Dr Bronwyn Berthon

Background: Chronic low-grade systemic inflammation is a characteristic of obesity that leads to various non-communicable diseases. Weight loss and SCFAs are potential strategies for attenuating obese systemic inflammation. Methods: Blood samples were collected from 43 obese subjects (BMI = 30 kg/m2) scheduled for laparoscopic bariatric sleeve surgery, 26 obese subjects at follow-up 12¿18 months post-surgery and 8 healthy weight subjects (BMI 18.5¿24.9 kg/m2). Mono-cytes were isolated from blood and adipose tissue macrophages from visceral adipose tissue of obese subjects only. Isolated cells stimulated with 1 ng/mL LPS and treated simultaneously with 300 mM of sodium acetate or 30 mM of sodium propionate or butyrate and supernatant were har-vested after 15 h incubation. TNF-a and IL-6 cytokines were measured via ELISA and mRNA gene expression of FFAR2 and FFAR3, HDAC1, HDAC2 and HDAC9, RELA and NFKB1 and MAPK1 via RT-qPCR. Results: TNF-a and IL-6 production and NFKB1 and RELA mRNA expression were significantly decreased in follow-up subjects compared to baseline. SCFAs significantly reduced TNF-a and IL-6 and altered FFAR and HDAC mRNA expression in monocytes and macrophages from obese subjects. Conclusion: Weight loss and ex vivo SCFA treatments were successful in combatting systemic inflammation in obesity. Results highlighted molecular changes that occur with weight loss and as a result of SCFA treatment.

Background: Soluble fibre modulates airway inflammation in animal models. The aim of this study was to investigate the effects of soluble fibre supplementation, with and without a probiotic, on plasma short chain fatty acids (SCFA), airway inflammation, asthma control and gut microbiome in adults with asthma. Methods: A randomised, double-blinded, placebo controlled 3-way cross-over trial in 17 subjects with stable asthma at the Hunter Medical Research Institute, Newcastle, Australia. Subjects received 3 × 7 day oral interventions in random order; soluble fibre (inulin 12 g/day), soluble fibre + probiotic (inulin 12 g/day + multi-strain probiotic >25 billion CFU) and placebo. Plasma SCFA, sputum cell counts and inflammatory gene expression, asthma control gut microbiota, adverse events including gastrointestinal symptoms were measured. Findings: There was no difference in change in total plasma SCFA levels (µmol/L) in the placebo versus soluble fibre (¿median [95% CI] 16·3 [-16·9, 49·5], p = 0·335) or soluble fibre+probiotic (18·7 [-14·5, 51·9], p = 0·325) group. Following the soluble fibre intervention there was an improvement in the asthma control questionnaire (ACQ6) (¿median (IQR) -0·35 (-0·5, -0·13), p = 0·006), sputum %eosinophils decreased (-1.0 (-2·5, 0), p = 0·006) and sputum histone deacetylase 9 (HDAC9) gene expression decreased (-0.49 (-0.83, -0.27) 2-¿Ct, p =.008). Individual bacterial operational taxonomic units changed following both inulin and inulin+probiotic arms. Interpretation: Soluble fibre supplementation for 7 days in adults with asthma did not change SCFA levels. Within group analysis showed improvements in airway inflammation, asthma control and gut microbiome composition following inulin supplementation and these changes warrant further investigation, in order to evaluate the potential of soluble fibre as a non-pharmacological addition to asthma management. Fund: John Hunter Hospital Charitable Trust.

Background: Prebiotic soluble fibers are fermented by beneficial bacteria in the colon to produce short-chain fatty acids (SCFAs), which are proposed to have systemic anti-inflammatory effects. Objective: This review examines the effect of SCFAs, prebiotics, and pre- and probiotic combinations (synbiotics) on systemic inflammation. Design: Relevant English language studies from 1947 to May 2017 were identified with the use of online databases. Studies were considered eligible if they examined the effects of SCFAs, prebiotics, or synbiotics; were delivered orally, intravenously, or per rectum; were on biomarkers of systemic inflammation in humans; and performed meta-analysis where possible. Results: Sixty-eight studies were included. Fourteen of 29 prebiotic studies and 13 of 26 synbiotic studies reported a significant decrease in =1 marker of systemic inflammation. Eight studies compared prebiotic and synbiotic supplementation, 2 of which reported a decrease in inflammation with synbiotics only, with 1 reporting a greater anti-inflammatory effect with synbiotics than with prebiotics alone. Meta-analyses indicated that prebiotics reduce C-reactive protein (CRP) [standardized mean difference (SMD): -0.60; 95% CI: -0.98, -0.23], and synbiotics reduce CRP (SMD: -0.40; 95% CI: -0.73, -0.06) and tumor necrosis factor-a (SMD -0.90; 95% CI: -1.50, -0.30). Conclusions: There is significant heterogeneity of outcomes in studies examining the effect of prebiotics and synbiotics on systemic inflammation. Approximately 50% of included studies reported a decrease in =1 inflammatory biomarker. The inconsistency in reported outcomes may be due to heterogeneity in study design, supplement formulation, dosage, duration, and subject population. Nonetheless, meta-analyses provide evidence to support the systemic anti-inflammatory effects of prebiotic and synbiotic supplementation.

Background: Oral corticosteroids (OCS) are an efficacious treatment for asthma exacerbations, yet risk of adverse effects may decrease patient adherence to therapy. In particular, changes in appetite and dietary intake, which lead to weight gain and changes in body composition, are considered undesirable. Objective: To determine whether 10-day OCS therapy in adults with asthma causes changes in leptin, appetite, dietary intake, body weight and body composition. Methods: Double-blinded, placebo-controlled randomized cross-over trial of 10 days prednisolone (50 mg) in adults with stable asthma (n = 55) (ACTRN12611000562976). Pre- and post-assessment included spirometry, body weight, body composition measured by dual-energy X-ray absorptiometry and bioelectrical impedance analysis, appetite measured using a validated visual analogue scale (VAS) and dietary intake assessed using 4-day food records. Leptin was measured as a biomarker of appetite and eosinophils as an adherence biomarker. Outcomes were analysed by generalized linear mixed models. Results: Subject adherence was confirmed by a significant decrease in blood eosinophils (× 109/L) following prednisolone compared to placebo [Coef. -0.29, 95% CI: (-0.39, -0.19) P < 0.001]. There was no difference in serum leptin (ng/mL) [Coef. 0.13, 95% CI: (-3.47, 3.72) P = 0.945] or appetite measured by VAS (mm) [Coef. -4.93, 95% CI: (-13.64, 3.79) P = 0.267] following prednisolone vs. placebo. There was no difference in dietary intake (kJ/day) [Coef. 255, 95% CI: (-380, 891) P = 0.431], body weight (kg) [Coef. -0.38, 95% CI: (-0.81, 0.05) P = 0.083] or body fat (%) [Coef. -0.31, 95% CI: (-0.81, 0.20) P = 0.230]. Symptoms including sleep and gastrointestinal disturbance were reported significantly more often during prednisolone vs. placebo. Conclusions and Clinical Relevance: Short-term OCS in stable asthma did not induce significant changes in appetite, dietary intake, body weight or composition, although other adverse effects may require medical management. This evidence may assist in increasing medication adherence of asthmatics prescribed OCS for exacerbations.

Background: Asthma prevalence has increased in recent years, and evidence suggests that diet may be a contributing factor. Increased use of processed foods has led to a decrease in diet quality, which may be creating a pro-inflammatory environment, thereby leading to the development and/or progression of various chronic inflammatory diseases and conditions. Recently, the dietary inflammatory index (DII) has been developed and validated to assess the inflammatory potential of individual diets. Objective: This study aimed to examine the DII in subjects with asthma compared to healthy controls and to relate the DII to asthma risk, lung function and systemic inflammation. Methods: Subjects with asthma (n = 99) and healthy controls (n = 61) were recruited. Blood was collected and spirometry was performed. The DII was calculated from food frequency questionnaires administered to study subjects. Results: The mean DII score for the asthmatics was higher than the mean DII score for healthy controls (- 1.40 vs. - 1.86, P = 0.04), indicating that their diets were more pro-inflammatory. For every 1 unit increase in DII score, the odds of having asthma increased by 70% (OR: 1.70, 95% CI: 1.03, 2.14; P = 0.040). FEV1 was significantly associated with DII score (ß = - 3.44, 95% CI: - 6.50, - 0.39; P = 0.020), indicating that for every 1 unit increase in DII score, FEV1 decreased by 3.44 times. Furthermore, plasma IL-6 concentrations were positively associated with DII score (ß = 0.13, 95% CI: 0.05, 0.21; P = 0.002). Conclusion and Clinical Relevance: As assessed using the DII score, the usual diet consumed by asthmatics in this study was pro-inflammatory relative to the diet consumed by the healthy controls. The DII score was associated with increased systemic inflammation and lower lung function. Hence, consumption of pro-inflammatory foods may contribute to worse asthma status, and targeting an improvement in DII in asthmatics, as an indicator of suitable dietary intake, might be a useful strategy for improving clinical outcomes in the disease.

Background: Recent studies have reported that asthma prevalence increases on migration to Australia. We hypothesised that changes in dietary intake contribute to this phenomenon. The aim of this study was to assess dietary intake in relation to migration status, length of stay in Australia and the association with self-reported wheeze. Methods: Students (n = 144) in a multicultural high school in Western Sydney completed the asthma symptoms ISAAC video questionnaire (AVQ3.0), spirometry and allergy skin prick tests. A dietitian administered a'Food Frequency' and 'Food Habits' questionnaire and a dietary history interview. Results: Students who spoke a language other than English, consumed a traditional or mixed dietary pattern, with lower consumption of saturated fat, compared to students who spoke English only. Saturated fat intake increased and fibre intake decreased with length of time in Australia. Intake of foods high in saturated or trans fatty acids were positively associated with length of stay in Australia. No associations between nutrient intake or whole food intake and self-reported wheeze were observed. Conclusion: As time progressed, dietary intake of immigrant children changed. While this was not associated with the development of wheeze in the students in this cohort, these changes are likely to have negative health consequences.