This is the first study on the effect of a probiotic agent in patients with IBS and ERBHAL. The findings show that Yakult®
-induced change in the fermentation pattern resulted in 64% patients no longer fulfilling the definition of ERBHAL at the end of the treatment period. While such a change may represent regression towards the mean due to the repetition of the breath test[16
], it more likely reflects a physiological change. This could conceivably be due to slower oro-caecal transit, however, there are no reports of L. casei
altering gastric emptying or small intestinal transit time. Alternatively, the effect may represent a more distal intestinal shift in the initial fermentation of lactulose. Formal radionuclide transit tests could address this issue in future studies, but the findings that ERBHAL represents SIBO in the majority of patients has been observed previously, along with the findings of reduction in functional gut symptoms, with the use of antibiotics and elemental diet[5,8,9,11
The criteria used for the diagnosis of SIBO by the lactulose breath test have varied with different investigators. Much of the earlier work used bacterial cultures of the proximal small bowel as the gold standard[6,17
]. However, such methodology is not helpful in detecting an increase in bacterial biofilm, if it occurs in the distal small bowel. The presence of findings such as a double peak in hydrogen production after lactulose, or high basal breath hydrogen are not well validated in patients with IBS, and are no longer considered appropriate diagnostic features. Glucose breath hydrogen test is useful for the detection of proximal bacterial overgrowth, but since glucose is readily absorbed in the proximal small intestine, SIBO occurring more distally is not detected[18
]. The most consistent and accepted measure is the time of the first significant rise (usually ≥ 10 ppm) in breath hydrogen after lactulose, which therefore was applied in the present study.
No consistent effect of treatment with Yakult®
was observed on abdominal symptoms or fatigue; some patients worsened whereas others improved. Three patients terminated the study early because of increasing nausea. All three complained of nausea at baseline and only one had previously been tested for lactose intolerance (that person was not lactose intolerant). However, regardless of whether these patients were lactose intolerant, it is unlikely that the small amount of lactose in 1 bottle of Yakult®
(1 g) was the cause of these symptoms, given that up to 7 g of lactose in one sitting is well tolerated even in true lactose intolerant patients[19
The loss of ERBHAL resulted in improvement in the overall abdominal symptom VAS score by at least 2 cm in 71% of the patients with moderate to severe baseline symptoms compared to 0% who maintained the early rise. However, one patient who lost ERBHAL developed more severe symptoms compared to the baseline findings. It cannot be expected that all patients will improve with the correction of ERBHAL, since only 35% improved symptomatically when ERBHAL was corrected with the use of antibiotics[9
]. Previous studies on IBS have identified a particular ability of probiotics to improve bloating and wind[20-22
]. While bloating did not improve with Yakult®
, a significant improvement was seen in the passage of wind. A pathogenic link between the passage of wind, bacterial overgrowth and fermentation can be postulated. The present study was not designed to specifically address the effect on symptoms. However, our findings raise the possibility that symptomatic benefit can be obtained when ERBHAL is corrected with the use of Yakult®
In conclusion, the hypothesis that treatment with Yakult® alters the fermentation pattern, exhibited by hydrogen breath testing after lactulose was supported in this uncontrolled, proof-of-concept study. A small dose of L. casei strain Shirota led to a statistically significant shift in the time of early rise of breath hydrogen after lactulose, suggesting a reduction in SIBO. Furthermore, the overall abdominal symptoms tended to improve when ERBHAL was corrected. Our findings suggest that probiotics may have a beneficial effect, but further work is required to determine the dose effects and clinical relevance with well powered, double blind, placebo-controlled trials including the measurement of transit time to support the interpretation of ERBHAL.