 45 days after the probiotic wash-out (T2). We observed in probiotic-treated CMA patients a decrease in naive T lymphocytes. Among the CD3+ cell subsets, both naive and activated CD4+ cells resulted markedly reduced after taking probiotics, with the lowest percentages at T2. A decreased basophil degranulation was observed in response to all analyzed CMP at T1 compared to T0. The probiotic treatment resulted in a decrease of circulating naive and activated CD4+ T cells, as well as degranulating basophils. These data suggest that the Bifidobacteria could have a beneficial effect in the modulation of oral tolerance to CMP. ISRCTN69069358. URL of registration: https://www.isrctn.com/ISRCTN69069358 . Probiotic treatment with Bifidobacteria induces a reduction of both naive and activated circulating CD4+ T cells in pediatric patients with cow's milk allergy (CMA). The probiotic supplementation induces a decreased basophil degranulation. The immunological tolerance persists even after 45 days of the probiotic wash-out. Bifidobacteria in vivo supplementation down-modulates the activation of innate and adaptive immunity in pediatric patients with cow's milk allergy. Bifidobacteria contribute to the development of immune tolerance in CMA patients.

Alterations in intestinal microbiota composition coincide with impaired intestinal morphology and dysfunctional ileal immune response in growing-finishing pigs under constant chronic heat stress

BackgroundPrevious studies had shown that short-term acute heat stress (HS) affected the host’s metabolism and intestinal microbiota independent of feed intake (FI) reduction, and long-term calorie restriction caused intestinal morphological injuries and gut microbial alterations. However, research on the effects of constant chronic HS on intestinal microbial composition and the roles of FI reduction played in is limited. This study aimed to investigate the effects of 7-day constant chronic HS on the composition of intestinal microbes in growing-finishing pigs, and its relationship with pigs’ performance, intestinal morphology, and ileal immune response. Twenty-four growing-finishing pigs (Duroc × Large White × Landrace, 30 ± 1 kg body weight) were randomly assigned to three treatments (n = 8), 1) thermal neutral (TN) conditions (25 ± 1 °C) with ad libitum FI, 2) HS conditions (35 ± 1 °C) with ad libitum FI, 3) pair-fed (PF) with HS under TN conditions to discriminate the confounding effects of dissimilar FI, and the FI was the previous day’s average FI of HS. The small intestinal segments (duodenum, jejunum, and ileum) and feces were collected on d 8.ResultsResults indicated that HS drastically declined (P < 0.05) average daily gain (ADG) and average daily feed intake (ADFI) (about 61%) in comparison with TN, and caused hyperpyrexia, meanwhile PF caused hypothermia. Morphological observation by light and electron microscopes showed that both HS and PF treatment decreased (P < 0.05) the villus and microvillus height compared with TN. Additionally, HS increased (P < 0.05) protein expression of heat shock protein 70 in the duodenum, jejunum, and ileum. Furthermore, the expression of tight junction protein zonula occluden-1 (ZO-1) in the duodenum and ileum, and Occludin in the ileum were enhanced (P < 0.05) compared with TN and PF. Moreover, HS significantly enhanced (P < 0.05) the mRNA relative expression of inflammatory cytokines (TLR-2, TLR-4, and tumor necrosis factor-α (TNF-α), IL-6, IL-8, PG1–5, β-defensin 2 (pBD-2)), mucins (mucin-1 and mucin-2) and P65 protein level in the ileal mucosa tissue. Intestinal microbiota analysis by 16S rRNA sequencing showed lower (P < 0.10) α diversity in both HS and PF, and a separated cluster of β diversity among groups. Compared with TN, HS but not PF mainly reduced (FDR < 0.05) Bacteroidetes (phylum), Bacteroidia (class) and elevated the proportions of Proteobacteria (phylum, FDR < 0.05), Bacillales (order, FDR < 0.05), Planococcaceae (family, FDR < 0.05), Kurthia (genus, FDR < 0.05), Streptococcaceae (family, FDR < 0.10) and Streptococcus (genus, FDR < 0.10). Notably, Lactobacillales (order) was decreased (FDR < 0.05) by PF alone. Furthermore, the Spearman correlation analysis indicated that the microbes prevalent in HS were positively (P < 0.05) associated with intestinal morphological injuries indicators and ileal immune response parameters, and the microbes reduced in HS were negatively (P < 0.05) with the performance data.ConclusionsIntestinal morphological injuries and ileal immune response caused by constant chronic HS independent of FI showed close connections with alterations in intestinal microbiota in growing-finishing pigs.

A Common Atoms Model for the Bayesian Nonparametric Analysis of Nested Data

The use of large datasets for targeted therapeutic interventions requires new ways to characterize the heterogeneity observed across subgroups of a specific population. In particular, models for partially exchangeable data are needed for inference on nested datasets, where the observations are assumed to be organized in different units and some sharing of information is required to learn distinctive features of the units. In this manuscript, we propose a nested common atoms model (CAM) that is particularly suited for the analysis of nested datasets where the distributions of the units are expected to differ only over a small fraction of the observations sampled from each unit. The proposed CAM allows a two-layered clustering at the distributional and observational level and is amenable to scalable posterior inference through the use of a computationally efficient nested slice sampler algorithm. We further discuss how to extend the proposed modeling framework to handle discrete measurements, and we conduct posterior inference on a real microbiome dataset from a diet swap study to investigate how the alterations in intestinal microbiota composition are associated with different eating habits. We further investigate the performance of our model in capturing true distributional structures in the population by means of a simulation study.

Reduced Plasma Short-Chain Fatty Acid (SCFA) Concentrations Are Not Associated With Markers of Muscle Health in Non-Small Cell Lung Cancer

Abstract Objectives Cancer patients were shown to have an altered intestinal microbiota composition and lower fecal concentrations of the bacterial metabolites short-chain fatty acids (SCFA), which among others serve as energy source to muscle. We previously described an association between reduced plasma SCFA concentrations and muscle dysfunction in chronic wasting diseases and now examined whether this relationship exists in non-small cell lung cancer (NSCLC) patients. Methods We recruited 13 male patients with advanced NSCLC (stage 3–4) without anticancer therapy or surgery in the previous 4 weeks (age: 65.8 [62.2, 69.5] yo, BMI: 27.7 [25.2, 30.2] kg/m2), and 11 healthy male, age-matched controls (age: 68.5 [64.0, 73.0] yo, BMI: 26.5 [24.0, 28.9] kg/m2). Venous plasma was collected in the postabsorptive state to determine SCFA concentrations (in μM) by GC-MS. Nutritional depletion was assessed by unintended weight loss &amp;gt;5% in the past 3 months, muscle mass by DXA, handgrip strength and endurance by dynamometry, and maximal expiratory and inspriratory pressure using a hand-held mouth pressure device. Statistics are by ANCOVA and Pearson's correlation adjusting for age and BMI. Data are mean [95% CI]. Results Acetate (−54.1 [−105.0, −3.1] μmol/L, P = 0.039), propionate (−0.72 [−1.29, −0.16] μmol/L, P = 0.015), and butyrate (−0.52 [−0.92, −0.12] μmol/L, P = 0.014) concentrations were reduced in NSCLC compared to controls. While a higher propionate concentration correlated with a higher life expectancy (P = 0.037), SCFA concentrations were not associated with disease severity (stage 3 vs. 4), presence of nutritional depletion, or cancer type (adenocarcinoma vs. squamous cell carcinoma) (all P &amp;gt; 0.05). We observed no differences in muscle mass, strength or endurance between cancer and healthy participants and SCFA concentrations did not correlate with muscle function and endurance in NSCLC patients (all P &amp;gt; 0.05). Conclusions Our data suggest that the reduced SCFA play a role in overall outcome but not in muscle health in NSCLC patients. Funding Sources AICR, NIH, National Center for Research Resources, Sydney and J.L. Huffines Institute for Sports Medicine and Human Performance.

Global research trends in the microbiome related to irritable bowel syndrome: A bibliometric and visualized study.

BACKGROUNDIrritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. Dysregulation of the gut–brain axis plays a central role in the pathophysiology of IBS. It is increasingly clear that the microbiome plays a key role in the development and normal functioning of the gut–brain axis.AIMTo facilitate the identification of specific areas of focus that may be of relevance to future research. This study represents a bibliometric analysis of the literature pertaining to the microbiome in IBS to understand the development of this field. METHODSThe data used in our bibliometric analysis were retrieved from the Scopus database. The terms related to IBS and microbiome were searched in titles or abstracts within the period of 2000–2019. VOSviewer software was used for data visualization. RESULTSA total of 13055 documents related to IBS were retrieved at the global level. There were 1872 scientific publications focused on the microbiome in IBS. There was a strong positive correlation between publication productivity related to IBS in all fields and productivity related to the microbiome in IBS (r = 0.951, P < 0.001). The United States was the most prolific country with 449 (24%) publications, followed by the United Kingdom (n = 176, 9.4%), China (n = 154, 8.2%), and Italy (n = 151, 8.1%). The h-index for all retrieved publications related to the microbiome in IBS was 138. The hot topics were stratified into four clusters: (1) The gut–brain axis related to IBS; (2) Clinical trials related to IBS and the microbiome; (3) Drug-mediated manipulation of the gut microbiome; and (4) The role of the altered composition of intestinal microbiota in IBS prevention. CONCLUSIONThis is the first study to evaluate and quantify global research productivity pertaining to the microbiome in IBS. The number of publications regarding the gut microbiota in IBS has continuously grown since 2013. This finding suggests that the future outlook for interventions targeting the gut microbiota in IBS remains promising.

Effects of Maternal Fiber Intake on Intestinal Morphology, Bacterial Profile and Proteome of Newborns Using Pig as Model.

Dietary fiber intake during pregnancy may improve offspring intestinal development. The aim of this study was to evaluate the effect of maternal high fiber intake during late gestation on intestinal morphology, microbiota, and intestinal proteome of newborn piglets. Sixteen sows were randomly allocated into two groups receiving the control diet (CD) and high-fiber diet (HFD) from day 90 of gestation to farrowing. Newborn piglets were selected from each litter, named as CON and Fiber group, respectively. Maternal high fiber intake did not markedly improve the birth weight, but increased the body length, the ileal crypt depth and colonic acetate level. In addition, maternal high fiber intake increased the α-diversity indices (Observed species, Simpson, and ACE), and the abundance of Acidobacteria and Bacteroidetes at phylum level, significantly increased the abundance of Bradyrhizobium and Phyllobacterium at genus level in the colon of newborn piglets. Moreover, maternal high fiber intake markedly altered the ileal proteome, increasing the abundances of proteins associated with oxidative status, energy metabolism, and immune and inflammatory responses, and decreasing abundances of proteins related to cellular apoptosis, cell structure, and motility. These findings indicated that maternal high fiber intake could alter intestinal morphology, along with the altered intestinal microbiota composition and proteome of offspring.

GASTROINTESTINAL DYSFUNCTIONS AND PERIPHERAL INFLAMMATORY CYTOKINES IN PARKINSON’S DISEASES

Parkinson’s disease (PD) is a neurodegenerative disease characterized by α-synucleinopathy, which involves all districts of the brain-gut axis, including the central, autonomic and enteric nervous systems. Previous findings suggest that the intestinal microbiome is altered in PD and is related to motor phenotype. However how dysbiosis arises and whether this feature contributes to PD pathogenesis remains unknown. The aim was to evaluate gut microbiome and the serum cytokine profile in PD. We quantified serum interleukin (IL) levels (IL-1β, IL-6, IL-10, TNF-α, IFN-γ) in 55 PD patients. Study of the fecal samples was performed by real time PCR method and bacteriologically. Discovered the relationship between the intensity of dysbiosis and the level of proinflammatory cytokine IFN-γ, IL-6.We show that disturbances in plasma cytokine level could be more profound in PD patients with altered composition of intestinal microbiota, which may explain the mechanism of influence of microbiota composition on the PD manifestations.

Probiotic Lactobacillus reuteri Prevents Postantibiotic Bone Loss by Reducing Intestinal Dysbiosis and Preventing Barrier Disruption.

Antibiotic treatment, commonly prescribed for bacterial infections, depletes and subsequently causes long-term alterations in intestinal microbiota composition. Knowing the importance of the microbiome in the regulation of bone density, we investigated the effect of postantibiotic treatment on gut and bone health. Intestinal microbiome repopulation at 4-weeks postantibiotic treatment resulted in an increase in the Firmicutes:Bacteroidetes ratio, increased intestinal permeability, and notably reduced femoral trabecular bone volume (approximately 30%, p < 0.01). Treatment with a mucus supplement (a high-molecular-weight polymer, MDY-1001 [MDY]) prevented the postantibiotic-induced barrier break as well as bone loss, indicating a mechanistic link between increased intestinal permeability and bone loss. A link between the microbiome composition and bone density was demonstrated by supplementing the mice with probiotic bacteria. Specifically, Lactobacillus reuteri, but not Lactobacillus rhamnosus GG or nonpathogenic Escherichia coli, reduced the postantibiotic elevation of the Firmicutes:Bacteroidetes ratio and prevented femoral and vertebral trabecular bone loss. Consistent with causing bone loss, postantibiotic-induced dysbiosis decreased osteoblast and increased osteoclast activities, changes that were prevented by both L. reuteri and MDY. These data underscore the importance of microbial dysbiosis in the regulation of intestinal permeability and bone health, as well as identify L. reuteri and MDY as novel therapies for preventing these adverse effects. © 2018 American Society for Bone and Mineral Research.

The presence of genetic risk variants within PTPN2 and PTPN22 is associated with intestinal microbiota alterations in Swiss IBD cohort patients.

BackgroundGenetic risk factors, intestinal microbiota and a dysregulated immune system contribute to the pathogenesis of inflammatory bowel disease (IBD). We have previously demonstrated that dysfunction of protein tyrosine phosphatase non-receptor type 2 (PTPN2) and PTPN22 contributes to alterations of intestinal microbiota and the onset of chronic intestinal inflammation in vivo. Here, we investigated the influence of PTPN2 and PTPN22 gene variants on intestinal microbiota composition in IBD patients.MethodsBacterial DNA from mucosa-associated samples of 75 CD and 57 UC patients were sequenced using 16S rRNA sequencing approach. Microbial analysis, including alpha diversity, beta diversity and taxonomical analysis by comparing to PTPN2 (rs1893217) and PTPN22 (rs2476601) genotypes was performed in QIIME, the phyloseq R package and MaAsLin pipeline.ResultsIn PTPN2 variant UC patients, we detected an increase in relative abundance of unassigned genera from Clostridiales and Lachnospiraceae families and reduction of Roseburia when compared to PTPN2 wild-type (WT) patients. Ruminoccocus was increased in PTPN22 variant UC patients. In CD patients with severe disease course, Faecalibacterium, Bilophila, Coprococcus, unclassified Erysipelotrichaeceae, unassigned genera from Clostridiales and Ruminococcaceae families were reduced and Bacteroides were increased in PTPN2 WT carriers, while Faecalibacterium, Bilophila, Coprococcus, and Erysipelotrichaeceae were reduced in PTPN22 WT patients when compared to patients with mild disease. In UC patients with severe disease, relative abundance of Lachnobacterium was reduced in PTPN2 and PTPN22 WT patients, Dorea was increased in samples from PTPN22 WT carriers and an unassigned genus from Ruminococcaceae gen. was increased in patients with PTPN2 variant genotype.ConclusionsWe identified that IBD-associated genetic risk variants, disease severity and the interaction of these factors are related to significant alterations in intestinal microbiota composition of IBD patients.

Inflammasomes make the case for littermate-controlled experimental design in studying host-microbiota interactions

ABSTRACTSeveral human diseases are thought to evolve due to a combination of host genetic mutations and environmental factors that include alterations in intestinal microbiota composition termed dysbiosis. Although in some cases, host genetics may shape the gut microbiota and enable it to provoke disease, experimentally disentangling cause and consequence in such host-microbe interactions requires strict control over non-genetic confounding factors. Mouse genetic studies previously proposed Nlrp6/ASC inflammasomes as innate immunity regulators of the intestinal ecosystem. In contrast, using littermate-controlled experimental setups, we recently showed that Nlrp6/ASC inflammasomes do not alter the gut microbiota composition. Our analyses indicated that maternal inheritance and long-term separate housing are non-genetic confounders that preclude the use of non-littermate mice when analyzing host genetic effects on intestinal ecology. Here, we summarize and discuss our gut microbiota analyses in inflammasome-deficient mice for illustrating the importance of littermate experimental design in studying host-microbiota interactions.

Differences in epidemiological features between ulcerative colitis and Crohn’s disease: The early life-programmed versus late dysbiosis hypothesis

It is increasingly admitted that Crohn’s disease and ulcerative colitis, the two entities of inflammatory bowel disease, are initiated and reactivated by environmental factors in genetically susceptible hosts, and result from aberrant immune response to specific intestinal microbes, in the context of altered composition of intestinal microbiota, called dysbiosis. We hypothesize that the role of the gut microbiota in Crohn’s disease pathogenesis is linked to early-life abnormal crosstalk with the host immune system under construction. By contrast, in ulcerative colitis, the detrimental effect of intestinal dysbiosis could occur at any time of life, due to instant environment. This hypothesis could explain why the incidence of Crohn’s disease raises many years later than that of ulcerative colitis in developing countries that adopt the Western lifestyle. This would also explain why many early-life events, such as caesarean section, increased hygiene and repeated antibiotic exposure, are risk factors for subsequent development of Crohn’s disease, but not ulcerative colitis.

Fecal microbiota transplantation for recurrent Clostridium difficile infection in a patient with ulcerative colitis.

Fecal microbiota transplantation (FMT) has been reported as a safe and effective therapy in patients with refractory and recurrent Clostridium difficile infection (CDI). FMT has also been reported as a promising therapy in patients with ulcerative colitis (UC). Both, CDI and UC, are believed to be caused by dysbiosis, such as altered compositions or decreased diversity of the intestinal microbiota. This report describes a patient with UC in remission with a second recurrent episode of CDI, who was treated with FMT. A single FMT performed via colonoscopy completely resolved the patient's diarrhea and eradicated C. difficile bacteriologically without any severe complications. Molecular biological analysis of the patient's fecal microbiota showed that FMT could dramatically change the altered composition of intestinal microbiota and restore its diversity. Despite the restoration of the intestinal microbiota, FMT could not prevent a relapse of UC in this patient. However, it improved the intestinal symptoms of CDI and could prevent further recurrences of CDI.

Faecal volatile organic compounds analysis using field asymmetric ion mobility spectrometry: non-invasive diagnostics in paediatric inflammatory bowel disease

Background and Objectives: Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), remains challenging to diagnose. Diagnostic work-up carries a high burden, especially in paediatric patients, due to invasive endoscopic procedures. IBD is associated with alterations in intestinal microbiota composition. Faecal volatile organic compounds (VOCs) reflect gut microbiota composition. The aim of this study was to assess the diagnostic accuracy of faecal VOC profiling as a non-invasive diagnostic biomarker for paediatric IBD. Methods: In this diagnostic accuracy study performed in two tertiary centres in the Netherlands, faecal VOC profiles of 36 de novo, treatment-naïve paediatric IBD patients (23 CD, 13 UC), and 24 healthy, matched controls were measured by field asymmetric ion mobility spectrometry (Owlstone Ltd, Lonestar®, UK). Results: Faecal VOC profiles of de novo paediatric IBD patients could be differentiated from healthy controls (AUC ± 95% CI, p-value, sensitivity, specificity; 0.76 ± 0.14, p < 0.001, 79%, 78%). This discrimination from controls was observed in both CD (0.90 ± 0.10, p < 0.0001, 83%, 83%) and UC (0.74 ± 0.19, p = 0.02, 77%, 75%). VOC profiles from UC could not be discriminated from CD (0.67 ± 0.19, p = 0.0996, 65%, 62%). Conclusion: Field asymmetric ion mobility spectrometry allowed for discrimination between faecal VOC profiles of de novo paediatric IBD patients and healthy controls, confirming the potential of faecal VOC analysis as a non-invasive diagnostic biomarker for paediatric IBD. This method may serve as a complementary, non-invasive technique in the diagnosis of IBD, possibly limiting the number of endoscopies needed in children suspected for IBD.

Intestinal Ralstonia pickettii augments glucose intolerance in obesity.

An altered intestinal microbiota composition has been implicated in the pathogenesis of metabolic disease including obesity and type 2 diabetes mellitus (T2DM). Low grade inflammation, potentially initiated by the intestinal microbiota, has been suggested to be a driving force in the development of insulin resistance in obesity. Here, we report that bacterial DNA is present in mesenteric adipose tissue of obese but otherwise healthy human subjects. Pyrosequencing of bacterial 16S rRNA genes revealed that DNA from the Gram-negative species Ralstonia was most prevalent. Interestingly, fecal abundance of Ralstonia pickettii was increased in obese subjects with pre-diabetes and T2DM. To assess if R. pickettii was causally involved in development of obesity and T2DM, we performed a proof-of-concept study in diet-induced obese (DIO) mice. Compared to vehicle-treated control mice, R. pickettii-treated DIO mice had reduced glucose tolerance. In addition, circulating levels of endotoxin were increased in R. pickettii-treated mice. In conclusion, this study suggests that intestinal Ralstonia is increased in obese human subjects with T2DM and reciprocally worsens glucose tolerance in DIO mice.

The Association of Bifidobacterium breve BR03 and B632 is Effective to Prevent Colics in Bottle-fed Infants: A Pilot, Controlled, Randomized, and Double-Blind Study.

To assess the effectiveness of Bifidobacterium breve B632 and BR03 association in the reduction of infants crying over time. The second endpoint was to observe the effect of the same strains on daily evacuations and on the number of regurgitations and vomits. Infant colics represent a clinical condition in childhood, characterized by an uncontrollable crying that occurs without any apparent organic cause. An altered intestinal microbiota composition in the very first months may induce intestinal colics in infants. Thus far, no treatment is really effective for this problem, but recent literature shows an increasing attention toward probiotics. A total of 83 subjects were enrolled, 60 breastfed infants and 23 bottle-fed infants. Sixty of them carried out the study: 29 infants were given probiotics, whereas 31 placebo. During the 90 days of the study, parents were asked to give 5 drops of active product (10 viable cells/strain) or placebo and to daily take note of: minutes of crying, number, color, and consistency of evacuations, and number of regurgitations or vomits. No significant differences were detected in the infants treated with probiotics, compared with placebo group (P=0.75). The analysis of the 3 months of treatment demonstrated that during the third month, the probiotic group cried 12.14 minutes on average and the placebo cried 46.65 minutes. This difference is statistically significant (P=0.016). The evidence of the usefulness of some probiotic strains in the treatment and prevention of infant colics is growing, and therefore their use in clinical practice is spreading.