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

Abstract

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

Virtual Drug Repositioning as a Tool to Identify Natural Small Molecules That Synergize with Lumacaftor in F508del-CFTR Binding and Rescuing

“…Probiotics can intervene on CF intestinal dysbiosis, reducing its negative effects (i.e., severe intestinal inflammation). Moreover, they may have a positive effect on glucose metabolism [ 64 , 65 ]. Fatty acids, vitamins (A, D, E, K and B12) [ 26 , 27 , 28 , 29 , 66 , 67 ], flaxseed [ 68 ], caffeic acid phenethyl ester [ 69 ], furocoumarins [ 70 ], curcumin, resveratrol, genistein [ 63 , 71 , 72 , 73 ] and rutin/quercetin [ 74 , 75 ] are endowed with antioxidant potential that may compensate the oxidative stress caused by the increased production of ROS during chronic pulmonary infections.…”

Donkey Colostrum and Milk: How Dietary Probiotics Can Affect Metabolomic Profile, Alkaline Sphingomyelinase and Alkaline Phosphatase Activity

“…The procedure utilized for 1H-NMR analysis was adapted for milk from the one described by Gur for urine [ 44 ]. Briefly, a stock solution composed of 3-(trimethylsilyl)-propionic-2,2,3,3-d4 acid sodium salt (TSP) 10 mmol/L and NaN3 2 mmol/L in D2O was obtained.…”

Positive and negative impacts of elexacaftor/tezacaftor/ivacaftor: Healthcare providers' observations across US centers

“…PwCF are at elevated risk for a variety of mental health conditions, including depression, anxiety, neurocognitive and attentional difficulties, sleep disturbance, body image/eating concerns, and substance misuse 13–16 . This may be driven by the mental health impacts of disease‐specific stressors including pulmonary exacerbations and treatment burden, 17–19 as well as by shared pathways affecting both physical and mental health in pwCF (e.g., inflammation and its metabolic effects, gut dysbiosis, social determinants of health) 20–22 . To date these negative side‐effects have been reported in single‐center studies, case reports, and case series 5,6,9–12,23,24 ; however, larger epidemiologic studies are needed to better characterize these relationships.…”

“…[13][14][15][16] This may be driven by the mental health impacts of disease-specific stressors including pulmonary exacerbations and treatment burden, [17][18][19] as well as by shared pathways affecting both physical and mental health in pwCF (e.g., inflammation and its metabolic effects, gut dysbiosis, social determinants of health). [20][21][22] To date these negative side-effects have been reported in singlecenter studies, case reports, and case series 5,6,[9][10][11][12]23,24 ; however, larger epidemiologic studies are needed to better characterize these relationships. Regardless of etiology, an understanding of the intersection of mental health and CFTR modulator use remains important when psychiatric management is indicated.…”