Specific urinary metabolites related to gut microbial metabolism differ between CD patients, UC patients, and controls. The emerging technique of urinary metabolic profiling with multivariate analysis was able to distinguish these cohorts.

The colonic crypt is home to several multipotent stem cells. These stem cells reside in a niche at the base of the crypt, which controls their behavior and maintains the stem cell's homeostasis through a variety of signaling pathways and interactions. Several attempts have been made to define markers that can identify colonic stem cells, the most useful of which is Lgr5, a Wnt target gene. Although the crypt base contains several stem cells, each colonic crypt comprises a single clone of cells. Investigators have attempted to reconcile these apparently contradictory observations by conducting research into stem cell division. The propagation of stem-cell-acquired mutations through a crypt results in a monocryptal adenoma that, through crypt fission, develops into a microadenoma. Some early adenomas become polyclonal through an as yet unknown mechanism. The discovery of subpopulations of cancer cells that can initiate tumors when implanted into mice has renewed interest in the existence of cancer stem cells, especially with regard to their implications for the use of chemotherapy. Various potential markers of cancer stem cells have been investigated, particularly CD133, but the cancer stem cell theory still has some limitations.

The findings of this study demonstrate that ethnicity and parasitemia are important independent risk factors for severe falciparum malaria in adults from malaria-nonendemic countries and that a history of previous clinical malaria significantly reduces the risk of WHO-defined severe falciparum malaria.

ObjectiveBarrett's oesophagus shows appearances described as ‘intestinal metaplasia’, in structures called ‘crypts’ but do not typically display crypt architecture. Here, we investigate their relationship to gastric glands.MethodsCell proliferation and migration within Barrett's glands was assessed by Ki67 and iododeoxyuridine (IdU) labelling. Expression of mucin core proteins (MUC), trefoil family factor (TFF) peptides and LGR5 mRNA was determined by immunohistochemistry or by in situ hybridisation, and clonality was elucidated using mitochondrial DNA (mtDNA) mutations combined with mucin histochemistry.ResultsProliferation predominantly occurs in the middle of Barrett's glands, diminishing towards the surface and the base: IdU dynamics demonstrate bidirectional migration, similar to gastric glands. Distribution of MUC5AC, TFF1, MUC6 and TFF2 in Barrett's mirrors pyloric glands and is preserved in Barrett's dysplasia. MUC2-positive goblet cells are localised above the neck in Barrett's glands, and TFF3 is concentrated in the same region. LGR5 mRNA is detected in the middle of Barrett's glands suggesting a stem cell niche in this locale, similar to that in the gastric pylorus, and distinct from gastric intestinal metaplasia. Gastric and intestinal cell lineages within Barrett's glands are clonal, indicating derivation from a single stem cell.ConclusionsBarrett's shows the proliferative and stem cell architecture, and pattern of gene expression of pyloric gastric glands, maintained by stem cells showing gastric and intestinal differentiation: neutral drift may suggest that intestinal differentiation advances with time, a concept critical for the understanding of the origin and development of Barrett's oesophagus.

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