Probiotic effects on intestinal fermentation patterns in patients with irritable bowel syndrome

AIM: To determine whether Lactobacillus casei strain Shirota (Yakult ) can alter small intestinal bacterial overgrowth (SIBO), as tested by the lactulose breath test, and whether this is associated with changes in symptoms in irritable bowel syndrome (IBS). METHODS: 18 patients with IBS (Rome Ⅱ criteria), who showed an early rise in breath hydrogen with lactulose (ERBHAL), consumed 65 mL of Yakult daily for 6 wk. Lactulose breath test was repeated at the end of the treatment period. Symptoms were recorded daily using a 10 cm visual analogue scale. RESULTS: 14 patients completed the study, 9 (64%) had reversal of ERBHAL, with the median time of f irst rise in breath hydrogen increasing from 45 to 75 min (P = 0.03). There was no signifi cant improvement in the symptom score with probiotic therapy, except for wind (P=0.04). Patients commencing with at least moderate symptoms and who no longer had ERBHAL at the end of treatment, showed improvement in the overall symptoms scores [median fi nal score 5.3 (IQR3.9-5.9), 55% reduction; n=6] to a greater extent than those who had had persisting ERBHAL [final score 6.9 (5.0-7.0), 12% reduction; n = 5; P = 0.18]. CONCLUSION: Yakult is effective in altering fermentation patterns in the small bowel, consistent with reducing SIBO. The loss of ERBHAL was associated with reduced symptoms. The true interpretation of these fi ndings awaits a randomised, controlled trial.

How should immunomodulators be optimized when used as combination therapy with anti-tumor necrosis factor agents in the management of inflammatory bowel disease?

In the last 15 years the management of inflammatory bowel disease has evolved greatly,largely through the increased use of immunomodulators and,especially,anti-tumor necrosis factor(anti-TNF) biologic agents. Within this time period,confidence in the use of anti-TNFs has increased,whilst,especially in recent years,the efficacy and safety of thiopurines has been questioned. Yet despite recent concerns regarding the risk: benefit profile of thiopurines,combination therapy with an immunomodulator and an anti-TNF has emerged as the recommended treatment strategy for the majority of patients with moderate-severe disease,especially those who are recently diagnosed. Concurrently,therapeutic drug monitoring has emerged as a means of optimizing the dosage of both immunomodulators and antiTNFs. However the recommended therapeutic target levels for both drug classes were largely derived from studies of monotherapy with either agent,or studies underpowered to analyze outcomes in combination therapy patients. It has been assumed that these target levels are applicable to patients on combination therapy also,however there are few data to support this. Similarly,the timing and duration of treatment with immunomodulators when used in combination therapy remains unknown. Recent attention,including post hoc analyses of the pivotal registration trials,has focused on the optimization of anti-TNF agents,when used as either monotherapy or combination therapy. This review will instead focus on how best to optimize immunomodulators when used in combination therapy,including an evaluation of recent data addressing unanswered questions regarding the optimal timing,dosage and duration of immunomodulator therapy in combination therapy patients.