Assessment of Intestinal Permeability and Inflammation Bio-Markers in Patients with Rheumatoid Arthritis.

Increased intestinal permeability and inflammation, both fueled by dysbiosis, appear to contribute to rheumatoid arthritis (RA) pathogenesis. This single-center pilot study aimed to investigate zonulin, a marker of intestinal permeability, and calprotectin, a marker of intestinal inflammation, measured in serum and fecal samples of RA patients using commercially available kits. We also analyzed plasma lipopolysaccharide (LPS) levels, a marker of intestinal permeability and inflammation. Furthermore, univariate, and multivariate regression analyses were carried out to determine whether or not there were associations of zonulin and calprotectin with LPS, BMI, gender, age, RA-specific parameters, fiber intake, and short-chain fatty acids in the gut. Serum zonulin levels were more likely to be abnormal with a longer disease duration and fecal zonulin levels were inversely associated with age. A strong association between fecal and serum calprotectin and between fecal calprotectin and LPS were found in males, but not in females, independent of other biomarkers, suggesting that fecal calprotectin may be a more specific biomarker than serum calprotectin is of intestinal inflammation in RA. Since this was a proof-of-principle study without a healthy control group, further research is needed to validate fecal and serum zonulin as valid biomarkers of RA in comparison with other promising biomarkers.

Different pattern of stool and plasma gastrointestinal damage biomarkers during primary and chronic HIV infection.

INTRODUCTION: Primary HIV infection (PHI) is the initial phase after HIV acquisition characterized by high viral replication, massive inflammatory response and irreversible immune-damage, particularly at the gastrointestinal level. In this study we aimed to characterize the dynamics of gastrointestinal damage biomarkers during the different phases of HIV infection and assess their association with HIV-disease markers and their accuracy to differentiate PHI from chronic HIV infection (CHI). METHODS: PHI-individuals (n = 57) were identified as HIV-seronegative/HIV-RNA positive and were followed up for one year at the Manhiça District Hospital in Mozambique. Ten plasma and 12 stool biomarkers were quantified by Luminex or ELISA and levels were compared to CHI-naive (n = 26), CHI on antiretroviral-treatment (ART; n = 30) and HIV-uninfected individuals (n = 58). Regression models adjusted by time point were used to estimate the association of the biomarkers with HIV-disease markers. Receiver operating curves were compared for the best accuracy to distinguish PHI from CHI. RESULTS: Soluble (s)CD14 was significantly associated with the CD4/CD8 ratio (P < 0.05) and viremia levels (P < 0.0001) during PHI. Plasma zonulin and stool lactoferrin were significantly higher in PHI as compared to CHI-individuals (P < 0.05). Plasma zonulin demonstrated the best accuracy to identify PHI among HIV-infected individuals (AUC = 0.85 [95% CI 0.75-0.94]). Using a cutoff value of plasma zonulin ≥ 8.75 ng/mL the model identified PHI with 87.7% sensitivity (95% CI 76.3-94.9) and 69.2% specificity (95% CI 48.2-85.7). An adjusted multivariate model including age, plasma zonulin and sCD14 further increased the classification performance (AUC = 0.92 [95% CI 0.86-0.99]). CONCLUSIONS: While the stool biomarkers did not provide any predictive ability to distinguish PHI from CHI-individuals, plasma sCD14 and zonulin were significantly associated with HIV-disease markers and PHI identification, respectively. These inflammatory biomarkers may be useful to monitor changes in gastrointestinal integrity during HIV infection.

Changes of Intestinal Microflora in Patients with Rheumatoid Arthritis during Fasting or a Mediterranean Diet.

BACKGROUND: therapeutic dietary interventions are effective treatments for rheumatoid arthritis (RA). The mechanisms to affect inflammation and clinical outcome in rheumatoid arthritis are only partly understood. Alterations in intestinal microflora are believed to be associated with disease activity in RA. AIM: to evaluate changes in short-chain fatty acid (SCFA) profiles and clinical outcome in RA during medical fasting or mediterranean diet. METHODS: Fifty consecutive in-patients from an Integrative Medicine Department were included in a prospective observational, non-randomised, clinical trial. Patients underwent a 7-day fasting (MF) therapy or a Mediterranean diet (MD) as part of a multimodal therapeutic treatment approach. RESULTS: the mean Disease Activity Score (DAS-28) significantly decreased in both groups (p < 0.001) from 5.7 ± 0.9 to 4.1 ± 1.3 in the MF and from 5.4 ± 1.4 to 4.5 ± 1.3 in the MG group, with no significant difference between the groups (p = 0.115). VAS showed a consecutive decrease of pain in both study groups which was significantly higher in the fasting group on day 7 (p = 0.049). No significant differences between the study groups were found in the profile of total-fatty acids (p = 0.069), butyrate (p = 0.611) and propionate (p = 0.419). Measurement of acetate, however, showed significant differences (p = 0.044) with an increase from 17,4 ± 9.8 µmol/g to 21,4 ± 16.4 µmol/g in MF compared to a decrease from 15,2 ± 10.4 µmol/g to 13,8 ± 9.3 µmol/g in MD. There was no significant correlation between dietary induced changes of SCFA and changes of disease activity. CONCLUSION: alterations in SCFA were found in terms of significant changes to increased acetate levels in the fasting group. A correlation between changes of SCFA from intestinal microflora and disease activity in RA could not be revealed. Further studies are needed in the field of dietary inducible changes of the intestinal microflora in patients with RA.