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      A role for the gut microbiota in IBS.

      Nature reviews. Gastroenterology & hepatology
      Animals, Anti-Bacterial Agents, pharmacology, therapeutic use, Behavior, physiology, Brain, Colon, microbiology, Dietary Carbohydrates, Dietary Fats, Fermentation, Humans, Infection, Intestine, Small, Intestines, Irritable Bowel Syndrome, immunology, physiopathology, therapy, Prebiotics, Probiotics, Stress, Psychological

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          Abstract

          The past decade has witnessed an explosion of knowledge regarding the vast microbial community that resides within our intestine-the gut microbiota. The topic has generated great expectations in terms of gaining a better understanding of disorders ranging from IBD to metabolic disorders and obesity. IBS is a condition for which investigators have long been in search of plausible underlying pathogeneses and it is inevitable that altered composition or function of the gut microbiota will be considered as a potential aetiological factor in at least a subset of patients with IBS. This Review describes the evidence implicating the gut microbiota in not only the expression of the intestinal manifestations of IBS, but also the psychiatric morbidity that coexists in up to 80% of patients with IBS. The evidence described herein ranges from proof-of-concept studies in animals to observational studies and clinical trials in humans. The gut microbiota is subject to influences from a diverse range of factors including diet, antibiotic usage, infection and stress. These factors have previously been implicated in the pathophysiology of IBS and further prompt consideration of a role for the gut microbiota in IBS.

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          Most cited references81

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          Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome.

          The mechanisms underlying abdominal pain perception in irritable bowel syndrome (IBS) are poorly understood. Intestinal mast cell infiltration may perturb nerve function leading to symptom perception. We assessed colonic mast cell infiltration, mediator release, and spatial interactions with mucosal innervation and their correlation with abdominal pain in IBS patients. IBS patients were diagnosed according to Rome II criteria and abdominal pain quantified according to a validated questionnaire. Colonic mucosal mast cells were identified immunohistochemically and quantified with a computer-assisted counting method. Mast cell tryptase and histamine release were analyzed immunoenzymatically. Intestinal nerve to mast cell distance was assessed with electron microscopy. Thirty-four out of 44 IBS patients (77%) showed an increased area of mucosa occupied by mast cells as compared with controls (9.2% +/- 2.5% vs. 3.3 +/- 0.8%, respectively; P < 0.001). There was a 150% increase in the number of degranulating mast cells (4.76 +/- 3.18/field vs. 2.42 +/- 2.26/field, respectively; P = 0.026). Mucosal content of tryptase was increased in IBS and mast cells spontaneously released more tryptase (3.22 +/- 3.48 pmol/min/mg vs. 0.87 +/- 0.65 pmol/min/mg, respectively; P = 0.015) and histamine (339.7 +/- 59.0 ng/g vs. 169.3 +/- 130.6 ng/g, respectively; P = 0.015). Mast cells located within 5 microm of nerve fibers were 7.14 +/- 3.87/field vs. 2.27 +/- 1.63/field in IBS vs. controls (P < 0.001). Only mast cells in close proximity to nerves were significantly correlated with severity and frequency of abdominal pain/discomfort (P < 0.001 and P = 0.003, respectively). Colonic mast cell infiltration and mediator release in proximity to mucosal innervation may contribute to abdominal pain perception in IBS patients.
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            Shifting the balance: antibiotic effects on host-microbiota mutualism.

            Antibiotics have been used effectively as a means to treat bacterial infections in humans and animals for over half a century. However, through their use, lasting alterations are being made to a mutualistic relationship that has taken millennia to evolve: the relationship between the host and its microbiota. Host-microbiota interactions are dynamic; therefore, changes in the microbiota as a consequence of antibiotic treatment can result in the dysregulation of host immune homeostasis and an increased susceptibility to disease. A better understanding of both the changes in the microbiota as a result of antibiotic treatment and the consequential changes in host immune homeostasis is imperative, so that these effects can be mitigated.
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              Innate immune recognition of the microbiota promotes host-microbial symbiosis.

              Pattern-recognition receptors (PRRs) are traditionally known to sense microbial molecules during infection to initiate inflammatory responses. However, ligands for PRRs are not exclusive to pathogens and are abundantly produced by the resident microbiota during normal colonization. Mechanism(s) that underlie this paradox have remained unclear. Recent studies reveal that gut bacterial ligands from the microbiota signal through PRRs to promote development of host tissue and the immune system, and protection from disease. Evidence from both invertebrate and vertebrate models reveals that innate immune receptors are required to promote long-term colonization by the microbiota. This emerging perspective challenges current models in immunology and suggests that PRRs may have evolved, in part, to mediate the bidirectional cross-talk between microbial symbionts and their hosts.
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