title: Gut microbial and short-chain fatty acid profiles in adults with chronic constipation before and after treatment with lubiprostone.
abstract: Identifying specific gut microorganisms associated with chronic constipation may be useful for diagnostic and therapeutic purposes. The objective of this study was to evaluate whether or not the gut microbial community of constipated subjects had specific microbial signatures and to assess the effects of lubiprostone treatment on the gut microbial community. Stool diaries, breath H2 and CH4 levels, and stool samples were collected from ten healthy subjects and nine patients meeting the Rome III criteria for chronic functional constipation. Constipated subjects received lubiprostone for four weeks, during which stool diaries were maintained. Stool samples were evaluated for gut microbial communities using pyrosequencing and quantitative real-time PCR (qPCR) targeting 16S-rRNA gene, along with concentrations of short-chain fatty acids (SCFAs) using high-performance liquid chromatography. Prior to treatment, gut microbial profiles were similar between constipated subjects and healthy subjects, while iso-butyrate levels were significantly higher in constipated subjects compared with healthy subjects. Despite increases in stool frequency and improvements in consistency after lubiprostone treatment, gut microbial profiles and community diversity after treatment showed no significant change compared to before treatment. While we did not observe a significant difference in either breath methane or archaeal abundance between the stool samples of healthy and constipated subjects, we confirmed a strong correlation between archaeal abundance measured by qPCR and the amount of methane gas exhaled in the fasting breath. Butyrate levels, however, were significantly higher in the stool samples of constipated subjects after lubiprostone treatment, suggesting that lubiprostone treatment had an effect on the net accumulation of SCFAs in the gut. In conclusion, lubiprostone treatment improved constipation symptoms and increased levels of butyrate without substantial modification of the gut microbial structure.
authors.affiliation: Swette Center for Environmental Biotechnology, Biodesign Institute, Arizona State University, 727 East Tyler Road, Tempe, AZ 85287-5701, USA.
authors.forename: Dae-Wook
authors.initials: DW
authors.lastname: Kang
authors.affiliation: Division of Gastroenterology, Mayo Clinic, 13400 East Shea Blvd., Scottsdale, AZ 85259, USA. Electronic address: Dibaise.john@mayo.edu.
authors.forename: John K
authors.initials: JK
authors.lastname: DiBaise
authors.affiliation: Swette Center for Environmental Biotechnology, Biodesign Institute, Arizona State University, 727 East Tyler Road, Tempe, AZ 85287-5701, USA.
authors.forename: Zehra Esra
authors.initials: ZE
authors.lastname: Ilhan
authors.affiliation: Division of Gastroenterology, Mayo Clinic, 13400 East Shea Blvd., Scottsdale, AZ 85259, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Crowell
authors.affiliation: Center for Microbial Genetics and Genomics, Northern Arizona University, 1298 South Knoles Dr., Flagstaff, AZ 86011, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl., New York, NY 10029, USA.
authors.forename: Jai Ram
authors.initials: JR
authors.lastname: Rideout
authors.affiliation: Center for Microbial Genetics and Genomics, Northern Arizona University, 1298 South Knoles Dr., Flagstaff, AZ 86011, USA; Department of Biological Sciences, Northern Arizona University, 617 South Beaver St., Flagstaff, AZ 86011, USA.
authors.forename: J Gregory
authors.initials: JG
authors.lastname: Caporaso
authors.affiliation: Swette Center for Environmental Biotechnology, Biodesign Institute, Arizona State University, 727 East Tyler Road, Tempe, AZ 85287-5701, USA; School of Sustainable Engineering and the Built Environment, Arizona State University, 501 East Tyler Mall, Tempe, AZ 85287, USA.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Rittmann
authors.affiliation: Swette Center for Environmental Biotechnology, Biodesign Institute, Arizona State University, 727 East Tyler Road, Tempe, AZ 85287-5701, USA; School of Sustainable Engineering and the Built Environment, Arizona State University, 501 East Tyler Mall, Tempe, AZ 85287, USA. Electronic address: Dr.Rosy@asu.edu.
authors.forename: Rosa
authors.initials: R
authors.lastname: Krajmalnik-Brown
mesh_terms: D000328:Adult; D000368:Aged; D044822:Biodiversity; D016022:Case-Control Studies; D065101:Chloride Channel Agonists / Q000627:therapeutic use; D002908:Chronic Disease; D003248:Constipation / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology*; D005232:Fatty Acids, Volatile / Q000378:metabolism*; D005260:Female; D000069196:Gastrointestinal Microbiome; D018628:Gene Dosage; D006801:Humans; D000068238:Lubiprostone / Q000627:therapeutic use; D008297:Male; D054892:Metagenome; D008875:Middle Aged; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D065101:Chloride Channel Agonists; D005232:Fatty Acids, Volatile; D012336:RNA, Ribosomal, 16S; D000068238:Lubiprostone
keywords: Constipation; Gut microbiome; Lubiprostone; Pyrosequencing; Short-chain fatty acids