Millie Garg1, Steven T Leach1, Tamara Pang1, Bronwen Needham2, Michael J Coffey1, Tamarah Katz3, Roxanne Strachan4, John Widger5, Penelope Field5, Yvonne Belessis5, Sandra Chuang5, Andrew S Day6, Adam Jaffe5, Chee Y Ooi7. 1. School of Women and Children's Health, Medicine, The University of New South Wales, High Street, Sydney Children's Hospital, Randwick 2031, New South Wales, Australia. 2. Sydney Medical Program, The University of Sydney, Camperdown 2050, New South Wales, Australia. 3. Department of Nutrition and Dietetics, Sydney Children's Hospital, High Street, Randwick 2031, New South Wales, Australia. 4. Department of Respiratory Medicine, Sydney Children's Hospital, High Street, Randwick 2031, New South Wales, Australia. 5. School of Women and Children's Health, Medicine, The University of New South Wales, High Street, Sydney Children's Hospital, Randwick 2031, New South Wales, Australia; Department of Respiratory Medicine, Sydney Children's Hospital, High Street, Randwick 2031, New South Wales, Australia. 6. Department of Paediatrics, University of Otago, Riccarton Ave, Christchurch 8011, Canterbury, New Zealand. 7. School of Women and Children's Health, Medicine, The University of New South Wales, High Street, Sydney Children's Hospital, Randwick 2031, New South Wales, Australia; Department of Gastroenterology, Sydney Children's Hospital, High Street, Randwick 2031, New South Wales, Australia. Electronic address: keith.ooi@unsw.edu.au.
Abstract
BACKGROUND: The pathogenesis of gut inflammation, bacterial dysbiosis and increased rates of malignancy in CF is unclear. Fecal M2-pyruvate kinase (M2-PK) is a biomarker indicative of cellular proliferation that may be raised in intestinal malignancy and inflammation. Biomarkers, including M2-PK, may be useful in assessing effects of novel therapies on the gastrointestinal tract. METHODS: M2-PK was measured in stools collected from patients with CF and HC (0-10years). Linear mixed model analysis was used. RESULTS: M2-PK levels did not significantly change in children with CF (36 patients, 77 samples) (P=0.998) or HC (45 patients, 45 samples) (P=0.21), over the age range 0-10years. Patients with CF had elevated M2-PK compared to HC (median [IQR; range]: 10.7 [5.7-28.6; 1.0-239.1] (n=77) vs. 1.0 [1.0-1.0; 1.0-50.0] (n=45) U/mL, respectively; P=0.001). CONCLUSIONS: Fecal M2-PK was elevated in children with CF compared with HC during infancy and throughout childhood suggesting abnormalities in the CF gut exist in early life.
BACKGROUND: The pathogenesis of gut inflammation, bacterial dysbiosis and increased rates of malignancy in CF is unclear. Fecal M2-pyruvate kinase (M2-PK) is a biomarker indicative of cellular proliferation that may be raised in intestinal malignancy and inflammation. Biomarkers, including M2-PK, may be useful in assessing effects of novel therapies on the gastrointestinal tract. METHODS: M2-PK was measured in stools collected from patients with CF and HC (0-10years). Linear mixed model analysis was used. RESULTS: M2-PK levels did not significantly change in children with CF (36 patients, 77 samples) (P=0.998) or HC (45 patients, 45 samples) (P=0.21), over the age range 0-10years. Patients with CF had elevated M2-PK compared to HC (median [IQR; range]: 10.7 [5.7-28.6; 1.0-239.1] (n=77) vs. 1.0 [1.0-1.0; 1.0-50.0] (n=45) U/mL, respectively; P=0.001). CONCLUSIONS: Fecal M2-PK was elevated in children with CF compared with HC during infancy and throughout childhood suggesting abnormalities in the CF gut exist in early life.
Authors: Michael J Coffey; Ivan Low; Sacha Stelzer-Braid; Bernd Wemheuer; Millie Garg; Torsten Thomas; Adam Jaffe; William D Rawlinson; Chee Y Ooi Journal: PLoS One Date: 2020-05-22 Impact factor: 3.240