The effect of probiotic administration on metabolomics and glucose metabolism in CF patients

BACKGROUND AND OBJECTIVES: Cystic fibrosis (CF)‐related diabetes (CFRD) affects 50% of CF adults. Gut microbial imbalance (dysbiosis) aggravates their inflammatory response and contributes to insulin resistance (IR). We hypothesized that probiotics may improve glucose tolerance by correcting dysbiosis. METHODS: A single‐center prospective pilot study assessing the effect of Vivomixx® probiotic (450 billion/sachet) on clinical status, spirometry, lung clearance index (LCI), and quality of life (QOL) questionnaires; inflammatory parameters (urine and stool metabolomics, blood cytokines); and glucose metabolism (oral glucose tolerance test [OGTT]), continuous glucose monitoring [CGM], and homeostasis model assessment of IR (HOMA‐IR) in CF patients. RESULTS: Twenty‐three CF patients (six CFRD), mean age 17.7 ± 8.2 years. After 4 months of probiotic administration, urinary cysteine (p = 0.018), lactulose (p = 0.028), arabinose (p = 0.036), mannitol (p = 0.041), and indole 3‐lactate (p = 0.046) significantly increased, while 3‐methylhistidine (p = 0.046) and N‐acetyl glutamine (p = 0.047) decreased. Stool 2‐Hydroxyisobutyrate (p = 0.022) and 3‐methyl‐2‐oxovalerate (p = 0.034) decreased. Principal component analysis, based on urine metabolites, found significant partitions between subjects at the end of treatment compared to baseline (p = 0.004). After 2 months of probiotics, the digestive symptoms domain of Cystic Fibrosis Questionnaire‐Revised improved (p = 0.007). In the nondiabetic patients, a slight decrease in HOMA‐IR, from 2.28 to 1.86, was observed. There was no significant change in spirometry results, LCI, blood cytokines and CGM. CONCLUSIONS: Changes in urine and stool metabolic profiles, following the administration of probiotics, may suggest a positive effect on glucose metabolism in CF. Larger long‐term studies are needed to confirm our findings. Understanding the interplay between dysbiosis, inflammation, and glucose metabolism may help preventing CFRD.