Clonal Parabacteroides from Gut Microfistulous Tracts as Transmissible Cytotoxic Succinate-Commensal Model of Crohn's Disease Complications.

Crohn's disease (CD) has been traditionally viewed as a chronic inflammatory disease that cause gut wall thickening and complications, including fistulas, by mechanisms not understood. By focusing on Parabacteroides distasonis (presumed modern succinate-producing commensal probiotic), recovered from intestinal microfistulous tracts (cavernous fistulous micropathologies CavFT proposed as intermediate between 'mucosal fissures' and 'fistulas') in two patients that required surgery to remove CD-damaged ilea, we demonstrate that such isolates exert pathogenic/pathobiont roles in mouse models of CD. Our isolates are clonally-related; potentially emerging as transmissible in the community and mice; proinflammatory and adapted to the ileum of germ-free mice prone to CD-like ileitis (SAMP1/YitFc) but not healthy mice (C57BL/6J), and cytotoxic/ATP-depleting to HoxB8-immortalized bone marrow derived myeloid cells from SAMP1/YitFc mice when concurrently exposed to succinate and extracts from CavFT-derived E. coli , but not to cells from healthy mice. With unique genomic features supporting recent genetic exchange with Bacteroides fragilis -BGF539, evidence of international presence in primarily human metagenome databases, these CavFT Pdis isolates could represent to a new opportunistic Parabacteroides species, or subspecies (' cavitamuralis' ) adapted to microfistulous niches in CD.

Sweets and Inflammatory Bowel Disease: Patients Favor Artificial Sweeteners and Diet Foods/Drinks Over Table Sugar and Consume Less Fruits/Vegetables.

BACKGROUND: While artificial sweeteners are deemed safe, preclinical studies indicate that artificial sweeteners contribute to gastrointestinal inflammation. Little is known about patients' perceptions and consumption of artificial sweeteners in inflammatory bowel disease (IBD). We surveyed the consumption frequency and beliefs of IBD patients and control participants regarding artificial sweeteners. METHODS: We surveyed 130 individuals (IBD patients, n = 93; control/non-IBD participants, n = 37) among our tertiary hospital population to determine consumption frequency and beliefs regarding artificial sweeteners (Splenda/sucralose, Stevia/stevia, NutraSweet/Equal/aspartame). A 14-question questionnaire surveyed the frequency of 9 dietary habits, preferences, and beliefs on health benefits of commercial artificial sweeteners, using the following as positive and negative control questions: table sugar, water, fruits/vegetables, and coconut-oil, among others. RESULTS: Despite the similarity in yes/no consumption data, artificial sweeteners (Q4 t test P = .023) and diet (low calorie) foods/drinks (Q4 t test P = .023) were consumed more frequently by patients with IBD than by control participants, while no difference in preference for water instead of juices/sodas was observed between IBD patients and control participants. Conversely, patients with IBD consumed table sugar less frequently than control participants (Q1 t test-P = .09), in agreement with their reporting of sugary foods as cause of symptoms (P < .01). A positive correlation was observed between artificial sweeteners and fresh fruits/vegetables among the first 31 IBD patients (Spearman P = .017) and confirmed with 62 new IBD patients (r = 0.232; 95% CI, 0.02-0.43; P = .031), indicating that artificial sweeteners are deemed a healthy habit in IBD. Excluding fresh fruits/vegetables, multivariate analyses to develop surrogate principal component analysis indexes of healthy habits confirmed that artificial sweeteners consumption follows healthy preferences among our IBD patients (adjusted P < .0001). CONCLUSIONS: Consumption of artificial sweeteners correlated with healthy habits, suggesting that our IBD population deemed artificial sweeteners as healthy and/or had preferences for naturally or artificially sweetened flavors and products.

Artificial sweeteners and artificially sweetened (diet, low calorie) foods/drinks are consumed more often by inflammatory bowel disease patients compared with control participants, and inflammatory bowel disease patients deem artificial sweeteners consumption as a healthy habit, when differentiating between table sugar and artificial sweeteners.

Validity of food additive maltodextrin as placebo and effects on human gut physiology: systematic review of placebo-controlled clinical trials.

PURPOSE: Maltodextrin (MDX) is a polysaccharide food additive commonly used as oral placebo/control to investigate treatments/interventions in humans. The aims of this study were to appraise the MDX effects on human physiology/gut microbiota, and to assess the validity of MDX as a placebo-control. METHODS: We performed a systematic review of randomized-placebo-controlled clinical trials (RCTs) where MDX was used as an orally consumed placebo. Data were extracted from study results where effects (physiological/microbial) were attributed (or not) to MDX, and from study participant outcomes data, before-and-after MDX consumption, for post-publication 're-analysis' using paired-data statistics. RESULTS: Of two hundred-sixteen studies on 'MDX/microbiome', seventy RCTs (n = 70) were selected for analysis. Supporting concerns regarding the validity of MDX as a placebo, the majority of RCTs (60%, CI 95% = 0.48-0.76; n = 42/70; Fisher-exact p = 0.001, expected < 5/70) reported MDX-induced physiological (38.1%, n = 16/42; p = 0.005), microbial metabolite (19%, n = 8/42; p = 0.013), or microbiome (50%, n = 21/42; p = 0.0001) effects. MDX-induced alterations on gut microbiome included changes in the Firmicutes and/or Bacteroidetes phyla, and Lactobacillus and/or Bifidobacterium species. Effects on various immunological, inflammatory markers, and gut function/permeability were also documented in 25.6% of the studies (n = 10/42). Notably, there was considerable variability in the direction of effects (decrease/increase), MDX dose, form (powder/pill), duration, and disease/populations studied. Overall, only 20% (n = 14/70; p = 0.026) of studies cross-referenced MDX as a justifiable/innocuous placebo, while 2.9% of studies (n = 2/70) acknowledged their data the opposite. CONCLUSION: Orally-consumed MDX often (63.9% of RCTs) induces effects on human physiology/gut microbiota. Such effects question the validity of MDX as a placebo-control in human clinical trials.

Artificial Sweeteners: History and New Concepts on Inflammation.

Since the introduction of artificial sweeteners (AS) to the North American market in the 1950s, a growing number of epidemiological and animal studies have suggested that AS may induce changes in gut bacteria and gut wall immune reactivity, which could negatively affect individuals with or susceptible to chronic inflammatory conditions such as inflammatory bowel disease (IBD), a disorder that has been growing exponentially in westernized countries. This review summarizes the history of current FDA-approved AS and their chemical composition, metabolism, and bacterial utilization, and provides a scoping overview of the disease mechanisms associated with the induction or prevention of inflammation in IBD. We provide a general outlook on areas that have been both largely and scarcely studied, emerging concepts using silica, and describe the effects of AS on acute and chronic forms of intestinal inflammation.

Regulation of Intestinal Inflammation by Soybean and Soy-Derived Compounds.

Environmental factors, particularly diet, are considered central to the pathogenesis of the inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis. In particular, the Westernization of diet, characterized by high intake of animal protein, saturated fat, and refined carbohydrates, has been shown to contribute to the development and progression of IBD. During the last decade, soybean, as well as soy-derived bioactive compounds (e.g., isoflavones, phytosterols, Bowman-Birk inhibitors) have been increasingly investigated because of their anti-inflammatory properties in animal models of IBD. Herein we provide a scoping review of the most studied disease mechanisms associated with disease induction and progression in IBD rodent models after feeding of either the whole food or a bioactive present in soybean.

Correction: The Influence of Second-Hand Cigarette Smoke Exposure during Childhood and Active Cigarette Smoking on Crohn's Disease Phenotype Defined by the Montreal Classification Scheme in a Western Cape Population, South Africa.

[This corrects the article DOI: 10.1371/journal.pone.0139597.].

Correction: The association between environmental exposures during childhood and the subsequent development of Crohn's disease: A score analysis approach.

[This corrects the article DOI: 10.1371/journal.pone.0171742.].

The association between environmental exposures during childhood and the subsequent development of Crohn's disease: A score analysis approach.

BACKGROUND: Environmental factors during childhood are thought to play a role in the aetiology of Crohn's Disease (CD). In South Africa, recently published work based on an investigation of 14 childhood environmental exposures during 3 age intervals (0-5, 6-10 and 11-18 years) has provided insight into the role of timing of exposure in the future development of CD. The 'overlapping' contribution of the investigated variables however, remains unclear. The aim of this study was to perform a post hoc analysis using this data and investigate the extent to which each variable contributes to the subsequent development of CD relative to each aforementioned age interval, based on a score analysis approach. METHODS: Three methods were used for the score analysis. Two methods employed the subgrouping of one or more (similar) variables (methods A and B), with each subgroup assigned a score value weighting equal to one. For comparison, the third approach (method 0) involved no grouping of the 14 variables. Thus, each variable held a score value of one. RESULTS: Results of the score analysis (Method 0) for the environmental exposures during 3 age intervals (0-5, 6-10 and 11-18 years) revealed no significant difference between the case and control groups. By contrast, results from Method A and Method B revealed a significant difference during all 3 age intervals between the case and control groups, with cases having significantly lower exposure scores (approximately 30% and 40% lower, respectively). CONCLUSION: Results from the score analysis provide insight into the 'compound' effects from multiple environmental exposures in the aetiology of CD.

The Influence of Second-Hand Cigarette Smoke Exposure during Childhood and Active Cigarette Smoking on Crohn's Disease Phenotype Defined by the Montreal Classification Scheme in a Western Cape Population, South Africa.

BACKGROUND: Smoking may worsen the disease outcomes in patients with Crohn's disease (CD), however the effect of exposure to second-hand cigarette smoke during childhood is unclear. In South Africa, no such literature exists. The aim of this study was to investigate whether disease phenotype, at time of diagnosis of CD, was associated with exposure to second-hand cigarette during childhood and active cigarette smoking habits. METHODS: A cross sectional examination of all consecutive CD patients seen during the period September 2011-January 2013 at 2 large inflammatory bowel disease centers in the Western Cape, South Africa was performed. Data were collected via review of patient case notes, interviewer-administered questionnaire and clinical examination by the attending gastroenterologist. Disease phenotype (behavior and location) was evaluated at time of diagnosis, according to the Montreal Classification scheme. In addition, disease behavior was stratified as 'complicated' or 'uncomplicated', using predefined definitions. Passive cigarette smoke exposure was evaluated during 3 age intervals: 0-5, 6-10, and 11-18 years. RESULTS: One hundred and ninety four CD patients were identified. Cigarette smoking during the 6 months prior to, or at time of diagnosis was significantly associated with ileo-colonic (L3) disease (RRR = 3.63; 95% CI, 1.32-9.98, p = 0.012) and ileal (L1) disease (RRR = 3.54; 95% CI, 1.06-11.83, p = 0.040) compared with colonic disease. In smokers, childhood passive cigarette smoke exposure during the 0-5 years age interval was significantly associated with ileo-colonic CD location (RRR = 21.3; 95% CI, 1.16-391.55, p = 0.040). No significant association between smoking habits and disease behavior at diagnosis, whether defined by the Montreal scheme, or stratified as 'complicated' vs 'uncomplicated', was observed. CONCLUSION: Smoking habits were associated with ileo-colonic (L3) and ileal (L1) disease at time of diagnosis in a South African cohort.