Letter to the Editor regarding “Metal ion coordinated tea polyphenol nanocoating for enhanced probiotic therapy in inflammatory bowel disease”

Dear Editor, We read with great interest the recent study titled “Metal ion coordinated tea polyphenol nanocoating for enhanced probiotic therapy in inflammatory bowel disease” and would like to offer some comments. The authors presented a novel strategy for enhancing Lactobacillus rhamnosus GG (LGG) therapy in inflammatory bowel disease using polyphenol-based metal-phenolic network (MPN) coatings[1]. The authors’ systematic evaluation of gallic acid (GA), epigallocatechin (EGC), and epigallocatechin gallate (EGCG) in coordination with ferric ions offers valuable guidance for selecting the optimal polyphenols for probiotic encapsulation. The authors employed a standard method to prepare the coated probiotics. Briefly, 100 μL of GA solution (20 mg/mL) was added to a suspension of LGG in phosphate-buffered saline (PBS; 10 mM, pH 7.4). However, the authors did not specify the solvent used to prepare the GA solutions. The choice of the solvent plays a pivotal role in studies involving GA. Polyphenolic compounds, such as GA, are highly susceptible to oxidative degradation, a process closely linked to their chemical structure[2,3] and influenced by the solvent environment. The oxidation of GA is a complex process driven by its core chemical structure. The vicinal trihydroxy group (pyrogallol structure) on its benzene ring is key, making it an excellent electron donor. The resulting phenolate ions directly transfer electrons to oxygen, generating superoxide anions and semiquinone radicals, which are further oxidized to quinones and accompanied by hydrogen peroxide production[3,4]. The oxidation rate of GA is highly dependent on the solution pH[3,4]. It remains relatively stable under acidic conditions, whereas autoxidation proceeds moderately in neutral buffers such as PBS (pH 7.4)[3]. However, the reaction becomes extremely rapid in alkaline solutions or in cell culture media, such as DMEM, where trace metal ions can further catalyze the process. The oxidation of GA in PBS proceeds rapidly. Previous studies indicated that oxidation became detectable within 30 min, reached a maximum rate at approximately 1 h, and was largely complete within 2 h, encompassing the primary oxidation event and H2O2 production. Notably, the onset of oxidation likely occurs within several minutes[4–6]. Our data showed that a 20 mg/mL GA solution underwent oxidation and developed a gray green color when stored in PBS for 1 h. Therefore, in this study, the method used to prepare the GA solution and the potential for oxidation after its addition to PBS were of critical importance. The authors reported that the MPN coating formed by GA exhibited low retention, resulting in weaker intestinal adhesions. Given GA’s susceptibility of GA to autoxidation, it is plausible that upon addition to PBS, GA undergoes oxidation, reducing its concentration and generating byproducts. This would limit the amount of GA available for incorporation into the MPN and could introduce bias into the experimental outcomes. We recommend that the authors could address the oxidation behavior of GA in PBS, either by refining their experimental design or by providing additional methodological details. Overall, this study provides valuable insights and highlights the potential of polyphenol-based MPN coatings in biomedical applications. The authors have made a commendable effort to address this important topic with clear experimental observations. At the same time, further clarification of the oxidation of GA in PBS would strengthen the reliability of the conclusions and enhance the impact of this work.