TY - JOUR
T1 - Gut microbial and short-chain fatty acid profiles in adults with chronic constipation before and after treatment with lubiprostone
AU - Kang, Dae Wook
AU - DiBaise, John K.
AU - Ilhan, Zehra Esra
AU - Crowell, Michael D.
AU - Rideout, Jai Ram
AU - Caporaso, J. Gregory
AU - Rittmann, Bruce
AU - Krajmalnik-Brown, Rosa
N1 - Funding Information:
We thank Michael Lee for serving as a study coordinator. This study was supported by an Investigator-initiated Sponsored Research (IISR) grant from Takeda Pharmaceuticals, Inc ( IISR Study 08-029LUB ). The funding source had no role in the study design, execution, data analysis and manuscript preparation. The study is registered on the ClinicalTrials.gov (NCT: NCT00934479 ).
Publisher Copyright:
© 2015.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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.
AB - 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.
KW - Constipation
KW - Gut microbiome
KW - Lubiprostone
KW - Pyrosequencing
KW - Short-chain fatty acids
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UR - http://www.scopus.com/inward/citedby.url?scp=84922467857&partnerID=8YFLogxK
U2 - 10.1016/j.anaerobe.2015.01.005
DO - 10.1016/j.anaerobe.2015.01.005
M3 - Article
C2 - 25617726
AN - SCOPUS:84922467857
SN - 1075-9964
VL - 33
SP - 33
EP - 41
JO - Anaerobe
JF - Anaerobe
ER -