Immune activation in irritable bowel syndrome: what is the evidence?

Aguilera‐Lizarraga, Javier; Hussein, Hind; Boeckxstaens, Guy E.

doi:10.1038/s41577-022-00700-9

Cited by 54 publications

(39 citation statements)

References 149 publications

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“…Increased levels of NGF, produced by mast cells, increase nerve fibre density. Along the same line, increased nerve sprouting was also observed with increased levels of brain-derived neurotrophic factor 51…”

Section: Update On Pathophysiology Of Ibs and Its Diagnosismentioning

confidence: 73%

“…Other studies explored the efficacy of the anti-inflammatory 5-aminosalicylcic acid compounds in the treatment of IBS, without evidence of clinical benefit 49 50. Nevertheless, current evidence suggesting that immune activation contributes to the pathology seen in patients with IBS has been summarised elsewhere51 including the role of mast cells.…”

Section: Update On Pathophysiology Of Ibs and Its Diagnosismentioning

confidence: 99%

“…The biochemical mechanisms have been reviewed recently with particular emphasis on how immune mediators, particularly those released by mast cells, can directly activate or sensitise pain-transmitting nerves, leading to increased pain signalling and abdominal pain 51. The putative mechanisms include several mechanisms involved in visceral hypersensitivity such as histamine, serotonin, proteases and nerve growth factor (NGF), all of which have been demonstrated in mucosa of patients with IBS, as reviewed by Aguilera-Lizarraga et al 51. Thus, histamine acts on histamine H1 receptors to sensitise TRPV1, TRPA1 and TRPV4 channels via H1R.…”

Section: Update On Pathophysiology Of Ibs and Its Diagnosismentioning

confidence: 99%

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Irritable bowel syndrome: treatment based on pathophysiology and biomarkers

Camilleri

Boeckxstaens

2022

Gut

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ObjectiveTo appraise the evidence that pathophysiological mechanisms and individualised treatment directed at those mechanisms provide an alternative approach to the treatment of patients with irritable bowel syndrome (IBS).DesignA PubMED-based literature review of mechanisms and treatment of IBS was conducted independently by the two authors, and any differences of perspective or interpretation of the literature were resolved following discussion.ResultsThe availability of several noninvasive clinical tests can appraise the mechanisms responsible for symptom generation in IBS, including rectal evacuation disorders, abnormal transit, visceral hypersensitivity or hypervigilance, bile acid diarrhoea, sugar intolerances, barrier dysfunction, the microbiome, immune activation and chemicals released by the latter mechanism. The basic molecular mechanisms contributing to these pathophysiologies are increasingly recognised, offering opportunities to intervene with medications directed specifically to food components, receptors and potentially the microbiome. Although the evidence supporting interventions for each mechanism is not at the same level of proof, the current state-of-the-art provides the opportunity to advance the practice from treatment based on symptoms to individualisation of treatment guided by pathophysiology and clinically identified biomarkers.ConclusionThese advances augur well for the implementation of evidence-based individualised treatment for patients with IBS based on actionable biomarkers or psychological disturbances.

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Section: Update On Pathophysiology Of Ibs and Its Diagnosismentioning

confidence: 73%

Section: Update On Pathophysiology Of Ibs and Its Diagnosismentioning

confidence: 99%

Section: Update On Pathophysiology Of Ibs and Its Diagnosismentioning

confidence: 99%

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Irritable bowel syndrome: treatment based on pathophysiology and biomarkers

Camilleri

Boeckxstaens

2022

Gut

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“…Studies of microbiota-host and food-microbiota-host interactions suggest that the concept of IBS as a subtle variant of IBD has been far too simplistic and suggest that more subtle interactions between microbes, their metabolites, the mucosal immune system and the enteric neuromuscular apparatus may be operative. [6][7][8][9][10] To whom these apply and how these can be successfully rectified remain to be seen.…”

Section: N V I T E D E D I T O R I a Lmentioning

confidence: 99%

Editorial: 5‐aminosalicylic acid fails to impact on irritable bowel syndrome—wrong population, intervention, target or hypothesis?

Quigley

2022

Aliment Pharmacol Ther

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“…Previous studies have reported that increased MCs were associated with intestinal permeability and diarrhea (Aguilera-Lizarraga et al, 2022). Tryptase is an important marker of MCs; therefore, the effect of SNS on MC infiltration was assessed by the immunochemistry staining of tryptase.…”

Section: Sns Inhibited the Increase Of Mcs In The Ileum Tissue Induce...mentioning

confidence: 99%

Ameliorative effect and mechanism of Si-Ni-San on chronic stress-induced diarrhea-irritable bowel syndrome in rats

et al. 2022

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Background: Chronic stress-induced diarrhea is a common clinical condition, characterized by an abnormal bowel movement and loose stools, which lacks effective treatment in the clinic. Si-Ni-San (SNS) is a compound traditional Chinese medicine extensively used in China for stress-related diarrhea. However, the mechanism is unclear.Methods: Male Wistar rats (200 ± 20 g) were placed in a restraint cylinder and fixed horizontally for 3 h once daily for 21 consecutive days to establish a chronic restraint stress (CRS) rat model. SNS (0.6944 g/kg or 1.3888 g/kg) was given by gavage 1 h before the restraint once daily for 21 consecutive days. We examined the fecal score, dopamine β hydroxylase (DβH), and c-fos expression in locus coeruleus, norepinephrine (NE) content in ileum and plasma, expression of α1 adrenergic receptors, MLCK, MLC, and p-MLC in the colon and mesenteric arteries, contraction of isolated mesenteric arteries, The expression of subunit δ of ATP synthase (ATP5D) in intestinal tissues, ATP, ADP, and AMP content in the ileum and colon, occludin expression between ileum epithelial cells, the number of enterochromaffin cells (ECs) and mast cells (MCs) in the ileum, and 5-hydroxytryptamine (5-HT) content in the ileum and plasma.Results: After SNS treatment, the fecal score was improved. The increased expression of DβH and c-fos in locus coeruleus was inhibited. SNS suppressed the increased NE content in the ileum and plasma, down-regulated α1 adrenergic receptors in mesenteric arteries and MLCK, MLC, p-MLC in the colon and mesenteric arteries, and inhibited the contraction of mesenteric arteries. SNS also increased the ATP content in the ileum and colon, inhibited low expression of ATP5D in intestinal tissues, inhibited the decrease of ATP/ADP in the ileum and ATP/AMP in the colon, and up-regulated the occludin expression between ileum epithelial cells. In addition, SNS inhibited the increase of ECs and MCs in the ileum and the increase of 5-HT content in the ileum and plasma.Conclusion: This study demonstrated that SNS could improve CRS-induced abnormal feces in rats. This effect was related to the inhibition of CRS-induced increased expression of DβH and c-fos in the locus coeruleus, NE content in the ileum and plasma, and the contraction of isolated mesenteric arteries; inhibition of energy metabolism abnormality and decreased occludin expression; inhibition of increased ECs and MCs in the ileum, and 5-HT content in the ileum and plasma.

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Immune activation in irritable bowel syndrome: what is the evidence?

Cited by 54 publications

References 149 publications

Irritable bowel syndrome: treatment based on pathophysiology and biomarkers

Irritable bowel syndrome: treatment based on pathophysiology and biomarkers

Editorial: 5‐aminosalicylic acid fails to impact on irritable bowel syndrome—wrong population, intervention, target or hypothesis?

Ameliorative effect and mechanism of Si-Ni-San on chronic stress-induced diarrhea-irritable bowel syndrome in rats

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