Inflammatory Bowel Diseases: Host-Microbial-Environmental Interactions in Dysbiosis.

Crohn's Disease (CD) and Ulcerative Colitis (UC) are world-wide health problems in which intestinal dysbiosis or adverse functional changes in the microbiome are causative or exacerbating factors. The reduced abundance and diversity of the microbiome may be a result of a lack of exposure to vital commensal microbes or overexposure to competitive pathobionts during early life. Alternatively, many commensal bacteria may not find a suitable intestinal niche or fail to proliferate or function in a protective/competitive manner if they do colonize. Bacteria express a range of factors, such as fimbriae, flagella, and secretory compounds that enable them to attach to the gut, modulate metabolism, and outcompete other species. However, the host also releases factors, such as secretory IgA, antimicrobial factors, hormones, and mucins, which can prevent or regulate bacterial interactions with the gut or disable the bacterium. The delicate balance between these competing host and bacteria factors dictates whether a bacterium can colonize, proliferate or function in the intestine. Impaired functioning of NOD2 in Paneth cells and disrupted colonic mucus production are exacerbating features of CD and UC, respectively, that contribute to dysbiosis. This review evaluates the roles of these and other the host, bacterial and environmental factors in inflammatory bowel diseases.

16S sequencing and functional analysis of the fecal microbiome during treatment of newly diagnosed pediatric inflammatory bowel disease.

The human microbiome is of considerable interest to pediatric inflammatory bowel disease (PIBD) researchers with 1 potential mechanism for disease development being aberrant immune handling of the intestinal bacteria. This study analyses the fecal microbiome through treatment in newly diagnosed PIBD patients and compares to cohabiting siblings where possible. Patients were recruited on clinical suspicion of PIBD before diagnosis. Treatment-naïve fecal samples were collected, with further samples at 2 and 6 weeks into treatment. Samples underwent 16S ribosomal ribonucleic acid (RNA) gene sequencing and short-chain fatty acids (SCFAs) analysis, results were analyzed using quantitative-insights-into-microbial-ecology. Six PIBD patients were included in the cohort: 4 Crohn disease (CD), 1 ulcerative colitis (UC), 1 inflammatory bowel disease (IBD) unclassified, and median age 12.6 (range 10-15.1 years); 3 patients had an unaffected healthy sibling recruited. Microbial diversity (observed species/Chao1/Shannon diversity) was reduced in treatment-naïve patients compared to siblings and patients in remission. Principal coordinate analysis using Bray-Curtis dissimilarity and UniFrac revealed microbial shifts in CD over the treatment course. In treatment-naïve PIBD, there was reduction in functional ability for amino acid metabolism and carbohydrate handling compared to controls (P = .038) and patients in remission (P = .027). Metabolic function returned to normal after remission was achieved. SCFA revealed consistent detection of lactate in treatment-naïve samples. This study adds in-depth 16S rRNA sequencing analysis on a small longitudinal cohort to the literature and includes sibling controls and patients with UC/IBD unclassified. It highlights the initial dysbiosis, reduced diversity, altered functional potential, and subsequent shifts in bacteria from diagnosis over time to remission.

Controlling the network type in self-assembled dipeptide hydrogels.

We show that the same low molecular weight gelator can form gels using three different methods. Gels were formed from a high pH solution either by adding a salt or by adding an acid; gels were also formed by adding water to a solution of the gelator in an organic solvent. The mechanical properties for the gels formed by the different methods are different from one another. We link this to the network type that is formed, as well as the fibrous structures that are formed. The salt-triggered gels show a significant number of fibres that tend to align. The acid-triggered gels contain many thin fibres, which form an entangled network. The solvent-triggered gels show the presence of spherulitic domains. We show that it is tractable to vary the trigger mechanism for an established, robust gelator to prepare gels with targeted properties as opposed to synthesising new gelators.

The effect of self-sorting and co-assembly on the mechanical properties of low molecular weight hydrogels.

Self-sorting in low molecular weight hydrogels can be achieved using a pH triggered approach. We show here that this method can be used to prepare gels with different types of mechanical properties. Cooperative, disruptive or orthogonal assembled systems can be produced. Gels with interesting behaviour can be also prepared, for example self-sorted gels where delayed switch-on of gelation occurs. By careful choice of gelator, co-assembled structures can also be generated, which leads to synergistic strengthening of the mechanical properties.

Aligning clinical resources to curriculum needs: the utility of a group of teaching hospitals.

This article describes a study in two acute NHS Trusts of the availability and curriculum relevance of inpatients for undergraduate medical student learning. The study was conducted to assist a new medical school plan on how best to utilise the clinical learning resources of adjacent hospitals, at a time when basic medical education is expanding, large academic hospitals are becoming more specialised and medical care provision is shifting to smaller hospital and ambulatory settings. We found that all three hospitals showed similar proportions, mean ages and gender ratios of available patients, and provided a wide range of clinical learning opportunities. The larger academic hospital appeared to offer a narrower, more specialised, range of patient problems that were necessary to meet curriculum objectives, while the smaller hospitals provided a broader range of common problems. Opportunities to participate in clinical skills were limited in all three hospitals. None of the hospitals appeared to provide sufficient clinical material to meet all curriculum learning objectives. As acute health care delivery models change, medical schools may have to be quite deliberate in their utilisation of academic hospitals, community hospitals and primary care, matching student allocations carefully to sources of relevant learning opportunities.