scholarly journals Mast Cells Mediate Stress‐Induced Breakdown in Mucosal Barrier Function in a Porcine Model of Irritable Bowel Syndrome

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Adam James Moeser ◽  
Elizabeth Lynne Overman ◽  
Anthony Thomas Blikslager
2021 ◽  
pp. 144-150
Author(s):  
E. Yu. Plotnikova

Irritable bowel syndrome (IBS) is one of the most prevalent gastrointestinal disorders affecting between 5 and 15% of the general adult population worldwide. Over the course of many years altered intestinal motility, visceral hypersensitivity, immune changes and, as it has recently been found, impaired epithelial barrier function were meant to explain the origin of symptoms in the IBS. We have come to realize now that the IBS warrants serious clinical and scientific study. Not that long ago, the connections between the gut and the brain have been expanded to include a new entrant, the microbiota, resulting in the creation of a new concept of a microbiota-gut-brain axis.Microbiota is a risk factor for the irritable bowel syndrome. Probiotics are defined as live microorganisms, which can alter the intestinal flora and regulate intestinal functions such as reduction of visceral hypersensitivity, improvement of mucosal barrier function, modulate immune responses and chronic inflammation, affect the central nervous system, gastrointestinal motility, etc. The correctness of this approach is confirmed by several studies of the probiotic Bifidobacterium longum subsp. longum 35624, which is widely used in the treatment of symptoms of irritable bowel syndrome. The dietary supplement Bifidobacterium longum subsp. longum 35624 contains 1 × 109 colony-forming units, which provides a clinically effective level of these beneficial bacteria. Bifidobacterium longum subsp. longum 35624 also reduces inflammation in the gastrointestinal tract and has positive results in reducing abdominal symptoms (e.g. abdominal pain / discomfort and bloating) associated with the irritable bowel syndrome and other conditions. 


2010 ◽  
Vol 298 (3) ◽  
pp. G352-G363 ◽  
Author(s):  
Feli Smith ◽  
Jessica E. Clark ◽  
Beth L. Overman ◽  
Christena C. Tozel ◽  
Jennifer H. Huang ◽  
...  

Early life stress is a predisposing factor for the development of chronic intestinal disorders in adult life. Here, we show that stress associated with early weaning in pigs leads to impaired mucosal barrier function. Early weaning (15- to 21-day weaning age) resulted in sustained impairment in intestinal barrier function, as indicated by reductions in jejunal transepithelial electrical resistance and elevations in mucosal-to-serosal flux of paracellular probes [3H]mannitol and [14C]inulin measured at 5 and 9 wk of age, compared with that shown in late-weaned pigs (23- to 28-day weaning age). Elevated baseline short-circuit current was observed in jejunum from early-weaned pigs and was shown to be mediated via enhanced Cl− secretion. Jejunal barrier dysfunction in early-weaned pigs coincided with increased lamina propria immune cell density particularly mucosal mast cells. The mast cell stabilizer drug sodium cromoglycolate ameliorated barrier dysfunction and hypersecretion in early-weaned pigs, demonstrating an important role of mast cells. Furthermore, activation of mast cells ex vivo with c48/80 and corticotrophin-releasing factor (CRF) in pig jejunum mounted in Ussing chambers induced barrier dysfunction and elevations in short-circuit current that were inhibited with mast cell protease inhibitors. Experiments in which selective CRF receptor antagonists were administered to early-weaned pigs revealed that CRF receptor 1 (CRFr1) activation mediates barrier dysfunction and hypersecretion, whereas CRFr2 activation may be responsible for novel protective properties in the porcine intestine in response to early life stress.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Laura Prospero ◽  
Giuseppe Riezzo ◽  
Michele Linsalata ◽  
Antonella Orlando ◽  
Benedetta D’Attoma ◽  
...  

Abstract Background Irritable bowel syndrome (IBS) is characterised by gastrointestinal (GI) and psychological symptoms (e.g., depression, anxiety, and somatization). Depression and anxiety, but not somatization, have already been associated with altered intestinal barrier function, increased LPS, and dysbiosis. The study aimed to investigate the possible link between somatization and intestinal barrier in IBS with diarrhoea (IBS-D) patients. Methods Forty-seven IBS-D patients were classified as having low somatization (LS = 19) or high somatization (HS = 28) according to the Symptom Checklist-90-Revised (SCL-90-R), (cut-off score = 63). The IBS Severity Scoring System (IBS-SSS) and the Gastrointestinal Symptom Rating Scale (GSRS) questionnaires were administered to evaluate GI symptoms. The intestinal barrier function was studied by the lactulose/mannitol absorption test, faecal and serum zonulin, serum intestinal fatty-acid binding protein, and diamine oxidase. Inflammation was assessed by assaying serum Interleukins (IL-6, IL-8, IL-10), and tumour necrosis factor-α. Dysbiosis was assessed by the urinary concentrations of indole and skatole and serum lipopolysaccharide (LPS). All data were analysed using a non-parametric test. Results The GI symptoms profiles were significantly more severe, both as a single symptom and as clusters of IBS-SSS and GSRS, in HS than LS patients. This finding was associated with impaired small intestinal permeability and increased faecal zonulin levels. Besides, HS patients showed significantly higher IL-8 and lowered IL-10 concentrations than LS patients. Lastly, circulating LPS levels and the urinary concentrations of indole were higher in HS than LS ones, suggesting a more pronounced imbalance of the small intestine in the former patients. Conclusions IBS is a multifactorial disorder needing complete clinical, psychological, and biochemical evaluations. Trial registration: https://clinicaltrials.gov/ct2/show/NCT03423069.


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