Reverse-engineered exclusive enteral nutrition in pediatric Crohn's disease: A pilot trial.

BACKGROUND: In pediatric Crohn's disease (CD), commercial formulas used as exclusive enteral nutrition (EEN) are effective at inducing remission. This study aims to assess the impact of a whole-food blended smoothie as EEN on CD activity and the intestinal microbiome. METHODS: A 4-week prospective trial assessed the impact of EEN with a whole-food smoothie on newly diagnosed mild-to-moderate active pediatric CD. The smoothie with a multivitamin were developed to meet age-appropriate nutritional requirements. Assessment over 4 weeks included Pediatric Crohn's Disease Activity Index (PCDAI), serum laboratories, fecal calprotectin (FCP), and stool collection for metagenomic shotgun sequencing and microbiota composition analysis. Clinical remission was defined as PCDAI ≤ 10 at week 4. RESULTS: Ten participants were enrolled with median age 14.5 years, and 8 completed the trial. Baseline mean PCDAI was 26.3 ± 9.1 and mean FCP 1149 ± 718 µg/g. At week 4, 80% of participants achieved clinical remission. FCP decreased by over half in 60% of participants, with FCP below 250 µg/g in 60% and below 100 µg/g in 40%. Microbiome analysis showed a significant increase in species richness over 4 weeks (p = 0.01). Compared to baseline, the relative abundance at week 2 and at week 4 was significantly increased for Bifidobacterium and Streptococcus and decreased for Blautia (p < 0.05 for all). CONCLUSION: A whole-food blended smoothie was effective for inducing clinical remission and decreasing FCP in pediatric CD similar to commercial EEN formulas. Further research may give insight into data-driven whole-food dietary approaches for CD management. CLINICALTRIALS: gov NCT03508193.

Maintenance tobramycin primarily affects untargeted bacteria in the CF sputum microbiome.

RATIONALE: The most common antibiotic used to treat people with cystic fibrosis (PWCF) is inhaled tobramycin, administered as maintenance therapy for chronic Pseudomonas aeruginosa lung infections. While the effects of inhaled tobramycin on P. aeruginosa abundance and lung function diminish with continued therapy, this maintenance treatment is known to improve long-term outcomes, underscoring how little is known about why antibiotics work in CF infections, what their effects are on complex CF sputum microbiomes and how to improve these treatments. OBJECTIVES: To rigorously define the effect of maintenance tobramycin on CF sputum microbiome characteristics. METHODS AND MEASUREMENTS: We collected sputum from 30 PWCF at standardised times before, during and after a single month-long course of maintenance inhaled tobramycin. We used traditional culture, quantitative PCR and metagenomic sequencing to define the dynamic effects of this treatment on sputum microbiomes, including abundance changes in both clinically targeted and untargeted bacteria, as well as functional gene categories. MAIN RESULTS: CF sputum microbiota changed most markedly by 1 week of antibiotic therapy and plateaued thereafter, and this shift was largely driven by changes in non-dominant taxa. The genetically conferred functional capacities (ie, metagenomes) of subjects' sputum communities changed little with antibiotic perturbation, despite taxonomic shifts, suggesting functional redundancy within the CF sputum microbiome. CONCLUSIONS: Maintenance treatment with inhaled tobramycin, an antibiotic with demonstrated long-term mortality benefit, primarily impacted clinically untargeted bacteria in CF sputum, highlighting the importance of monitoring the non-canonical effects of antibiotics and other treatments to accurately define and improve their clinical impact.