Review Article

Small Intestinal Bacterial Overgrowth

Prevalence, Clinical Features, Current and Developing Diagnostic Tests, and Treatment

E. Grace; C. Shaw; K. Whelan; H. J. N. Andreyev


Aliment Pharmacol Ther. 2013;38(7):674-688. 

In This Article

Diagnostic Challenges in SIBO

Traditionally, many authors have regarded the direct aspiration and culture of duodenal fluid as the 'gold standard' approach for diagnosing SIBO.[74,75] However, having applied the criteria of Reid et al. for the development and application of a diagnostic test to the currently available approaches for diagnosing SIBO[76] in their systematic review, Khoshini et al. concluded that no gold standard diagnostic test for SIBO exists.[1] All of the commonly used methods of diagnosing SIBO have inherent limitations; clinicians should be cautious when interpreting the results of such tests (Table 3).

In terms of microbiological quantification, there is a lack of clarity on the cut-offs that define a positive culture and technical difficulties associated with transporting and culturing the aspirate. Aspiration-based approaches also suffer from being invasive, costly and potentially risky to the patient. Furthermore, culturing reveals only a fraction (estimated at 20%) of microbiota compared with genomic methods.[77]

In recent years, owing to the invasive nature of the direct aspiration and culture technique, indirect tests have been developed and are now commonly used alternatives. Breath tests have advantages over the direct culture method, in that they are simple to use, cheap and non-invasive. However, there is no breath test specifically validated for the diagnosis of SIBO. Hydrogen-based breath tests are currently the most popular and work on the assumption that the only source of hydrogen (H2) production in the body is from fermentation of carbohydrates by GI microbiota.[73]

The most commonly used substrates in breath tests are glucose and lactulose, with the former having a greater diagnostic accuracy than the latter. Compared with the direct aspiration method, the glucose-H2 breath test has a sensitivity of 62.5% and a specificity of 81.7%.[71] For this test, it is considered positive if there is a clearly recognisable H2 peak, exceeding 10–20 parts per million.[74] The lactulose-H2 breath test has a sensitivity of 52.4% and a specificity of 85.7% when compared with the direct aspiration method.[71]

The original definition of a positive lactulose-H2 breath test in detecting SIBO[78] was later revised, so as to minimise false-positive results. The modified criteria for a positive test are as follows: an increase in breath H2 of >10 parts per million (resulting from small intestinal bacterial fermentation) above basal that occurs >15 min before the prolonged peak (resulting from colonic fermentation) and also within 20 min of ingestion of the lactulose.[79]

However, 8–27% of humans do not have detectable H2 production from their GI microbiota, but instead produce methane (CH4) gas.[80,81] For example, Staphylococcus aureus,Streptococcus viridans, Enterococci, Serratia and Pseudomonas species do not produce H2. Therefore, if H2 is analysed in isolation, the test may miss overgrowth of non-H2-producing bacteria, leading to false-negative tests.

Again, there is a lack of consensus how to define an abnormal breath test. There is neither agreement on the optimal duration of the breath tests nor on the cut-off levels that define a positive result. Ultimately, there are theoretical and practical problems underlying the use of breath tests that limit their potential for substantial improvement in diagnosing SIBO.

The third approach for diagnosing SIBO is to treat it when symptoms and/or non-invasive surrogate markers are clinically suggestive of SIBO (Table 4) and to use the clinical response to antibiotics as an affirmation of SIBO as the cause of the patient's complaints – the so-called 'therapeutic trial'.[30] With the problems associated with culture and breath testing methods, it is unsurprising that Khoshini et al. found that almost one third of studies used this therapeutic trial approach for diagnostic purposes. There is, however, no standardised approach towards the type, dose or duration of the antibiotics and reported clinical response rates range from 35% to 100%.[1]

A therapeutic trial can also be used in association with other diagnostic tests, i.e. all of the following could be taken into consideration, so as to confirm the presence of SIBO: abnormal GI symptoms/non-invasive surrogate markers, abnormal test(s) (e.g. breath test and/or aspirate and culture) and clinical response to antibiotics. Measuring response necessitates assessing symptom change systematically, as well as the resolution of abnormal parameters such as low serum vitamin B12 concentrations or improved body weight.

As SIBO is often a manifestation of other GI disorders, there is as yet no typical patient. Part of the difficulty in establishing a confident diagnosis of SIBO in patients with common GI symptoms is the lack of a standardised investigative tool.