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Impaired distal colonic pH in adults with cystic fibrosis

  • Dhiren Patel
    Correspondence
    Corresponding author at: Pediatric Gastroenterology, Hepatology and Nutrition, SSM Cardinal Glennon Children's Medical Center, Saint Louis University School of Medicine, 1465 S. Grand Blvd. St. Louis, MO 63104, USA.
    Affiliations
    Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cardinal Glennon Children's Medical Center, Saint Louis University School of Medicine, St Louis, MO, USA

    The AHEAD Institute, Saint Louis University School of Medicine, St Louis, MO, USA
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  • Stacy Mathews
    Affiliations
    Department of Pediatrics, Cardinal Glennon Children's Medical Center, Saint Louis University School of Medicine, St Louis, MO, USA
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  • Vincent van Unen
    Affiliations
    Department of Medicine, Division of Hematology, Stanford University, Stanford, CA, USA

    Stanford Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA
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  • Joshua E. Chan
    Affiliations
    Department of Medicine, Division of Hematology, Stanford University, Stanford, CA, USA
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  • Noor Al-Hammadi
    Affiliations
    The AHEAD Institute, Saint Louis University School of Medicine, St Louis, MO, USA
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  • Drucy Borowitz
    Affiliations
    Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA
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  • Daniel Gelfond
    Affiliations
    WNY Pediatric Gastroenterology and Nutrition, DGRD, Buffalo NY, USA
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  • Zachary M. Sellers
    Correspondence
    Co-corresponding author at: Pediatric Gastroenterology, Hepatology, and Nutrition, Stanford University, 1701 Page Mill Road, Palo Alto, CA 94304, USA.
    Affiliations
    Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Stanford University, Palo Alto, CA, USA
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Published:December 24, 2022DOI:https://doi.org/10.1016/j.jcf.2022.12.011

      Highlights

      • We provide the first study attempting to understand colonic pH, bicarbonate, and motility profiles from patients with cystic fibrosis.
      • Colonic pH and bicarbonate concentration is impaired in PwCF, particularly in the distal rectosigmoid.
      • These changes likely originate from alterations in intestinal ion transport rather than colonic dysmotility.
      • SLC26A3 is abundantly expressed in the human colon and rectum and may be a potential therapeutic target for restoration of bicarbonate transport in PwCF.
      • Our findings may help better understand the gastrointestinal symptoms in PwCF and provides the framework for future studies in this area.

      Abstract

      Previous wireless motility capsule (WMC) studies demonstrated decreased small intestinal pH in people with CF (PwCF) however the data is lacking on the colonic pH profile. We re-analyzed previously published WMC data to determine colonic pH/bicarbonate concentration and single cell RNA sequencing (sc-RNAseq) to examine the normal expression of acid-base transporters in the colon/rectum.CF patients showed significantly lower pH and bicarbonate concentration values, particularly in the distal rectosigmoid region. There was no difference in colonic motility parameters between CF and non-CF subjects. SLC26A3 is highly expressed bicarbonate transporter in the colon and rectum, more so than CFTR. While dysmotility can alter intraluminal pH, observed changes likely originate from alterations in intestinal ion transport rather than colonic dysmotility. SLC26A3 is abundantly expressed in the human colon and rectum and may be a therapeutic target for restoration of bicarbonate transport. These findings may help better understand the gastrointestinal symptoms in PwCF

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      References

        • Howden C.W.
        • Hunt R.H.
        Relationship between gastric secretion and infection.
        Gut. 1987; 28: 96-107
        • Ishiguro H.
        • Steward M.
        • Naruse S.
        Cystic fibrosis transmembrane conductance regulator and SLC26 transporters in HCO(3)(-) secretion by pancreatic duct cells.
        Sheng Li Xue Bao. 2007; 59: 465-476
      1. Seidler U., Nikolovska K. Slc26 family of anion transporters in the gastrointestinal tract: expression, function, regulation, and role in disease. 9 2019. p. 839–72.

        • den Besten G.
        • van Eunen K.
        • Groen A.K.
        • Venema K.
        • Reijngoud D.J.
        • Bakker B.M.
        The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism.
        J Lipid Res. 2013; 54: 2325-2340
        • Roy C.C.
        • Kien C.L.
        • Bouthillier L.
        • Levy E.
        Short-chain fatty acids: ready for prime time?.
        Nutr Clin Pract. 2006; 21: 351-366
        • Borowitz D.
        CFTR, bicarbonate, and the pathophysiology of cystic fibrosis.
        Pediatr Pulmonol. 2015; 50 (Suppl): S24-S30
        • Gelfond D.
        • Ma C.
        • Semler J.
        • Borowitz D.
        Intestinal pH and gastrointestinal transit profiles in cystic fibrosis patients measured by wireless motility capsule.
        Dig Dis Sci. 2013; 58: 2275-2281
        • Koga I.
        • Stiernstrom H.
        • Christiansson L.
        • Wiklund L.
        Intraperitoneal and sigmoid colon tonometry in porcine hypoperfusion and endotoxin shock models.
        Acta Anaesthesiol Scand. 1999; 43: 702-707
        • Hao Y.
        • Hao S.
        • Andersen-Nissen E.
        • Mauck 3rd, W.M.
        • Zheng S.
        • Butler A.
        • et al.
        Integrated analysis of multimodal single-cell data.
        Cell. 2021; 184 (e29): 3573-3587
        • Wang Y.
        • Song W.
        • Wang J.
        • Wang T.
        • Xiong X.
        • Qi Z.
        • et al.
        Single-cell transcriptome analysis reveals differential nutrient absorption functions in human intestine.
        J Exp Med. 2020; 217
        • Corral J.E.
        • Dye C.W.
        • Mascarenhas M.R.
        • Barkin J.S.
        • Salathe M.
        • Moshiree B.
        Is gastroparesis found more frequently in patients with cystic fibrosis? A Systematic Review.
        Scientifica (Cairo). 2016; (2016)2918139
        • Hogan D.L.
        • Crombie D.L.
        • Isenberg J.I.
        • Svendsen P.
        • Schaffalitzky de Muckadell O.B.
        • Ainsworth M.A.
        Acid-stimulated duodenal bicarbonate secretion involves a CFTR-mediated transport pathway in mice.
        Gastroenterology. 1997; 113: 533-541
        • Pratha V.S.
        • Thompson S.M.
        • Hogan D.L.
        • Paulus P.
        • Dreilinger A.D.
        • Barrett K.E.
        • et al.
        Utility of endoscopic biopsy samples to quantitate human duodenal ion transport.
        J Lab Clin Med. 1998; 132: 512-518
        • Farmer A.D.
        • Mohammed S.D.
        • Dukes G.E.
        • Scott S.M.
        • Hobson A.R.
        Caecal pH is a biomarker of excessive colonic fermentation.
        World J Gastroenterol. 2014; 20: 5000-5007
        • Nugent S.G.
        • Kumar D.
        • Rampton D.S.
        • Evans D.F.
        Intestinal luminal pH in inflammatory bowel disease: possible determinants and implications for therapy with aminosalicylates and other drugs.
        Gut. 2001; 48: 571-577
        • Brun R.
        • Michalek W.
        • Surjanhata B.C.
        • Parkman H.P.
        • Semler J.R.
        • Kuo B.
        Comparative analysis of phase III migrating motor complexes in stomach and small bowel using wireless motility capsule and antroduodenal manometry.
        Neurogastroent Motil. 2012; 24
        • Kloetzer L.
        • Chey W.D.
        • McCallum R.W.
        • Koch K.L.
        • Wo J.M.
        • Sitrin M.
        • et al.
        Motility of the antroduodenum in healthy and gastroparetics characterized by wireless motility capsule.
        Neurogastroenterol Motil. 2010; 22 (e117): 527-533
        • Malagelada C.
        • Bendezu R.A.
        • Segui S.
        • Vitria J.
        • Merino X.
        • Nieto A.
        • et al.
        Motor dysfunction of the gut in cystic fibrosis.
        Neurogastroenterol Motil. 2020; 32: e13883
        • Dekkers J.F.
        • Wiegerinck C.L.
        • de Jonge H.R.
        • Bronsveld I.
        • Janssens H.M.
        • de Winter-de Groot K.M.
        • et al.
        A functional CFTR assay using primary cystic fibrosis intestinal organoids.
        Nat Med. 2013; 19: 939-945
        • Silva I.A.L.
        • Duarte A.
        • Marson F.A.L.
        • Centeio R.
        • Dousova T.
        • Kunzelmann K.
        • et al.
        Assessment of distinct electrophysiological parameters in rectal biopsies for the choice of the best diagnosis/prognosis biomarkers for cystic fibrosis.
        Front Physiol. 2020; 11604580
        • Veeze H.J.
        • Sinaasappel M.
        • Bijman J.
        • Bouquet J.
        • de Jonge H.R.
        Ion transport abnormalities in rectal suction biopsies from children with cystic fibrosis.
        Gastroenterology. 1991; 101: 398-403
        • Tse C.M.
        • Yin J.
        • Singh V.
        • Sarker R.
        • Lin R.
        • Verkman A.S.
        • et al.
        cAMP Stimulates SLC26A3 Activity in Human Colon by a CFTR-Dependent Mechanism That Does Not Require CFTR Activity.
        Cell Mol Gastroenterol Hepatol. 2019; 7: 641-653