Adipose Tissue-Derived Biomarkers of Intestinal Barrier Functions for the Characterization of Diarrhoea-Predominant IBS

BACKGROUND: Alterations of the small-intestinal permeability (s-IP) might play an essential role in a subgroup of diarrhoea-predominant IBS (D-IBS) patients. GOALS: (a) To analyse in D-IBS patients the symptom profile in relation to the altered (+) or not (−) s-IP using the Gastrointestinal Symptom Rating Scale (GSRS). (b) To assess the circulating levels of the adipokines IL-6, IL-8, TNF-α, leptin, and adiponectin, along with LPS, TLR-4, neurotensin, and brain-derived neurotrophic factor (BDNF). The frequency distribution of SNPs at the loci for the investigated molecules and leptin receptor was evaluated. STUDY: The study included 34 D-IBS patients and 17 healthy controls (HC). s-IP permeability was assayed by high-performance liquid chromatography determination in the urine of the lactulose to mannitol ratio. Concentrations of IL-6, IL-8, TNF-α, LPS, TLR-4, leptin, adiponectin, neurotensin, and BDNF were assayed by ELISA. Screening of genetic variants was done employing the restriction fragment length polymorphism-polymerase chain reaction method. RESULTS: D-IBS(−) patients had a significantly higher GSRS cluster pain and diarrhoea profile than D-IBS(+) ones. Significant correlations were found between the symptoms clusters and immune activation and inflammation markers. The levels of adipo(cyto)kines in D-IBS(+) patients were higher than those of controls, and IL-6 levels correlated with those of LPS. Leptin and BDNF were significantly higher, and neurotensin levels were significantly lower in D-IBS(+) than in controls. No differences were found in the frequency distribution of genotypes among the study groups. CONCLUSIONS: Results from this study could be of some help in the characterization of the D-IBS and highlight the contribution of an altered intestinal barrier in the pathogenesis of this syndrome. Besides, a role could be ascribed to molecules secreted by the visceral adipose tissue that can impact on barrier functions.