{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:26:43Z","timestamp":1791548803800,"version":"4.3.4"},"reference-count":66,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,11,11]],"date-time":"2015-11-11T00:00:00Z","timestamp":1447200000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Observational studies show a strong association between delayed intestinal transit and the production of methane. Experimental data suggest a direct inhibitory activity of methane on the colonic and ileal smooth muscle and a possible role for methane as a gasotransmitter. Archaea are the only confirmed biological sources of methane in nature and <jats:italic>Methanobrevibacter smithii<\/jats:italic> is the predominant methanogen in the human intestine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To review the biosynthesis and composition of archaeal cell membranes, archaeal methanogenesis and the mechanism of action of statins in this context.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Narrative review of the literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Statins can inhibit archaeal cell membrane biosynthesis without affecting bacterial numbers as demonstrated in livestock and humans. This opens the possibility of a therapeutic intervention that targets a specific aetiological factor of constipation while protecting the intestinal microbiome. While it is generally believed that statins inhibit methane production via their effect on cell membrane biosynthesis, mediated by inhibition of the <jats:styled-content style=\"fixed-case\">HMG<\/jats:styled-content>\u2010CoA reductase, there is accumulating evidence for an alternative or additional mechanism of action where statins inhibit methanogenesis directly. It appears that this other mechanism may predominate when the lactone form of statins, particularly lovastatin lactone, is administered.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Clinical development appears promising. A phase 2 clinical trial is currently in progress that evaluates the effect of lovastatin lactone on methanogenesis and symptoms in patients with irritable bowel syndrome with constipation. The review concludes with an outlook for the future and subsequent work that needs to be done.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.13469","type":"journal-article","created":{"date-parts":[[2015,11,12]],"date-time":"2015-11-12T02:16:43Z","timestamp":1447294603000},"page":"197-212","source":"Crossref","is-referenced-by-count":81,"title":["Review article: inhibition of methanogenic archaea by statins as a targeted management strategy for constipation and related disorders"],"prefix":"10.1111","volume":"43","author":[{"given":"K.","family":"Gottlieb","sequence":"first","affiliation":[{"name":"Synthetic Biologics Inc. Rockville MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Wacher","sequence":"additional","affiliation":[{"name":"Synthetic Biologics Inc. Rockville MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Sliman","sequence":"additional","affiliation":[{"name":"Synthetic Biologics Inc. Rockville MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Pimentel","sequence":"additional","affiliation":[{"name":"Gastroenterology Cedars\u2010Sinai Medical Center Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,11,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v13.i40.5295"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.12.4576"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/915828"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00574.2004"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.5056\/jnm.2014.20.1.31"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12568"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anaerobe.2015.01.005"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.12306"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2015.47"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102015\u2010309618"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep12693"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2006.01020.x"},{"key":"e_1_2_11_14_1","first-page":"139","article-title":"Results of small intestinal bacterial overgrowth testing in irritable bowel syndrome patients: clinical profiles and effects of antibiotic trial","volume":"52","author":"Majewski M","year":"2007","journal-title":"Adv Med Sci"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2011.01819.x"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-7915.2011.00320.x"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008926"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/0-387-30742-7_34"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atmosenv.2015.05.019"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1088\/1752-7155\/9\/1\/014001"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0065388"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuv010"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1088\/1752-7155\/7\/2\/024001"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.27.6.698"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0103171"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2014.03.003"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706495"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2014.11.010"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4433"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e31823dae05"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2006.1841"},{"key":"e_1_2_11_32_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/978-3-642-38954-2_407","volume-title":"The Prokaryotes","author":"Whitman WB","year":"2014"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365520510023585"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.food.102308.124101"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-30197-1_258"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-05062-6_7"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20121899"},{"key":"e_1_2_11_38_1","first-page":"641","article-title":"Biosynthesis of archaeal membrane ether lipids","volume":"5","author":"Jain S","year":"2014","journal-title":"Microb Physiol Metab"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.3168\/jds.S0022-0302(01)70177-4"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2012.03913.x"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-4063-5_1"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-1981(99)00130-4"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.orggeochem.2015.03.009"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.6026\/97320630006015"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015803"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M710352200"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0704189104"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2014.03.002"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2014.08.037"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8647-3"},{"key":"e_1_2_11_51_1","first-page":"282","article-title":"A comparison of the effects of 3\u2010hydroxy\u20103\u2010methylglutaryl\u2010coenzyme a (HMG\u2010CoA) reductase inhibitors on the CYP3A4\u2010dependent oxidation of mexazolam in vitro","volume":"29","author":"Ishigami M","year":"2001","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2013.02.013"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00196860"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12223-010-0058-x"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anaerobe.2011.03.001"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114510005684"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.3168\/jds.2006-644"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1080\/1745039X.2011.588845"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/196264"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/397934"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/604721"},{"key":"e_1_2_11_62_1","doi-asserted-by":"crossref","unstructured":"MarshE MoralesW MarshZ et al.Lovastatin lactone inhibits methane production in human stool homogenates. Poster Presentation presented at: American College of Gastroenterology Annual Meeting; 16 October 2015; Honolulu HI.","DOI":"10.14309\/00000434-201510001-01771"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(15)32660-3"},{"key":"e_1_2_11_64_1","unstructured":"Synthetic Biologics.A Randomized Double\u2010Blind Parallel\u2010Group Placebo\u2010Controlled Study of the Effect of SYN\u2010010 on Subjects With IBS\u2010C [Internet]. Clinicaltrials.gov 2015June. Report No.: SB\u20102\u2010010\u2010001. Available at:https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02495623. Accessed 3 November 2015."},{"key":"e_1_2_11_65_1","unstructured":"ITIS Standard Report Page: Methanobrevibacter [Internet]. Integrated Taxonomic Information System. Available at:http:\/\/www.itis.gov\/servlet\/SingleRpt\/SingleRpt(accessed 30 June 2015)."},{"key":"e_1_2_11_66_1","unstructured":"Global Catalogue of Microorganisms [Internet]. Available at:http:\/\/gcm.wfcc.info\/(accessed 30 June 2015)."},{"key":"e_1_2_11_67_1","volume-title":"Brock Biology of Microorganisms","author":"Madigan MT","year":"2010"}],"container-title":["Alimentary Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fapt.13469","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fapt.13469","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apt.13469","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T02:12:21Z","timestamp":1694311941000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apt.13469"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,11]]},"references-count":66,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,1]]}},"alternative-id":["10.1111\/apt.13469"],"URL":"https:\/\/doi.org\/10.1111\/apt.13469","archive":["Portico"],"relation":{},"ISSN":["0269-2813","1365-2036"],"issn-type":[{"value":"0269-2813","type":"print"},{"value":"1365-2036","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,11]]}}}