Background and AimsUlcerative colitis (UC) is associated with increased dietary intake of fat and n-6 polyunsaturated fatty acids (PUFA). Modification of fat metabolism may alter inflammation and disease severity. Our aim was to assess differences in dietary and serum fatty acid levels between control and UC subjects and associations with disease activity and inflammatory cytokines.MethodsDietary histories, serum, and colonic tissue samples were prospectively collected from 137 UC subjects and 38 controls. Both histologic injury and the Mayo Disease Activity Index were assessed. Serum and tissue cytokines were measured by Luminex assay. Serum fatty acids were obtained by gas chromatography.ResultsUC subjects had increased total fat and oleic acid (OA) intake, but decreased arachidonic acid (AA) intake vs controls. In serum, there was less percent saturated fatty acid (SFA) and AA, with higher monounsaturated fatty acids (MUFA), linoleic acid, OA, eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA) in UC. Tissue cytokine levels were directly correlated with SFA and inversely correlated with PUFA, EPA, and DPA in UC subjects, but not controls. 5-aminosalicylic acid therapy blunted these associations.ConclusionsIn summary, we found differences in serum fatty acids in UC subjects that correlated with pro-inflammatory tissue cytokines. We propose that fatty acids may affect cytokine production and thus be immunomodulatory in UC.

Aim There is limited information on the nutrition impact of antitumor necrosis factor-α treatment in adult Crohn's disease (CD). This study was performed to examine the effect of a 6-month course of infliximab on enterocyte function, nutrient status, metabolism, and body composition in these patients. Methods Seven CD patients were assessed for disease activity, enterocyte function, and body composition prior to, after 6 weeks, and after 6 months of infliximab treatment. Measurements included (1) disease activity: Inflammatory Bowel Disease Questionnaire, Harvey Bradshaw Index, and C-reactive protein; (2) enterocyte function: folate, homocysteine, vitamin B12, citrulline, vitamin D, β-carotene, d-xylose absorption; (3) Prognostic Inflammatory and Nutritional Index (PINI); and (4) body composition and metabolism: body mass index (BMI), fat and lean body mass, resting energy expenditure (RRE), and respiratory quotient. Results Most patients had improvement in disease activity with infliximab. PINI decreased in all patients (–3.35, P = .04). Plasma folate concentration significantly increased. There was an increase in BMI, fat mass, and lean body mass. The respiratory quotient increased in most patients. Changes in citrulline level and REE were inconsistent. Conclusions Crohn's disease patients have improvements in an index that measures both inflammation and nutrition (PINI) with infliximab therapy. Increases in plasma folate suggest improvement in enterocyte function and/or increased oral intake. The increase in respiratory quotient suggests decreased lipolysis and the lack of a starvation state. It was unclear whether weight gain was predominantly fat or lean muscle mass. These finding also support the use of PINI in Crohn's patients as an overall marker of inflammation and nutrition, and as a measure of response to infliximab therapy.

Airway inflammation and pulmonary disease are heterogeneous phenotypes in cystic fibrosis (CF) patients, even among patients with the same cystic fibrosis transmembrane conductance regulator (CFTR) genotype. Endothelin, a proinflammatory peptide and smooth muscle agonist, is increased in CF airways, potentially contributing to the pulmonary phenotype. Four cohorts of CF patients were screened for variants in endothelin pathway genes to determine whether any of these variants associated with pulmonary function. An initial cohort of 808 CF patients homozygous for the common CF mutation, DeltaF508, showed significant association for polymorphisms in the endothelin receptor A gene, EDNRA (P = 0.04), but not in the related endothelin genes (EDN1, EDN2, EDN3, or EDNRB) or NOS1, NOS2A, or NOS3. Variants within EDNRA were examined in three additional cohorts of CF patients, 238 patients from Seattle, WA, 303 from Ireland and the U.K., and 228 from Cleveland, OH, for a total of 1,577 CF patients. The three additional groups each demonstrated a significant association between EDNRA 3'-untranslated region (UTR) variant rs5335 and pulmonary function (P = 0.002). At the molecular level, single nucleotide primer extension assays suggest that the effect of the variants is quantitative. EDNRA mRNA levels from cultured primary tracheal smooth muscle cells are greater for the allele that appears to be deleterious to lung function than for the protective allele, suggesting a mechanism by which increased receptor function is harmful to the CF airway. Finally, cell proliferation studies using human airway smooth muscle cells demonstrated that cells homozygous for the deleterious allele proliferate at a faster rate than those homozygous for the protective allele.

In this placebo-controlled, pilot study, L. reuteri twice daily for 4 weeks significantly decreased AAD among hospitalized adults. L. reuteri was safe and well tolerated.