The colonic mucus barrier is commonly described as a continuous double layer covering the epithelium, separating the microbiota from the intestinal tissue. This model is currently considered valid throughout the colon. The colon is characterised by regional anatomo-functional specificities such as presence and consistency of contents and location. In this study, we characterised the organisation of the colonic mucus barrier in proximal and distal colon of rodents by histological and FISH staining, taking into account aforementioned specificities. By using longitudinal sections and imaging extensive areas of tissue with and without colonic contents, we have obtained a spatiotemporal overview of mucus organisation in the colon. We describe for the first time that the colonic mucus layer covers the faeces instead of the epithelium in the distal colon. This faecal mucus layer confines the microbiota to the faeces and prevents it from remaining in empty distal colon. In the proximal colon, the mucus did not form a separating layer between bacteria and epithelium. We conclude that the organisation of colonic mucus is reliant on the presence of the colonic content, and the location within the colon. Our findings reopen the discussion on the nature of the colonic mucus barrier.

The respiratory system is directly exposed to low levels of lipopolysaccharide (LPS), present as a contaminant on airborne particles. In cystic fibrosis, the prevailing data identify structural changes of the airway epithelium, as well as tight junction dilatation. This study was aimed at determining the contribution of myosin light chain kinase to maintaining airway epithelium barrier integrity in the lung inflammatory response to LPS in rats.The effects of the selective myosin light chain kinase inhibitor, 5-iodonaphthalene-1-sulphonyl-homopiperazine (ML-7), were evaluated: 1) on pulmonary inflammation and airway epithelium barrier permeability alterations induced by intra-tracheal LPS fromPseudomonas aeruginosa; and 2) on levels of the phosphorylated form of the myosin light chain, which is increased in a human airway epithelial cell line (NCI-H292) and tracheal tissue after LPS exposure.The results show that LPS increased airway epithelium barrier paracellular permeability and lung inflammation, and that pre-treatment with ML-7 inhibited both effects. This effect of ML-7 was associated with the inhibition of phosphorylated myosin light chain in both NCI-H292 cells and tracheal tissue.The data, obtained usingin vivoandin vitroapproaches, demonstrate a key role for myosin light chain kinase in lung inflammation, and suggest that myosin light chain kinase could be a potential target for novel drugs intended for relief of lung injury.

Stress results in activation of the hypothalamic pituitary adrenal axis and affects illnesses such as neuroinflammatory syndrome. In vivo acute stress (restraint stress) induces gastrointestinal function disturbances through colonic mast cell activation. This study investigated the effect of acute stress in histamine content of colonic mast cells, and the central role of interleukin‐1 (IL‐1) and corticotropin‐releasing factor (CRF) in this effect. After a restraint stress session colonic segments were isolated and submitted to three protocols: (i) determination of histamine levels by radioimmunoassay (RIA) after incubation with 48/80 compound, (ii) evaluation by histology of mucosal mast cell (MMC) number and (iii) determination of histamine immunoreactivity of MMC. These procedures were conducted (1) in sham or stressed rats, (2) in stressed rats previously treated with intracerebroventricular (i.c.v.) IL‐1ra or α‐helical CRF9‐41, (3) in naive rats pretreated with i.c.v. rhIL‐1β or CRF and (4) in rats treated with central IL‐1β and CRF plus α‐helical CRF and IL‐1ra, respectively (cross‐antagonism reaction). Acute stress increases histamine content in colonic mast cells, without degranulation. i.c.v. pretreatment with IL‐1ra or α‐helical CRF9‐41 blocked stress‐induced mast cell histamine content increase. Both i.c.v. rhIL‐1β and CRF injections reproduced the stress‐linked changes. i.c.v. treatment with CRF antagonist blocked i.c.v. rhIL‐1β‐induced mast cell histamine content increase, whereas central IL‐1ra did not affect stress events induced by i.c.v. CRF administration. These results suggest that in rats acute stress increases colonic mast cell histamine content. This effect is mediated by the release in cascade in the brain first of IL‐1 and secondly of CRF.

Probiotics organise gut microflora for better regulation of the HPA axis not only in the early years but also during adulthood