INTRODUCTION
Endoscopic mucosal resection (EMR) is a minimally invasive yet highly effective endoscopic technique that allows en bloc or piecemeal resection of superficial gastrointestinal lesions, especially colorectal adenomas and early neoplasms[1-3]. Despite its favorable safety profile, EMR disrupts the mucosal architecture and alters the local microbial habitat. Emerging evidence indicates that surgical interventions can trigger transient microbial dysbiosis, compromise barrier integrity, and initiate systemic immune responses[4]. Given the fundamental role of the gut microbiota in modulating epithelial repair, immune homeostasis, and inflammation, strategies to restore microbial equilibrium post-EMR are clinically relevant. In this context, Niu et al[5] examined whether dietary fiber supplementation could modulate gut microbiota and improve postoperative outcome. This editorial assesses their findings from a translational, mechanistic, and microbiome-informed lens.
MICROBIAL DISTURBANCE POST-EMR: CLINICAL IMPLICATIONS
The mucosal barrier acts not only as a physical defense but also as a dynamic interface between host immune cells and microbial communities. Following EMR, this interface is transiently compromised, potentially triggering microbial translocation, altered immune signaling, and dysbiosis[6]. In the retrospective analysis conducted by Niu et al[5], significant reductions in microbial alpha-diversity were observed post-EMR in the control group. Taxonomic analysis revealed a shift toward a dysbiotic configuration, with increased relative abundance of facultative anaerobes such as Enterococcus and Escherichia-Shigella, alongside a decrease in obligate anaerobes including Bifidobacterium, Lactobacillus, and Faecalibacterium prausnitzii-genera typically associated with epithelial homeostasis and immunomodulation[7,8]. Such microbial alterations have critical clinical implications[9]. Dysbiosis following gastrointestinal interventions has been linked to delayed wound healing, reduced epithelial regenerative capacity, and heightened inflammatory responses through increased expression of proinflammatory cytokines such as interleukin 6 and tumor necrosis factor-alpha[10-12].
Moreover, depletion of commensals that produce short-chain fatty acids (SCFAs) notably butyrate can impair regulatory T cell differentiation and mucin production, contributing to increased epithelial permeability and systemic immune activation[13-15]. In line with this, Herman et al[2] have emphasized that EMR, though technically precise, introduces a transient window of vulnerability during which epithelial injury, microbial imbalance, and immune dysregulation intersect[16]. This is particularly relevant in older adults or individuals with pre-existing microbiota disruptions due to antibiotics, diet, or comorbidities such as diabetes or inflammatory bowel disease[17,18]. Furthermore, microbial imbalance may not only hinder acute recovery but could also have long-term consequences[19]. Emerging evidence suggests that chronic dysbiosis can contribute to the recurrence of neoplastic lesions through altered bile acid metabolism, genotoxic metabolite production, and suppression of anti-tumor immune surveillance pathways[20]. Hence, restoring microbial eubiosis post-EMR is not merely an adjunctive strategy but a potentially essential component of holistic post-procedural care.
Niu et al’s findings[5] reinforce this concept by demonstrating that patients who did not receive dietary fiber intervention had prolonged microbial instability and increased incidence of postoperative complications, including abdominal discomfort, bloating, and low-grade inflammation, as evidenced by elevated C-reactive protein and reduced expression of tight junction proteins. These observations strongly support the inclusion of microbiota-targeted therapies, particularly those utilizing prebiotic interventions as a clinically meaningful adjunct to endoscopic treatment protocols. Microbial disturbances following EMR extend beyond transient flora fluctuations and can directly influence mucosal healing trajectories, immune homeostasis, and potentially even oncological outcomes. Recognizing and addressing this biological vulnerability through targeted nutritional and microbiota-restorative strategies may markedly enhance recovery, reduce complications, and improve long-term gastrointestinal health.
FIBER AS A THERAPEUTIC MODULATOR: WHAT DO WE KNOW?
Dietary fiber has long been recognized for its role in gastrointestinal motility and metabolic regulation; however, recent advances in microbiome science have redefined fiber as a key therapeutic modulator of gut microbial composition and host immune function[12,21,22]. In the context of EMR-induced mucosal injury, dietary fiber offers a promising, non-invasive means to restore intestinal homeostasis via microbiota-mediated mechanisms.
Classification of dietary fibers and microbiota-specific effects
Fibers are broadly categorized based on solubility, fermentability, and viscosity, each of which dictates their interaction with colonic microbiota and the host epithelium[23]. So et al[24] provide a comprehensive classification into: Non-starch polysaccharides such as cellulose and hemicellulose, which are poorly fermentable and mainly function as bulking agents; resistant starches escape small intestinal digestion and undergo saccharolytic fermentation in the colon, especially by Faecalibacterium and Eubacterium species; and resistant oligosaccharides which are rapidly fermented by Bifidobacterium, Lactobacillus, and other SCFA-producing bacteria.
The fermentability and selectivity of fiber types are crucial. For instance, inulin and fructooligosaccharides have demonstrated prebiotic effects in numerous clinical trials, significantly increasing bifidobacterial counts and promoting anti-inflammatory SCFAs such as acetate and butyrate. In contrast, psyllium - though only moderately fermentable has gel-forming properties that slow gut transit time and have been associated with improved stool consistency and mucosal protection in patients with irritable bowel syndrome[24]. Notably, resistant starches are linked to increased butyrate production, whereas inulin ferments preferentially to acetate. These SCFA preferences may guide targeted fiber therapy. For example, in conditions where epithelial healing is critical, butyrogenic fibers such as resistant starch might offer superior outcomes compared to acetate-dominant fibers. Targeted therapy is affected by these metabolic preferences; for example, butyrogenic fibers might be more advantageous in situations involving barrier repair[25].
In the study by Niu et al[5], the fiber intervention combined multiple types (inulin, psyllium, resistant starch), thereby maximizing both fermentability and physical mucosal benefits. However, the relative contribution of each fiber component remains undefined, and the potential for synergistic or antagonistic microbial effects warrants further investigation. It remains unclear whether combining inulin, psyllium, and resistant starch leads to additive or counteractive effects. Dissecting these interactions is essential for the development of optimized prebiotic therapies. While Niu et al[5] employed a combination of inulin, psyllium, and resistant starch, the synergistic or antagonistic interactions among these fibers remain poorly characterized. Understanding whether their effects are additive, synergistic, or competitive is critical for optimizing prebiotic formulations.
SCFA production and barrier function
Fermentation of dietary fiber by the colonic microbiota yields SCFAs - particularly acetate, propionate, and butyrate that exert pleiotropic effects on gut and systemic health[25]. Butyrate is of particular relevance post-EMR due to its ability to: Serve as the primary energy source for colonocytes; enhance expression of tight junction proteins [e.g., claudins (CLDN), occluding (OCLN), zonula occludens-1]; induce forkhead box protein 3 regulatory T cells via G-protein-coupled receptor 43 (GPR43) and GPR109A signaling; suppress proinflammatory cytokines such as interleukin-1 beta, interleukin 6, and tumor necrosis factor-alpha[26-30].
This effect has been directly demonstrated in vitro by Peng et al[29], who showed that butyrate enhances tight junction assembly via adenosine monophosphate-activated protein kinase activation in epithelial cells. By promoting butyrogenic bacterial populations (e.g., Faecalibacterium prausnitzii, Roseburia), dietary fiber may actively participate in restoring mucosal immunity and accelerating epithelial restitution following EMR[31]. In Niu et al’s study[5], upregulation of barrier-protective genes such as CLDN1, OCLN, and defensin alpha 5 in the fiber group supports this mechanism. While SCFAs were not directly measured, the correlation between microbial shifts and gene expression suggests that fiber-driven fermentation contributed to mucosal recovery.
Fiber-microbiota-immune axis in post-EMR recovery
The role of dietary fiber extends beyond the luminal environment. SCFAs produced via fiber fermentation can translocate across the epithelium and modulate immune responses in the lamina propria and mesenteric lymph nodes[32]. These metabolites influence the epigenetic landscape of immune cells through histone deacetylase inhibition, thereby shaping dendritic cell function and promoting immune tolerance[33]. Furthermore, fiber-derived SCFAs can increase the number and function of regulatory T cells; decrease intestinal permeability by modulating myosin light chain kinase and mucin protein 2 expression; interfere with nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain- containing receptor 3 inflammasome activation, which is implicated in epithelial injury and fibrosis[34]. These immunoregulatory effects are especially pertinent in the immediate post-EMR period, during which inflammation must be tightly controlled to facilitate efficient wound healing without promoting pathological fibrosis or neoplasia recurrence.
Clinical data supporting fiber in gastrointestinal recovery
Clinical studies outside the EMR context provide additional support. For example, dietary fiber has been shown to reduce postoperative ileus, normalize bowel function, and decrease antibiotic-associated diarrhea in colorectal surgery patients[35]. A meta-analysis by Yang et al[35] found that high-fiber interventions reduced inflammatory markers and improved stool frequency in both healthy individuals and patients with gastrointestinal disorders. These observations, previously highlighted in the introduction, are reinforced by Niu et al’s findings[5], confirming the clinical promise of fiber-based recovery. However, these outcomes, though promising, require validation in randomized, controlled trials with longer follow-up.
HOST-MICROBIOTA-IMMUNE INTERPLAY: MOLECULAR OUTCOMES OF FIBER INTERVENTION
The gut mucosa represents a dynamic immunological interface where dietary antigens, microbial metabolites, and host epithelial responses converge to maintain intestinal homeostasis[36]. Post-EMR, this balance is particularly fragile due to mucosal disruption, local inflammation, and shifts in microbial populations[37]. In this context, Niu et al’s study[5] makes a noteworthy contribution by demonstrating that dietary fiber supplementation is associated with measurable improvements not only in microbial composition but also in host gene expression profiles related to barrier function and immune defense. The fiber group exhibited increased transcription of tight junction proteins such as OCLN and CLDN1, as well as antimicrobial peptides like defensin-5 and Reg3 gamma, all of which are essential components of the intestinal epithelial barrier[38]. These findings suggest a restoration of epithelial integrity, potentially mediated through microbial fermentation products such as SCFAs, particularly butyrate. Although SCFAs were not directly quantified in the study, the observed enrichment of SCFA-producing taxa such as Lactobacillus, Bifidobacterium, and Roseburia in the fiber group provides indirect evidence of increased microbial metabolic activity with downstream host effects[39]. However, the lack of direct SCFA quantification limits the strength of the causal inference between microbial changes and host gene expression. The reliance on taxonomic shifts as a surrogate for metabolic activity introduces uncertainty, as microbial presence does not necessarily equate to functional output. Future studies should incorporate targeted metabolomic approaches such as gas chromatography-mass spectrometry (GC-MS) to quantify fecal and serum SCFA concentrations. This would allow for more definitive mechanistic validation of the proposed microbiota-immune pathways and strengthen the translational value of dietary fiber interventions in post-EMR care.
From an immunological perspective, these microbial metabolites are known to regulate dendritic cell maturation, promote the expansion of regulatory T cells, and suppress the secretion of proinflammatory cytokines through mechanisms involving GPR43, GPR109A and inhibition of histone deacetylases[40]. Thus, the fiber-induced modulation of the microbiota-immune axis observed by Niu et al[5] likely reflects a cascade of molecular interactions in which fermentable fiber acts as a primary trigger, reshaping the microbial ecosystem and activating host regulatory pathways that restore mucosal immunity. Taken together, these results underscore the therapeutic potential of targeted nutritional strategies to promote epithelial healing and immune recalibration in the post-endoscopic setting.
LIMITATIONS, CRITICAL APPRAISAL, AND FUTURE DIRECTIONS IN PRECISION NUTRITION AFTER EMR
While the study by Niu et al[5] presents an important step forward in integrating nutritional immunology into post-EMR recovery, several methodological limitations and interpretative considerations temper the generalizability and mechanistic conclusiveness of their findings. Foremost among these is the absence of direct metabolomic analysis - specifically, the quantification of SCFAs such as butyrate and propionate, which would have provided stronger causal linkage between microbial changes and observed improvements in epithelial gene expression[41]. To strengthen mechanistic inferences, future studies should incorporate metabolomic analyses such as GC-MS to directly quantify SCFA levels in stool or serum. This would provide a functional readout linking microbial shifts to host metabolic and immune outcomes. The reliance on indirect microbiota profiling, without accompanying functional data, limits the ability to differentiate between compositional shifts and actual metabolic activity, a distinction that is critical when interpreting the immunomodulatory effects attributed to dietary fiber. To address this gap, future studies should incorporate metabolomic profiling using GC-MS to quantify fecal or serum SCFA concentrations, thereby directly validating the mechanistic role of fiber-driven microbial metabolism.
Moreover, the study does not stratify patients based on their baseline microbiota composition or dietary habits, which are known to significantly influence responsiveness to prebiotic interventions[42]. Individual differences in baseline gut microbiota composition and dietary habits can have a significant impact on how receptive a person is to fiber supplements. These inter-individual differences may stem from enterotype-specific microbial communities, habitual fiber intake, recent antibiotic use, or genetic variants influencing fiber metabolism. While these variables present an opportunity for personalized nutrition, they also pose challenges in standardizing interventions, requiring adaptive dosing strategies or stratified subgroup analysis in future trials. For example, reduced responses may be seen in people with low microbial diversity or decreased butyrogenic taxa. These variations highlight the necessity for pre-intervention classification and potentially even adaptive dosing models in further trials, underscoring the potential and difficulty of putting personalized nutrition techniques into practice.
Recent literature emphasizes that fiber efficacy is highly context-dependent, shaped by individual microbial enterotypes, enzymatic capacities, and even host genetic polymorphisms in SCFA receptors and immune signaling pathways[41,43]. Furthermore, host genetic variants in SCFA receptors (e.g., GPR41, GPR43, GPR109A) may modulate individual responsiveness to fiber supplementation, suggesting a potential path for genotype-guided nutritional strategies. Without such stratification or personalization, the findings, although encouraging, risk being overly generalized. The intervention itself also combines multiple types of dietary fiber (inulin, psyllium, resistant starch) without disentangling their specific contributions or synergistic interactions. Given the differential fermentability and microbial targets of these fibers, future studies should aim to deconvolute their individual and combined effects to develop optimized, targeted formulations. Another limitation lies in the study of design. As a single-center, retrospective study with a relatively short follow-up period, it does not provide insight into long-term outcomes such as mucosal regeneration durability, recurrence of neoplastic lesions, or sustained immune modulation.
The integration of personalized nutritional strategies into post-EMR care represents an emerging frontier in gastroenterology. Based on current evidence, we advocate for a precision nutrition model, wherein fiber type, dose, and timing are tailored to the patient’s microbial and immunological profile. Such an approach would not only optimize mucosal recovery but also reduce postoperative complications, potentially decreasing healthcare burden and improving long-term gastrointestinal health. As understanding deepens regarding the microbiota’s role in epithelial repair, immune regulation, and tumor surveillance, dietary fiber may be positioned not merely as a supportive therapy but as a cornerstone of individualized, microbiota-informed endoscopic recovery protocols.
Additional limitations include the absence of standardized dietary intake or recent antibiotic use documentation, both of which can significantly influence gut microbiota. Furthermore, the lack of metagenomic or metabolomic data prevents functional interpretation of microbial shifts. Long-term outcomes, including recurrence rates and sustained mucosal recovery, also remain unexplored. Moreover, long-term outcomes such as recurrence of neoplastic lesions or sustained immune modulation remain unexplored. Functional microbiota analysis using metagenomics or targeted metabolomics was not performed, limiting mechanistic interpretation.
It is impossible to rule out selection bias and residual confounding due to the retrospective design of the Niu et al’s study[5]. To overcome the limitations of retrospective design and potential selection bias, future research should prioritize prospective, multicenter randomized controlled trials. These trials should incorporate stratified randomization based on baseline gut microbiota composition, dietary habits, or other host factors such as comorbidities and medication use. Such design enhancements would strengthen causal inference, reduce confounding, and better elucidate the differential response to fiber interventions among patient subgroups. In addition, long-term follow-up is critical to assess sustained effects on mucosal healing, tumor recurrence, and chronic inflammatory outcomes, which remain unexplored in the current study. To lessen confounding, future research should give priority to prospective, multicenter randomized controlled trials that use stratified randomization according to baseline microbiota composition or dietary patterns. Furthermore, to assess the long-term effects of fiber therapies on outcomes including tumor recurrence, mucosal integrity, and chronic inflammation, long-term follow-up will be necessary. Specifically, evaluating whether fiber supplementation confers sustained improvements in epithelial barrier function or reduces rates of neoplastic recurrence would significantly enhance the prognostic value of these interventions and justify their inclusion in standard postoperative protocols.
Using high-resolution microbiome sequencing to find enterotype-specific responses could greatly improve personalized nutrition strategies. A route toward genotype-guided dietary interventions may also be provided by host genetic variants, which may affect response to fiber-based therapies, especially in SCFA receptor genes like GPR41, GPR43, and GPR109A. Well-defined intervention protocols, such as particular fiber types (such as inulin, psyllium, and resistant starch), consistent dosage schedules, and supplementation timing in relation to EMR (such as before or after the operation), should be incorporated into future randomized controlled trials. Clinical outcomes like complication rates, mucosal healing, and symptom resolution, as well as microbiological indicators like microbial diversity, SCFA levels, and barrier-related gene expression, should be the main goals.
CONCLUSION
The work by Niu et al[5] represents a pivotal contribution to a growing field that intersects gastroenterology, microbiology, and nutritional immunology. Their data suggest that microbiota-informed dietary fiber supplementation can enhance post-EMR recovery by restoring microbial diversity, modulating immune responses, and improving barrier function. By improving mucosal regeneration durability, preserving epithelial barrier function, and possibly lowering neoplastic recurrence through modulation of inflammatory and immunological surveillance pathways, dietary fiber therapies may have long-term advantages beyond short-term healing. The predictive significance of microbiota-based postoperative care would be further enhanced by investigating these results in long-term follow-up investigations. As the field of precision nutrition evolves, we envision a future where individualized fiber regimens tailored by baseline microbiota and host immunogenetic profiles - become an integral part of endoscopic post-care algorithms.
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Gastroenterology and hepatology
Country of origin: Türkiye
Peer-review report’s classification
Scientific Quality: Grade B, Grade B, Grade B, Grade B, Grade C
Novelty: Grade B, Grade B, Grade C, Grade C, Grade C
Creativity or Innovation: Grade B, Grade B, Grade C, Grade C, Grade C
Scientific Significance: Grade B, Grade C, Grade C, Grade C, Grade C
P-Reviewer: Li B, PhD, Professor, China; Ren L, PhD, China; Zhou HX, PhD, Assistant Professor, Post Doctoral Researcher, China S-Editor: Bai SR L-Editor: A P-Editor: Xu ZH
