- Email: [email protected]
Only the nose knows
EDITORIALS
December 1987
11. Ranson JHC, Rifkind KM, Roses DF, et al. Prognostic signs and the role of operative management in acute pancreatitis. Surg Gynecol Obstet 1974;139:69-81. 12. Becker JM, Pemberton JH, DiMagno EP, et al. Prognostic factors in pancreatic abscess. Surgery 1984;96:455-60. 13. Malangoni MA, Shallcross JC, Seiler JG, et al. Factors contributing to fatal outcome after treatment of pancreatic abscess. Ann Surg 1986;203:605-13. 14. Warshaw AL. Pancreatic abscesses. N Engl J Med 1972;287: 1234-6. 15. Beger HG, Bittner R, Biichler M, et al. Hemodynamic data
1437
pattern in patients with acute pancreatitis. Gastroenterology 1988;90:74-9. 16. Reber HA. Surgical intervention in necrotizing pancreatitis. Gastroenterology 1986;91:479-82. 17. Hiatt JR, Fink AS, King W, Pitt HA. Percutaneous aspiration of peripancreatic fluid collections: a safe method to detect infection. Surgery 1987;101:523-30. Address requests for reprints to: Andrew L. Warshaw, M.D., Massachusetts General Hospital, 15 Parkman Street, ACC 336, Boston, Massachusetts 02114. 0 1987 by the American Gastroenterological Association
Only the Nose Knows Virtually all studies of flatus composition have measured the quantitatively important, but odorless, intestinal gases Hz, COZ, CH4, 02, and N2. However, patients do not complain about the quantity of rectal gas passed but rather its aroma. Thus, the study of fecal odors by Moore et al. in this issue of GASTROENTEROLOGY (1)represents a new contribution to flatulogical literature. This long-standing neglect of odoriferous intestinal gases has not been merely an oversight, but rather a reflection of technological difficulties. These gases are present in extremely low concentrations but make their presence known because the nose is an extremely sensitive detector of noxious odors. Detection by laboratory equipment requires concentration of the sample before gas chromatographic analysis, a much more complex analytical process than is required for measurement of the major gut gases. More important, although instruments can measure the mass of a gas, there is only one instrument that can detect and interpret odor-the human nose. Thus, the detector in odor studies is an “experienced sniffer” (2). Although there is an ample supply of professional sniffers in the perfume industry, there has been a distinct shortage of technicians willing to sit with their nose applied to the end of a chromatographic column to detect the exit of fecal odors. This dependence on the nose to detect odors reflects our incomplete understanding of the physiology of olfaction. It is known that odiferous molecules stimulate some of the 10-20 million olfactory cells located at the top of the nasal cavity. The central projection of these cells (olfactory nerves) penetrate the cribriform plate and synapse with neurons in the olfactory bulbs, which in turn communicate with the brain via the olfactory tracts.
Exactly how the brain differentiates between thousands of different odors is not totally clear. Presumably, at the nasal level specific odoriferous molecules must stimulate a specific set of olfactory cells. Despite a vast amount of research, investigators have been unable to characterize the specific feature of a molecule that makes possible the reaction that results in odor. It is known that strongly odoriferous compounds are lipid-soluble molecules with relatively low molecular weights (<3OO daltons). It also is known that organic molecules containing sulfur or nitrogen at reactive sites often have very powerful, offensive odors (3). However, molecules with very similar chemical structures may have odors of widely diverse quality and intensity, whereas molecules with no apparent structural similarity may have very comparable odors. As a result, various theories have been developed to explain the molecular characteristics that account for odor including molecular vibration (4), adsorption to various materials (5)) and molecular cross section (6). Presumably this characteristic allows the molecule to interact with a specific receptor or set of receptors on the olfactory neurons giving rise to a specific, recognizable odor impulse to the brain. The inability to chemically define odors lends a peculiarly subjective flavor to odor research. For many years, it has been taught that bacterial metabolites of amino acids, indole and skatole, account for the unpleasant odor of feces. However, Moore and coworkers claim that the smell of these compounds bears no relation to fecal odor. Rather, they have identified several methyl sulfides, methanethiol, dimethyl disulfide, and dimethyl trisulfide, which they propose have smells comparable to that of human feces. These compounds are among the most potent known stimulants of the human nose with a
1438
GASTROENTEROLOGY
EDITORIALS
detectable level of less than one part per billion or <5 rig/L of gas. These compounds are also extremely toxic with an LDsO in the same range as cyanide. -As an illustration of the subjective nature of odor research, consider the following: on the one occasion I had to sniff skatole, I was rather impressed with its feculant odor. On the other hand, I do not believe that either methanethiol or dimethyl disulfide have a fecal odor. Methanethiol is sometimes used as an odorant in natural gas. When I smell the characteristic odor of natural gas, I look for a leaking gas jet rather than a nearby outhouse. Thus, in my purely subjective opinion, several of the compounds proposed by Moore et al. are unlikely candidates to be the primary odorants that I detect in human feces. A blinded, sniffing experiment employing fecal specimens and putative odorants derived from a given specimen could provide objective evidence that specific compounds were the predominant odorants in feces. At a more basic level, one could raise questions as to whether human feces truly have a characteristic odor and if just a few compounds could comprise this odor. The smells of bread and coffee are said to result from a mixture of 70 and 103 different odoriferous compounds, respectively (7). Presumably, feces are at least as complicated a biological mixture as bread or coffee. Although food may contain very trace quantities of compounds with noxious odors (such as the methyl sulfides), it is clear that there is a distinct change in aroma with passage of material through the gut. This alteration of odor apparently results from the metabolism of gut bacteria. Identification of the bacterial metabolites responsible for the offensive odor could have appreciable clinical importance in the control of flatus odor. One could interrupt the process by which these gases are liberated into the atmosphere by (a) manipulation of the diet to reduce the substrates available for the bacterial reaction yielding
Vol. 93, No. 6
the odorant; (b) elimination of the bacteria responsible for the reaction; or (c) administration of a compound that binds or reacts with the odorants. Although all of the above have been tried empirically over the years without much success, knowledge of the specific odoriferous compounds in feces would permit a renewed, more rational approach to this age-old clinical problem. MICHAEL
D. LEVITT,
M.D.
Research Service Veterans Administration Medical Center and Department of Medicine University of Minnesota Minneapolis, Minnesota References 1. Moore JG, Jessop LD, Osborne DN. Gas-chromatographic and mass-spectrometric analysis of the odor of human feces. Gastroenterology 1987;93:1321-9. 2. Moore JG, Krotoszynski BK, O’Neill HJ, Fecal odorgrams. A method for partial reconstruction of ancient and modern diets. Dig Dis Sci 1984;29:907-11. 3. Schiffman SS. Characterization of odor quality utilizing multidimensional sealing techniques. In: Moskowitz HR, Warren CB, eds. Odor quality and chemical structure. Washington, D.C.: American Chemical Society, 1981:1-21. 4. Wright RH. Odor and molecular vibration: a possible membrane interaction mechanism. Chem Senses and Flavor 1976; 2:203-6. 5. Laffort P, Patte F, Etcheto M. Olfactory coding on the basis of physicochemical properties. Ann NY Acad Sci 1974; 237:193-208. 6. Davies JT. A theory of the quality of odours. J Theoret Biol 1965;8:1-7. 7. Encyclopedia Brittanica. Chemoreception. Hemmingway Benton Publishers. 1975;4:176-89. Address requests for reprints to: Michael D. Levitt, M.D., ACOS for Research (15l), Veterans Administration Medical Center, 54th Street and 48th Avenue South, Minneapolis, Minnesota 55417. This work was supported by a Veterans Administration Merit Review Grant. 0 1987 by the American Gastroenterological Association
December 1987
11. Ranson JHC, Rifkind KM, Roses DF, et al. Prognostic signs and the role of operative management in acute pancreatitis. Surg Gynecol Obstet 1974;139:69-81. 12. Becker JM, Pemberton JH, DiMagno EP, et al. Prognostic factors in pancreatic abscess. Surgery 1984;96:455-60. 13. Malangoni MA, Shallcross JC, Seiler JG, et al. Factors contributing to fatal outcome after treatment of pancreatic abscess. Ann Surg 1986;203:605-13. 14. Warshaw AL. Pancreatic abscesses. N Engl J Med 1972;287: 1234-6. 15. Beger HG, Bittner R, Biichler M, et al. Hemodynamic data
1437
pattern in patients with acute pancreatitis. Gastroenterology 1988;90:74-9. 16. Reber HA. Surgical intervention in necrotizing pancreatitis. Gastroenterology 1986;91:479-82. 17. Hiatt JR, Fink AS, King W, Pitt HA. Percutaneous aspiration of peripancreatic fluid collections: a safe method to detect infection. Surgery 1987;101:523-30. Address requests for reprints to: Andrew L. Warshaw, M.D., Massachusetts General Hospital, 15 Parkman Street, ACC 336, Boston, Massachusetts 02114. 0 1987 by the American Gastroenterological Association
Only the Nose Knows Virtually all studies of flatus composition have measured the quantitatively important, but odorless, intestinal gases Hz, COZ, CH4, 02, and N2. However, patients do not complain about the quantity of rectal gas passed but rather its aroma. Thus, the study of fecal odors by Moore et al. in this issue of GASTROENTEROLOGY (1)represents a new contribution to flatulogical literature. This long-standing neglect of odoriferous intestinal gases has not been merely an oversight, but rather a reflection of technological difficulties. These gases are present in extremely low concentrations but make their presence known because the nose is an extremely sensitive detector of noxious odors. Detection by laboratory equipment requires concentration of the sample before gas chromatographic analysis, a much more complex analytical process than is required for measurement of the major gut gases. More important, although instruments can measure the mass of a gas, there is only one instrument that can detect and interpret odor-the human nose. Thus, the detector in odor studies is an “experienced sniffer” (2). Although there is an ample supply of professional sniffers in the perfume industry, there has been a distinct shortage of technicians willing to sit with their nose applied to the end of a chromatographic column to detect the exit of fecal odors. This dependence on the nose to detect odors reflects our incomplete understanding of the physiology of olfaction. It is known that odiferous molecules stimulate some of the 10-20 million olfactory cells located at the top of the nasal cavity. The central projection of these cells (olfactory nerves) penetrate the cribriform plate and synapse with neurons in the olfactory bulbs, which in turn communicate with the brain via the olfactory tracts.
Exactly how the brain differentiates between thousands of different odors is not totally clear. Presumably, at the nasal level specific odoriferous molecules must stimulate a specific set of olfactory cells. Despite a vast amount of research, investigators have been unable to characterize the specific feature of a molecule that makes possible the reaction that results in odor. It is known that strongly odoriferous compounds are lipid-soluble molecules with relatively low molecular weights (<3OO daltons). It also is known that organic molecules containing sulfur or nitrogen at reactive sites often have very powerful, offensive odors (3). However, molecules with very similar chemical structures may have odors of widely diverse quality and intensity, whereas molecules with no apparent structural similarity may have very comparable odors. As a result, various theories have been developed to explain the molecular characteristics that account for odor including molecular vibration (4), adsorption to various materials (5)) and molecular cross section (6). Presumably this characteristic allows the molecule to interact with a specific receptor or set of receptors on the olfactory neurons giving rise to a specific, recognizable odor impulse to the brain. The inability to chemically define odors lends a peculiarly subjective flavor to odor research. For many years, it has been taught that bacterial metabolites of amino acids, indole and skatole, account for the unpleasant odor of feces. However, Moore and coworkers claim that the smell of these compounds bears no relation to fecal odor. Rather, they have identified several methyl sulfides, methanethiol, dimethyl disulfide, and dimethyl trisulfide, which they propose have smells comparable to that of human feces. These compounds are among the most potent known stimulants of the human nose with a
1438
GASTROENTEROLOGY
EDITORIALS
detectable level of less than one part per billion or <5 rig/L of gas. These compounds are also extremely toxic with an LDsO in the same range as cyanide. -As an illustration of the subjective nature of odor research, consider the following: on the one occasion I had to sniff skatole, I was rather impressed with its feculant odor. On the other hand, I do not believe that either methanethiol or dimethyl disulfide have a fecal odor. Methanethiol is sometimes used as an odorant in natural gas. When I smell the characteristic odor of natural gas, I look for a leaking gas jet rather than a nearby outhouse. Thus, in my purely subjective opinion, several of the compounds proposed by Moore et al. are unlikely candidates to be the primary odorants that I detect in human feces. A blinded, sniffing experiment employing fecal specimens and putative odorants derived from a given specimen could provide objective evidence that specific compounds were the predominant odorants in feces. At a more basic level, one could raise questions as to whether human feces truly have a characteristic odor and if just a few compounds could comprise this odor. The smells of bread and coffee are said to result from a mixture of 70 and 103 different odoriferous compounds, respectively (7). Presumably, feces are at least as complicated a biological mixture as bread or coffee. Although food may contain very trace quantities of compounds with noxious odors (such as the methyl sulfides), it is clear that there is a distinct change in aroma with passage of material through the gut. This alteration of odor apparently results from the metabolism of gut bacteria. Identification of the bacterial metabolites responsible for the offensive odor could have appreciable clinical importance in the control of flatus odor. One could interrupt the process by which these gases are liberated into the atmosphere by (a) manipulation of the diet to reduce the substrates available for the bacterial reaction yielding
Vol. 93, No. 6
the odorant; (b) elimination of the bacteria responsible for the reaction; or (c) administration of a compound that binds or reacts with the odorants. Although all of the above have been tried empirically over the years without much success, knowledge of the specific odoriferous compounds in feces would permit a renewed, more rational approach to this age-old clinical problem. MICHAEL
D. LEVITT,
M.D.
Research Service Veterans Administration Medical Center and Department of Medicine University of Minnesota Minneapolis, Minnesota References 1. Moore JG, Jessop LD, Osborne DN. Gas-chromatographic and mass-spectrometric analysis of the odor of human feces. Gastroenterology 1987;93:1321-9. 2. Moore JG, Krotoszynski BK, O’Neill HJ, Fecal odorgrams. A method for partial reconstruction of ancient and modern diets. Dig Dis Sci 1984;29:907-11. 3. Schiffman SS. Characterization of odor quality utilizing multidimensional sealing techniques. In: Moskowitz HR, Warren CB, eds. Odor quality and chemical structure. Washington, D.C.: American Chemical Society, 1981:1-21. 4. Wright RH. Odor and molecular vibration: a possible membrane interaction mechanism. Chem Senses and Flavor 1976; 2:203-6. 5. Laffort P, Patte F, Etcheto M. Olfactory coding on the basis of physicochemical properties. Ann NY Acad Sci 1974; 237:193-208. 6. Davies JT. A theory of the quality of odours. J Theoret Biol 1965;8:1-7. 7. Encyclopedia Brittanica. Chemoreception. Hemmingway Benton Publishers. 1975;4:176-89. Address requests for reprints to: Michael D. Levitt, M.D., ACOS for Research (15l), Veterans Administration Medical Center, 54th Street and 48th Avenue South, Minneapolis, Minnesota 55417. This work was supported by a Veterans Administration Merit Review Grant. 0 1987 by the American Gastroenterological Association