Colonization of mucin by human intestinal bacteria and establishment of biofilm communities in a two-stage continuous culture system

The human large intestine is covered with a protective mucus coating, which is heavily colonized by complex bacterial populations that are distinct from those in the gut lumen. Little is known of the composition and metabolic activities of these biofilms, although they are likely to play an important role in mucus breakdown. The aims of this study were to determine how intestinal bacteria colonize mucus and to study physiologic and enzymatic factors involved in the destruction of this glycoprotein. Colonization of mucin gels by fecal bacteria was studied in vitro, using a two-stage continuous culture system, simulating conditions of nutrient availability and limitation characteristic of the proximal (vessel 1) and distal (vessel 2) colon. The establishment of bacterial communities in mucin gels was investigated by selective culture methods, scanning electron microscopy, and confocal laser scanning microscopy, in association with fluorescently labeled 16S rRNA oligonucleotide probes. Gel samples were also taken for analysis of mucin-degrading enzymes and measurements of residual mucin sugars. Mucin gels were rapidly colonized by heterogeneous bacterial populations, especially members of the Bacteroides fragilis group, enterobacteria, and clostridia. Intestinal bacterial populations growing on mucin surfaces were shown to be phylogenetically and metabolically distinct from their planktonic counterparts.     

Effect of pH on an in vitro model of gastric microbiota in enteral nutrition patients

Patients with dysphagia due to oropharyngeal disease or cerebrovascular accident require long-term nutritional support via enteral feeding, which often results in microbial overgrowth in the upper gastrointestinal (GI) tract. Gastric acid is the primary innate defense mechanism in the stomach and has been assumed to provide an effective barrier to microbial colonization at pH values of <4. To evaluate the efficacy of gastric acid as a barrier to overgrowth, the microbiota of gastric and duodenal aspirates was assessed by culturing methods. Additionally, a fermentor-based model incorporating enteral nutrition tubing of the gastric microbiota of enteral nutrition (EN) patients was constructed to assess the effect of pH on the microbiota. Results showed that gastric acidity had a relatively small effect on the numbers of microorganisms recovered from intestinal aspirates but did influence microbiota composition. Similarly, at pH 3 in the fermentor, a complex microbiota developed in the planktonic phase and in biofilms. The effect of pH on microbiota composition was similar in aspirates and in the fermentors. Candidas and lactobacilli were aciduric, while recoveries of Escherichia coli and Klebsiella pneumoniae decreased as pH was reduced, although both were still present in significant numbers at pH 3. Only Staphylococcus aureus and Bifidobacterium adolescentis persisted at higher pH values both in vitro and in vivo. Lactate and acetate were the main organic acids detected in both aspirates and fermentors. These data show that the simulator used in this investigation was capable of modeling the effects of environmental influences on the upper GI microbiota of EN patients and that gastric pH of <4 is not sufficient to prevent microbial overgrowth in these individuals.     

Widespread body pain and mortality: prospective population based study

ObjectiveTo determine whether there is excess mortality in groups of people who report widespread body pain, and if so to establish the nature and extent of any excess.DesignProspective follow up study over eight years. Mortality rate ratios were adjusted for age group, sex, and study location.SettingNorth west England.Participants6569 people who took part in two pain surveys during 1991-2.Results1005 (15%) participants had widespread pain, 3176 (48%) had regional pain, and 2388 (36%) had no pain. During follow up mortality was higher in people with regional pain (mortality rate ratio 1.21, 95% confidence interval 1.01 to 1.44) and widespread pain (1.31, 1.05 to 1.65) than in those who reported no pain. The excess mortality among people with regional and widespread pain was almost entirely related to deaths from cancer (1.55 (1.09 to 2.19) for regional pain and 2.07 (1.37 to 3.13) for widespread pain). The excess cancer mortality remained after exclusion of people in whom cancer had been diagnosed before the original survey and after adjustment for potential confounding factors. There were also more deaths from causes other than disease (for example, accidents, suicide, violence) among people with widespread pain (5.21, 0.94 to 28.78).ConclusionThere is an intriguing association between the report of widespread pain and subsequent death from cancer in the medium and long term. This may have implications for the long term follow up of patients with “unexplained” widespread pain symptoms, such as those with fibromyalgia.

What is already known on this topic

Widespread body pain, the cardinal symptom of fibromyalgia, is commonAn organic basis for symptoms is found in only a small proportion of peopleTreatment is difficult, and studies with short term follow up have shown that symptoms commonly persist

What this study adds

This was the first study with long term follow up of people with widespread pain in the communityThese people experience an increased mortality and the excess is principally related to deaths from cancer     

The Indications for Dilatation and Curettage

Historical aspects of dilatation and curettage are discussed and the indications reviewed for this procedure in three major age-groups: (1) childhood and adolescence, (2) maturity and reproductive period, (3) menopause and post-menopause. As the most frequently performed obstetrical and gynecological procedure, it is not an innocuous operation, and clear-cut indications for its use are presented with reference to abnormal vaginal bleeding in all age groups, infertility, functional ovarian tumours, neoplasia of the uterus, cervical biopsy, and major pelvic surgery. It is concluded that dilatation and curettage has a major place in the diagnostic and the therapeutic armamentarium of the thorough obstetrician and gynecologist.     

A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p≤5×10⁻⁷). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10⁻⁸) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2×10⁻⁸) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5×10⁻⁸; rs1229984-ADH1B, p = 7×10⁻⁹; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.