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Abstract. Despite extensive use in clinicalpractice, difficulties regarding interpretation ofhydrogen breath test are still very frequent,even on research grounds. After the administra-tion of a non-absorbable sugar, such as lactu-l o s e , a n i n c r e a s e o f b r e a t h h y d r o g e n a n dmethane is evident; this phenomenon is consid-ered an index of colonic fermentation. It is not

clear, however, if the levels of these compoundscorrelate with the presence and severity offunctional symptoms, nor if they accurately re-flect gas production at colonic level. So far,apart from flatulence, we have no indications re-garding the ability of hydrogen or methane toact as biomarkers of intraluminal events. On theother hand, it has been shown that in functionalbowel disease a colonic dysbiosis exists, andthat the modification of bacterial flora might re-sult in a reduction of symptom severity. Conse-quently, it is not clear if hydrogen and methanecolonic production could have a role in thepathophysiology of functional complaints, but it

is possible that other fermentation productsshould be taken into consideration, such as ac-etate, propionate, and alcohol.

Keywords:Breath test, Hydrogen, Methane, Colonic fermenta-

tion, Bloating.

Five years ago, the activities of a WorkingTeam aimed at producing data for a ConsensusConference on the clinical application and accura-cy of the hydrogen breath test started and in 2009an articulated paper summarizing the statements

was published1. The need for a global reassess-ment of the indications, methodology and, moreextensively, the clinical utility of the test arosefrom many criticisms: despite extensive use inclinical practice, controversial and divergent re-sults, difficulties regarding interpretation of thetests and sometimes erroneous conclusions werefrequent, even on research grounds. A previousItalian survey, published in 1997, stigmatized thepresence of many methodological issues amonggastroenterological centers2, but this paper was not

Corresponding Author:Gino Roberto Corazza, MD; e-mail: gr.corazza@smatteo.pv.it

followed by any standardization. The aim of theRome Consensus was, therefore, to establish theuse, indications and methodology of the test in or-der to define a correct approach. In the last fewyears, a considerable reduction in the absolutenumber of scientific papers dealing with the hy-drogen breath test was evident and the reason can

be found in the lack of effort aimed at improvingthe accuracy of the test or at defining new clinicalapplications. Under this light, functional symp-toms due to alteration of intestinal gas production,possibly linked to intestinal microbiota alterations,such us bloating, abdominal discomfort, abdomi-nal distention, increased borborygmi, might bestudied with the hydrogen breath test. Intendingovergrowth as the numeric increase of bacterialpopulation, the term dysbiosis defines the modi-fication of the normal composition and activity ofthe microbiota, configuring a pathologic condition

for the host. In IBS there is a clear evidence ofqualitative modifications of intestinal microbiota,while the few studies reporting quantitative datashowed negative results3-5. The term dysbiosisthus seems more appropriate.

The importance of functional complaints inclinical practice and, in particular, how frequentbloating is, is well known as also shown by a re-cent Italian survey on chronic constipation6. It isconceivable that in a subgroup of bloaters themodification of bacterial flora might result in areduction of bacterial gas production and a con-sequent reduction of symptom severity. Anecdo-

tal cases of bloater patients successfully treatedwith antibiotics are reported in the medical litera-ture7, and it is common experience to encounterthem. This makes it difficult to categorically ex-clude that, in such a subgroup of patients, themodification of bacterial flora fermentation is notthe target of treatment and, consequently, bacteri-al fermentation capacity is not an appropriate tar-get of a diagnostic test. Oral administration oflactulose, a non absorbable sugar, increases bac-terial fermentation at colonic level in a dose-de-

EuropeanReview forMedical andPharmacologicalSciences

Hydrogen breath test and intestinal gas production

M. DI STEFANO, C. MENGOLI, M. BERGONZI, E. PAGANI, G.R. CORAZZA

1st Department of Internal Medicine, University of Pavia, IRCCS S. Matteo Hospital Foundation,Pavia, Italy

2013; 17(Suppl 2): 36-38

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pendent manner8,9 . However, if we calculatebreath hydrogen excretion per g of administeredsubstrate, the rate of production is the same, sug-gesting that this parameter should be consideredas a characteristic of that patient, harbouring thatspecific microbiota9. As intestinal gas productionstrictly correlates with breath excretion10, the cal-culation of the area under the time-concentrationcurve may offer a numeric quantification of thisparameter.

In an unselected group of patients with func-tional gastrointestinal disorders and bloating, weshowed that cumulative breath hydrogen excre-tion is higher than healthy volunteers11. However,this result was not subsequently confirmed byother studies12, and even by our group13, suggest-

ing that other variables should be considered. Inthe relationship between intraluminal events andsymptom occurrence, it is obvious that, first ofall, visceral sensitivity plays a pivotal role, as werecently showed in the subgroup of intolerant pa-tients with lactose malabsorption14. However, torule out the possibility that the measurement ofthe parameter reflecting the biologic event wasimperfect, we modified this calculation in orderto optimize its accuracy. Considering the 4-hourperiod from the oral administration of the sub-strate makes the parameter strictly dependent on

the transit of the substrate. Accordingly, we calcu-lated the AUC for a 4-hour period starting fromthe arrival of the substrate in the cecum15. Thismodification makes it possible to significantlyimprove the accuracy of the measurement, as cu-mulative breath hydrogen excretion was signifi-cantly higher in patients with severe flatulence, asymptom exclusively dependent on intestinal gasproduction16, than in non flatulent patients. Unfor-tunately, cumulative breath hydrogen excretiondid not correlate with flatulence severity and itwas not possible to show a significant differencebetween bloater and non bloater patients. Similar-

ly conflicting results were also evident when con-sidering a group of IBS patients15 and, taken to-gether, these observations make us doubtful aboutthe accuracy of the test and its clinical utility.

The real question, however, is whether hydro-gen and/or methane cumulative breath excretionare really accurate biomarkers of colonic fermen-tation. Accordingly, simultaneous breath and rec-tal sampling after oral lactulose administrationwas performed, in order to clarify gas kinetics atcolonic level. Hydrogen and methane cumulativebreath excretion and cumulative rectal produc-

tion were not significantly correlated and, more

interestingly, while every patient who producedhydrogen at colonic level showed hydrogen ex-cretion in the breath, a considerable number ofpatients showed methane production at coloniclevel, but not breath methane excretion. This re-sult excludes the use of breath methane as a bio-marker of colonic events17. Finally, both hydro-gen and methane cumulative colonic productiondid not correlate with symptom severity, nor withstool characteristics.

These results, if confirmed, exclude a role ofhydrogen and methane gas production in thepathophysiology of functional complaints, but al-so disagree with a putative role of methane ongastrointestinal transit18 and IBS-C subtype19,20. Itis possible that other fermentation products

should be taken into consideration, such as ac-etate, propionate, and alcohol, but so far, apartfrom flatulence, we have no indications regard-ing the ability of hydrogen or methane to act asbiomarkers of intraluminal events, apart from asubgroup of lactose malabsorbers, non hydrogenproducing patients21.

-Conflict of interest

The Authors declare that they have no conflict of inter-ests.

References

1) GASBARRINIA, CORAZZAGR, GASBARRINIG, MONTALTOM, D ISTEFANOM, BASILISCOG, PARODIA, USAI-SATTAP,VERNIAP, ANANIAC, ASTEGIANOM, BARBARAG, BENINIL, BONAZZI P, CAPURS O G, CERTO M, COLECCHIA A,CUOCOL, DISARIOA, FESTID, LAURITANOC, MICELIE,NARDONEG, PERRI F, PORTINCASAP, RISICATO R, SORGEM, TURSIA; 1st Rome H2-Breath Testing Consen-sus Conference Working Group. Methodologyand indications of H2-breath testing in gastroin-

testinal diseases: the Rome Consensus Confer-ence. Aliment Pharmacol Ther 2009; 29(Suppl 1):1-49.

2) STROCCHI A, CORAZZA GR, ANANIA C, BENATI G,MALSER VISI S, CHERCHI MV, CERTO M, MALORGI O E,MARANOM, MAZZEOV, GINALDIL, GIORGETTIGM, PIM-POT, SCIARRETTAG, VENTRUCCI M, QUONDAMCARLO C,PELLI MA, PERRI F. Quality control study of H2breath testing for the diagnosis of carbohydratemalabsorption in Italy. It J Gastroenterol Hepatol1997; 29: 122-127.

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