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

Undseth,Ragnhild; Berstad,Arnold; Valeur,Jørgen

doi:10.3892/mmr.2016.5878

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

Authors:
- Ragnhild Undseth
- Arnold Berstad
- Jørgen Valeur
View Affiliations

Affiliations: Department of Radiology, Lovisenberg Diaconal Hospital, NO‑0440 Oslo, Norway, Unger‑Vetlesen Institute, Lovisenberg Diaconal Hospital, NO‑0440 Oslo, Norway
Published online on: October 21, 2016 https://doi.org/10.3892/mmr.2016.5878
Pages: 5072-5076
Copyright: © Undseth et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

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.

View Figures

View References

1	Sperber AD and Dekel R: Irritable bowel syndrome and co-morbid gastrointestinal and extra-gastrointestinal functional syndromes. J Neurogastroenterol Motil. 16:113–119. 2010. View Article : Google Scholar : PubMed/NCBI
2	Berstad A, Undseth R, Lind R and Valeur J: Functional bowel symptoms, fibromyalgia and fatigue: A food-induced triad? Scand J Gastroenterol. 47:914–919. 2012. View Article : Google Scholar : PubMed/NCBI
3	Vandvik PO, Lydersen S and Farup PG: Prevalence, comorbidity and impact of irritable bowel syndrome in Norway. Scand J Gastroenterol. 41:650–656. 2006. View Article : Google Scholar : PubMed/NCBI
4	Kim SE and Chang L: Overlap between functional GI disorders and other functional syndromes: What are the underlying mechanisms? Neurogastroenterol Motil. 24:895–913. 2012. View Article : Google Scholar : PubMed/NCBI
5	Valeur J, Morken MH, Norin E, Midtvedt T and Berstad A: Carbohydrate intolerance in patients with self-reported food hypersensitivity: Comparison of lactulose and glucose. Scand J Gastroenterol. 44:1416–1423. 2009. View Article : Google Scholar : PubMed/NCBI
6	Undseth R, Berstad A, Kløw NE, Arnljot K, Moi KS and Valeur J: Abnormal accumulation of intestinal fluid following ingestion of an unabsorbable carbohydrate in patients with irritable bowel syndrome: An MRI study. Neurogastroenterol Motil. 26:1686–1693. 2014. View Article : Google Scholar : PubMed/NCBI
7	Le Nevé B, Posserud I, Böhn L, Guyonnet D, Rondeau P, Tillisch K, Naliboff B, Mayer EA and Simrén M: A combined nutrient and lactulose challenge test allows symptom-based clustering of patients with irritable bowel syndrome. Am J Gastroenterol. 108:786–795. 2013. View Article : Google Scholar : PubMed/NCBI
8	Le Nevé B, Brazeilles R, Derrien M, Tap J, Guyonnet D, Ohman L, Törnblom H and Simrén M: Lactulose challenge determines visceral sensitivity and severity of symptoms in patients with irritable bowel syndrome. Clin Gastroenterol Hepatol. 14:226-233.e1–e3. 2016.
9	Ohman L and Simrén M: Pathogenesis of IBS: Role of inflammation, immunity and neuroimmune interactions. Nat Rev Gastroenterol Hepatol. 7:163–173. 2010. View Article : Google Scholar : PubMed/NCBI
10	Wilcz-Villega E, McClean S and O'Sullivan M: Reduced E-cadherin expression is associated with abdominal pain and symptom duration in a study of alternating and diarrhea predominant IBS. Neurogastroenterol Motil. 26:316–325. 2014. View Article : Google Scholar : PubMed/NCBI
11	Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F and Spiller RC: Functional bowel disorders. Gastroenterology. 130:1480–1491. 2006. View Article : Google Scholar : PubMed/NCBI
12	Francis CY, Morris J and Whorwell PJ: The irritable bowel severity scoring system: A simple method of monitoring irritable bowel syndrome and its progress. Aliment Pharmacol Ther. 11:395–402. 1997. View Article : Google Scholar : PubMed/NCBI
13	Fisk JD, Ritvo PG, Ross L, Haase DA, Marrie TJ and Schlech WF: Measuring the functional impact of fatigue: Initial validation of the fatigue impact scale. Clin Infect Dis. 18:(Suppl 1). S79–S83. 1994. View Article : Google Scholar : PubMed/NCBI
14	Aaron LA, Burke MM and Buchwald D: Overlapping conditions among patients with chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder. Arch Intern Med. 160:221–227. 2000. View Article : Google Scholar : PubMed/NCBI
15	Trøseid M, Nowak P, Nyström J, Lindkvist A, Abdurahman S and Sonnerborg A: Elevated plasma levels of lipopolysaccharide and high mobility group box-1 protein are associated with high viral load in HIV-1 infection: Reduction by 2-year antiretroviral therapy. AIDS. 24:1733–1737. 2010. View Article : Google Scholar : PubMed/NCBI
16	Gajda AM and Storch J: Enterocyte fatty acid-binding proteins (FABPs): Different functions of liver and intestinal FABPs in the intestine. Prostaglandins Leukot Essent Fatty Acids. 93:9–16. 2015. View Article : Google Scholar : PubMed/NCBI
17	Sacchettini JC, Hauft SM, Van Camp SL, Cistola DP and Gordon JI: Developmental and structural studies of an intracellular lipid binding protein expressed in the ileal epithelium. J Biol Chem. 265:19199–19207. 1990.PubMed/NCBI
18	Bottasso Arias NM, García M, Bondar C, Guzman L, Redondo A, Chopita N, Córsico B and Chirdo FG: Expression pattern of fatty acid binding proteins in celiac disease Enteropathy. Mediators Inflamm. 2015:7385632015.PubMed/NCBI
19	Bingold TM, Franck K, Holzer K, Zacharowski K, Bechstein WO, Wissing H and Scheller B: Intestinal fatty acid binding protein: A sensitive marker in abdominal surgery and abdominal infection. Surg Infect (Larchmt). 16:247–253. 2015. View Article : Google Scholar : PubMed/NCBI
20	González-Castro AM, Martínez C, Salvo-Romero E, Fortea M, Pardo-Camacho C, Pérez-Berezo T, Alonso-Cotoner C, Santos J and Vicario M: Mucosal pathobiology and molecular signature of epithelial barrier dysfunction in the small intestine in Irritable Bowel Syndrome. J Gastroenterol Hepatol. 18–Apr;2016.(Epub ahead of print). View Article : Google Scholar
21	Arslan G, Kahrs GE, Lind R, Frøyland L, Florvaag E and Berstad A: Patients with subjective food hypersensitivity: The value of analyzing intestinal permeability and inflammation markers in gut lavage fluid. Digestion. 70:26–35. 2004. View Article : Google Scholar : PubMed/NCBI
22	Berstad A, Arslan G and Folvik G: Relationship between intestinal permeability and calprotectin concentration in gut lavage fluid. Scand J Gastroenterol. 35:64–69. 2000. View Article : Google Scholar : PubMed/NCBI
23	Lau E, Marques C, Pestana D, Santoalha M, Carvalho D, Freitas P and Calhau C: The role of I-FABP as a biomarker of intestinal barrier dysfunction driven by gut microbiota changes in obesity. Nutr Metab (Lond). 13:312016. View Article : Google Scholar : PubMed/NCBI
24	Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, et al: Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 56:1761–1772. 2007. View Article : Google Scholar : PubMed/NCBI
25	Layé S, Parnet P, Goujon E and Dantzer R: Peripheral administration of lipopolysaccharide induces the expression of cytokine transcripts in the brain and pituitary of mice. Brain Res Mol Brain Res. 27:157–162. 1994. View Article : Google Scholar : PubMed/NCBI
26	Dlugosz A, Nowak P, D'Amato M, Mohammadian KG, Nyström J, Abdurahman S and Lindberg G: Increased serum levels of lipopolysaccharide and antiflagellin antibodies in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol Motil. 27:1747–1754. 2015. View Article : Google Scholar : PubMed/NCBI
27	Maes M, Mihaylova I and Leunis JC: Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): Indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J Affect Disord. 99:237–240. 2007. View Article : Google Scholar : PubMed/NCBI
28	Han CJ and Yang GS: Fatigue in irritable bowel syndrome: A systematic review and meta-analysis of pooled frequency and severity of Fatigue. Asian Nurs Res (Korean Soc Nurs Sci). 10:1–10. 2016. View Article : Google Scholar : PubMed/NCBI
29	Tülübaş F, Oran M, Mete R, Turan F, Yilmaz A, Yildiz ZD and Gürel A: Investigation of serum macrophage migration inhibitor factor and monocyte chemotactic protein-1 levels in irritable bowel syndrome. Turk J Med Sci. 44:967–971. 2014. View Article : Google Scholar : PubMed/NCBI