motilin and Cystic-Fibrosis

Cystic Fibrosis (CF) is a genetic condition characterized by neutrophilic inflammation and recurrent infection of the airways. How these processes are initiated and perpetuated in CF remains largely unknown. We have demonstrated a link between the intestinal microbiota-related metabolites bile acids (BA) and inflammation in the bronchoalveolar lavage fluid (BALF) from children with stable CF lung disease. To establish if BA indicate early pathological processes in CF lung disease, we combined targeted mass spectrometry and amplicon sequencing-based microbial characterization of 121 BALF specimens collected from 12-month old infants with CF enrolled in the COMBAT-CF study, a multicentre randomized placebo-controlled clinical trial comparing azithromycin versus placebo. We evaluated whether detection of BA in BALF is associated with the establishment of the inflammatory and microbial landscape of early CF lung disease, and whether azithromycin, a motilin agonist that has been demonstrated to reduce aspiration of gastric contents, alters the odds of detecting BA in BALF. We also explored how different prophylactic antibiotics regimens impact the early life BALF microbiota.. Detection of BA in BALF was strongly associated with biomarkers of airway inflammation, more exacerbation episodes during the first year of life, increased use of oral antibiotics with prolonged treatment periods, a higher degree of structural lung damage, and distinct microbial profiles. Treatment with azithromycin, a motilin agonist, which has been reported to reduce aspiration of gastric contents, did not reduce the odds of detecting BA in BALF. Culture and molecular methods showed that azithromycin does not alter bacterial load or diversity in BALF. Conversely, penicillin-type prophylaxis reduced the odds of detecting BAs in BALF, which was associated with elevated levels of circulating biomarkers of cholestasis. We also observed that environmental factors such as penicillin-type prophylaxis or BAs detection were linked to distinct early microbial communities of the CF airways, which were associated with different inflammatory landscapes but not with structural lung damage.. Detection of BA in BALF portend early pathological events in CF lung disease. Benefits early in life associated with azithromycin are not linked to its antimicrobial properties. Video Abstract.

Topics: Anti-Bacterial Agents; Azithromycin; Bile Acids and Salts; Bronchoalveolar Lavage Fluid; Cystic Fibrosis; Humans; Infant; Inflammation; Motilin; Penicillins

Intestinal dysmotility may be an important factor contributing to various gastrointestinal complications associated with cystic fibrosis. Motilin, enteroglucagon, neurotensin, and peptide YY may each play a role as endocrine hormones influencing gastrointestinal motor activity. Fasting children with cystic fibrosis (N = 8) and controls (N = 18) received a liquid nutrient test meal (fat 4 g/100 ml, protein 4 g/100 ml, carbohydrate 20 g/100 ml, 125 kcal/100 ml; 200 ml/m2) containing lactulose (5 g/100 ml), and the plasma concentrations of these peptides were studied. Mouth-to-cecum transit time was simultaneously studied using the breath H2 technique. Fasting levels of peptide YY and the postprandial response of all four peptides were significantly increased in those with cystic fibrosis. In repeat studies on those with cystic fibrosis after a period of altered pancreatic enzyme supplementation, no significant changes in peptide concentrations were observed. A rise in breath H2 permitting estimation of mouth-to-cecum transit time was noted in 17 control subjects (70-220 min, median 140). In contrast, a rise occurred in only two with cystic fibrosis after low-dose enzyme (70 and 180 min), and four after high-dose enzyme replacement (120-230 min, median 155). Altered gut hormone secretion may play a role in the pathophysiology of intestinal dysmotility in patients with cystic fibrosis.

Topics: Adolescent; Breath Tests; Child; Cystic Fibrosis; Fasting; Food; Gastrointestinal Motility; Glucagon-Like Peptides; Humans; Hydrogen; Motilin; Neuropeptides; Neurotensin; Peptide YY; Peptides

The number of peptide hormones which have been localized in the gut and in neurons of the central and peripheral nervous system has increased considerably. As there is almost no information about their importance in children with gastrointestinal diseases, we developed highly sensitive radioimmunoassays and measured postprandial serum/plasma levels of gastrin, secretin, vasoactive intestinal polypeptide (VIP) and motilin in 112 healthy children (N), 28 patients with cystic fibrosis (CF) and 17 children with Crohn's disease (CD). Gastrin values were not pathologic in children with CF nor those with Crohn's disease (N = 56.2 +/- 29.6 pg/ml; CF = 57.0 +/- 34.2 pg/ml; CD = 43.6 +/- 26.6 pg/ml). A significant age dependency was established for secretin and VIP. These peptides were elevated in CF-patients. In children with Crohn's disease only Secretin was increased. Motilin was elevated in all patients: N = 78.0 (49.1-124.0) pg/ml; CF = 148.0 (70.8-309) pg/ml; CD = 153.0 (87.6-266).

Topics: Adolescent; Adult; Child; Child, Preschool; Crohn Disease; Cystic Fibrosis; Gastrins; Humans; Infant; Motilin; Radioimmunoassay; Secretin; Vasoactive Intestinal Peptide