Resilience and stability of the CF- intestinal and respiratory microbiome during nutritional and exercise intervention.

BACKGROUND: Impaired respiratory and intestinal microbiome composition is linked to cystic fibrosis lung disease severity. In people with cystic fibrosis (pwCF), regular exercise is recommended to delay disease progression and preserve a stable lung function. An optimal nutritional status is vital for best clinical outcomes. Our study investigated whether regular and monitored exercise and nutritional support promotes CF microbiome health. METHODS: A personalized nutrition and exercise program promoted nutritional intake and physical fitness in 18 pwCF for 12 months. Throughout the study, patients performed strength and endurance training monitored by a sports scientist via an internet platform. After three months, food supplementation with Lactobacillus rhamnosus LGG was introduced. Nutritional status and physical fitness were assessed before the study started, after three and nine months. Sputum and stool were collected, and microbial composition was analyzed by 16S rRNA gene sequencing. RESULTS: Sputum and stool microbiome composition remained stable and highly specific to each patient during the study period. Disease-associated pathogens dominated sputum composition. Lung disease severity and recent antibiotic treatment had the highest impact on taxonomic composition in stool and sputum microbiome. Strikingly, the long-term antibiotic treatment burden had only a minor influence. CONCLUSION: Despite the exercise and nutritional intervention, respiratory and intestinal microbiomes proved to be resilient. Dominant pathogens drove the composition and functionality of the microbiome. Further studies are required to understand which therapy could destabilize the dominant disease-associated microbial composition of pwCF.

Feasibility and implementation of a personalized, web-based exercise intervention for people with cystic fibrosis for 1 year.

BACKGROUND: Regular participation in exercise is important for people with cystic fibrosis (CF). Therefore, we implemented a personalized, web-based exercise intervention over the course of one year for people with CF. The aims were to investigate the feasibility of the intervention and to evaluate changes in exercise participation, lung function, and exercise capacity. METHODS: In total, 11/17 participants [aged 12-52 years; FEV1%pred. 72.3 (SD: 17.3)] were included in the final data analysis. Every week, the participants received an individual training recommendation at the start and uploaded their training report on our website at the end of each week. The number of training minutes and sessions performed were analyzed over 13 four-week training sections. The participation in exercise (physical activity questionnaire), lung function and exercise capacity were assessed at baseline (T0), after 12 weeks (T1) and after 52 weeks (T2). RESULTS: A training duration of 178 min (SD: 75.5) and 3.3 (SD: 0.89) training sessions could be achieved weekly. In the first four-week training section, the participants performed 137.31 (SD: 95.7) minutes of training, with an increase of 42% in the third training section (195.01, SD: 134.99). Minutes of training reported on the questionnaire increased by 39.7% from T0 (179.38 min, SD: 120.9) to T1 (250.63 min, SD: 124.1) but decreased at T2 (166.88, SD: 155.4). There were slight decreases in lung function (FEV1 - 3.9%pred.; FVC - 1.9%pred.) and slight increases in exercise capacity (VO2peak + 1.5 ml/min/kg; six-minute-walk-test-distance + 26 m). Noticeably, five participants experienced deteriorations in their FEV1 of more than 5% but simultaneously experienced improvements in the parameters of exercise capacity of more than 5% throughout the year. CONCLUSIONS: The web-based concept was feasible for the participants over the course of a year and supported exercise participation. The improvement in exercise capacity due to increased exercise participation over a prolonged period of time, despite a decrease in lung function, should be further investigated. Finally, if integrated into usual care, this approach could facilitate the prescription of regular personalized exercise and promote exercise participation in the daily lives of people with CF.

Patterns of mucosal inflammation in pediatric inflammatory bowel disease: striking overexpression of IL-17A in children with ulcerative colitis.

BACKGROUND: Aberrant immune responses play a key role in the pathogenesis of inflammatory bowel disease (IBD). Most studies conducted to delineate the underlying molecular mechanisms focus on adults; an understanding of these mechanisms in children remains to be determined. Here, cytokines and transcription factors produced by immune cells within the intestinal mucosa of pediatric patients stricken with ulcerative colitis (UC) and Crohn's disease (CD) are characterized; potential diagnostic and therapeutic targets are identified. METHODS: Fifty-two pediatric IBD and non-IBD patients were enrolled in the study. Specimens were taken during ileocolonoscopy. Expression of 16 genes that encode cytokines or transcription molecules was determined by quantitative polymerase chain reaction. Clinical data were collected via retrospective chart review. RESULTS: Overexpression of interleukin-17A (IL-17A) was evident in children with UC compared to both non-IBD and CD patients. IL-22 was strongly increased in UC patients only. Typical proinflammatory and immunoregulatory cytokines were pronounced in IBD patients, although to a lower extent in the latter case. Clustered gene expression enabled differentiation between UC and non-IBD patients. CONCLUSION: Our findings highlight the crucial involvement of IL-17A immunity in the early course of IBD, particularly UC, and the potential value of gene panels in diagnosing pediatric IBD.