Application of traditional Chinese medicine integrated therapy based on Tuina and herbal medicine in pediatric diarrhea

Abstract

This review examines the distinct mechanisms of Tuina massage and topical herbal medicine in pediatric diarrhea management, focusing on their independent regulation of gastrointestinal metabolism and barrier function. Tuina therapy primarily enhances gastrointestinal motility through the stimulation of targeted acupoints such as Tianshu (ST25) and Shenque (CV8), activating vagal efferent pathways to normalize motility hormones including motilin while suppressing pro-inflammatory cytokines such interleukin-6 and tumor necrosis factor-alpha. It further reinforces mucosal defense by inhibiting mast cell degranulation and augmenting microcirculation via nitric oxide-mediated vasodilation. Herbal medicine containing bioactive compounds from Atractylodes macrocephala and Poria cocos directly restores intestinal barrier integrity by upregulating tight junction proteins occludin and zonula occludens-1, inhibiting epithelial apoptosis, and stimulating MUC2 production. These formulations additionally reprogram enterocyte metabolism by reactivating mitochondrial tricarboxylic acid cycle flux and modulating short-chain fatty acid profiles, with the independent prebiotic effects enhancing commensal butyrate production. Tuina primarily modulates neuroimmune pathways and motility, and herbal medicine directly targets epithelial repair and metabolism. These therapeutic pathways may address core diarrhea pathophysiology, providing holistic complementary therapies. Standardized protocols and interdisciplinary research are urgently needed for clinical translation.

Key Words: Pediatric; Diarrhea; Traditional Chinese medicine; Tuina; Herbal medicine

Core Tip: This review elucidates the distinct mechanisms by which integrated traditional Chinese medicine therapies Tuina massage and topical herbal medicine ameliorate pediatric diarrhea. We highlight that Tuina primarily modulates neuro-immune pathways to regulate motility and inflammation, while herbal applications directly restore intestinal barrier integrity and reprogram enterocyte metabolism. Crucially, this work synthesizes evidence for their synergistic action in repairing the gut barrier, a core pathophysiological defect, providing a mechanistic foundation for non-pharmacological, holistic complementary strategies in children.

INTRODUCTION

Global burden and clinical challenges of pediatric diarrhea

Pediatric diarrhea remains a leading cause of morbidity and mortality in children under 5 years old, accounting for approximately 500000 annual deaths worldwide according to World Health Organization 2023 surveillance data[1-3]. Beyond acute mortality, recurrent episodes contribute to malnutrition, growth retardation, and compromised immune development[4-6]. Current first-line therapies primarily involve oral rehydration solutions (ORS), zinc supplementation, and antibiotics for bacterial pathogens[7-10]. However, significant limitations persist: ORS fails to reduce stool volume or duration[11,12], antibiotics induce gut dysbiosis and antimicrobial resistance, and symptomatic treatments such as loperamide are contraindicated in young children[13]. These gaps underscore the urgent need for safe, mechanism-targeted alternatives[14,15].

Theoretical rationale for integrated traditional Chinese medicine approaches

In traditional Chinese medicine (TCM), pediatric diarrhea is pathophysiologically characterized as Xiao’er Xiexie (pediatric diarrhea syndrome), a condition fundamentally attributed to spleen deficiency complicated by dampness accumulation. This paradigm postulates that compromised spleen-Qi impairs fluid and nutrient transportation, leading to dysfunctional digestion and intestinal barrier disruption. Contemporary TCM strategies employ external and internal interventions to address this pathomechanism. In particular, therapeutic massage (Tuina) modulates neuroimmunological pathways through stimulation of specific acupoints, especially Tianshu (ST25) and Shenque (CV8), thereby enhancing gastrointestinal motility and visceral sensitivity regulation[16]. Transdermal delivery of bioactive compounds from herbal applications, such as umbilical compresses containing Atractylodis Macrocephalae Rhizoma, directly targets intestinal mucosal metabolism[17-19].

METHODOLOGY OF INTEGRATED TCM THERAPIES

TCM offers distinct nonpharmacological or adjunctive therapeutic strategies for pediatric diarrhea, primarily utilizing Tuina and topical herbal applications. While these modalities are frequently employed within a broad TCM management plan, either concurrently or sequentially depending on clinical judgment and presentation, they possess unique methodologies grounded in TCM theory and clinical practice. This section details the specific application procedures, core techniques, and key herbal formulations for Tuina and topical herbal therapy as documented in clinical research and practice for managing childhood diarrhea.

Tuina techniques for pediatric diarrhea

Pediatric Tuina, a specialized form of therapeutic massage adapted for the unique physiological and pathological characteristics of infants and children, constitutes a cornerstone of the integrated approach[20-22]. Its efficacy in pediatric diarrhea management is attributed to its ability to regulate gastrointestinal function through the precise stimulation of key acupoints and meridians using gentle, noninvasive manual techniques[23,24]. The selection of acupoints is guided by TCM syndrome differentiation, typically focusing on points known to fortify the spleen, harmonize the stomach, warm the middle jiao, arrest diarrhea, and regulate intestinal peristalsis[25].

Among the most clinically significant acupoints is ST25, bilaterally located adjacent to the umbilicus. Stimulation at ST25, primarily achieved through the application of Rou Fa (kneading technique), is fundamental for regulating intestinal movement, alleviating abdominal distension, and harmonizing the function of the large intestine[26]. CV8, the umbilicus itself, serves as a vital center for energy and is a primary site for Tuina manipulation and topical herbal application[27]. Gentle Mo Fu (circular rubbing) techniques centered on CV8 are routinely employed to warm the abdomen, strengthen the spleen yang, and dispel cold-dampness and are particularly relevant in deficiency or cold-type diarrhea presentations[28]. The lumbosacral region, specifically the Qijiegu (seven-segment bone, spanning from the lumbosacral depression to the coccyx tip) and Guwei (turtle tail, GV1, located at the tip of the coccyx), is another critical therapeutic focus. Manipulations in this area, particularly the technique of Tui Shang Qijiegu (pushing upward along the Qijiegu) and Rou Fa applied to GV1, are highly valued for their potent ability to warm and tonify the spleen and kidney yang, consolidate the intestines, and effectively stop chronic or deficiency-type diarrhea[29]. Furthermore, the manipulation of the spleen meridian (Pi Jing) on the radial aspect of the thumb, often using Bu Pi Jing (supplementing the spleen meridian technique) involving pushing toward the thumb tip, is essential for invigorating spleen qi, resolving dampness accumulation, and improving digestive and absorptive capacities[30]. Zusanli (ST36), located below the knee, is frequently stimulated with kneading techniques to broadly tonify the spleen and stomach qi, enhancing overall digestive function and nutrient assimilation[31,32].

The application of Tuina involves a repertoire of standardized, gentle manual techniques specifically adapted for pediatric patients[33,34]. Rou Fa (kneading) entails applying rhythmic, circular pressure using the pad of the thumb or the thenar eminence over specific acupoints such as ST25, ST36, or GV1 to generate a sensation that is soothing and regulatory[35]. Mo Fu (abdominal rubbing) involves broad, clockwise circular motions performed with the palm over the entire abdominal region, with particular emphasis around the umbilicus (CV8); this technique promotes overall abdominal warmth, regulates peristaltic activity, and alleviates discomfort[36]. Nie Ji (spine pinching) is a foundational pediatric Tuina technique where the skin and underlying tissue along the governor vessel (Du meridian, typically from the lower thoracic to the sacral region) are gently pinched and lifted sequentially; this powerful technique is believed to strengthen the spleen and lung, boost yang qi throughout the body, enhance overall resistance (Zheng Qi), and regulate autonomic nervous function influencing the gut[37]. Tui Shang Qijiegu (pushing upwards on the seven-segment bone) involves applying unidirectional, firm yet gentle strokes upward along the Qijiegu region, usually by using the radial side of the thumb or the pads of the index and middle fingers, specifically to warm yang and lift sinking qi to arrest diarrhea[38]. Treatment sessions are conducted with careful attention to the child’s comfort and response, with typical session durations falling within a clinically established range suitable for pediatric tolerance and administered at a frequency commonly employed in practice over a therapeutic course determined by the severity and chronicity of the condition[39,40].

Topical herbal applications

Complementing Tuina manipulations, topical medicinal herbs, most frequently applied via the umbilical region, represents the second pillar of the integrated TCM approach for pediatric diarrhea[41]. This method leverages the unique anatomical and physiological properties of the umbilicus, recognized in TCM as a highly permeable gateway connected to the internal organs and in biomedicine as a site with relatively thin stratum corneum, rich vascularity, and absence of subcutaneous, all of which facilitate the efficient transdermal and transmucosal absorption of bioactive compounds[42,43]. This absorption efficiency may be further heightened in infants and young children because of their thinner stratum corneum and greater skin permeability compared with adults. While these features enhance the delivery of therapeutic compounds, they underscore the importance of careful dosage calibration and monitoring for potential local or systemic adverse effects in this vulnerable population. Topical herbal therapy circumvents the challenges of oral administration in young children, such as poor compliance, gastric irritation, or first-pass metabolism, allowing for the direct delivery of therapeutic agents to the affected abdominal region[44-46].

The selection of herbal formulas for umbilical compresses (Fu Qi Liao Fa) is meticulously based on TCM syndrome differentiation to address the core patterns underlying pediatric diarrhea, predominantly spleen deficiency, dampness encumbrance, yang deficiency, or food stagnation. Spleen-strengthening and dampness-resolving formulas are central to the treatment. These formulations typically incorporate herbs such as Baizhu (Rhizoma Atractylodis Macrocephalae and Atractylodes macrocephala) and Fuling (Poria and Poria cocos), renowned for their abilities to fortify the spleen, promote diuresis, and drain pathogenic dampness, which address a fundamental pathological factor in diarrhea[47-49]. Spleen function-regulating formulas might include components such as Taizishen (Radix Pseudostellariae and Pseudostellaria heterophylla) and Cangzhu (Rhizoma Atractylodis and Atractylodes lancea) to restore the spleen’s crucial role in transportation and transformation (Jian Yun Pi Wei), which are essential for normal digestion and stool formation[50,51]. Warm herbal compresses (Re Yan Bao) are often utilized for presentations involving cold patterns, abdominal pain, or yang deficiency[52]. These warm packs contain herbs with thermogenic and dispersing properties, such as Wuzhuyu (Fructus Evodiae and Evodia rutaecarpa) and Laifuzi (Semen Raphani and Raphanus sativus seeds), applied to warm the middle jiao, dispel cold pathogens, alleviate cramping pain, and promote the downward flow of qi to regulate bowel movements[53,54].

The preparation and application of these topical herbs follow specific protocols. Selected herbs are typically processed into fine powders or blended into thick, paste-like consistencies using appropriate excipients to enhance adhesion and transdermal penetration[55]. Before application, the umbilical region and sometimes the surrounding lower abdomen are meticulously cleansed. The prepared herbal mixture is then applied directly to the umbilicus, covered with a sterile gauze pad or a specialized adhesive patch designed for prolonged wear[56,57]. While generally safe, topical medicinal herbs may occasionally cause local skin reactions, such as erythema or pruritus, particularly in children with sensitive skin or herbal allergies. Contraindications include broken skin or known hypersensitivity to specific herbal components. The compress is typically retained for a duration considered optimal for therapeutic effect while minimizing potential skin irritation, applied daily over a treatment course aligned with clinical need and response monitoring. This method ensures the sustained contact and delivery of bioactive constituents through the highly vascularized umbilical area[58,59]. The core Tuina techniques and herbal formulations applied in clinical practice are systematically categorized in Table 1.

Table 1 Key techniques and herbal formulations in integrated traditional Chinese medicine therapy.

Therapy modality	Specific technique/herbal formula type	Key components/target	Standard application	Primary proposed therapeutic mechanisms
Tuina	Rou Fa (kneading)	ST25, ST36, GV1	Gentle rhythmic pressure applied to specific points during sessions	Local stimulation modulating neural reflexes influencing gut motility/secretion; promoting local Qi/blood flow
Tuina	Mo Fu (abdominal rubbing)	Abdomen centered on CV8	Broad clockwise circular motions over abdomen	Regulating peristalsis, alleviating spasm/distension; warming the middle jiao; resolving abdominal Qi stagnation
Tuina	Nie Ji (spine pinching)	Skin along Du meridian (GV14-GV4 region)	Gentle sequential pinching and lifting	Regulating autonomic nervous system; strengthening overall Zheng Qi (spleen/Lung); influencing gut-brain axis
Tuina	Tui Shang Qijiegu	Qijiegu region (GV2-GV1)	Upward unidirectional pushing	Warming spleen/kidney Yang; lifting sinking Qi to consolidate intestines and stop diarrhea
Tuina	Bu Pi Jing (supp spleen meridian)	Radial side of thumb (spleen meridian)	Pushing towards thumb tip	Tonifying spleen Qi; resolving dampness; enhancing digestive and absorptive functions
Topical herbal (umbilical)	Spleen-fortifying and damp-resolving	Atractylodes macrocephala (Baizhu), Poria cocos (Fuling)	Paste applied to CV8 region daily	Transdermal absorption of compounds modulating intestinal fluid transport/ion channels; reducing inflammation; strengthening spleen function
Topical herbal (umbilical)	Spleen-transporting and stagnation-resolving	Pseudostellaria heterophylla (Taizishen), Atractylodes lancea (Cangzhu), Crataegus pinnatifida (Shanzha)	Paste applied to CV8 region daily	Enhancing digestive enzyme activity; promoting gastrointestinal motility; resolving food accumulation; regulating gut microbiota
Topical herbal (umbilical)	Warm compress (Re Yan Bao) for cold	Evodia rutaecarpa (Wuzhuyu), Raphanus sativus (Laifuzi)	Warmed paste applied to CV8 region daily	Dispelling cold pathogen; warming middle jiao; alleviating smooth muscle spasm/pain; promoting downward Qi movement

REGULATION OF GASTROINTESTINAL MOTILITY AND METABOLIC HOMEOSTASIS

The pathophysiology of pediatric diarrhea involves the complex dysregulation of intestinal motor function and metabolic processes. TCM interventions exert therapeutic effects through distinct mechanistic pathways. Tuina therapy primarily modulates neuroimmunological circuits, whereas transdermal herbal applications directly influence epithelial metabolism and restore gastrointestinal homeostasis. Figure 1 illustrates the mechanisms through which Tuina therapy and transdermal herbal applications regulate gastrointestinal motility and metabolic homeostasis in the management of pediatric diarrhea, as detailed in the following subsections.

Figure 1 Key mechanisms of traditional Chinese medicine combined therapy in regulating gastrointestinal motility and metabolic homeostasis in pediatric diarrhea. IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-alpha; TCA: Tricarboxylic acid cycle; ATP: Adenosine triphosphate.

Neural pathway activation through cutaneous stimulation

Pediatric Tuina exerts profound effects on gastrointestinal motility through somatovisceral neural reflex arcs[60]. The mechanical stimulation of specific abdominal and lumbosacral acupoints generates afferent signals transmitted via spinal cord pathways to central autonomic nuclei. ST25 and CV8 stimulation activates vagal efferent projections to the enteric nervous system[61,62]. This neural modulation enhances the synthesis and release of key gastrointestinal hormones including motilin and gastrin, which serve as critical regulators of intestinal contractile activity and migrating motor complex patterns[63]. The subsequent normalization of peristaltic rhythms facilitates efficient luminal content transit, reducing fluid sequestration in the intestinal lumen that characterizes diarrheal states[36]. Furthermore, afferent signals from spinal manipulation sites such as Qijiegu converge in the nucleus tractus solitarius, establishing bidirectional communication along the gut–brain axis that modulates the central processing of visceral sensitivity[64].

Immunomodulatory effects on intestinal wall integrity

Concurrent with its neurological actions, Tuina demonstrates significant immunoregulatory properties relevant to diarrheal pathophysiology. Manual stimulation at key acupoints reduces the systemic and local intestinal concentrations of pro-inflammatory cytokines, particularly interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α)[65-67]. This cytokine downregulation attenuates the inflammatory cascade that disrupts epithelial tight junctions and increases vascular permeability[68]. Clinical studies further indicated measurable reductions in acute-phase reactants such as C-reactive protein following Tuina regimens, suggesting its systemic anti-inflammatory effects[66]. The amelioration of intestinal wall edema through these mechanisms contributes substantially to the restoration of normal mucosal barrier function and reduction in fluid exudation into the intestinal lumen[69].

Transdermal bioactive compounds modulating epithelial function

Topical herbal applications directly affects intestinal epithelial metabolism through the systemic absorption and enterohepatic recirculation of bioactive constituents[70]. Pharmacokinetic studies demonstrated that lipophilic compounds from umbilical compresses, including sesquiterpenes from Atractylodes macrocephala and triterpenoids from Poria cocos, are significantly concentrated in intestinal tissues[71]. These phytochemicals enhance epithelial integrity through multiple pathways: Modulating the expression of tight junction proteins including occludin and zonula occludens-1 (ZO-1), reducing epithelial apoptosis rates, and stimulating mucin production from goblet cells[71,72]. From a clinical perspective, these effects correlate with decreased serum levels of intestinal permeability biomarkers, reflecting improved mucosal barrier competence and reduced translocation of luminal antigens[72,73]. For instance, treatment with Fushen granule, a Chinese medicine formula, significantly decreased the serum levels of intestinal permeability biomarkers D-lactate and diamine oxidase while upregulating the expression of tight junction proteins ZO-1 and occludin in a rat model. This effect was mediated by the inhibition of the pro-inflammatory p38 mitogen-activated protein kinase signaling pathway, providing a comprehensive mechanistic link among herbal intervention, anti-inflammatory action, and structural barrier reinforcement[74].

Metabolic reprogramming of enterocytes

Beyond their structural effects, herb permeates significantly reprogram cellular metabolism within the intestinal epithelium[75]. Metabolomic analyses revealed that key herbal compounds influence mitochondrial function, particularly by restoring tricarboxylic acid cycle flux and enhancing fatty acid β oxidation[76,77]. This metabolic shift increases adenosine triphosphate production capacity in enterocytes, providing the energy substrate necessary for active nutrient transport and epithelial repair[77]. Certain herbal constituents demonstrate inhibitory effects on sodium glucose cotransporter overactivity, thereby reducing osmotically driven water secretion into the intestinal lumen. The net effect is a reestablishment of the normal absorptive-secretory balance in the intestinal epithelium[78].

Gut microbiota-derived metabolite regulation

Tuina and herbal therapies may indirectly influence host metabolism by modulating microbial-derived metabolites. Herbal compounds such as berberine undergo microbial biotransformation into active metabolites that inhibit bacterial pathogen virulence factors while stimulating the commensal production of short-chain fatty acids (SCFAs)[79]. These microbiota-derived SCFAs serve as preferential energy substrates for colonocytes and activate G-protein-coupled receptors (GPCRs) that regulate gastrointestinal motility reflexes[80,81]. The mechanical pressure from abdominal Tuina may further enhance microbial metabolite absorption through improved mucosal perfusion, creating a metabolic environment that supports epithelial repair[82].

These integrated effects collectively reverse the pathophysiological triad of diarrhea: Accelerated transit, reduced absorption, and increased secretion. While clinical studies often reported these outcomes as a whole, mechanistic research increasingly delineated the distinct contributions of neural modulation vs direct metabolic intervention, providing a scientific foundation for their application in pediatric diarrheal disorders.

MULTIDIMENSIONAL RESTORATION OF INTESTINAL BARRIER INTEGRITY

The intestinal barrier constitutes a critical defense system comprising physical, immunological, and microbial components. Its dysfunction in pediatric diarrhea involves epithelial damage, impaired tight junctions, reduced mucus production, and dysregulated immune responses. TCM interventions target these pathological alterations through distinct mechanistic pathways, facilitating comprehensive barrier restoration.

Structural reinforcement of epithelial tight junctions

Herbal applications demonstrate significant efficacy in enhancing epithelial structural integrity. Bioactive compounds such as polysaccharides from Poria cocos and atractylenolides from Atractylodes macrocephala upregulate the expression of tight junction proteins, particularly occludin and ZO-1[83,84]. These proteins form the primary seal between adjacent enterocytes, regulating paracellular permeability. Experimental models confirmed that herbal permeates reduce intestinal permeability by reinforcing these protein complexes, thereby limiting the translocation of luminal antigens and endotoxins[85]. This effect correlates with decreased intestinal permeability, reflecting improved barrier competence[86]. The molecular mechanisms involve modulating the signaling pathways for actin cytoskeleton organization and suppressing myosin light chain kinase activation, which disrupts junctional complexes during inflammation[87].

Enhancement of the mucus barrier system

The mucus layer serves as the primary chemical barrier against pathogens in the gut lumen[88]. Topical herbal formulations, which contain compounds such berberine from Coptis species, promote the differentiation of goblet cells and increase expression of the MUC2 gene[89]. MUC2 forms the primary structural component of the protective gel layer, trapping pathogens and facilitating their clearance[88]. The reduced activity of intestinal mast cells (MCs) observed with Tuina might indirectly aid mucus production. Activated MCs release histamine and TNF-α, which inhibit goblet cell function and deplete mucin reserves[90]. By inhibiting MC degranulation in the colon, Tuina mitigates this suppression and allows unimpeded herbal-induced mucin upregulation[91]. The central effect of Tuina on hippocampal MCs is postulated to be modulating the brain-gut axis via descending pathways. This regulation likely involves the vagus nerve, i.e., increasing acetylcholine release to promote intestinal motility and reduce inflammation and rebalancing serotonin signaling, which is crucial in gut secretion and sensation[90]. In addition, Tuina therapy provides protection through mechanotransduction pathways. Gentle manipulation of the abdomen lowers the rate of epithelial cell death by decreasing the levels of pro-apoptotic factors such as caspase-3 while boosting cell growth[92]. The mucus production induced by medicinal herbs and the cytoprotective effect of Tuina work together to thicken the mucus layer and maintain epithelial integrity, resulting in a strong barrier against harmful substances in the gut lumen.

Immunomodulation of mucosal inflammation

Herbal-directed suppression operates primarily through phytochemical interactions, where compounds such as evodiamine from Evodia rutaecarpa inhibit nuclear factor-kappa B nuclear translocation, thereby suppressing the downstream expression of pro-inflammatory cytokines including IL-6 and TNF-α, which collectively reduce neutrophil infiltration and mitigate epithelial cytokine exposure[93]. By contrast, Tuina-mediated regulation leverages neuroimmunological pathways. Pediatric Tuina targeting spleen-meridian and large-intestine-meridian acupoints significantly reduces MC infiltration and tryptase release in colonic tissues, directly ameliorating mucosal inflammation and barrier disruption in spleen-deficiency diarrhea[94]. This finding aligns with the established role of MCs in rapidly responding to intestinal anomalies by triggering local inflammation[95]. Clinical studies further confirmed that heightened MC activation correlates with symptom severity in diarrheal conditions[96], supporting Tuina’s therapeutic mechanism. Abdominal massage similarly reduces colonic MC hypertrophy in irritable bowel syndrome models[97], validating the broad relevance of MC modulation. Furthermore, mechanical stimulation at acupoints such as ST25 can activate the vagal-adrenal anti-inflammatory axis to increase the systemic release of anti-inflammatory mediators such as IL-10, ultimately attenuating dendritic cell maturation and T-helper 17 cell polarization within the lamina propria[98,99]. The convergence of these interventions disrupts the inflammatory cascade responsible for tight junction degradation and elevated epithelial permeability, establishing a microenvironment conducive to mucosal repair through the coordinated resolution of immunopathological processes[100].

Microvascular integrity and tissue perfusion

Intestinal barrier dysfunction involves microvascular compromise and ischemia-reperfusion injury. Tuina techniques, particularly abdominal Mo Fu, enhance local microcirculation through neurogenic vasodilation and nitric oxide release. Improved tissue perfusion alleviates hypoxia-induced epithelial damage and supports cellular repair[101]. Certain herbal components (e.g., paeoniflorin from Paeonia lactiflora) further stabilize endothelial tight junctions and reduce vascular permeability, limiting edema formation in the submucosa. This vascular normalization reduces hydrostatic pressure on the epithelial barrier and facilitates nutrient delivery for tissue regeneration[102].

Microbiota-dependent barrier reinforcement

Emerging evidence highlights the gut microbiota’s role in barrier maintenance through metabolite production. Herbal compounds serve as prebiotic substrates for commensal bacteria, stimulating the production of SCFAs, particularly butyrate[103]. Butyrate serves as the primary energy source for colonocytes, enhances mucin synthesis, and strengthens tight junctions via the activation of GPCRs[104]. Tuina may indirectly support this by improving luminal SCFA absorption through enhanced mucosal blood flow. Pediatric Tuina modulates the skin-brain-gut axis by suppressing hippocampal MC activation and tryptase release, implicating neuroimmune pathways in gut barrier restoration[94]. This systemic regulation is critical because brain–gut axis dysregulation exacerbates intestinal barrier failure in chronic diarrhea[105]. Both interventions reduce pathogenic bacterial adherence to the epithelium by downregulating host adhesion molecules.

The multidimensional barrier restoration mechanisms detailed above spanning epithelial reinforcement, mucus enhancement, immunomodulation, and microbiota regulation were empirically validated through preclinical and clinical studies of herbal medicine interventions. Table 2 systematically synthesizes key evidence demonstrating herbal-mediated repair across physical, chemical, and immunological barrier components. Meanwhile, Figure 2 illustrates the critical interplay between herbal-modulated gut microbiota and intestinal barrier subsystems[106]. Together, these visual summaries consolidate how TCM strategies collectively resolve barrier dysfunction to ameliorate pediatric diarrhea.

Figure 2 The relationship between intestinal flora and the intestinal barrier system under the action of herbal medicine. SCFAs: Short-chain fatty acids; Th17: T helper 17 cells; Treg: Regulatory T cells; PPAR-γ: Peroxisome proliferator-activated receptor gamma; Hes-1: Hairy and enhancer of split-1; Hath-1: Hairy/enhancer-of-split related with YRPW motif protein 1; ZO-1: Zonula occludens-1.

Table 2 Evidence of barrier function restoration with herbal medicine interventions[107-110].

Barrier component	Assessment marker	Intervention modality	Observed effect	Proposed mechanism	Ref.
Physical barrier	Intestinal permeability/tight junction proteins	TCM monomer (baicalein)	Reduced intestinal permeability/restored colonic tight junction integrity/attenuated gut inflammation	Activation of AhR in ILC3s-promotes IL-22 production-upregulates TJ proteins	Li et al[107]
	Serum DAO/gastrointestinal dysfunction score/first exhaust and defecation time	Modified Huanglian Jiedu decoction + electroacupuncture	Reduced serum DAO levels, gastrointestinal dysfunction scores and mechanical ventilation time/accelerated first exhaust/defecation time	Purgation and detoxification reduced intestinal permeability and restored barrier integrity/DAO reduction indicates attenuated epithelial damage	Wang et al[108]
Chemical barrier	Goblet cell density/MUC2 mRNA expression/mucin production	Gegen Qinlian decoction	Goblet cell differentiation/MUC2 synthesis/restored mucus layer/promoted mucosal healing	Bidirectional regulation of Notch signaling	Zhao et al[109]
Immune barrier	SIgA expression/plasma DAO/D-lactate/gut microbiota diversity	Hetiao Jianpi decoction	SIgA in colon tissue (increase)/beneficial bacteria (increase)/plasma DAO/D-lactate (decrease)/pathogenic bacteria (decrease)	Enhanced mucosal immunity via SIgA secretion-reduced intestinal permeability-modulated gut microbiota to restore immune homeostasis	Li et al[110]

TCM: Traditional Chinese medicine; DAO: Diamine oxidase; mRNA: Messenger RNA; D-lactate: D-lactic acid; SIgA: Secretory immunoglobulin A; AhR: Aryl hydrocarbon receptor; ILC3s: Group 3 innate lymphoid cells; IL-22: Interleukin-22; TJ: Tight Junction.

Consideration of age-specific mechanisms in pediatric populations

The mechanisms discussed above, particularly those involving the gut microbiota and immune development, may exhibit age-dependent variations. The majority of clinical evidence supporting the efficacy of TCM interventions, such as the Tuina trials in children aged 0-6 years[21,107] and herbal applications in children aged from 6 months to 12 years[52], comes from a broad pediatric age range. The infant gut microbiome is highly dynamic and undergoes sequential maturation, which may influence the response to herbal prebiotics and the anti-inflammatory effects of Tuina. Similarly, the development of the intestinal immune system and the integrity of the epithelial barrier are age-related processes. While the core pathophysiological mechanisms targeted by TCM therapies are consistent, the magnitude of response and the relative contribution of each pathway (e.g., microbial modulation vs neural-immune regulation) might differ between infants and older children. Future mechanistic studies should stratify participants by age to elucidate these developmental nuances, which will be crucial for optimizing personalized treatment protocols.

FUTURE PERSPECTIVES

While the integrated application of Tuina and herbal medicine shows promise for pediatric diarrhea management, several key challenges must be addressed to solidify its evidence base and optimize its clinical implementation. Standardization represents a primary hurdle. Variations in Tuina techniques among practitioners and the individualized nature of TCM herbal prescriptions based on pattern differentiation complicate the design of rigorous, reproducible clinical trials and hinder the development of universally applicable protocols. Future efforts should prioritize establishing detailed, consensus-driven guidelines for Tuina manipulation specific to pediatric diarrhea and exploring strategies for standardizing core herbal components or formulations while respecting TCM principles to facilitate large-scale, high-quality studies.

The heterogeneity in Tuina techniques and herbal formulations across practitioners currently poses a significant limitation in interpreting clinical outcomes. This variability may affect the reproducibility and generalizability of study results, thereby underscoring the need for standardized protocols in future research.

To move past clinical observations, we need to deeply understand the specific biological pathways affected by these combined therapies. Sophisticated in vitro models such as patient-derived intestinal organoids and gut-on-a-chip systems provide a valuable tool for this investigation. They allow researchers to pinpoint how mechanical forces that mimic Tuina, along with individual herbal compounds or their combinations, influence key aspects of diarrhea, such as the epithelial barrier, cell metabolism, interactions with microbes, and immune signaling pathways.

Integrating new technologies also offers important benefits. Developing novel delivery systems may improve practicality and adherence, especially for children. This step involves creating wearable devices that deliver controlled, standardized physical stimulation similar to Tuina at specific acupoints. It also includes designing advanced transdermal patches for the sustained, localized release of optimized herbal extracts. Longitudinal multi-omics analyses, including metagenomics, metabolomics, and proteomics, within clinical groups are also crucial. This comprehensive approach will map the body’s and gut microbes’ responses to integrated TCM therapy. It will identify reliable biomarkers of effectiveness and further clarify the complex network of interactions responsible for its therapeutic benefits.

Ultimately, progress hinges on interdisciplinary collaboration. Bridging the expertise of TCM practitioners, pediatric gastroenterologists, microbiologists, immunologists, pharmacologists, and biomedical engineers is paramount. Such collaborative frameworks are necessary to rigorously validate the efficacy and safety of integrated TCM approaches, refine treatment protocols based on mechanistic insights, and effectively translate this knowledge into tangible improvements in the management of pediatric diarrhea within broad healthcare systems.

CONCLUSION

Pediatric diarrhea remains a significant global health challenge, demanding effective and well-tolerated therapeutic strategies. This review synthesizes evidence supporting the application of integrated TCM therapies, specifically Tuina manipulation and herbal medicine, for managing this condition. The therapeutic rationale centers on their modulation of two fundamental pathophysiological aspects: Gastrointestinal metabolic dysfunction and impaired intestinal barrier integrity. Evidence indicates that Tuina, by applying physical stimulation to specific acupoints and abdominal areas, can improve gastrointestinal motility, help regulate fluid secretion and absorption, and enhance local microcirculation. The bioactive compounds found in TCM herbal formulas seem to help normalize enterocyte metabolism and energy production, supporting the digestion and absorption of nutrients. Tuina and herbal medicine demonstrate significant effects on restoring intestinal barrier function. Herbal components often aid in epithelial repair, strengthen tight junctions, and encourage mucus production. Tuina may additionally enhance mucosal defense mechanisms. Although not the main focus (i.e., metabolism and barrier function), the positive effects on gut microbiota composition and mucosal immune responses are also notable. Herbal medicine can modulate immune factors such as secretory immunoglobulin A secretion and immune cell balance, and Tuina may also influence these areas. Together, these actions support barrier restoration and help establish a resilient gut environment. The integrated TCM approach of Tuina and herbal medicine offers a promising strategy for pediatric diarrhea. Its strength lies in the potential role of physically stimulating gastrointestinal function and biochemically repairing barrier integrity and metabolic capacity, addressing core pathophysiological mechanisms in a holistic manner. Future research emphasizing rigorous standardization and mechanistic exploration using advanced tools is essential to further validate and optimize this multidimensional therapeutic paradigm for integration into comprehensive pediatric care.