Harnessing multi-omics approaches to elucidate the role of Chinese herbal compounds in chemotherapy-induced gastrointestinal damage

Abstract

In this editorial, we discuss the findings reported by Wang et al in the latest issue of the World Journal of Gastrointestinal Oncology. Various research methodologies, including microbiome analysis, assert that the Tzu-Chi Cancer-Antagonizing and Life-Protecting II Decoction of Chinese herbal compounds mitigates inflammatory responses by inhibiting the NF-κB signaling pathway. This action helps maintain the dynamic equilibrium of the intestinal microecology and lessens chemotherapy-induced gastrointestinal damage. The efficacy of these compounds is intimately linked to the composition of intestinal microbes. These compounds regulate intestinal microecology by virtue of their specific compatibility and effectiveness, thereby enhancing the overall therapeutic outcomes of cancer chemotherapy. Nonetheless, the exact mechanisms underlying these effects warrant further investigation. Multi-omics technologies offer a systematic approach to elucidate the mechanisms and effectiveness of Chinese herbal compounds in vivo. This manuscript reviews the application of multi-omics technologies to Chinese herbal compounds and explores their potential role in modulating the gastrointestinal microenvironment following cancer chemotherapy, thus providing a theoretical foundation for their continued use in adjunct cancer treatment.

Key Words: Chinese herbal compounds; Gastrointestinal microenvironment; Chemotherapy; Multi-omics; Intestinal microecology

Core Tip: We discussed the mechanism and advantages of Chinese herbal compounds based on metabolomics, transcriptomics, microbiomes, and other multi-omics technologies in regulating the gastrointestinal microenvironment after cancer chemotherapy, providing theoretical support for Chinese herbal compounds to assist cancer chemotherapy.

INTRODUCTION

During cancer chemotherapy, between 40% and 100% of patients suffer gastrointestinal-related damage. This triggers inflammatory responses in the gastrointestinal tract and disrupts the gut microbiota[1,2], leading to significant health issues, including indigestion, nutrient malabsorption, and decreased immune function. Consequently, finding effective ways to mitigate chemotherapy's adverse effects on the gastrointestinal tract has emerged as a crucial area of clinical research[3].

In recent years, the potential of Chinese herbal compounds to improve chemotherapy-related side effects has gained increasing attention. Rich in bioactive components and characterized by multiple mechanisms of action, these compounds are progressively recognized as a viable option for alleviating chemotherapy-induced gastrointestinal damage[4]. They reduce inflammation and enhance the diversity and stability of the gut microbiota, thus restoring a healthy gut ecosystem[5].

Against this background, the study by Wang et al[6] offers insightful revelations into how the Tzu-Chi Cancer-Antagonizing and Life-Protecting II Decoction mitigates gastrointestinal inflammation and reestablishes microbial balance[6]. Employing a systematic experimental approach, the research delineates how this Chinese herbal compound alleviates chemotherapy-induced gastrointestinal damage by modulating immune responses, bolstering gut barrier function, and fostering the growth of beneficial microbes. These discoveries underpin its clinical application and guide future research directions.

Understanding the protective effects of Chinese herbal compounds on the gastrointestinal tract during chemotherapy is pivotal for enhancing patient quality of life and treatment outcomes. To expand on these findings, we propose integrating omics technologies—such as genomics, transcriptomics, proteomics, and metabolomics—to further dissect the mechanisms at play and provide new insights into their modes of action.

SYMPHONY OF GENOMICS AND TRANSCRIPTOMICS: UNVEILING THE GENETIC DIALOGUE BETWEEN CHINESE HERBAL COMPOUNDS AND HOST CELLS

Genomic studies have significantly advanced our understanding of the genetic interactions between Chinese herbal compounds and host cells. With recent advancements in high-throughput sequencing technologies, researchers can now analyze the effects of these compounds on the cellular genome[7]. Evidence suggests that certain Chinese herbal compounds can modulate cancer cell migration and invasion by influencing specific gene expression[8]. Identifying these gene targets helps elucidate the mechanisms behind the therapeutic effects of Chinese herbal compounds and provides potential biomarkers for clinical application.

Transcriptomic analysis further enhances our understanding by detailing changes in gene expression profiles following treatment with Chinese herbal compounds. This allows researchers to examine how these compounds affect transcriptional activities within host cells[9]. Utilizing next-generation sequencing technologies enables the efficient collection of extensive transcriptomic data, facilitating the identification of upregulated or downregulated genes in response to inflammation and cellular repair processes. For example, the research conducted by Wang et al[6] highlights the critical role of the NF-κB signaling pathway, with observed changes in gene expression revealing the impact of Chinese herbal compounds on inflammatory response modulation. Additionally, Li et al[10] employed transcriptomic methods to investigate the effects of Xiao-Ban-Xia-Tang on a rat model of chemotherapy-induced pica. Their findings suggest that Xiao-Ban-Xia-Tang may alleviate symptoms of vomiting by suppressing the overexpression of gastrointestinal inflammatory genes and reducing serotonin synthesis triggered by the chemotherapeutic agent cisplatin[10].

By integrating genomics and transcriptomics, scientists achieve a more comprehensive understanding of the mechanisms of action of Chinese herbal compounds[11]. This holistic approach deepens our insight into the molecular pathways influenced by these compounds and establishes a theoretical foundation for developing innovative therapeutic strategies[12]. Researchers are enabled to craft more effective Chinese herbal formulations by targeting specific genes or signaling pathways, thus enhancing therapeutic outcomes.

Furthermore, combining genomic and transcriptomic data analysis can illuminate individual variances in response to treatment with Chinese herbal compounds, laying the groundwork for personalized therapy. This integrated research approach not only opens new avenues for understanding the biological effects of Chinese herbal compounds but also reveals their potential in treating cancer and its associated complications. Ongoing investigations in this domain are crucial for advancing the modernization and clinical integration of Chinese herbal medicine.

POWER OF PROTEOMICS: UNVEILING THE DEEP IMPACT OF CHINESE HERBAL COMPOUNDS ON GASTROINTESTINAL FUNCTION

Proteomic analysis enriches our understanding of the functional outcomes of gene expression changes[13]. In Chinese herbal medicine, proteomics aids in examining alterations in protein expression levels and post-translational modifications in the gastrointestinal tract following treatment. These changes mirror the dynamic regulation of gene expression and delineate the specific impacts of Chinese herbal compounds on cellular functions[14].

Researchers can pinpoint critical proteins that play crucial roles in inflammatory responses and microbial regulation by analyzing the proteome post-treatment with Chinese herbal compounds. Specific herbal components are known to upregulate proteins that enhance mucosal barrier function, which is crucial for protecting intestinal epithelial cells and bolstering intestinal barrier integrity. Furthermore, these proteins support the regeneration of epithelial cells, restoring a healthy intestinal environment and mitigating the adverse effects of chemotherapy[15].

Mass spectrometry has significantly improved the efficiency and precision of proteomics research. This technology allows for the quantitative assessment of a vast array of proteins and the identification of their post-translational modifications, such as phosphorylation and glycosylation, etc.[16]. These modifications can profoundly influence protein function and interactions, impacting cellular signaling pathways and thus regulating inflammatory responses and cell survival[17].

The analysis of protein interaction networks offers a deeper insight into how these key proteins interplay within the cellular milieu. By mapping these networks, researchers can unravel how Chinese herbal compounds modulate cellular functions by influencing protein interactions, providing a comprehensive understanding of their therapeutic mechanisms and potential[18].

Proteomics is essential for deciphering the mechanisms by which Chinese herbal compounds exert their therapeutic effects. Researchers can explore how these compounds regulate gastrointestinal functions, ameliorate inflammatory responses, and restore microbial balance by conducting systematic analyses of protein expression and interactions. This field of study deepens our understanding of the action mechanisms of Chinese herbal compounds and supplies crucial scientific evidence that supports their future clinical applications.

TRADITIONAL CHINESE MEDICINE THERAPY FROM THE PERSPECTIVE OF METABOLOMICS: REVEALING THE PROFOUND IMPACT OF HERBAL MEDICINE ON INTESTINAL HEALTH

Metabolomics, a rapidly expanding field, provides a distinctive lens for analyzing the metabolites produced in response to herbal treatments, deepening our comprehension of the mechanisms by which Chinese herbal compounds operate within the body. This field not only concentrates on the components and effects of drugs but also examines how drugs modify the metabolic state of an organism, thereby uncovering shifts in biochemical pathways[19]. For instance, treatments with Chinese herbal compounds, such as the Tzu-Chi Cancer-Antagonizing and Life-Protecting II Decoction, have been shown to induce changes in metabolites, particularly those involved in metabolic pathways linked to the production of short-chain fatty acids (SCFAs). SCFAs, which are byproducts of dietary fiber fermentation by intestinal microbes, play a vital role in maintaining intestinal health. They provide energy, modulate inflammatory responses, promote the repair and regeneration of intestinal epithelial cells, and support microbial diversity. Recent studies highlight that SCFAs such as acetic acid, propionic acid, and butyric acid enhance intestinal health by inhibiting inflammation-related signaling pathways[20].

To investigate the effects of Chinese herbal compounds on metabolism, researchers employ advanced analytical techniques such as nuclear magnetic resonance and liquid chromatography-mass spectrometry[21]. These methods enable the efficient and precise detection and quantification of metabolites in biological samples, creating a detailed map of the metabolic alterations induced by herbal treatments.

These metabolomic analysis identify specific metabolites associated with the treatment of Chinese herbal compounds, clarifying their role in regulating the gastrointestinal microenvironment. For example, Hou et al[22] used gas chromatography-time-of-flight mass spectrometry in their metabolomic study. They concluded that Jianpi Yangzheng Xiaozheng Decoction could reduce chemotherapy-related gastrointestinal side effects such as nausea and vomiting by influencing amino acid metabolic pathways, thereby improving patients' quality of life[22]. Additionally, metabolomics offers avenues to discover potential biomarkers to assess the efficacy of Chinese herbal treatments and individual response variations, further supporting the clinical application and personalized approach to using these compounds[23].

Metabolomics offers a fresh perspective, aiding our understanding of the mechanisms through which Chinese herbal compounds act within the body and influence metabolism. By systematically analyzing metabolites, researchers can uncover the potential of these compounds to regulate the intestinal microenvironment, ameliorate inflammatory responses, and promote overall health. Ongoing research in this field will yield crucial scientific evidence to support the modernization and clinical application of Chinese herbal compounds.

CONCERTO OF MULTI-OMICS AND AI: DECIPHERING THE INTERACTIONS BETWEEN TRADITIONAL CHINESE MEDICINE AND GUT MICROBIOTA

Integrating omics data provides a robust strategy to elucidate the complex interactions between Chinese herbal compounds and the gut microbiome[24]. By amalgamating genomic, transcriptomic, proteomic, and metabolomic data, researchers can construct comprehensive biological models that illustrate the dynamic changes occurring during therapeutic responses[25]. This multi-level omics integration enhances understanding of the action mechanisms of Chinese herbal compounds and elucidates the interconnections among different biological layers. Genomics offers insights into genetic variations and backgrounds, transcriptomics discloses changes in gene expression, proteomics examines protein functions and interactions, and metabolomics focuses on the changes in metabolites and their physiological implications. Integrating these diverse data levels allows researchers to more thoroughly comprehend how Chinese herbal compounds affect the gut microbiome and its ecological balance by modulating gene expression, protein functionality, and metabolic pathways. Zhou et al[26] demonstrated that the combined administration of ginseng polysaccharides and ginsenosides can counteract the abnormal spleen and peripheral blood lymphocyte subset ratios induced by cyclophosphamide in immunosuppressed mice and stimulate the proliferation of CD4+ T cells and IgA-secreting cells in the small intestine, thus addressing cyclophosphamide-induced gut immune disorders. This combination also promotes the recovery of gut barrier function, with its mechanism of action linked to the regulation of gut microbiota and alterations in fecal metabolites[26].

Furthermore, deploying artificial intelligence (AI) and machine learning algorithms has significantly enhanced the capability to analyze these extensive datasets[27]. AI technologies can process and interpret vast quantities of omics data, identifying potential patterns and correlations that may not be evident through traditional statistical analysis. Machine learning algorithms can forecast the impact of various Chinese herbal compounds on specific microbial communities by training models, aiding researchers in pinpointing the most effective treatment approaches. This cutting-edge method expedites the identification of new therapeutic targets and fosters the development of personalized treatment strategies based on individual microbiome traits. By evaluating patients' microbiome data alongside omics integration results, physicians can devise more targeted treatment regimens to enhance efficacy and minimize adverse effects.

The synergistic application of omics integration and AI heralds new avenues for research into Chinese herbal compounds. By harnessing diverse omics data and advanced AI analytical techniques, researchers can gain profound insights into the mechanisms of Chinese herbal compounds and advance personalized medicine. Continued research in this domain will solidify the scientific basis for the modernization and clinical application of Chinese herbal compounds.

FUTURE DIRECTIONS

Although the research findings of Wang et al[6] are promising, additional studies are essential to delineate the specific mechanisms through which Chinese herbal compound formulas mitigate chemotherapy-induced gastrointestinal damage. Future research should employ an integrated omics approach to thoroughly investigate the interactions between these compounds and the gut microbiome. Furthermore, clinical trials assessing the efficacy of these herbal treatments in cancer patients are critical for validating their therapeutic potential and formulating clinical practice guidelines. In summary, the confluence of omics technologies and AI presents exciting new avenues for exploring Chinese herbal compounds. By methodically examining the mechanisms by which these compounds influence the gastrointestinal microenvironment, we can facilitate the development of novel adjuvant therapies, thus enhancing the efficacy of cancer chemotherapy and improving patient outcomes.

CONCLUSION

In summary, this editorial highlights the potential of Chinese herbal compounds to modulate the gastrointestinal microenvironment following cancer chemotherapy, showing their unique advantages as an adjunct therapy. The integration of multi-omics technologies heralds a promising future for research, facilitating a comprehensive analysis of the mechanisms of action of Chinese medicine and the identification of potential biomarkers, which contribute to personalized treatment. Future efforts should aim to elucidate the specific pathways through which Chinese medicine operates, integrating AI and big data analysis to enhance the application of Chinese medicine in modern medical practices and improve the quality of life for cancer patients.