TO THE EDITOR
Liu et al[1] recently published study was a rigorous randomized, double-blind, placebo-controlled trial, providing valuable insights into the potential role of probiotics as an adjunctive therapy to mitigate the gastrointestinal side effects associated with bismuth quadruple therapy (BQT) for Helicobacter pylori (H. pylori) eradication[1]. They also put forward constructive opinions on the shortcomings and future directions of research, which provided a reference for further optimization of H. pylori eradication therapy. This letter focuses on the role of complementary traditional Chinese medicine (TCM) in the prevention and treatment of H. pylori and relief of gastrointestinal symptoms after BQT.
BQT is currently recommended by international guidelines as the first-line treatment for H. pylori eradication[2]. However, this therapy still has several limitations: Combination antibiotic therapy often disrupts the gut microbiome, leading to other gastrointestinal symptoms. This often leads to poor patient compliance, increasing the risk of treatment failure, and antibiotic resistance. In the article by Zhang et al[3], antibiotic exposure can lead to ecological imbalance of the intestinal flora and damage the integrity of the intestinal barrier. This disruption affects the secretory, physical, and immune components of the barrier and may lead to a range of complications. Therefore, based on the "3R concept" (remove, remodel, repair), the authors emphasized the holistic integration of traditional Chinese and Western medicine, a patient-centered approach that addresses disease through systematic observation and comprehensive evaluation of health outcomes. By removing H. pylori, remodeling intestinal microenvironment and repairing mucosal injury, the BQT induced gastrointestinal dysfunction can be alleviated[3].
Probiotics mainly play a role in regulating intestinal flora, reducing the side effects of antibiotics and assisting in the improvement of gastrointestinal symptoms. Although there is no direct description of "probiotics" in the theoretical system of TCM, many TCM herbal formulas have achieved similar effects with probiotics, especially in alleviating gastrointestinal discomfort caused by BQT, showing the comprehensive advantages of multi-targets. Previous experiments have shown that Gancao Xiexin decoction and Huangqi Jianzhong decoction can regulate the balance of intestinal microbiota and facilitate the eradication of H. pylori[4,5]. Moreover, whether it is a herbal formula or a compound, it can effectively inhibit or kill H. pylori, destroy its biofilm, reduce the virulence and adhesion ability of H. pylori, change the living environment of H. pylori, thereby improving the pathological state of stomach and relieving the symptoms of the disease[6,7]. A meta-analysis of Chinese herbal formula in the treatment of H. pylori positive peptic ulcer showed that among 51 randomized controlled trials included, involving 5172 patients, herbal formula supplementation could significantly improve the H. pylori eradication rate, clinical efficiency and reduce the recurrence rate, and was relatively safe[8]. The efficacy of TCM in eradicating H. pylori or alleviate symptoms after BQT is mainly influenced by the accuracy of syndrome differentiation, individual differences and compliance of patients, especially the complex mechanism. TCM exerts therapeutic effects through multiple targets; this multitarget nature is both advantageous and limiting, as it complicates the identification of specific active constituents, thereby impeding therapeutic standardization[9].
Several years ago, a similar clinical research were published by He et al[10]. It was a multicenter, double-blind, randomized trial conducted in China. Among 276 treatment-naive H. pylori positive patients randomized to BQT for 14 days, probiotics resulted in lower rates of gastrointestinal adverse events than placebo, as well as dramatic perturbations of the gut microbiota after eradication[10]. What's interesting about these two studies is that patients in the treatment groups were given probiotics along with their antibiotics, which might seem contradictory. In the design of the trial, Liu et al[1] carefully mentioned that the probiotics was "taken with warm water 2 hours after antibiotic administration". This is the most critical and widely recommended procedure. In order to maximize the survival of probiotics, a 2-3 hours interval between administration and antibiotics is usually recommended. Recent research is also exploring more advanced methods to protect probiotics. Scientists have developed alginate microspheres loaded with tannic acid, which can both protect probiotics safely through the gastric acid environment, and use tannic acid to "neutralize" some antibiotics in the gut, creating more favorable conditions for the survival of probiotics[11]. In addition to the timing of probiotic administration, the type of probiotic also plays a pivotal role in its therapeutic efficacy. Other studies have found that the triple treatment of H. pylori infection with probiotic or sulforaphane neither increased the eradication rate nor reduced the incidence of adverse events[12,13]. Given these conflicting findings, probiotic supplementation necessitates additional rigorous investigation prior to its clinical implementation, with particular emphasis on probiotic strain, dosage, appropriate treatment durations, and safety assessments[14].
In conclusion, the study by Liu et al[1] is an important step toward optimizing H. pylori eradication therapy. Probiotics can help to improve BQT compliance by reducing side effects and improving patient comfort. TCM has similar advantages to probiotics with its holistic regulation and multi-target intervention, which can also significantly improve gastrointestinal dysfunction after BQT. Future studies can improve the formula of probiotics on this basis, or increase the clinical research related to the improvement of symptoms after BQT by TCM, explore its long-term effect, and clarify its role in achieving a higher eradication rate and reducing H. pylori-related dyspepsia.
