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 (R) 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.