Irritable Bowel Syndrome, Particularly the Constipation-Predominant Form, Involves an Increase in Methanobrevibacter smithii, Which Is Associated with Higher Methane Production

Ujjala Ghoshal, Ratnakar Shukla, Deepakshi Srivastava, Uday C Ghoshal, Ujjala Ghoshal, Ratnakar Shukla, Deepakshi Srivastava, Uday C Ghoshal

Abstract

Background/aims: Because Methanobrevibacter smithii produces methane, delaying gut transit, we evaluated M. smithii loads in irritable bowel syndrome (IBS) patients and healthy controls (HC).

Methods: Quantitative real-time polymerase chain reaction for M. smithii was performed on the feces of 47 IBS patients (Rome III) and 30 HC. On the lactulose hydrogen breath test (LHBT, done for 25 IBS patients), a fasting methane result ≥10 ppm using 10 g of lactulose defined methane-producers.

Results: Of 47, 20 had constipation (IBS-C), 20 had diarrhea (IBS-D) and seven were not sub-typed. The M. smithii copy number was higher among IBS patients than HC (Log₁₀5.4, interquartile range [IQR; 3.2 to 6.3] vs 1.9 [0.0 to 3.4], p<0.001), particularly among IBS-C compared to IBS-D patients (Log₁₀6.1 [5.5 to 6.6] vs 3.4 [0.6 to 5.7], p=0.001); the copy number negatively correlated with the stool frequency (R=-0.420, p=0.003). The M. smithii copy number was higher among methane-producers than nonproducers (Log₁₀6.4, IQR [5.7 to 7.4] vs 4.1 [1.8 to 5.8], p=0.001). Using a receiver operating characteristic curve, the best cutoff for M. smithii among methane producers was Log₁₀6.0 (sensitivity, 64%; specificity, 86%; area under curve [AUC], 0.896). The AUC for breath methane correlated with the M. smithii copy number among methane producers (r=0.74, p=0.008). Abdominal bloating was more common among methane producers (n=9/11 [82%] vs 5/14 [36%], p=0.021).

Conclusions: Patients with IBS, particularly IBS-C, had higher copy numbers of M. smithii than HC. On LHBT, breath methane levels correlated with M. smithii loads.

Keywords: Gut transit; Lactulose hydrogen breath test; Methanogenic flora; Real-time polymerase chain reaction.

Figures

Fig. 1
Fig. 1
(A) Copy numbers of Methanobrevibacter smithii among patients with irritable bowel syndrome (IBS) and healthy controls (HC). (B) Copy numbers of M. smithii among patients with constipation-predominant IBS (IBS-C), diarrhea-predominant IBS (IBS-D), and HC. (C) Correlation between copy numbers of M. smithii and number of stools per week. p<0.05 was considered as significant. *Bonferroni corrected p-value.
Fig. 2
Fig. 2
(A) Copy numbers of Methanobrevibacter smithii among methane producers and nonproducers. (B) Receiver operating characteristic curve showing the area under the curve (AUC). (C) Correlation between copy numbers of M. smithii and the AUC. p<0.05 was considered as significant.

References

    1. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006;130:1480–1491. doi: 10.1053/j.gastro.2005.11.061.
    1. Ghoshal UC, Shukla R, Ghoshal U, Gwee KA, Ng SC, Quigley EM. The gut microbiota and irritable bowel syndrome: friend or foe? Int J Inflam. 2012;2012:151085. doi: 10.1155/2012/151085.
    1. Parkes GC, Brostoff J, Whelan K, Sanderson JD. Gastrointestinal microbiota in irritable bowel syndrome: their role in its pathogenesis and treatment. Am J Gastroenterol. 2008;103:1557–1567. doi: 10.1111/j.1572-0241.2008.01869.x.
    1. Ohman L, Simrén M. New insights into the pathogenesis and pathophysiology of irritable bowel syndrome. Dig Liver Dis. 2007;39:201–215. doi: 10.1016/j.dld.2006.10.014.
    1. Pimentel M, Lembo A, Chey WD, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011;364:22–32. doi: 10.1056/NEJMoa1004409.
    1. Cash BD. Emerging role of probiotics and antimicrobials in the management of irritable bowel syndrome. Curr Med Res Opin. 2014;30:1405–1415. doi: 10.1185/03007995.2014.908278.
    1. Shukla R, Ghoshal U, Dhole TN, Ghoshal UC. Fecal microbiota in patients with irritable bowel syndrome compared with healthy controls using real-time polymerase chain reaction: an evidence of dysbiosis. Dig Dis Sci. 2015;60:2953–2962. doi: 10.1007/s10620-015-3607-y.
    1. Attaluri A, Jackson M, Valestin J, Rao SS. Methanogenic flora is associated with altered colonic transit but not stool characteristics in constipation without IBS. Am J Gastroenterol. 2010;105:1407–1411. doi: 10.1038/ajg.2009.655.
    1. Rana SV, Sinha SK, Sharma S, Kaur H, Bhasin DK, Singh K. Effect of predominant methanogenic flora on outcome of lactose hydrogen breath test in controls and irritable bowel syndrome patients of north India. Dig Dis Sci. 2009;54:1550–1554. doi: 10.1007/s10620-008-0532-3.
    1. Pimentel M, Lin HC, Enayati P, et al. Methane, a gas produced by enteric bacteria, slows intestinal transit and augments small intestinal contractile activity. Am J Physiol Gastrointest Liver Physiol. 2006;290:G1089–G1095. doi: 10.1152/ajpgi.00574.2004.
    1. Chatterjee S, Park S, Low K, Kong Y, Pimentel M. The degree of breath methane production in IBS correlates with the severity of constipation. Am J Gastroenterol. 2007;102:837–841. doi: 10.1111/j.1572-0241.2007.01072.x.
    1. Ghoshal UC, Srivastava D, Verma A, Misra A. Slow transit constipation associated with excess methane production and its improvement following rifaximin therapy: a case report. J Neurogastroenterol Motil. 2011;17:185–188. doi: 10.5056/jnm.2011.17.2.185.
    1. Pimentel M, Chatterjee S, Chow EJ, Park S, Kong Y. Neomycin improves constipation-predominant irritable bowel syndrome in a fashion that is dependent on the presence of methane gas: sub-analysis of a double-blind randomized controlled study. Dig Dis Sci. 2006;51:1297–1301. doi: 10.1007/s10620-006-9104-6.
    1. Ghoshal UC, Srivastava D, Misra A. Sa1378 Reduction of breath methane using rifaximin shortens colon transit time and improves constipation: a randomized double-blind placebo controlled trial. Gastroenterology. 2015;148:4 S. doi: 10.1016/S0016-5085(15)31017-9. uppl 1:S308–S309.
    1. Kim G, Deepinder F, Morales W, et al. Methanobrevibacter smithii is the predominant methanogen in patients with constipation-predominant IBS and methane on breath. Dig Dis Sci. 2012;57:3213–3218. doi: 10.1007/s10620-012-2197-1.
    1. Bajaj JS, Gillevet PM, Hylemon PB. Methanogenesis in irritable bowel syndrome: a lot of hot air? Dig Dis Sci. 2012;57:3045–3046. doi: 10.1007/s10620-012-2419-6.
    1. Rana SV, Sharma S, Sinha SK, Kaur H, Sikander A, Singh K. Incidence of predominant methanogenic flora in irritable bowel syndrome patients and apparently healthy controls from North India. Dig Dis Sci. 2009;54:132–135. doi: 10.1007/s10620-008-0315-x.
    1. Hattori T, Fukudo S. Use of Rome III criteria for diagnosing irritable bowel syndrome. Nihon Rinsho. 2006;64:1425–1428.
    1. Ghoshal UC, Gwee KA, Chen M, et al. Development, translation and validation of enhanced Asian Rome III questionnaires for diagnosis of functional bowel diseases in major Asian languages: a Rome Foundation-Asian Neurogastroenterology and Motility Association Working Team report. J Neurogastroenterol Motil. 2015;21:83–92. doi: 10.5056/jnm14045.
    1. Bartosch S, Fite A, Macfarlane GT, McMurdo ME. Characterization of bacterial communities in feces from healthy elderly volunteers and hospitalized elderly patients by using real-time PCR and effects of antibiotic treatment on the fecal microbiota. Appl Environ Microbiol. 2004;70:3575–3581. doi: 10.1128/AEM.70.6.3575-3581.2004.
    1. Dridi B, Henry M, El Khéchine A, Raoult D, Drancourt M. High prevalence of Methanobrevibacter smithii and Methanosphaera stadtmanae detected in the human gut using an improved DNA detection protocol. PLoS One. 2009;4:e7063. doi: 10.1371/journal.pone.0007063.
    1. Lyra A, Rinttilä T, Nikkilä J, et al. Diarrhoea-predominant irritable bowel syndrome distinguishable by 16S rRNA gene phylotype quantification. World J Gastroenterol. 2009;15:5936–5945. doi: 10.3748/wjg.15.5936.
    1. Ghoshal UC. How to interpret hydrogen breath tests. J Neurogastroenterol Motil. 2011;17:312–317. doi: 10.5056/jnm.2011.17.3.312.
    1. Ghoshal UC, Srivastava D, Ghoshal U, Misra A. Breath tests in the diagnosis of small intestinal bacterial overgrowth in patients with irritable bowel syndrome in comparison with quantitative upper gut aspirate culture. Eur J Gastroenterol Hepatol. 2014;26:753–760. doi: 10.1097/MEG.0000000000000122.
    1. Jang SI, Kim JH, Youn YH, Park H, Lee SI, Conklin JL. Relationship between intestinal gas and the development of right colonic diverticula. J Neurogastroenterol Motil. 2010;16:418–423. doi: 10.5056/jnm.2010.16.4.418.
    1. Triantafyllou K, Chang C, Pimentel M. Methanogens, methane and gastrointestinal motility. J Neurogastroenterol Motil. 2014;20:31–40. doi: 10.5056/jnm.2014.20.1.31.
    1. Rajilić-Stojanović M, Biagi E, Heilig HG, et al. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology. 2011;141:1792–1801. doi: 10.1053/j.gastro.2011.07.043.
    1. Weaver GA, Krause JA, Miller TL, Wolin MJ. Incidence of methanogenic bacteria in a sigmoidoscopy population: an association of methanogenic bacteria and diverticulosis. Gut. 1986;27:698–704. doi: 10.1136/gut.27.6.698.
    1. Agrawal A, Whorwell PJ. Review article: abdominal bloating and distension in functional gastrointestinal disorders: epidemiology and exploration of possible mechanisms. Aliment Pharmacol Ther. 2008;27:2–10. doi: 10.1111/j.1365-2036.2007.03549.x.
    1. Lacy BE, Gabbard SL, Crowell MD. Pathophysiology, evaluation, and treatment of bloating: hope, hype, or hot air? Gastroenterol Hepatol (N Y) 2011;7:729–739.
    1. Low K, Hwang L, Hua J, Zhu A, Morales W, Pimentel M. A combination of rifaximin and neomycin is most effective in treating irritable bowel syndrome patients with methane on lactulose breath test. J Clin Gastroenterol. 2010;44:547–550.

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