Correction: Gut microbiota-metabolome crosstalk in allergic diseases: mechanistic insights and translational opportunities

Hanbin Qin^1,2Jiaxin Sui^2,3Shuang Wang^1,2Xiaojing Lv^2,3Zile Zhang^2,4Xinhua Lin^1,2Xuexia Liu^5*Hua Zhang^2*

• ¹Shandong Second Medical University, Weifang, China
• ²Yantai Yuhuangding Hospital, Yantai, China
• ³Qingdao University, Qingdao, China
• ⁴Binzhou Medical University, Binzhou, China
• ⁵Shandong Stem Cell Engineering Research Center, Yantai, China

In the published article, there was an error. [The content presented in Paragraphs 5 and 6 of the Conclusion section (Page 10) has been incorrectly placed. This material is the figure notes accompanying the two relevant figures. Its inclusion in the Conclusion is both redundant and unsuitable. It is therefore recommended that this content be removed from its current location].A correction has been made to [Conclusion], [Paragraphs 5 and6]. This sentence previously stated: In recent years, with the rapid advancement of urbanization and changes in lifestyle, there has been a significant increase in the incidence of allergic diseases. The WHO predicts that allergic diseases associated with industrialization and Western lifestyles will double in the future, potentially due to gut microbiota imbalance. In contemporary medicine and life sciences, research into gut microbiota imbalance and its role in the prevention of allergic diseases has gained increasing attention. Investigation the interactions between the microbiome, metabolome, and host, as well as their collaborative mechanisms in maintaining intestinal homeostasis, has become a critical factor in developing more convenient and efficient treatment methods, as well as enabling early disease prevention. With the advent of high-throughput sequencing technology, we have achieved a deeper understanding of the composition and diversity of gut microbiota. The extensive application of multi-omics technologies, including metagenomics, metatranscriptomics, metaproteomics, and metabolomics, enables us to study the interactions between gut microbiota and hosts at multiple levels. These studies provide a theoretical foundation for the development of diagnostic markers and therapeutic strategies based on gut microbiota.In the context of personalized treatment, a randomized controlled trial (N = 1591 participants) demonstrated that eight out of nine probiotics could alleviate at least one clinical symptom of allergic rhinitis. Furthermore, lactate, ornithine, and six additional metabolites were identified as potential predictors of the efficacy of sublingual immunotherapy for allergic rhinitis. These metabolites regulate metabolic pathways, modulate immune system function, and mitigate symptoms of allergic rhinitis. Conversely, another double-blind randomized controlled study revealed that a probiotic mixture did not exhibit significant therapeutic effects on moderate to severe atopic dermatitis in children. Regarding the overall treatment process for allergic diseases, probiotics can alleviate allergy symptoms, reduce medication usage, and lower medical expenses. However, prolonged use may increase costs. Metabolite supplementation can enhance treatment effectiveness, decrease disease recurrence, and reduce long-term medical expenses. Nevertheless, the high cost of metabolite supplements may also lead to increased treatment expenses.Notwithstanding these findings, there are notable limitations in the gut microbiota research. Significant inter-individual variability in gut microbiota communities limits the generalizability of research findings. Therefore, mother-infant cohort studies and cross-regional, multi-center collaborations are essential for addressing these generalizability issues. Individual genetic background, dietary habits, lifestyle, and environmental factors all influence the composition and function of the gut microbiota, adding complexity and challenges to the research. Currently, most studies can only establish correlations between gut microbiota and disease, making it difficult to determine causation. Although some intervention studies (e.g., probiotics, prebiotics, fecal microbiota transplantation) offer insights into causal relationships, these studies often suffer from small sample sizes and lack of long-term follow-up, hindering definitive conclusions. The interaction between gut microbiota and the host is a complex process influenced by multiple factors, involving systems such as the immune, metabolic, and nervous systems. Current research often focuses on single factor or pathway, which makes it challenging to comprehensively elucidate the intricate interactive mechanisms between gut microbiota and the host.Therefore, future research should place greater emphasis on individual differences and actively pursue personalized investigations based on individual characteristics. By integrating multiple-omics datasets, incorporating individual genetic, dietary, lifestyle information, and constructing personalized gut microbiota models, a foundation for precision diagnosis and treatment can be established. Through the application of advanced experimental designs and analysis methods, such as randomized controlled trials and causal inference analyses, further exploration of the causal relationship between gut microbiota and diseases can be achieved. Simultaneously, combining animal models with clinical studies will help validate the reliability and reproducibility of these causal relationships. Based on findings regarding the relationship between gut microbiota and diseases, novel intervention strategies have been developed, including personalized probiotics formulations, prebiotics, fecal microbiota transplantation, and microbiota-derived metabolic products. Their safety and efficacy can be confirmed through rigorous clinical trials, providing new avenues for diseases prevention and treatment. Long-term follow-up studies should be conducted to monitor the dynamic changes in gut microbiotacommunities and their impact on host health and diseases progression. Through continuous monitoring and data analysis, the long-term associations between gut microbiota communities and disease development can be elucidated, offering a basis for early warning and intervention strategies. In conclusion, while significant advancements have been made in the study of gut microbiota and metabolites, numerous challenges remain. Future research should aim to uncover the specific mechanisms underlying the roles of gut microbiota and metabolomics in allergic diseases, develop personalized treatment plans, and enhance the effectiveness of disease management.Immune response following allergen exposure in the body. Upon entry through the intestinal epithelium, allergens are captured by dendritic cells (DCs) and presented to naïve T cell expressing IL-4 (Th0), which subsequently differentiate into Th2 cells. Th2 cells secrete cytokines such as IL-4, IL-5, and IL-13, promoting B cell production of IgE antibodies while also recruiting eosinophils and basophils to the site of inflammation. IgE antibodies blind to receptors on mast cells and basophils, upon re-exposure to the same allergen, these cells become activated, releasing inflammatory mediators including histamine and thereby inducing allergic symptoms. Simultaneously, the gut microbiota and mucus layer play critical roles in modulating immune responses and preventing allergen penetration. SCFAs are produced via the fermentation of dietary fibers by the gut microbiota and exert antiinflammatory effects in allergic diseases through the activation of GPR41/GPR43 receptors on immune cells. SCFAs suppress DCs from releasing pro-inflammatory cytokines such as IL-33 and TSLP, thereby attenuating Th2 immune responses. Simultaneously, they promote the differentiation of Tregs and enhance IL-10 secretion, contributing to immune tolerance. Additionally, SCFAs downregulate pro-inflammatory mediators, including TNF-α and IL-6, in macrophages, inhibit eosinophil degranulation and basophil chemetaxis, and reduce levels of Th2-associated cytokines (IL-5, IL-13) and eosinophil cationic protein (ECP), thus comprehensively mitigating allergic inflammation.]"The corrected sentence appears below: In recent years, with the rapid advancement of urbanization and changes in lifestyle, there has been a significant increase in the incidence of allergic diseases. The WHO predicts that allergic diseases associated with industrialization and Western lifestyles will double in the future, potentially due to gut microbiota imbalance. In contemporary medicine and life sciences, research into gut microbiota imbalance and its role in the prevention of allergic diseases has gained increasing attention. Investigation the interactions between the microbiome, metabolome, and host, as well as their collaborative mechanisms in maintaining intestinal homeostasis, has become a critical factor in developing more convenient and efficient treatment methods, as well as enabling early disease prevention. With the advent of high-throughput sequencing technology, we have achieved a deeper understanding of the composition and diversity of gut microbiota. The extensive application of multi-omics technologies, including metagenomics, metatranscriptomics, metaproteomics, and metabolomics, enables us to study the interactions between gut microbiota and hosts at multiple levels. These studies provide a theoretical foundation for the development of diagnostic markers and therapeutic strategies based on gut microbiota.In the context of personalized treatment, a randomized controlled trial (N = 1591 participants) demonstrated that eight out of nine probiotics could alleviate at least one clinical symptom of allergic rhinitis. Furthermore, lactate, ornithine, and six additional metabolites were identified as potential predictors of the efficacy of sublingual immunotherapy for allergic rhinitis. These metabolites regulate metabolic pathways, modulate immune system function, and mitigate symptoms of allergic rhinitis. Conversely, another double-blind randomized controlled study revealed that a probiotic mixture did not exhibit significant therapeutic effects on moderate to severe atopic dermatitis in children. Regarding the overall treatment process for allergic diseases, probiotics can alleviate allergy symptoms, reduce medication usage, and lower medical expenses. However, prolonged use may increase costs. Metabolite supplementation can enhance treatment effectiveness, decrease disease recurrence, and reduce long-term medical expenses. Nevertheless, the high cost of metabolite supplements may also lead to increased treatment expenses.Notwithstanding these findings, there are notable limitations in the gut microbiota research. Significant inter-individual variability in gut microbiota communities limits the generalizability of research findings. Therefore, mother-infant cohort studies and cross-regional, multi-center collaborations are essential for addressing these generalizability issues. Individual genetic background, dietary habits, lifestyle, and environmental factors all influence the composition and function of the gut microbiota, adding complexity and challenges to the research. Currently, most studies can only establish correlations between gut microbiota and disease, making it difficult to determine causation. Although some intervention studies (e.g., probiotics, prebiotics, fecal microbiota transplantation) offer insights into causal relationships, these studies often suffer from small sample sizes and lack of long-term follow-up, hindering definitive conclusions. The interaction between gut microbiota and the host is a complex process influenced by multiple factors, involving systems such as the immune, metabolic, and nervous systems. Current research often focuses on single factor or pathway, which makes it challenging to comprehensively elucidate the intricate interactive mechanisms between gut microbiota and the host.Therefore, future research should place greater emphasis on individual differences and actively pursue personalized investigations based on individual characteristics. By integrating multiple-omics datasets, incorporating individual genetic, dietary, lifestyle information, and constructing personalized gut microbiota models, a foundation for precision diagnosis and treatment can be established. Through the application of advanced experimental designs and analysis methods, such as randomized controlled trials and causal inference analyses, further exploration of the causal relationship between gut microbiota and diseases can be achieved. Simultaneously, combining animal models with clinical studies will help validate the reliability and reproducibility of these causal relationships. Based on findings regarding the relationship between gut microbiota and diseases, novel intervention strategies have been developed, including personalized probiotics formulations, prebiotics, fecal microbiota transplantation, and microbiota-derived metabolic products. Their safety and efficacy can be confirmed through rigorous clinical trials, providing new avenues for diseases prevention and treatment. Long-term follow-up studies should be conducted to monitor the dynamic changes in gut microbiotacommunities and their impact on host health and diseases progression. Through continuous monitoring and data analysis, the long-term associations between gut microbiota communities and disease development can be elucidated, offering a basis for early warning and intervention strategies. In conclusion, while significant advancements have been made in the study of gut microbiota and metabolites, numerous challenges remain. Future research should aim to uncover the specific mechanisms underlying the roles of gut microbiota and metabolomics in allergic diseases, develop personalized treatment plans, and enhance the effectiveness of disease management.Immune response following allergen exposure in the body. Upon entry through the intestinal epithelium, allergens are captured by dendritic cells (DCs) and presented to naïve T cell expressing IL-4 (Th0), which subsequently differentiate into Th2 cells. Th2 cells secrete cytokines such as IL-4, IL-5, and IL-13, promoting B cell production of IgE antibodies while also recruiting eosinophils and basophils to the site of inflammation. IgE antibodies blind to receptors on mast cells and basophils, upon re-exposure to the same allergen, these cells become activated, releasing inflammatory mediators including histamine and thereby inducing allergic symptoms. Simultaneously, the gut microbiota and mucus layer play critical roles in modulating immune responses and preventing allergen penetration.SCFAs are produced via the fermentation of dietary fibers by the gut microbiota and exert anti-inflammatory effects in allergic diseases through the activation of GPR41/GPR43 receptors on immune cells. SCFAs suppress DCs from releasing pro-inflammatory cytokines such as IL-33 and TSLP, thereby attenuating Th2 immune responses. Simultaneously, they promote the differentiation of Tregs and enhance IL-10 secretion, contributing to immune tolerance. Additionally, SCFAs downregulate pro-inflammatory mediators, including TNF-α and IL-6, in macrophages, inhibit eosinophil degranulation and basophil chemetaxis, and reduce levels of Th2-associated cytokines (IL-5, IL-13) and eosinophil cationic protein (ECP), thus comprehensively mitigating allergic inflammation.]" The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.