Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Intestinal gases: influence on gut disorders and the role of dietary manipulations

Nature Reviews Gastroenterology & Hepatology volume 16, pages 733–747 (2019)Cite this article

Subjects

Abstract

The inner workings of the intestines, in which the body and microbiome intersect to influence gut function and systemic health, remain elusive. Carbon dioxide, hydrogen, methane and hydrogen sulfide, as well as a variety of trace gases, are generated by the chemical interactions and microbiota within the gut. Profiling of these intestinal gases and their responses to dietary changes can reveal the products and functions of the gut microbiota and their influence on human health. Indeed, different tools for measuring these intestinal gases have been developed, including newly developed gas-sensing capsule technology. Gases can, according to their type, concentration and volume, induce or relieve abdominal symptoms, and might also have physiological, pathogenic and therapeutic effects. Thus, profiling and modulating intestinal gases could be powerful tools for disease prevention and/or therapy. As the interactions between the microbiota, chemical constituents and fermentative substrates of the gut are principally influenced by dietary intake, altering the diet, which, in turn, changes gas profiles, is the main therapeutic approach for gastrointestinal disorders. An improved understanding of the complex interactions within the intestines that generate gases will enhance our ability to prevent, diagnose, treat and monitor many gastrointestinal disorders.

Key points

  • Profiling intestinal gases enables assessment of the functions of the gut microbiome.

  • Intestinal gas composition can influence gut physiology and generate abdominal symptoms in patients with gastrointestinal disorders such as IBS and IBD.

  • Multiple different techniques have been developed for assessing intestinal gases, all of which are limited by the fact that they either measure intestinal gases indirectly or are highly invasive.

  • Ingestible gas-sensing capsules seem to be a very promising alternative to indirect or invasive techniques as they provide direct gas concentration measurements and are minimally invasive.

  • Intestinal gas profiles are predominantly influenced by the composition of the luminal microbiota and by consumed dietary substrates.

  • Dietary manipulations readily alter intestinal gas production and composition and are, therefore, attractive tools in the management of patients with gas-associated gastrointestinal disorders.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Transit of gases and food along the gut.
Fig. 2: Physiology of intestinal gases.
Fig. 3: Microbial pathways of gas and SCFA production for polysaccharides as the substrate intake.
Fig. 4: Indirect techniques for the measurement of gut gases.
Fig. 5: Breath testing for gut gases.
Fig. 6: Intestinal gas measurement using ingestible capsules.

Similar content being viewed by others

References

  1. Zmora, N., Suez, J. & Elinav, E. You are what you eat: diet, health and the gut microbiota. Nat. Rev. Gastroenterol. Hepatol. 16, 35–56 (2019).

    Article  CAS  PubMed  Google Scholar 

  2. David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2014).

    Article  CAS  PubMed  Google Scholar 

  3. Newlove-Delgado, T. V. et al. Dietary interventions for recurrent abdominal pain in childhood. Cochrane Database Syst. Rev. 3, CD010972 (2017).

    PubMed  Google Scholar 

  4. Bohn, L. et al. Diet low in FODMAPs reduces symptoms of irritable bowel syndrome as well as traditional dietary advice: a randomized controlled trial. Gastroenterology 149, 1399–1407 (2015).

    Article  PubMed  CAS  Google Scholar 

  5. Carbonero, F., Benefiel, A. C. & Gaskins, H. R. Contributions of the microbial hydrogen economy to colonic homeostasis. Nat. Rev. Gastroenterol. Hepatol. 9, 504–518 (2012).

    Article  CAS  PubMed  Google Scholar 

  6. Topping, D. L. & Clifton, P. M. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol. Res. 81, 1031–1064 (2001).

    CAS  Google Scholar 

  7. Arasaradnam, R. P., Covington, J. A., Harmston, C. & Nwokolo, C. U. Review article: next generation diagnostic modalities in gastroenterology – gas phase volatile compound biomarker detection. Aliment. Pharmacol. Ther. 39, 780–789 (2014).

    Article  CAS  PubMed  Google Scholar 

  8. Berean, K. J. et al. The safety and sensitivity of a telemetric capsule to monitor gastrointestinal hydrogen production in vivo in healthy subjects: a pilot trial comparison to concurrent breath analysis. Aliment. Pharmacol. Ther. 48, 646–654 (2018).

    Article  CAS  PubMed  Google Scholar 

  9. Pillai, N. et al. An in-vitro upper gut simulator for assessing continuous gas production: a proof-of-concept using milk digestion. J. Funct. Foods 47, 200–210 (2018).

    Article  CAS  Google Scholar 

  10. Lacy, B. E., Gabbard, S. L. & Crowell, M. D. Pathophysiology, evaluation, and treatment of bloating: hope, hype, or hot air? Gastroenterol. Hepatol. 7, 729–739 (2011).

    Google Scholar 

  11. Suarez, F., Furne, J., Springfield, J. & Levitt, M. Insights into human colonic physiology obtained from the study of flatus composition. Am. J. Physiol. Gastrointest. Liver Physiol. 272, G1028–G1033 (1997).

    Article  CAS  Google Scholar 

  12. Sahakian, A. B., Jee, S. R. & Pimentel, M. Methane and the gastrointestinal tract. Dig. Liver Dis. 55, 2135–2143 (2010).

    Google Scholar 

  13. Levitt, M. D. Volume and composition of human intestinal gas determined by means of an intestinal washout technic. N. Engl. J. Med. 284, 1394–1398 (1971).

    Article  CAS  PubMed  Google Scholar 

  14. Levitt, M. D. & Bond, J. H. Volume, composition, and source of intestinal gas. Gastroenterology 59, 921–929 (1970).

    Article  CAS  PubMed  Google Scholar 

  15. Bettinger, C. J. Materials advances for next-generation ingestible electronic medical devices. Trends Biotechnol. 33, 575–585 (2015).

    Article  CAS  PubMed  Google Scholar 

  16. Konturek, P. C., Konturek, S. J. & Ochmański, W. Neuroendocrinology of gastric H+ and duodenal HCO3 − secretion: the role of brain–gut axis. Eur. J. Pharmacol. 499, 15–27 (2004).

    Article  CAS  PubMed  Google Scholar 

  17. Yao, C. K., Muir, J. G. & Gibson, P. R. Review article: insights into colonic protein fermentation, its modulation and potential health implications. Aliment. Pharmacol. Ther. 43, 181–196 (2016).

    Article  CAS  PubMed  Google Scholar 

  18. Marchesi, J. R. et al. The gut microbiota and host health: a new clinical frontier. Gut 65, 330–339 (2016).

    Article  PubMed  Google Scholar 

  19. El Kaoutari, A., Armougom, F., Gordon, J. I., Raoult, D. & Henrissat, B. The abundance and variety of carbohydrate-active enzymes in the human gut microbiota. Nat. Rev. Microbiol. 11, 497–504 (2013).

    Article  CAS  PubMed  Google Scholar 

  20. Eckburg, P. B. et al. Diversity of the human intestinal microbial flora. Science 308, 1635–1638 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Ze, X., Duncan, S. H., Louis, P. & Flint, H. J. Ruminococcus bromii is a keystone species for the degradation of resistant starch in the human colon. ISME J. 6, 1535–1543 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Mowat, A. M. & Agace, W. W. Regional specialization within the intestinal immune system. Nat. Rev. Immunol. 14, 667–685 (2014).

    Article  CAS  PubMed  Google Scholar 

  23. Simren, M. et al. Intestinal microbiota in functional bowel disorders: a Rome Foundation report. Gut 62, 159–176 (2013).

    Article  PubMed  Google Scholar 

  24. Kalantar-Zadeh, K. et al. A human pilot trial of ingestible electronic capsules capable of sensing different gases in the gut. Nat. Electron. 1, 79–87 (2018).

    Article  Google Scholar 

  25. Gill, P. A., van Zelm, M. C., Muir, J. G. & Gibson, P. R. Short chain fatty acids as potential therapeutic agents in human gastrointestinal and inflammatory disorders. Aliment. Pharmacol. Ther. 48, 15–34 (2018).

    Article  CAS  PubMed  Google Scholar 

  26. Scott, K. P., Gratz, S. W., Sheridan, P. O., Flint, H. J. & Duncan, S. H. The influence of diet on the gut microbiota. Pharmacol. Res. 69, 52–60 (2013).

    Article  CAS  PubMed  Google Scholar 

  27. Ong, A. M. L. et al. Diaphragmatic breathing reduces belching and proton pump inhibitor refractory gastroesophageal reflux symptoms. Clin. Gastroenterol. Hepatol. 16, 407–416.e2 (2018).

    Article  PubMed  Google Scholar 

  28. Gasbarrini, A. et al. Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome Consensus Conference. Aliment. Pharmacol. Ther. 29, 1–3 (2009).

    PubMed  Google Scholar 

  29. Vernia, P., Di Camillo, M. & Marinaro, V. Lactose malabsorption, irritable bowel syndrome and self-reported milk intolerance. Dig. Liver Dis. 33, 234–239 (2001).

    Article  CAS  PubMed  Google Scholar 

  30. Drossman, D. A. The functional gastrointestinal disorders and the Rome II process. Gut 45, 1–5 (1999).

    Article  Google Scholar 

  31. Basilisco, G., Marino, B., Passerini, L. & Ogliari, C. Abdominal distension after colonic lactulose fermentation recorded by a new extensometer. J. Neurogastroenterol. Motil. 15, 427–433 (2003).

    Article  CAS  Google Scholar 

  32. Attar, A. et al. Comparison of a low dose polyethylene glycol electrolyte solution with lactulose for treatment of chronic constipation. Gut 44, 226–230 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wang, R. Physiological implications of hydrogen sulfide: a whiff exploration that blossomed. Physiol. Res. 92, 791–896 (2012).

    CAS  Google Scholar 

  34. Medani, M. et al. Emerging role of hydrogen sulfide in colonic physiology and pathophysiology. Inflamm. Bowel Dis. 17, 1620–1625 (2011).

    Article  PubMed  Google Scholar 

  35. Matsunami, M. et al. Luminal hydrogen sulfide plays a pronociceptive role in mouse colon. Gut 58, 751–761 (2009).

    Article  CAS  PubMed  Google Scholar 

  36. Li, H., Wang, Y. J., Wang, S. R. & Chen, O. Y. Comments and hypotheses on the mechanism of methane against ischemia/reperfusion injury. Med. Gas Res. 7, 120–123 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Naito, Y., Uchiyama, K. & Takagi, T. Redox-related gaseous mediators in the gastrointestinal tract. J. Clin. Biochem. Nutr. 63, 1–4 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Dupont, A. W. & Dupont, H. L. The intestinal microbiota and chronic disorders of the gut. Nat. Rev. Gastroenterol. Hepatol. 8, 523–531 (2011).

    Article  PubMed  Google Scholar 

  39. Laine, L., Takeuchi, K. & Tarnawski, A. Gastric mucosal defense and cytoprotection: bench to bedside. Gastroenterology 135, 41–60 (2008).

    Article  CAS  PubMed  Google Scholar 

  40. Abdel-Salam, O. M. E., Czimmer, J., Debreceni, A., Szolcsányi, J. & Mózsik, G. Gastric mucosal integrity: gastric mucosal blood flow and microcirculation. An overview. J. Physiol. Paris 95, 105–127 (2001).

    Article  CAS  PubMed  Google Scholar 

  41. Ou, J. Z. et al. Potential of in vivo real-time gastric gas profiling: a pilot evaluation of heat-stress and modulating dietary cinnamon effect in an animal model. Sci. Rep. 6, 33387 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Gäbel, G., Vogler, S. & Martens, H. Short-chain fatty acids and CO2 as regulators of Na+ and Cl− absorption in isolated sheep rumen mucosa. J. Comp. Physiol. B 161, 419–426 (1991).

    Article  PubMed  Google Scholar 

  43. Kurada, S., Alkhouri, N., Fiocchi, C., Dweik, R. & Rieder, F. Review article: breath analysis in inflammatory bowel diseases. Aliment. Pharmacol. Ther. 41, 329–341 (2016).

    Article  CAS  Google Scholar 

  44. Ma, N., Tian, Y., Wu, Y. & Ma, X. Contributions of the interaction between dietary protein and gut microbiota to intestinal health. Curr. Protein Pept. Sci. 18, 795–808 (2017).

    CAS  PubMed  Google Scholar 

  45. Yao, C. K. et al. Modulation of colonic hydrogen sulfide production by diet and mesalazine utilizing a novel gas-profiling technology. Gut Microbes 9, 510–522 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Ahlquist, D. A. Universal cancer screening: revolutionary, rational, and realizable. NPJ Precis. Oncol. 2, 23 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Altomare, D. F. et al. Exhaled volatile organic compounds identify patients with colorectal cancer. Br. J. Surg. 100, 144–150 (2013).

    Article  CAS  PubMed  Google Scholar 

  48. Bond, A. et al. Volatile organic compounds emitted from faeces as a biomarker for colorectal cancer. Aliment. Pharmacol. Ther. 49, 1005–1012 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Krilaviciute, A., Stock, C., Leja, M. & Brenner, H. Potential of non-invasive breath tests for preselecting individuals for invasive gastric cancer screening endoscopy. J. Breath Res. 12, 036009 (2018).

    Article  CAS  PubMed  Google Scholar 

  50. Modak, A. S. Stable isotope breath tests in clinical medicine: a review. J. Breath Res. 1, 014003 (2007).

    Article  PubMed  Google Scholar 

  51. Kolkman, J. J., Otte, J. A. & Groeneveld, A. B. J. Gastrointestinal luminal P(CO2) tonometry: an update on physiology, methodology and clinical applications. Br. J. Anaesth. 84, 74–86 (2000).

    Article  CAS  PubMed  Google Scholar 

  52. Ghoos, Y. F. et al. Measurement of gastric emptying rate of solids by means of a carbon-labeled octanoic acid breath test. Gastroenterology 104, 1640–1647 (1993).

    Article  CAS  PubMed  Google Scholar 

  53. Modak, A. Breath tests with 13C substrates. J. Breath Res. 3, 040201 (2009).

    Article  PubMed  Google Scholar 

  54. Louis, P., Hold, G. L. & Flint, H. J. The gut microbiota, bacterial metabolites and colorectal cancer. Nat. Rev. Microbiol. 12, 661–672 (2014).

    Article  CAS  PubMed  Google Scholar 

  55. Nakamura, N., Lin, H. C., McSweeney, C. S., MacKie, R. I. & Rex Gaskins, H. Mechanisms of microbial hydrogen disposal in the human colon and implications for health and disease. Annu. Rev. Food Sci. Technol. 1, 363–395 (2010).

    Article  CAS  PubMed  Google Scholar 

  56. Levitt, M. D. Production and excretion of hydrogen gas in man. N. Engl. J. Med. 281, 122–127 (1969).

    Article  CAS  PubMed  Google Scholar 

  57. Christl, S. U., Murgatroyd, P. R., Gibson, G. R. & Cummings, J. H. Production, metabolism, and excretion of hydrogen in the large-intestine. Gastroenterology 102, 1269–1277 (1992).

    Article  CAS  PubMed  Google Scholar 

  58. Chassard, C. et al. Assessment of metabolic diversity within the intestinal microbiota from healthy humans using combined molecular and cultural approaches. FEMS Microbiol. Ecol. 66, 496–504 (2008).

    Article  CAS  PubMed  Google Scholar 

  59. Nava, G. M., Carbonero, F., Croix, J. A., Greenberg, E. & Gaskins, H. R. Abundance and diversity of mucosa-associated hydrogenotrophic microbes in the healthy human colon. ISME J. 6, 57–70 (2012).

    Article  CAS  PubMed  Google Scholar 

  60. Duncan, S. H., Hold, G. L., Barcenilla, A., Stewart, C. S. & Flint, H. J. Roseburia intestinalis sp nov., a novel saccharolytic, butyrate-producing bacterium from human faeces. Int. J. Syst. Evol. Microbiol. 52, 1615–1620 (2002).

    CAS  PubMed  Google Scholar 

  61. Simmering, R. et al. Ruminococcus luti sp nov., isolated from a human faecal sample. Syst. Appl. Microbiol. 25, 189–193 (2002).

    Article  CAS  PubMed  Google Scholar 

  62. Chassard, C., Delmas, E., Lawson, P. A. & Bernalier-Donadille, A. Bacteroides xylanisolvens sp nov., a xylan-degrading bacterium isolated from human faeces. Int. J. Syst. Evol. Microbiol. 58, 1008–1013 (2008).

    Article  CAS  PubMed  Google Scholar 

  63. Cummings, J. H. & Englyst, H. N. Measurement of starch fermentation in the human large-intestine. Can. J. Physiol. Pharmacol. 69, 121–129 (1991).

    Article  CAS  PubMed  Google Scholar 

  64. Skoog, S. M., Bharucha, A. E. & Zinsmeister, A. R. Comparison of breath testing with fructose and high fructose corn syrups in health and IBS. J. Neurogastroenterol. Motil. 20, 505–511 (2008).

    Article  CAS  Google Scholar 

  65. Marthinsen, D. & Fleming, S. E. Excretion of breath and flatus gases by humans consuming high-fiber diets. J. Nutr. 112, 1133–1143 (1982).

    Article  CAS  PubMed  Google Scholar 

  66. Miller, T. L. & Wolin, M. J. Methanosphaera-stadtmaniae gen. nov., sp. nov.: a species that forms methane by reducing methanol with hydrogen. Arch. Microbiol. 141, 116–122 (1985).

    Article  CAS  PubMed  Google Scholar 

  67. Gottlieb, K., Wacher, V., Sliman, J. & Pimentel, M. Review article: inhibition of methanogenic archaea by statins as a targeted management strategy for constipation and related disorders. Aliment. Pharmacol. Ther. 43, 197–212 (2016).

    Article  CAS  PubMed  Google Scholar 

  68. Triantafyllou, K., Chang, C. & Pimentel, M. Methanogens, methane and gastrointestinal motility. J. Neurogastroenterol. Motil. 20, 31–40 (2014).

    Article  PubMed  Google Scholar 

  69. Pochart, P., Dore, J., Lemann, F., Goderel, I. & Rambaud, J. C. Interrelations between populations of methanogenic archaea and sulfate-reducing bacteria in the human colon. FEMS Microbiol. Lett. 98, 225–228 (1992).

    Article  CAS  Google Scholar 

  70. Miller, T. L. & Wolin, M. J. Methanogens in human and animal intestinal tracts. Syst. Appl. Microbiol. 7, 223–229 (1986).

    Article  CAS  Google Scholar 

  71. Ong, D. K. et al. Manipulation of dietary short chain carbohydrates alters the pattern of gas production and genesis of symptoms in irritable bowel syndrome. J. Gastroenterol. Hepatol. 25, 1366–1373 (2010).

    Article  CAS  PubMed  Google Scholar 

  72. Bond, J. H., Engel, R. R. & Levitt, M. D. Factors influencing pulmonary methane excretion in man – indirect method of studying in-situ metabolism of methane-producing colonic bacteria. J. Exp. Med. 133, 572–588 (1971).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Peled, Y., Gilat, T., Liberman, E. & Bujanover, Y. The development of methane production in childhood and adolescence. J. Pediatr. Gastroenterol. Nutr. 4, 575–579 (1985).

    Article  CAS  PubMed  Google Scholar 

  74. 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. 102, 837–841 (2007).

    Article  CAS  PubMed  Google Scholar 

  75. Houben, E., De Preter, V., Billen, J., Van Ranst, M. & Verbeke, K. Additional value of CH4 measurement in a combined C-13/H2 lactose malabsorption breath test: a retrospective analysis. Nutrients 7, 7469–7485 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Gibson, G. R., Macfarlane, S. & Macfarlane, G. T. Metabolic interactions involving sulfate-reducing and methanogenic bacteria in the human large-intestine. FEMS Microbiol. Ecol. 12, 117–125 (1993).

    Article  CAS  Google Scholar 

  77. Wang, R. Two’s company, three’s a crowd: can H2S be the third endogenous gaseous transmitter? FASEB J. 16, 1792–1798 (2002).

    Article  CAS  PubMed  Google Scholar 

  78. Roediger, W. E. W. Review article: nitric oxide from dysbiotic bacterial respiration of nitrate in the pathogenesis and as a target for therapy of ulcerative colitis. Aliment. Pharmacol. Ther. 27, 531–541 (2008).

    Article  CAS  PubMed  Google Scholar 

  79. Tomasova, L., Konopelski, P. & Ufnal, M. Gut bacteria and hydrogen sulfide: the new old players in circulatory system homeostasis. Molecules 21, E1558 (2016).

    Article  PubMed  CAS  Google Scholar 

  80. Lefebvre, R. A. Non-adrenergic non-cholinergic neurotransmission in the proximal stomach. Gen. Pharmacol. 24, 257–266 (1993).

    Article  CAS  PubMed  Google Scholar 

  81. Stark, M. E. & Szurszewski, J. H. Role of nitric oxide in gastrointestinal and hepatic function and disease. Gastroenterology 103, 1928–1949 (1992).

    Article  CAS  PubMed  Google Scholar 

  82. Kalff, J. C., Schraut, W. H., Billiar, T. R., Simmons, R. L. & Bauer, A. J. Role of inducible nitric oxide synthase in postoperative intestinal smooth muscle dysfunction in rodents. Gastroenterology 118, 316–327 (2000).

    Article  CAS  PubMed  Google Scholar 

  83. Magierowski, M., Magierowska, K., Kwiecien, S. & Brzozowski, T. Gaseous mediators nitric oxide and hydrogen sulfide in the mechanism of gastrointestinal integrity, protection and ulcer healing. Molecules 20, 9099–9123 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Reade, S. et al. Potential role of fecal volatile organic compounds as biomarkers of chemically induced intestinal inflammation in mice. FASEB J. 33, 3129–3136 (2018).

    Article  PubMed  Google Scholar 

  85. Rossi, M. et al. Volatile organic compounds in feces associate with response to dietary intervention in patients with irritable bowel syndrome. Clin. Gastroenterol. Hepatol. 16, 385–391.e1 (2018).

    Article  CAS  PubMed  Google Scholar 

  86. Japikse, C. (ed) Fart Proudly: Writings of Benjamin Franklyn You Never Read in School (Frog Books, 2003).

  87. Kim, K. H., Jahan, S. A. & Kabir, E. A review of breath analysis for diagnosis of human health. TrAC Trends Anal. Chem. 33, 1–8 (2012).

    Article  CAS  Google Scholar 

  88. Kalantar-Zadeh, K., Ha, N., Ou, J. Z. & Berean, K. J. Ingestible sensors. ACS Sens. 2, 468–483 (2017).

    Article  CAS  PubMed  Google Scholar 

  89. Zhang, S., Wang, H. & Zhu, M. J. A sensitive GC/MS detection method for analyzing microbial metabolites short chain fatty acids in fecal and serum samples. Talanta 196, 249–254 (2019).

    Article  CAS  PubMed  Google Scholar 

  90. Wu, H. et al. Metabolomic study for diagnostic model of oesophageal cancer using gas chromatography/mass spectrometry. J. Chromatogr. B 877, 3111–3117 (2009).

    Article  CAS  Google Scholar 

  91. Braden, B. Methods and functions: breath tests. Best Pract. Res. Clin. Gastroenterol. 23, 337–352 (2009).

    Article  CAS  PubMed  Google Scholar 

  92. Sivieri, K. et al. Prebiotic effect of fructooligosaccharide in the simulator of the human intestinal microbial ecosystem (SHIME(®) model). J. Med. Food 17, 894–901 (2014).

    Article  CAS  PubMed  Google Scholar 

  93. Venema, K. & van den Abbeele, P. Experimental models of the gut microbiome. Best Pract. Res. Clin. Gastroenterol. 27, 115–126 (2013).

    Article  CAS  PubMed  Google Scholar 

  94. Aguirre, M. et al. Evaluation of an optimal preparation of human standardized fecal inocula for in vitro fermentation studies. J. Microbiol. Methods 117, 78–84 (2015).

    Article  PubMed  Google Scholar 

  95. Dura, A., Rose, D. J. & Rosell, C. M. Enzymatic modification of corn starch influences human fecal fermentation profiles. J. Agric. Food Chem. 65, 4651–4657 (2017).

    Article  CAS  PubMed  Google Scholar 

  96. Moon, J. S., Li, L., Bang, J. & Han, N. S. Application of in vitro gut fermentation models to food components: a review. Food Sci. Biotechnol. 25, 1–7 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Wang, X. & Gibson, G. R. Effects of the in vitro fermentation of oligofructose and inulin by bacteria growing in the human large intestine. J. Appl. Bacteriol. 75, 373–380 (1993).

    Article  CAS  PubMed  Google Scholar 

  98. Rotbart, A. et al. Designing an in-vitro gas profiling system for human faecal samples. Sens. Actuators B Chem. 238, 754–764 (2017).

    Article  CAS  Google Scholar 

  99. Hernot, D. C. et al. In vitro fermentation profiles, gas production rates, and microbiota modulation as affected by certain fructans, galactooligosaccharides, and polydextrose. J. Agric. Food Chem. 57, 1354–1361 (2009).

    Article  CAS  PubMed  Google Scholar 

  100. Riviere, A., Selak, M., Lantin, D., Leroy, F. & De Vuyst, L. Bifidobacteria and butyrate-producing colon bacteria: importance and strategies for their stimulation in the human gut. Front. Microbiol. 7, 979 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  101. Williams, B. A., Grant, L. J., Gidley, M. J. & Mikkelsen, D. Gut fermentation of dietary fibres: physico-chemistry of plant cell walls and implications for health. Int. J. Mol. Sci. 18, E2203 (2017).

    Article  PubMed  CAS  Google Scholar 

  102. Dear, K. L. E., Elia, M. & Hunter, J. O. Do interventions which reduce colonic bacterial fermentation improve symptoms of irritable bowel syndrome? Dig. Liver Dis. 50, 758–766 (2005).

    CAS  Google Scholar 

  103. Sonko, B. J., Prentice, A. M., Coward, W. A., Murgatroyd, P. R. & Goldberg, G. R. Dose-response relationship between fat ingestion and oxidation: quantitative estimation using whole-body calorimetry and C-13 isotope ratio mass spectrometry. Dig. Liver Dis. 55, 10–18 (2001).

    CAS  Google Scholar 

  104. King, T. S., Elia, M. & Hunter, J. O. Abnormal colonic fermentation in irritable bowel syndrome. Lancet 352, 1187–1189 (1998).

    Article  CAS  PubMed  Google Scholar 

  105. Hanf, S., Bogozi, T., Keiner, R., Frosch, T. & Popp, J. Fast and highly sensitive fiber-enhanced raman spectroscopic monitoring of molecular H2 and CH4 for point-of-care diagnosis of malabsorption disorders in exhaled human breath. Analyt. Chem. 87, 982–988 (2015).

    Article  CAS  Google Scholar 

  106. Rezaie, A. et al. Hydrogen and methane-based breath testing in gastrointestinal disorders: the North American consensus. Am. J. Gastroenterol. 112, 775–784 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Ghoshal, U. C. How to interpret hydrogen breath tests. J. Neurogastroenterol. Motil. 17, 312–317 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  108. Lin, E. C. & Massey, B. T. Scintigraphy demonstrates high rate of false-positive results from glucose breath tests for small bowel bacterial overgrowth. Clin. Gastroenterol. Hepatol. 14, 203–208 (2016).

    Article  PubMed  Google Scholar 

  109. Nucera, G. et al. Abnormal breath tests to lactose, fructose and sorbitol in irritable bowel syndrome may be explained by small intestinal bacterial overgrowth. Aliment. Pharmacol. Ther. 21, 1391–1395 (2005).

    Article  CAS  PubMed  Google Scholar 

  110. Szilagyi, A. et al. Comparison of a real-time polymerase chain reaction assay for lactase genetic polymorphism with standard indirect tests for lactose maldigestion. Clin. Gastroenterol. Hepatol. 5, 192–196 (2007).

    Article  CAS  PubMed  Google Scholar 

  111. Ghoshal, U. C., Kumar, S., Misra, A. & Mittal, B. Lactose malabsorption diagnosed by 50-g dose is inferior to assess clinical intolerance and to predict response to milk withdrawal than 25-g dose in an endemic area. J. Gastroenterol. Hepatol. 28, 1462–1468 (2013).

    Article  CAS  PubMed  Google Scholar 

  112. Perez, F., Accarino, A., Azpiroz, F., Quiroga, S. & Malagelada, J. R. Gas distribution within the human gut: effect of meals. Am. J. Gastroenterol. 102, 842–849 (2007).

    Article  PubMed  Google Scholar 

  113. Mc Williams, S. R. et al. Computed tomography assessment of intestinal gas volumes in functional gastrointestinal disorders. J. Neurogastroenterol. Motil. 18, 419–425 (2012).

    Article  Google Scholar 

  114. Murray, K. et al. Differential effects of FODMAPs (fermentable oligo-, di-, mono-saccharides and polyols) on small and large intestinal contents in healthy subjects shown by MRI. Am. J. Gastroenterol. 109, 110–119 (2014).

    Article  CAS  PubMed  Google Scholar 

  115. Park, S. Y., Khemani, D., Nelson, A. D., Eckert, D. & Camilleri, M. Rectal gas volume measured by computerized tomography identifies evacuation disorders in patients with constipation. Clin. Gastroenterol. Hepatol. 15, 543–552 (2017).

    Article  PubMed  Google Scholar 

  116. Major, G. et al. Colon hypersensitivity to distension, rather than excessive gas production, produces carbohydrate-related symptoms in individuals with irritable bowel syndrome. Gastroenterology 152, 124–133 (2017).

    Article  PubMed  Google Scholar 

  117. Furne, J. K. & Levitt, M. D. Factors influencing frequency of flatus emission by healthy subjects. Dig. Dis. Sci. 41, 1631–1635 (1996).

    Article  CAS  PubMed  Google Scholar 

  118. Dickson, I. Gas-sensing gut capsules. Nat. Rev. Gastroenterol. Hepatol. 15, 130–131 (2018).

    PubMed  Google Scholar 

  119. Steiger, C. et al. Ingestible electronics for diagnostics and therapy. Nat. Rev. Mater. 4, 83–98 (2019).

    Article  CAS  Google Scholar 

  120. Tang, T. B. et al. Toward a miniature wireless integrated multisensor microsystem for industrial and biomedical applications. IEEE Sens. J. 2, 628–635 (2002).

    Article  CAS  Google Scholar 

  121. Kalantar-Zadeh, K. et al. Intestinal gas capsules: a proof-of-concept demonstration. Gastroenterology 150, 37–39 (2016).

    Article  PubMed  Google Scholar 

  122. Ou, J. Z. et al. Human intestinal gas measurement systems: in vitro fermentation and gas capsules. Trends Biotechnol. 33, 208–213 (2015).

    Article  CAS  PubMed  Google Scholar 

  123. Wu, G. D. et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 334, 105–108 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Gibson, P. R., Varney, J., Malakar, S. & Muir, J. G. Food components and irritable bowel syndrome. Gastroenterology 148, 1158–1174 (2015).

    Article  PubMed  Google Scholar 

  125. Burri, E. et al. Mechanisms of postprandial abdominal bloating and distension in functional dyspepsia. Gut 63, 395–400 (2014).

    Article  PubMed  Google Scholar 

  126. Eswaran, S., Tack, J. & Chey, W. D. Food: the forgotten factor in the irritable bowel syndrome. Gastroenterol. Clin. North Am. 40, 141–162 (2011).

    Article  PubMed  Google Scholar 

  127. Gibson, P. R., Newnham, E., Barrett, J. S., Shepherd, S. J. & Muir, J. G. Review article: fructose malabsorption and the bigger picture. Aliment. Pharmacol. Ther. 25, 349–363 (2007).

    Article  CAS  PubMed  Google Scholar 

  128. Halmos, E. P., Power, V. A., Shepherd, S. J., Gibson, P. R. & Muir, J. G. A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology 146, 67–75 (2014).

    Article  CAS  PubMed  Google Scholar 

  129. Manichanh, C. et al. Anal gas evacuation and colonic microbiota in patients with flatulence: effect of diet. Gut 63, 401–408 (2014).

    Article  PubMed  Google Scholar 

  130. Tomlin, J., Lowis, C. & Read, N. W. Investigation of normal flatus production in healthy-volunteers. Gut 32, 665–669 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Cummings, J. H. & Englyst, H. N. What is dietary fibre? Trends Food Sci. Technol. 2, 99–103 (1991).

    Article  CAS  Google Scholar 

  132. Swallow, D. M., Poulter, M. & Hollox, E. J. Intolerance to lactose and other dietary sugars. Drug Metab. Dispos. 29, 513–516 (2001).

    CAS  PubMed  Google Scholar 

  133. Shepherd, S. J., Parker, F. C., Muir, J. G. & Gibson, P. R. Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebo-controlled evidence. Clin. Gastroenterol. Hepatol. 6, 765–771 (2008).

    Article  CAS  PubMed  Google Scholar 

  134. De Preter, V. et al. Baseline microbiota activity and influence responses to prebiotic initial bifidobacteria counts dosing in healthy subjects. Aliment. Pharmacol. Ther. 27, 504–513 (2008).

    Article  PubMed  CAS  Google Scholar 

  135. Barrett, J. S. & Gibson, P. R. Fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) and nonallergic food intolerance: FODMAPs or food chemicals? Ther. Adv. Gastroenterol. 5, 261–268 (2012).

    Article  Google Scholar 

  136. Flint, H. J., Scott, K. P., Duncan, S. H., Louis, P. & Forano, E. Microbial degradation of complex carbohydrates in the gut. Gut Microbes 3, 289–306 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  137. Tran, T. H. T. et al. Adding mucins to an in vitro batch fermentation model of the large intestine induces changes in microbial population isolated from porcine feces depending on the substrate. FEMS Microbiol. Ecol. 92, fiv165 (2016).

    Article  CAS  Google Scholar 

  138. Roberfroid, M. et al. Prebiotic effects: metabolic and health benefits. Br. J. Nutr. 104, S1–S63 (2010).

    Article  CAS  PubMed  Google Scholar 

  139. Shepherd, S. J., Lomer, M. C. E. & Gibson, P. R. Short-chain carbohydrates and functional gastrointestinal disorders. Am. J. Gastroenterol. 108, 707–717 (2013).

    Article  CAS  PubMed  Google Scholar 

  140. Eswaran, S., Muir, J. & Chey, W. D. Fiber and functional gastrointestinal disorders. Am. J. Gastroenterol. 108, 718–727 (2013).

    Article  CAS  PubMed  Google Scholar 

  141. Gibson, G. R. et al. Expert consensus document: the International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat. Rev. Gastroenterol. Hepatol. 14, 491–502 (2017).

    Article  PubMed  Google Scholar 

  142. Cummings, J. H. & Macfarlane, G. T. The control and consequences of bacterial fermentation in the human colon. J. Appl. Bacteriol. 70, 443–459 (1991).

    Article  CAS  PubMed  Google Scholar 

  143. Davila, A. M. et al. Intestinal luminal nitrogen metabolism: role of the gut microbiota and consequences for the host. Pharmacol. Res. 68, 95–107 (2013).

    Article  CAS  PubMed  Google Scholar 

  144. Rawlings, N. D., Barrett, A. J. & Finn, R. Twenty years of the MEROPS database of proteolytic enzymes, their substrates and inhibitors. Nucleic Acids Res. 44, D343–D350 (2016).

    Article  CAS  PubMed  Google Scholar 

  145. Windey, K., de Preter, V. & Verbeke, K. Relevance of protein fermentation to gut health. Mol. Nutr. Food Res. 56, 184–196 (2012).

    Article  CAS  PubMed  Google Scholar 

  146. Kim, J., Hetzel, M., Boiangiu, C. D. & Buckel, W. Dehydration of (R)-2-hydroxyacyl-CoA to enoyl-CoA in the fermentation of alpha-amino acids by anaerobic bacteria. FEMS Microbiol. Rev. 28, 455–468 (2004).

    Article  CAS  PubMed  Google Scholar 

  147. Portune, K. J. et al. Gut microbiota role in dietary protein metabolism and health-related outcomes: the two sides of the coin. Trends Food Sci. Technol. 57, 213–232 (2016).

    Article  CAS  Google Scholar 

  148. Hughes, R., Magee, E. A. M. & Bingham, S. Protein degradation in the large intestine: relevance to colorectal cancer. Curr. Issues Intest. Microbiol. 1, 51–58 (2000).

    CAS  PubMed  Google Scholar 

  149. Magee, E. A., Richardson, C. J., Hughes, R. & Cummings, J. H. Contribution of dietary protein to sulfide production in the large intestine: an in vitro and a controlled feeding study in humans. Am. J. Gastroenterol. 72, 1488–1494 (2000).

    CAS  Google Scholar 

  150. Lust, M., Nandurkar, S. & Gibson, P. R. Measurement of faecal fat excretion: an evaluation of attitudes and practices of Australian gastroenterologists. J. Gen. Intern. Med. 36, 77–85 (2006).

    CAS  Google Scholar 

  151. Brinkworth, G. D., Noakes, M., Clifton, P. M. & Bird, A. R. Comparative effects of very low-carbohydrate, high-fat and high-carbohydrate, low-fat weight-loss diets on bowel habit and faecal short-chain fatty acids and bacterial populations. Br. J. Nutr. 101, 1493–1502 (2009).

    Article  CAS  PubMed  Google Scholar 

  152. Zhang, C. H. et al. Structural resilience of the gut microbiota in adult mice under high-fat dietary perturbations. ISME J. 6, 1848–1857 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Cani, P. D. et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56, 1761–1772 (2007).

    Article  CAS  PubMed  Google Scholar 

  154. Masset, J. et al. Fermentative hydrogen production from glucose and starch using pure strains and artificial co-cultures of Clostridium spp. Biotechnol. Biofuels 5, 35 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Calusinska, M., Happe, T., Joris, B. & Wilmotte, A. The surprising diversity of clostridial hydrogenases: a comparative genomic perspective. Microbiology 156, 1575–1588 (2010).

    Article  CAS  PubMed  Google Scholar 

  156. Molly, K., Woestyne, M. V., Smet, I. D. & Verstraete, W. Validation of the simulator of the human intestinal microbial ecosystem (SHIME) reactor using microorganism-associated activities. Microb. Ecol. Health Dis. 7, 191–200 (1994).

    Article  Google Scholar 

Download references

Acknowledgements

The authors acknowledge financial support from the National Health and Medical Research Council (NHMRC) of Australia (Development Grant, APP1154969).

Author information

Authors and Affiliations

  1. School of Chemical Engineering, University of New South Wales (UNSW), Kensington, NSW, Australia

    Kourosh Kalantar-Zadeh & Kyle J. Berean

  2. School of Engineering, RMIT University, Melbourne, VIC, Australia

    Kyle J. Berean

  3. Atmo Biosciences, Box Hill, VIC, Australia

    Kyle J. Berean

  4. Department of Gastroenterology, Monash University and Alfred Health, Melbourne, VIC, Australia

    Rebecca E. Burgell, Jane G. Muir & Peter R. Gibson

Authors
  1. Kourosh Kalantar-Zadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kyle J. Berean
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rebecca E. Burgell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jane G. Muir
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peter R. Gibson
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

K.K.-Z., K.J.B., R.E.B. and P.R.G. researched data for the article. K.K.-Z. and P.R.G. made substantial contributions to discussion of the article contents. K.K.-Z., R.E.B. and P.R.G. wrote the manuscript. All authors reviewed and/or edited the manuscript before submission.

Corresponding authors

Correspondence to Kourosh Kalantar-Zadeh or Peter R. Gibson.

Ethics declarations

Competing interests

K.K.-Z, P.R.G. and K.J.B. are the lead scientific advisor, lead medical advisor and chief technical officer for Atmo Biosciences, respectively, a company that owns the patents related to swallowable capsules for profiling gases along the gut. R.E.B., J.G.M. and P.R.G. declare that their affiliation, Monash University, financially gains from the sales of digital applications, booklets and education tools associated with the low FODMAP diet.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Fermentation

The chemical breakdown of a substance by microorganisms, typically involving effervescence and the production of heat.

Volatile organic compounds

(VOCs). Organic chemicals that have a high vapour pressure at near room temperature.

Flatus

Gas that is expelled from the colon via the anus.

Headspace gas

The gas that occupies the volume of the gut that is not filled with the gut liquid.

Short-chain fatty acids

(SCFAs). Fatty acids with fewer than six carbon atoms.

Visceral sensitivity

A response to stretching of the intestinal wall by distension.

Prebiotic

A substrate that is selectively utilized by host microorganisms conferring a health benefit.

Gasotransmitter effect

Whereby certain gases, termed gasotransmitters, exert specific physiological functions through interaction with cells expressing specific target chemical components.

Probiotics

Live microorganisms intended to provide health benefits when consumed, generally by improving gut microbiota composition.

Heat stress

A situation in which too much heat is absorbed by the organ or tissue, causing stress, pathological processes and/or illness to occur.

Colonic compliance

The ability of the colon to yield elastically when a force is applied.

Carbohydrate malabsorption

The passage of dietary carbohydrates to the colon, as the result of a failure to completely absorb monosaccharides during passage through the small intestine, or of a lack of hydrolases in the small intestine to digest the carbohydrates into absorbable monosaccharides.

Small-intestinal bacterial overgrowth

(SIBO). Excessive bacterial growth in the small intestine (greater than considered normal).

Nonadrenergic noncholinergic inhibition

The inhibition of nerve cells in which epinephrine (adrenaline), norepinephrine (noradrenaline), a similar adrenergic substance or acetylcholine (a ‘cholinergic’) functions as a neurotransmitter.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kalantar-Zadeh, K., Berean, K.J., Burgell, R.E. et al. Intestinal gases: influence on gut disorders and the role of dietary manipulations. Nat Rev Gastroenterol Hepatol 16, 733–747 (2019). https://doi.org/10.1038/s41575-019-0193-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41575-019-0193-z

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing