To the Editor:

A recently published randomized controlled trial by Oh et al.¹ elucidated the efficacy of specific synbiotics in older patients with irritable bowel syndrome (IBS), regardless of disease subtype, by assessing the rates of improvement in global IBS symptoms and abdominal symptom reduction. The synbiotic combination of Lactobacillus paracasei DKGF1 and prebiotics from Opuntia humifusa appears to provide relief from IBS symptoms, particularly abdominal pain, and psychological well-being in older patients. Subgroup analysis revealed that patients with constipation-dominant IBS or diarrhea-dominant IBS experienced improvements in altered bowel habits and abdominal pain. To the best of our knowledge, this is the first randomized controlled trial to evaluate the efficacy and safety of synbiotics in older patients with IBS.

The interest for clinical efficacy of gut microbiome has gained momentum since van Nood et al.² reported the efficacy of fecal microbiota transplantation in patients with Clostridioides difficile infection. Since then, numerous studies have reported on the efficacy of microbiome in various diseases and phenotypes.^3-6 IBS was no exception; it has been a significant concern in the realm of gastrointestinal disorder due to its high prevalence. It has been reported to affect approximately 11% of the global population, surpassing the numerical impact of most other diseases.⁷ Several studies have explored the relationship between the gut microbiome and IBS.^8-10 The prevailing hypothesis suggests that dysbiosis may lead to alteration in the immune system within the gastrointestinal tract, resulting in low-grade inflammation and the onset of IBS. However, as reported in this study, various microbial treatments for IBS have shown controversial results. From this perspective, this study provides clinically important results.

While this study is interesting and significant in the context of the microbial treatment of IBS, I would like to address some concerns. First, although the authors mentioned a similar limitation in the Discussion section, because the treatment was related to the gut microbiome, it is advisable to conduct an analysis of the fecal microbiota, including measures of alpha- and beta-diversity, 16s RNA sequencing profile, and additional assessments of the metabolomic pathway, as well as related cytokine or messenger RNA expression levels. Microbial analysis may be performed at the initiation and conclusion of the study, enabling the comparison of differences between the two groups and intragroup changes before and after treatment. Given that this was a randomized controlled trial, these microbial-level differences could be adjusted to assess the efficacy of microbial treatment in comparison to a placebo.

Second, it would have been beneficial to gather baseline dietary data from the study population. Dietary intake is also associated with IBS symptoms. Although it shows heterogeneity according to individuals, regions, and ethnicities, it seems to play a role in modulating the gut microbiome.^11,12 As the synbiotics in this study were a combination of ingredients from kimchi and cactus, the dietary intake of these items might have had a similar impact on the synbiotics. Furthermore, other dietary components could alleviate IBS symptoms, such as turmeric or prunes, which have been proven to help improve altered gastrointestinal symptoms.^13,14 Although dietary control might be challenging in practice, it could introduce a bias in estimating the efficacy of microbial treatments.

In addition, there are some minor concerns. Although the role of the appendix has not yet been clearly elucidated, it is believed to play a role in modulating the gut microbiome. Therefore, a stratification analysis based on the history of appendectomy might be included. Additionally, the sample sizes for diarrhea-dominant IBS and constipation-dominant IBS were relatively small, and the number of patients in each treatment group was insufficient to obtain statistically significant results. More patients are required for a robust analysis. Finally, there seemed to be a typographical error in the phrase “Allocated to placebo (n=33)” in Figure 1, the last flowchart of the “allocation to synbiotics.”

In conclusion, as the authors noted, combining microbial analysis and dietary profiles with a large sample size would further strengthen the findings of this study. Despite these concerns, this study provided meaningful and essential evidence for microbial treatment in older patients with IBS.

No potential conflict of interest relevant to this article was reported.