The human intestinal microbiota is a crucial factor in the pathogenesis of various diseases, such as metabolic syndrome or inflammatory bowel disease (IBD). Yet, knowledge about the role of environmental factors such as smoking (which is known to influence theses aforementioned disease states) on the complex microbial composition is sparse. We aimed to investigate the role of smoking cessation on intestinal microbial composition in 10 healthy smoking subjects undergoing controlled smoking cessation.
To assess whether the use of dipeptidyl peptidase-4 inhibitors is associated with the incidence of inflammatory bowel disease in patients with type 2 diabetes.
To determine the effect of the specific carbohydrate diet (SCD) on active inflammatory bowel disease (IBD).
We present bacterial biogeography as sampled from the human gastrointestinal tract of four healthy subjects. This study generated >32 million paired-end sequences of bacterial 16S rRNA genes (V3 region) representing >95,000 unique operational taxonomic units (OTUs; 97% similarity clusters), with >99% Good’s coverage for all samples. The highest OTU richness and phylogenetic diversity was found in the mouth samples. The microbial communities of multiple biopsy sites within the colon were highly similar within individuals and largely distinct from those in stool. Within an individual, OTU overlap among broad site definitions (mouth, stomach/duodenum, colon and stool) ranged from 32-110 OTUs, 25 of which were common to all individuals and included OTUs affiliated with Faecalibacterium prasnitzii and the TM7 phylum. This first comprehensive characterization of the abundant and rare microflora found along the healthy human digestive tract represents essential groundwork to investigate further how the human microbiome relates to health and disease.
It is increasingly perceived that gut host-microbial interactions are important elements in the pathogenesis of functional gastrointestinal disorders (FGID). The most convincing evidence to date is the finding that functional dyspepsia and irritable bowel syndrome (IBS) may develop in predisposed individuals following a bout of infectious gastroenteritis. There has been a great deal of interest in the potential clinical and therapeutic implications of small intestinal bacterial overgrowth in IBS. However, this theory has generated much debate because the evidence is largely based on breath tests which have not been validated. The introduction of culture-independent molecular techniques provides a major advancement in our understanding of the microbial community in FGID. Results from 16S rRNA-based microbiota profiling approaches demonstrate both quantitative and qualitative changes of mucosal and faecal gut microbiota, particularly in IBS. Investigators are also starting to measure host-microbial interactions in IBS. The current working hypothesis is that abnormal microbiota activate mucosal innate immune responses which increase epithelial permeability, activate nociceptive sensory pathways and dysregulate the enteric nervous system. While we await important insights in this field, the microbiota is already a therapeutic target. Existing controlled trials of dietary manipulation, prebiotics, probiotics, synbiotics and non-absorbable antibiotics are promising, although most are limited by suboptimal design and small sample size. In this article, the authors provide a critical review of current hypotheses regarding the pathogenetic involvement of microbiota in FGID and evaluate the results of microbiota-directed interventions. The authors also provide clinical guidance on modulation of gut microbiota in IBS.
Vitamin D deficiency has been associated or implicated with the pathophysiology of the gastrointestinal conditions inflammatory bowel disease and colorectal cancer, as well as with depression. No trials or epidemiology studies to date have investigated a link with irritable bowel syndrome (IBS). A single case report has suggested a benefit in IBS of vitamin D supplementation. We hypothesised that IBS participants with vitamin D insufficiency would benefit from repletion in terms of their IBS symptoms. We undertook a pilot trial to provide data to support a power calculation and to justify a full trial.
BACKGROUND: PEG-based laxatives are considered today the gold standard for the treatment of constipation in children. PEG formulations differ in terms of composition of inactive ingredients which may have an impact on acceptance, compliance and adherence to treatment. We therefore compared the efficacy, tolerability, acceptance and compliance of a new PEG-only formulation compared to a reference PEG-electrolyte (PEG-EL) formulation in resolving faecal impaction and in the treatment of chronic constipation. METHODS: Children aged 2–16 years with functional chronic constipation for at least 2 months were randomized to receive PEG-only 0.7 g/kg/day in 2 divided doses or 6.9 g PEG-EL 1–4 sachets according to age for 4 weeks. Children with faecal impaction were randomized to receive PEG-only 1.5/g/kg in 2 divided doses until resolution or for 6 days or PEG-EL with an initial dose of 4 sachets and increasing 2 sachets a day until resolution or for 7 days. RESULTS: Ninety-six children were randomized into the study. Five patients withdrew consent before starting treatment. Three children discontinued treatment for refusal due to bad taste of the product (1 PEG-only, 2 PEG-EL); 1 (PEG-EL) for an adverse effect (abdominal pain). Intent-to-treat analysis was carried out in 49 children in the PEG-only group and 42 in the PEG-EL group.No significant differences were observed between the two treatment groups at baseline.Adequate relief of constipation in terms of normalized frequency and painless defecation of soft stools was achieved in all patients in both groups. The number of stools/week was 9.2 +/- 3.2 (mean +/- SD) in the PEG-only group and 7.8 +/- 2.4 in the PEG-EL group (p = 0.025); the number of days with stool was 22.4 +/- 5.1 in the PEG-only group and 19.6 +/- 7.2 in the PEG-EL group (p = 0.034).In the PEG-only group faecaloma resolution was observed in 5 children on the second day and in 2 children on the third day, while in the PEG-EL group it was observed in 2 children on the second day, in 3 children on the third day and in 1 child on the fifth day.Only 2 patients reported mild treatment-related adverse events: 1 child in the PEG-only group had diarrhoea and vomiting and 1 child in the PEG-EL group had abdominal pain requiring treatment discontinuation. The PEG-only preparation was better tolerated as shown by the lower frequency of nausea than in the PEG-EL group.In the PEG-only group, 96% of patients did not demonstrate any difficulties associated with treatment, as compared with 52% of patients in the PEG-EL group (p < 0.001). Also, the PEG-only formulation taste was better than that of PEG-EL (p < 0.001). The difference between the percentage of subjects who took > 80% of the prescribed dose was in favour of the PEG-only group (98% vs. 88%), though it did not reach a conventional statistical level (p = 0.062). CONCLUSION: PEG-only was better tolerated and accepted than PEG-EL in children with chronic constipation. At the higher PEG doses recommended by the manufactures children in the PEG-only group had higher and more regular soft stool frequency than PEG-EL.Trial registrationClinicalTrials.gov: NCT01592734.
To explore whether patients with a defective ileocecal valve (ICV)/cecal distension reflex have small intestinal bacterial overgrowth.
BACKGROUND & AIMS: Little is known about the long-term outcomes of patients with Crohn’s disease (CD) who have a complete response to therapy with azathioprine. We assessed the long-term effects of azathioprine in responders. METHODS: We collected data from the MICISTA registry (a database from the Rothschild and Saint-Antoine Hospitals in Paris, France) on consecutive CD patients treated with azathioprine 1987-1999 who responded to therapy (steroid-free clinical remission at 1 year); they were followed until 2011 (n=220; 86 male; median age 32 years; median follow-up period, 12.6 years). Data were compared with those from 440 matched patients with CD who did not receive immunosuppressants during the same period of inclusion (controls). RESULTS: The cumulative rate of sustained remission 10 years after treatment with azathioprine was 3%. Among patients exposed to azathioprine during a prospective follow-up period (1995-2011, 1936 patient-years), the percent of patient-years with active disease (flare or complication during the calendar year) was 17.6%. Compared to the control group, at baseline, responders were more often active smokers with significantly more extensive disease, perianal lesions, and extra-digestive manifestations. During follow-up, responders had a significantly reduced risk of intestinal surgery (adjusted odds ratio [AOR], 0.69; 95% confidence interval [CI], 0.52-0.91) and of perianal surgery (AOR, 0.36; 95% CI, 0.27-0.46). A significantly higher percentage of responders developed cancers, including non-melanoma skin cancers, compared with controls (9.5% vs 4.1%;P <.01). Survival rates after 20 years were 92.8%±2.3% of responders vs 97.9%±0.8% of controls ( P =.01). CONCLUSION: Based on a study at a single center, patients with CD that responds to azathioprine have a smaller proportion of patient-years with active disease, and are less likely to be hospitalized or undergo intestinal surgery, than patients with CD who did not receive immunosuppressants. These benefits, however, could be offset by increased risk of malignancies.
Upper gastrointestinal (GI) bleeding is one of the most common, high risk emergency disorders in the western world. Almost nothing has been reported on longer term prognosis following upper GI bleeding. The aim of this study was to establish mortality up to three years following hospital admission with upper GI bleeding and its relationship with aetiology, co-morbidities and socio-demographic factors.