Increased serum levels of lipopolysaccharide and antiflagellin antibodies in patients with diarrhea‐predominant irritable bowel syndrome

Dlugosz, Aldona; Nowak, Piotr; D’Amato, Mauro; Kermani, G. Mohammadian; Nyström, Jessica; Abdurahman, Samir; Lindberg, Greger

doi:10.1111/nmo.12670

Cited by 79 publications

(79 citation statements)

References 45 publications

(51 reference statements)

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“…Whether lactulose challenge may impair mucosal barrier function at a tight junction level, without causing ‘mucosal damage’ as measured by iFABP, remains unclear. Intravenous infusion of LPS in healthy volunteers triggers visceral hypersensitivity with characteristics similar to those observed in IBS patients (25), and elevated plasma levels of LPS were associated with IBS (IBS-D) in a recent study (26). A separate study demonstrated elevated serum immunoglobulin A against LPS in patients with fatigue (27), a condition often linked to IBS (28).…”

Section: Discussionmentioning

confidence: 81%

Systemic symptoms in irritable bowel syndrome: An investigative study on the role of enterocyte disintegrity, endotoxemia and inflammation

Undseth

Berstad

Valeur

2016

Molecular Medicine Reports

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Irritable bowel syndrome (IBS) is often accompanied by extra-intestinal symptoms, including fatigue and musculoskeletal pain. The present study aimed to investigate whether these symptoms were associated with markers of enterocyte disintegrity, endotoxemia and inflammation. Patients with IBS were recruited consecutively from our outpatient clinic (n=94) and compared with a group of healthy controls (n=20). Habitual symptoms were assessed using the IBS Severity Scoring System, the Fatigue Impact Scale and Visual Analogue Scales for measuring musculoskeletal pain. A lactulose challenge test was performed to induce post-prandial symptoms, and blood samples were obtained prior to and 90 min following lactulose ingestion to determine levels of intestinal fatty acid binding protein (iFABP), lipopolysaccharide (LPS), the LPS co-receptor soluble cluster of differentiation (sCD) 14, monocyte chemoattractant protein-1 (MCP-1) and calprotectin. Habitual symptom scores were high among the included patients, and lactulose ingestion induced significantly more symptoms in the patient group compared with the healthy control group (P=0.0001). Serum levels of iFABP were reduced in IBS patients compared with healthy controls, prior to and following lactulose ingestion (P=0.0002 and P=0.0001, respectively). Following lactulose ingestion, iFABP levels decreased in IBS patients (P=0.0001) and in healthy controls (P=0.02). Fasting levels of LPS, sCD14, MCP-1 and calprotectin were not significantly different between IBS patients and healthy controls. However, following lactulose ingestion, LPS levels increased in healthy controls (P=0.03), whereas MCP-1 levels decreased in IBS patients (P=0.008). Intestinal and extra-intestinal symptom severities were not correlated with levels of circulating biomarkers. No assessed biomarker in the present study appeared to be associated with symptom development in IBS patients. However, the implications of the low levels of iFABP observed require further investigation.

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Section: Discussionmentioning

confidence: 81%

Systemic symptoms in irritable bowel syndrome: An investigative study on the role of enterocyte disintegrity, endotoxemia and inflammation

Undseth

Berstad

Valeur

2016

Molecular Medicine Reports

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“…Evidence of bacterial translocation in IBS is also provided by higher peripheral levels of LPS as well as higher concentrations of anti-flagellin antibodies [86] . Moreover, Escherichia coli LPS-induced IL-6 secretion is elevated in IBS, indicating an enhanced response against Gram-negative bacteria in this disorder [82] .…”

Section: Gut Dysbiosis and Bacterial Translocation As A Link Between mentioning

confidence: 99%

Gut Microbiota, Bacterial Translocation, and Interactions with Diet: Pathophysiological Links between Major Depressive Disorder and Non-Communicable Medical Comorbidities

Slyepchenko

Maes

Jacka

et al. 2016

Psychother Psychosom

211

136

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Background: Persistent low-grade immune-inflammatory processes, oxidative and nitrosative stress (O&NS), and hypothalamic-pituitary-adrenal axis activation are integral to the pathophysiology of major depressive disorder (MDD). The microbiome, intestinal compositional changes, and resultant bacterial translocation add a new element to the bidirectional interactions of the gut-brain axis; new evidence implicates these pathways in the patho-aetiology of MDD. In addition, abnormalities in the gut-brain axis are associated with several chronic non-communicable disorders, which frequently co-occur in individuals with MDD, including but not limited to irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS), obesity, and type 2 diabetes mellitus (T2DM). Methods: We searched the PubMed/MEDLINE database up until May 1, 2016 for studies which investigated intestinal dysbiosis and bacterial translocation (the ‘leaky gut') in the pathophysiology of MDD and co-occurring somatic comorbidities with an emphasis on IBS, CFS, obesity, and T2DM. Results: The composition of the gut microbiota is influenced by several genetic and environmental factors (e.g. diet). Several lines of evidence indicate that gut-microbiota-diet interactions play a significant pathophysiological role in MDD and related medical comorbidities. Gut dysbiosis and the leaky gut may influence several pathways implicated in the biology of MDD, including but not limited to immune activation, O&NS, and neuroplasticity cascades. However, methodological inconsistencies and limitations limit comparisons across studies. Conclusions: Intestinal dysbiosis and the leaky gut may constitute a key pathophysiological link between MDD and its medical comorbidities. This emerging literature opens relevant preventative and therapeutic perspectives.

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“…Diarrhea, constipation and intestinal inflammation are the main symptoms of the patients with IBD and IBS [1112]. Clinical and epidemiological studies indicate that the inflammation is found from the jejunum to the rectum in both IBS and IBD [1314151617]. Diarrhea is the common symptoms of IBD; IBS may have constipation-predominant symptom or diarrhea-predominant symptom [181920].…”

Section: Introductionmentioning

confidence: 99%

Ameliorative effects of atractylodin on intestinal inflammation and co-occurring dysmotility in both constipation and diarrhea prominent rats

Xiong

Chen

et al. 2017

Korean J Physiol Pharmacol

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Intestinal disorders often co-occur with inflammation and dysmotility. However, drugs which simultaneously improve intestinal inflammation and co-occurring dysmotility are rarely reported. Atractylodin, a widely used herbal medicine, is used to treat digestive disorders. The present study was designed to characterize the effects of atractylodin on amelioration of both jejunal inflammation and the co-occurring dysmotility in both constipation-prominent (CP) and diarrhea-prominent (DP) rats. The results indicated that atractylodin reduced proinflammatory cytokines TNF-α, IL-1β, and IL-6 in the plasma and inhibited the expression of inflammatory mediators iNOS and NF-kappa B in jejunal segments in both CP and DP rats. The results indicated that atractylodin exerted stimulatory effects and inhibitory effects on the contractility of jejunal segments isolated from CP and DP rats respectively, showing a contractile-state-dependent regulation. Atractylodin-induced contractile-state-dependent regulation was also observed by using rat jejunal segments in low and high contractile states respectively (5 pairs of low/high contractile states). Atractylodin up-regulated the decreased phosphorylation of 20 kDa myosin light chain, protein contents of myosin light chain kinase (MLCK), and MLCK mRNA expression in jejunal segments of CP rats and down-regulated those increased parameters in DP rats. Taken together, atractylodin alleviated rat jejunal inflammation and exerted contractile-state-dependent regulation on the contractility of jejunal segments isolated from CP and DP rats respectively, suggesting the potential clinical implication for ameliorating intestinal inflammation and co-occurring dysmotility.

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Increased serum levels of lipopolysaccharide and antiflagellin antibodies in patients with diarrhea‐predominant irritable bowel syndrome

Abstract: Our results support the concept that immune reactivity to luminal antigens may have a role in the development of D-IBS. The serum level of antiflagellin antibodies was found to correlate with patients' self-reported anxiety score.

Cited by 79 publications

References 45 publications

Systemic symptoms in irritable bowel syndrome: An investigative study on the role of enterocyte disintegrity, endotoxemia and inflammation

Systemic symptoms in irritable bowel syndrome: An investigative study on the role of enterocyte disintegrity, endotoxemia and inflammation

Gut Microbiota, Bacterial Translocation, and Interactions with Diet: Pathophysiological Links between Major Depressive Disorder and Non-Communicable Medical Comorbidities

Ameliorative effects of atractylodin on intestinal inflammation and co-occurring dysmotility in both constipation and diarrhea prominent rats

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