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Review Postoperative gut dysbiosis and its clinical implications, with an emphasis on probiotic strategies in gastric cancer patients undergoing gastrectomy: a narrative review
Cheong Ah Ohorcid
Annals of Clinical Nutrition and Metabolism 2025;17(2):114-124.
DOI: https://doi.org/10.15747/ACNM.25.0023
Published online: August 1, 2025

Department of Surgery, Samsung Medical Center, Seoul, Korea

Corresponding author: Cheong Ah Oh email: cheongah.oh@samsung.com
• Received: June 2, 2025   • Revised: July 23, 2025   • Accepted: July 23, 2025

© 2025 The Korean Society of Surgical Metabolism and Nutrition · The Korean Society for Parenteral and Enteral Nutrition · Asian Society of Surgical Metabolism and Nutrition

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Purpose
    This review explores alterations in gut microbiota following gastrointestinal surgery, with a focus on gastrectomy for gastric cancer, and evaluates the therapeutic potential of probiotics in restoring microbial balance and reducing postoperative complications, including infections, inflammation, immune dysfunction, and cancer recurrence.
  • Current concept
    Gastrointestinal surgery disrupts gut microbial homeostasis via surgical stress, oxygen exposure, altered bile flow, and perioperative antibiotic use. Gastrectomy, in particular, induces marked changes in the microbiota, including increased oral-origin and aerotolerant bacteria, decreased short-chain fatty acid–producing species, and elevated bile acid-transforming organisms. These alterations contribute to complications such as small intestinal bacterial overgrowth, surgical site infections, postoperative ileus, nutrient malabsorption, and potentially a higher risk of colorectal cancer. Probiotics—especially strains of Lactobacillus, Bifidobacterium, and Clostridium—have demonstrated beneficial effects by modulating the gut ecosystem, enhancing epithelial barrier integrity, and regulating immune and metabolic pathways. Randomized clinical trials support using probiotics in improving gastrointestinal recovery, reducing systemic inflammation, restoring microbial diversity, and shortening hospital stays after gastrectomy. Multi-strain probiotic formulations, particularly when administered perioperatively, show the greatest promise. However, safety concerns remain, especially for immunocompromised or critically ill patients, underscoring the need for rigorous clinical oversight and adherence to regulatory standards such as the European Food Safety Authority’s Qualified Presumption of Safety guidelines.
  • Conclusion
    Postoperative dysbiosis is a modifiable factor in adverse surgical outcomes. Probiotic supplementation offers promising therapeutic potential in patients undergoing gastrectomy, though optimal strains, dosing, and timing remain to be determined. Tailored, evidence-based strategies may ultimately enhance both recovery and long-term outcomes after gastric cancer surgery.
  • Keywords: Dysbiosis; Gastrectomy; Gastrointestinal microbiome; Gastrointestinal neoplasms; Probiotics
Background
The human gastrointestinal tract harbors a complex and dynamic community of microorganisms—collectively termed the gut microbiota—that play an essential role in host physiology and immune regulation [1]. These microbial communities support intestinal homeostasis by strengthening the epithelial barrier, modulating both innate and adaptive immune responses, and preventing colonization by pathogenic organisms [1,2]. Disruption of this microbial equilibrium, referred to as dysbiosis, has been increasingly recognized as a key factor in the pathogenesis of various diseases, including inflammatory bowel disease, metabolic syndrome (such as type 2 diabetes and obesity), and certain malignancies [1]. Among the multiple contributors to dysbiosis, gastrointestinal surgery is particularly notable for its profound disruption of microbial balance. Surgical stress, exposure of the bowel lumen to oxygen, ischemia-reperfusion injury resulting from disrupted local blood flow, and perioperative antibiotic use are all recognized as causes of significant shifts in gut microbiota composition [1,3]. These perturbations have been linked to a broad range of postoperative complications [1].
Among surgical interventions, gastrectomy, which is a standard procedure for gastric cancer, induces major anatomical and physiological changes in the gastrointestinal tract. Alterations in luminal pH, oxygen tension, and bile acid composition collectively generate an environment conducive to dysbiosis [4]. Post-gastrectomy microbial profiles are typically characterized by an increased prevalence of oral-origin microbes, oxygen-tolerant species, and bile acid-transforming bacteria [4]. Such shifts have been implicated in the development of small intestinal bacterial overgrowth (SIBO), gastrointestinal symptoms such as bloating, flatulence, and diarrhea, intestinal inflammation, and possibly an increased risk of colorectal neoplasia [4].
Given the clinical significance of postoperative dysbiosis, there is growing interest in strategies aimed at restoring microbial homeostasis. Among these, probiotics—defined as live microorganisms that provide health benefits to the host when administered in adequate amounts—have attracted considerable attention [5]. Probiotics are believed to confer benefits by enhancing microbial diversity, reinforcing mucosal barrier function, and modulating immune responses and cytokine profiles [5]. In the context of surgical oncology, both probiotics and synbiotics (which combine probiotics with prebiotics) have been linked to improved postoperative outcomes, including reduced complication rates, better gastrointestinal function, and accelerated recovery [5].
Collectively, these observations highlight the therapeutic potential of microbiota-modulating interventions in the perioperative management of patients undergoing gastrectomy for gastric cancer.
Objectives
This review aims to investigate changes in the gut microbiota following gastrointestinal surgery, with particular emphasis on gastrectomy for gastric cancer, and to assess the effectiveness of probiotic interventions in addressing postoperative dysbiosis and its associated clinical outcomes.
A fundamental step in understanding how gastrointestinal surgery and probiotic interventions affect microbial homeostasis is to examine key parameters of gut microbiota composition, such as microbial diversity and the Firmicutes-to-Bacteroidetes (F/B) ratio.
Microbial diversity in gut microbiome studies is generally evaluated using two principal approaches: alpha-diversity and beta-diversity. Alpha-diversity measures the variety within a single microbial community or sample, encompassing both species richness (i.e., the total number of different species present) and evenness, which reflects the uniformity of their distribution [6]. In contrast, beta-diversity compares the differences in microbial composition between distinct communities, thus revealing variations among individuals or groups [6,7].
Among various compositional indicators, the F/B ratio is often employed as an approximate marker of microbial balance and dysbiosis [8]. These two dominant bacterial phyla—Firmicutes (e.g., Clostridium and Lactobacillus) and Bacteroidetes (e.g., Bacteroides and Prevotella)—together comprise approximately 60% of the gut microbiota. Other phyla, including Actinobacteria, Proteobacteria, and Fusobacteria, exist in smaller proportions but still contribute to the functional and ecological complexity of the gut ecosystem [1,5].
While both Firmicutes and Bacteroidetes encompass species capable of producing short-chain fatty acids (SCFAs), their metabolic roles are distinct. Members of the Firmicutes phylum, especially Faecalibacterium and Clostridium clusters IV and XIVa, are major producers of butyrate, an SCFA critical for maintaining gut epithelial barrier function and providing anti-inflammatory effects [9]. In contrast, Bacteroidetes predominantly produce acetate and propionate, which influence hepatic gluconeogenesis, lipid metabolism, and immune modulation [9]. Given these functional differences, shifts in the F/B ratio can impact key metabolic and immunological processes and have been implicated in diverse conditions, including obesity, inflammatory bowel disease, and metabolic syndrome [5,10].
Surgical interventions involving the gastrointestinal tract have been closely associated with significant changes in gut microbiota composition [1]. According to Shi et al. [2], postoperative microbial shifts are commonly marked by an increased abundance of facultative anaerobes, such as Enterobacteriaceae and Lactobacillus, along with a marked reduction in obligate anaerobes, including Clostridia and Bacteroides. These changes are largely attributed to increased oxygen exposure within the intestinal lumen, which disrupts the anaerobic environment necessary to sustain obligate anaerobic species [2]. In addition, surgical reconstruction of the gastrointestinal tract can significantly alter the unique microbial ecosystems inhabiting each intestinal segment. These regional microbial communities are crucial for nutrient metabolism, absorption, and the maintenance of host metabolic homeostasis. Disruption of these anatomical and functional niches can thus profoundly impact microbial composition, resulting in downstream effects on host metabolism and immune regulation [11]. Such dysbiosis is often characterized by a shift toward a proinflammatory and disease-prone state, further compromising mucosal immunity and gut barrier integrity [12]. Given the potential clinical implications of postoperative microbiota dysregulation, active strategies to promote microbial recovery and ecological restoration are of paramount importance [13]. Recent approaches, such as enhanced recovery after surgery protocols, are designed to optimize perioperative care and support microbial recovery. Although preliminary data suggest these protocols may benefit microbial refaunation and immune modulation, further research is needed to clarify their full effects on gut microbiota and infection outcomes [2,13].
Associations with anastomotic leakage and surgical site infections
Postoperative complications are increasingly recognized as being influenced by alterations in the gut microbiota, in addition to traditional mechanical and surgical factors. Among these, anastomotic leakage (AL) represents a serious complication with multifactorial origins. While surgical technique has long been regarded as the primary determinant, emerging evidence highlights significant roles for both host-related and microbial factors [1]. In particular, dysbiosis and changes in microbial activity at the anastomotic site have been implicated in impaired healing and an increased risk of leakage [1,14]. The gut microbiota contributes to intestinal wound healing and epithelial regeneration by activating innate immune receptors such as Toll-like receptors (TLR2 and TLR4) and by producing SCFAs, particularly butyrate. These mechanisms help preserve mucosal integrity, regulate inflammation, and prevent colonization by pathogenic organisms [11,15].
Conversely, certain bacterial species—including Enterococcus faecalis and Pseudomonas aeruginosa—may respond to surgical stress by adopting a more pathogenic phenotype. These bacteria are capable of adhering to injured tissue and secreting collagen-degrading enzymes, such as collagenases that activate matrix metalloproteinase-9 (MMP9), thereby weakening anastomotic integrity and increasing the risk of leakage [11]. Commensal SCFA-producing bacteria may counteract this process by suppressing the expansion of pathobionts.
Despite perioperative measures such as prophylactic antibiotics, nutritional support, and fluid optimization, which aim to maintain microbial homeostasis, surgical stress can disrupt the microbiota and create an environment conducive to dysbiosis. This is especially evident in patients undergoing complex or prolonged procedures, where tissue injury and operative stress serve as triggers for microbial virulence activation [2]. Tissue damage and operative stress thus act as environmental cues for opportunistic pathogens such as E. faecalis and P. aeruginosa, facilitating their proliferation and increasing the risks of AL and surgical site infections (SSIs) [2]. Therapeutic strategies targeting these microbial mechanisms—including localized antimicrobial delivery and MMP9 inhibition—are currently under investigation and may represent promising interventions to reduce AL risk [2,16].
SSIs remain a major contributor to postoperative morbidity and mortality, and accumulating evidence implicates the gut microbiota in their development [1]. While Staphylococcus aureus is often isolated [1], gut-derived organisms such as Escherichia coli, E. faecalis, and P. aeruginosa, as noted by Agnes et al. [3], are also frequent causative agents, particularly in gastrointestinal surgery.
Taken together, these findings suggest that disruption of mucosal defenses and the onset of dysbiosis after surgery can facilitate microbial translocation, enabling gut-derived opportunistic organisms to colonize surgical sites and contribute to complications such as AL and SSIs.
Associations with postoperative ileus
Dysbiosis induced by major gastrointestinal surgery is increasingly recognized as a contributor to postoperative ileus (POI) and impaired gastrointestinal motility [11,17]. Mechanistically, the gut microbiota may influence POI by modulating enteric nervous system signaling and activating immune cells such as macrophages, dendritic cells, and monocytes. A key pathway involves the microbial induction of pathogenic inducible nitric oxide synthase in macrophages and monocytes, which impairs smooth muscle contractility. Experimental evidence shows that antibiotic treatment reduces inducible nitric oxide synthase expression and alleviates POI symptoms, thereby implicating a microbiota-dependent mechanism [1,3,17].
Impact on nutrient malabsorption
Nutrient malabsorption following major intestinal operations—such as Roux-en-Y gastric bypass, ileal pouch-anal anastomosis, or pancreatoduodenectomy—results from both anatomical changes and postoperative shifts in gut microbiota [1,2]. The gut microbiota plays a pivotal role in nutrient metabolism, and alterations in its composition may impair nutrient absorption and energy extraction. For example, bariatric procedures such as sleeve gastrectomy and Roux-en-Y gastric bypass have been associated with altered F/B ratios and significant changes in microbial diversity. These changes affect not only the efficiency of dietary energy extraction but also intestinal barrier function, potentially worsening malabsorption syndromes and influencing metabolic outcomes [11].
Associations with cancer recurrence
Beyond immediate postoperative outcomes, changes in the gut microbiota may also influence long-term oncologic risks, including cancer recurrence. Zheng et al. [11] reported that gut dysbiosis can contribute to colorectal cancer (CRC) recurrence after surgical resection. Surgical disruption of the local environment, including altered oxygen gradients, tissue injury, and immune suppression, creates favorable conditions for pathogenic bacteria such as E. faecalis to expand [11]. By stimulating macrophage-mediated MMP9 activation, these bacteria contribute to extracellular matrix degradation, thereby impairing anastomotic healing and establishing a microenvironment that supports the survival and invasion of disseminated tumor cells [11]. These findings highlight the importance of maintaining microbial homeostasis not only for immediate recovery but also for long-term cancer control.
Gastrectomy, the standard surgical approach for treating gastric cancer, results in substantial anatomical and physiological modifications throughout the gastrointestinal tract [4]. These changes—including the loss of gastric acid secretion, increased distal gut oxygenation, and altered bile flow—disrupt the gut environment and promote bacterial overgrowth, impaired nutrient absorption, and reduced oral intake [4,18]. Collectively, these alterations can lead to significant perturbations in the gut microbiota, with potential downstream effects on host metabolism, immunity, and overall health [10]. Table 1 provides a summary of the content discussed below [4,5,11,18-28].
Loss of the gastric barrier and oralization of the gut microbiota
Subtotal gastrectomy leads to a marked reduction in gastric acid secretion [4,18], disrupting the physiological acid barrier [19]. This shift results in an elevation of gastric pH from approximately 2.0 to above 6.0, regardless of the reconstruction method [19]. Similar pH changes are observed with proton pump inhibitor (PPI) use, and in both scenarios, the critical bactericidal threshold of pH 4.0 is exceeded [18]. Under these less acidic conditions, oral bacteria can survive gastric transit and colonize the distal gastrointestinal tract—a process termed gut microbiome oralization, which has been previously documented in PPI users [4,20]. Thus, disruption of gastric acid homeostasis by both subtotal gastrectomy and PPI therapy may similarly alter the gut microbial landscape by compromising the gastric acid barrier [4].
Post-gastrectomy microbiome studies have consistently reported increased abundance of oral cavity–derived bacteria—such as Streptococcus, Veillonella, Prevotella, Oribacterium, and Mogibacterium—within the gut microbiota [4,10,18]. Among these, Streptococcus is particularly notable due to its established role in PPI-induced dysbiosis and its association with intestinal inflammation and increased permeability after gastrectomy [4,18,20]. This inflammation may contribute to chronic diarrhea, a long-term complication affecting up to 40% of gastrectomy survivors [4,21].
Reduced gastric acidity following gastrectomy is also associated with a decrease in beneficial gut bacteria. In the gastrectomy cohort studied by Seo et al. [22], levels of Streptococcus and Blautia increased, whereas Bacteroides—a key producer of SCFAs—was significantly reduced in gastric cancer patients who underwent resection. SCFAs (particularly, butyrate) are critical for maintaining intestinal barrier integrity, modulating immune responses, and suppressing gut inflammation [22,23]. A decline in SCFA production may weaken mucosal defenses, enhance intestinal permeability, and increase the risk of inflammatory bowel disease and CRC [22,23].
Increased gut oxygenation and aerotolerant bacterial overgrowth
In addition to the loss of the acid barrier, gastrectomy leads to elevated oxygen levels in the distal gut, creating an environment favorable for aerotolerant microbes [6]. Multiple studies have documented an increased abundance of aerobes such as Streptococcus and Enterococcus, as well as facultative anaerobes including Escherichia and Enterobacter, in post-gastrectomy patients [4,18,24]. Notably, Escherichia (a key organism implicated in SIBO) was markedly elevated, which aligns with the high prevalence of SIBO-related symptoms such as bloating and diarrhea observed in this population [21].
Altered bile flow and bile acid-driven dysbiosis
Surgical reconstruction after gastrectomy alters bile flow dynamics. Billroth I and II procedures are associated with bile regurgitation into the upper gastrointestinal tract, whereas Roux-en-Y reconstruction diverts bile toward the distal small intestine [25,26]. These anatomical changes affect both the site and extent of bile acid exposure, thereby fostering the proliferation of bile acid-transforming bacteria [4,24]. Fecal metabolomic analyses have demonstrated elevated levels of the secondary bile acid deoxycholic acid (DCA) in gastrectomized patients [4,24]. DCA is produced via 7α-dehydroxylation specifically by certain bacteria within the genus Clostridium [4,27]. Several studies have reported an enrichment of Clostridium species after gastrectomy [4]. Secondary bile acids, especially DCA, exert genotoxic effects through mechanisms such as oxidative stress and DNA alkylation. DCA also activates oncogenic pathways, including epidermal growth factor receptor and Wnt signaling, which are implicated in colorectal carcinogenesis [24]. This may help explain the increased risk of metachronous CRC observed in gastric cancer survivors [27].
In total gastrectomy patients, there is also an enrichment of bacteria associated with CRC, such as Fusobacterium nucleatum and Atopobium parvulum, alongside elevated levels of genotoxic bile acids such as DCA [11,24]. Fusobacterium, in particular, contributes to CRC progression through proinflammatory, adhesive, and invasive mechanisms [5,28]. It also induces MMP9 expression in epithelial cells, while Alistipes onderdonkii promotes MMP9-mediated collagen degradation via tumor necrosis factor (TNF)-α and interleukin (IL)-1β production—mechanisms that may compromise anastomotic healing by facilitating submucosal matrix breakdown [11].
These findings raise the question of whether different reconstruction methods might differentially influence gut microbiota composition and bile acid metabolism. In this context, Imai et al. [29] compared microbial profiles between Billroth I and Roux-en-Y reconstructions following distal gastrectomy. Although significant shifts in microbial diversity and structure were observed between pre- and post-gastrectomy states, no significant differences in alpha- or beta-diversity were found between the two reconstruction methods. This suggests that reconstruction type may exert only a limited influence on the postoperative microbiota. However, due to the scarcity of direct comparative studies, further research is needed to clarify how distinct anatomical configurations shape microbial communities and modulate bile acid-driven carcinogenic pathways.
General benefits of probiotics in surgical oncology patients
In surgical oncology, gut microbiota modulation is increasingly recognized as a crucial factor influencing both recovery and prognosis. In this context, probiotics and synbiotics have emerged as promising adjunctive therapies for restoring microbial balance and improving postoperative outcomes in cancer patients [5,30].
Probiotics are live microorganisms that confer health benefits by reestablishing gut microbial homeostasis [30]. Prebiotics—nondigestible fibers that selectively promote the growth of beneficial bacteria—are frequently combined with probiotics to form synbiotics, which may exert synergistic effects [31].
Among the most extensively studied probiotic strains for safety and efficacy are Lactobacillus and Bifidobacterium. These organisms play key roles in maintaining mucosal integrity, preventing pathogenic colonization, and modulating host immune responses [30,32]. In addition, they have demonstrated therapeutic potential in a variety of metabolic and inflammatory diseases, including cancer, obesity, and diabetes [30,32].
Synbiotics, which combine probiotics with prebiotics, appear to be even more effective than single-strain formulations. Multispecies preparations, often containing Bifidobacterium, Lactobacillus, Lactococcus, and occasionally Bacillus and Saccharomyces, have demonstrated synergistic benefits in supporting gut health and immune regulation [33].
Evidence from systematic reviews, meta-analyses, and randomized controlled trials indicates that microbiota-targeted interventions can reduce the incidence of SSIs, enhance immune responses, and promote postoperative recovery [34].
According to Marotta et al. [35], the primary goal of probiotic use in oncology is to restore commensal microbial populations—particularly Lactobacillus—which are often depleted by surgery or chemotherapy. Beyond simply restoring microbial populations, probiotics may also exert direct functional effects on the host. For instance, Hibberd et al. [33] demonstrated that certain strains, such as Bifidobacterium lactis and Lactobacillus acidophilus, can induce epigenetic modifications in colorectal tumor tissues, suggesting a potential mechanism by which probiotics may influence host gene expression and long-term cancer outcomes.
Furthermore, Rousseaux et al. [36] reported that oral administration of Lactobacillus species during the perioperative period can modulate opioid and cannabinoid receptors on intestinal epithelial cells, thereby increasing the pain threshold through a mechanism similar to that of morphine.
Beyond local gastrointestinal effects, probiotics may also influence systemic and neuropsychological health via the gut-brain axis. Certain strains are capable of producing neuroactive compounds such as serotonin, γ-aminobutyric acid, and histamine [37]. Clinical studies have shown that multispecies probiotic supplementation can reduce cognitive reactivity to negative mood states [38] and improve sleep quality under psychological stress [35,39]. These psychobiotic effects may be especially relevant in oncology, where emotional distress and sleep disturbances are common, though further research is needed to elucidate the underlying mechanisms [5].
Probiotic interventions in gastrectomy for gastric cancer: clinical evidence and applications
Several clinical studies and meta-analyses have evaluated perioperative and postoperative probiotic—and to a lesser extent, synbiotic—supplementation in patients undergoing gastrectomy for gastric cancer. Collectively, these studies demonstrate consistent benefits across gastrointestinal function, immune modulation, nutritional recovery, and microbial restoration, as summarized in Table 2 [10,40-47].
In a meta-analysis of randomized controlled trials, Ye et al. [40] reported that perioperative probiotic supplementation accelerated gastrointestinal recovery, as indicated by shorter times to first flatus and defecation in gastric cancer patients undergoing surgery. It also reduced hospital stay duration, increased serum albumin levels, and decreased postoperative infectious complications, although no significant effects were observed on body weight or prealbumin concentrations.
In a double-blind trial, Park et al. [41] found that oral administration of Saccharomyces boulardii (250 mg twice daily for 1 to 4 weeks postoperatively) significantly improved nutritional status following subtotal or total gastrectomy in gastric cancer patients. Treated patients showed significantly higher serum albumin levels compared to controls, suggesting a potential benefit of S. boulardii in supporting protein metabolism and recovery after gastrectomy.
Similarly, Xiong et al. [42] conducted a controlled clinical trial in gastric cancer patients in which perioperative probiotic supplementation—comprising Lactobacillus plantarum, Lactobacillus rhamnosus, L. acidophilus, and Bifidobacterium animalis—was administered from 3 days before surgery and resumed from postoperative day 2 to day 7 at a dose of one capsule per day. This intervention led to attenuated systemic inflammation, evidenced by a more rapid decline in the neutrophil-to-lymphocyte ratio and faster normalization of serum albumin levels. Additionally, patients in the probiotic group experienced shorter hospital stays, reduced medical costs, and improved postoperative quality of life. Fecal microbiome analysis further revealed that the probiotic group preserved microbial diversity and abundance, while the control group exhibited an elevated F/B ratio and other inflammation-associated microbial shifts.
Cao et al. [43] conducted a randomized controlled trial involving 100 gastric cancer patients who had undergone gastrectomy, aiming to evaluate the clinical efficacy of Clostridium butyricum. Patients were randomized to receive either C. butyricum (six capsules twice daily for 21 days) or placebo. The probiotic group showed a significant attenuation of postoperative systemic inflammation, with marked reductions in leukocyte counts, neutrophil percentage, and proinflammatory cytokines, including IL-1β, IL-6, and TNF-α. Concurrently, immune parameters such as serum immunoglobulin and lymphocyte levels, as well as nutritional markers such as albumin and total protein, were significantly improved. Analysis of the gut microbiota revealed that C. butyricum helped restore microbial balance by increasing beneficial bacteria (e.g., Bacteroides, Faecalibacterium, and Gemmiger) and decreasing potentially harmful genera (Streptococcus, Desulfovibrio, and Actinomyces). Metabolite profiling also showed increased levels of fecal SCFAs, reflecting enhanced microbial activity. Together, these effects were associated with fewer early complications and faster postoperative recovery.
Zheng et al. [10] evaluated the effects of a multi-strain probiotic formulation—including Bifidobacterium infantis, L. acidophilus, E. faecalis, and Bacillus cereus—in patients following partial gastrectomy for gastric cancer. The probiotics were given twice daily, starting a few days postoperatively and continued for about a week. Patients receiving the probiotics showed reduced systemic inflammation, as reflected by decreased leukocyte counts, along with improved immune and nutritional status, including higher lymphocyte counts and increased serum albumin and total protein. Additionally, the fecal microbiota of the probiotic group exhibited a lower F/B ratio, enrichment of beneficial taxa such as Bacteroides, Faecalibacterium, and Akkermansia, and a reduction in Streptococcus abundance.
Focusing on symptom relief and modulation of the stress response, Niu et al. [44] evaluated the effects of Bifidobacterium triple viable bacteria administered once daily during the first postoperative week following radical gastrectomy in patients with comorbid depression. Compared with the mirtazapine-only control group, patients receiving adjunctive probiotics experienced fewer gastrointestinal complications, including reflux, vomiting, abdominal distension, diarrhea, and constipation, and showed greater improvements in intestinal microbiota composition. Notably, the probiotic group exhibited significantly lower serum corticotropin-releasing factor levels, along with enhanced neuroendocrine markers and nutritional status. These findings suggest that Bifidobacterium may help restore microbial homeostasis, alleviate stress-related responses, and improve overall recovery after surgery.
Liu et al. [45] conducted a clinical trial in gastric cancer patients undergoing gastrectomy to assess the effects of a multi-strain probiotic regimen, comprising B. infantis, L. acidophilus, E. faecalis, and B. cereus, administered orally three times daily for 5 to 7 days before surgery. The preoperative use of probiotics led to significant reductions in postoperative systemic inflammation (leukocyte count, P<0.05) and insulin resistance, as indicated by improvements in fasting glucose, fasting insulin, and homeostasis model assessment of insulin resistance scores (all P<0.05). Additionally, the incidence of postoperative insulin resistance (P<0.001) and infectious complications (P<0.05) was lower in the probiotic group. Fecal microbiota analysis revealed enrichment of SCFA-producing species such as Faecalibacterium prausnitzii and Gemmiger formicilis, alongside decreased abundance of pathogenic species including Bacteroides fragilis, Prevotella copri, and Clostridium difficile. These findings suggest that in gastric cancer patients, preoperative probiotic administration may help stabilize postoperative metabolism, modulate immune response, and restore microbial homeostasis.
In a mechanistic study incorporating both clinical and animal models, Zheng et al. [46] investigated the effects of a multi-strain probiotic formulation—comprising L. plantarum MH-301, L. rhamnosus LGG-18, L. acidophilus, and B. animalis subsp. Lactis LPL-RH—on postoperative recovery following gastrectomy. In gastrectomized rats, probiotic supplementation significantly reduced inflammatory responses, preserved intestinal barrier integrity, and modulated signaling pathways related to inflammation and permeability. These preclinical findings were supported by clinical data, which showed reductions in systemic inflammatory markers, enhancement of immune function, restoration of gut microbiota composition, and improved recovery trajectories in postoperative patients with gastric cancer.
Finally, Liu et al. [47] conducted a randomized, double-blind, controlled trial in gastric cancer patients undergoing gastrectomy following neoadjuvant chemotherapy, administering a probiotic combination of Bifidobacterium longum, L. acidophilus, and E. faecalis (three capsules, twice daily) from 1 week before surgery until postoperative day 7 or discharge. The probiotic intervention significantly reduced the incidence of postoperative infections (P=0.027), accelerated gastrointestinal functional recovery—reflected by shorter times to first flatus (P=0.001) and bowel movement (P<0.001)—and lowered systemic inflammatory markers. In addition, probiotic-treated patients experienced shorter hospital stays (P=0.001) and were able to initiate adjuvant chemotherapy earlier (P<0.001), likely due to reduced complications and more rapid clinical recovery.
Taken together, these findings underscore that probiotic supplementation—whether single- or multi-strain, administered pre-, peri-, or postoperatively—can enhance gastrointestinal function, improve immune and nutritional parameters, mitigate inflammatory and infectious complications, and support microbial and mucosal recovery in patients undergoing gastrectomy for gastric cancer. While synbiotic formulations remain underexplored in the context of gastrectomy, current evidence provides a compelling rationale for the perioperative use of probiotics. To fully realize their clinical potential, future large-scale, standardized trials are necessary to define optimal microbial strains, dosing regimens, and timing strategies tailored to surgical oncology settings.
The clinical use of probiotics must be guided by rigorous scientific and regulatory standards. In the European Union, the European Food Safety Authority establishes a framework for safety assessment through the Qualified Presumption of Safety approach and Novel Food criteria, which evaluate strain-specific genomic, phenotypic, and toxicological characteristics [34,48,49]. Such regulatory oversight is particularly critical when administering probiotics to vulnerable populations, including critically ill or immunocompromised patients. Although probiotics are generally regarded as safe and well tolerated, specific risks remain for certain patient groups. For instance, S. boulardii is not recommended for patients with central venous catheters, those in intensive care units, or individuals with significant immunosuppression—such as patients undergoing chemotherapy or radiotherapy, especially when intestinal barrier function is compromised [34,50]. In these settings, careful risk–benefit assessment is essential [34].
Given these safety considerations, particularly in vulnerable populations, the clinical use of probiotics should follow a personalized, evidence-based approach. Accordingly, future research should focus on identifying optimal strains, dosing regimens, and timing strategies tailored to specific surgical settings and patient populations.
Gastrointestinal surgery, particularly gastrectomy for gastric cancer, induces profound alterations in gut microbiota composition, contributing to postoperative complications such as infections, inflammation, immune dysregulation, and impaired recovery. Accumulating clinical evidence supports the use of probiotics—and to a lesser extent, synbiotics—as adjunctive therapies to mitigate these adverse outcomes. Multiple randomized controlled trials and mechanistic studies have demonstrated that specific probiotic formulations can enhance gastrointestinal function, restore microbial balance, modulate immune and metabolic responses, and reduce postoperative morbidity.
Importantly, strain selection, dosing strategies, and timing of administration appear to significantly influence clinical efficacy, underscoring the need for standardized protocols. While probiotics are generally safe, their use in vulnerable populations, such as immunocompromised or critically ill patients, warrants careful consideration and should be guided by appropriate regulatory and safety measures.
Given the promising therapeutic potential of microbiota-targeted interventions, future large-scale, well-controlled studies are essential to optimize probiotic and synbiotic strategies for individual surgical contexts. Integration of such approaches into perioperative care may not only improve short-term outcomes but also support long-term health and recovery in patients undergoing gastrectomy for gastric cancer.
Table 1.
Changes in the gut microbiota and clinical implications after gastrectomy for gastric cancer
Mechanism Microbial changes Key microbial taxa Metabolites/effects Clinical implications References
Loss of gastric barrier and oralization Colonization of oral bacteria due to loss of acid barrier from hypoacidity ↑ Streptococcus - Gut microbiota oralization [4,18-21]
↑ Veillonella - ↑ Streptococcus-associated inflammation and gut permeability
↑ Prevotella - Chronic diarrhea (up to 40%)
↑ Oribacterium
↑ Mogibacterium
Loss of beneficial gut bacteria ↑ Blautia ↓ SCFAs (e.g., butyrate) - Impaired epithelial barrier [22,23]
↓ Bacteroides - ↑ Inflammation in the gut
(a key SCFA producer) - ↑ IBD and CRC risk
Increased gut oxygenation Overgrowth of aerotolerant and facultative anaerobic bacteria ↑ Streptococcus - SIBO-like symptoms (bloating, diarrhea) [4,18,21,24]
↑ Enterococcus - Microbial dysbiosis
↑ Escherichia
↑ Enterobacter
Altered bile flow and bile acid-driven dysbiosis Overgrowth of bile acid-transforming bacteria due to anatomical bile rerouting ↑ Clostridium spp. (leading to 7α-dehydroxylation) ↑ Secondary bile acids (e.g., DCA) - Genotoxicity and oxidative stress [4,24-27]
- Activation of EGFR and Wnt oncogenic pathways
- ↑ Risk of metachronous CRC
CRC-associated bacterial enrichment after total gastrectomy ↑ Fusobacterium nucleatum ↑ DCA - CRC progression via inflammation and invasion [5,11,24,27,28]
↑ Atopobium parvulum ↑ MMP9 - Potential impairment of anastomotic healing (via collagen matrix degradation)
↑ Alistipes onderdonkii ↑TNF-α & IL-1β

SCFA, short-chain fatty acid; IBD, inflammatory bowel disease; CRC, colorectal cancer; SIBO, small intestinal bacterial overgrowth; DCA, deoxycholic acid; EGFR, epidermal growth factor receptor; MMP9, matrix metalloproteinase-9; TNF-α, tumor necrosis factor alpha; IL-1β, interleukin 1 beta.

Table 2.
Clinical trials of probiotics in gastrectomy for gastric cancer
Study Study design Probiotic(s) used Timing & duration Key clinical outcomes
Ye et al. [40] Meta-analysis of RCTs Various strains (not specified) Perioperative (exact duration and regimen not specified) - Faster GI recovery (earlier flatus/defecation)
- ↓ Hospital stay
- ↑ Albumin
- ↓ Infections
Park et al. [41] Double-blind RCT Saccharomyces boulardii Postoperative; POD 1–28; 250 mg twice daily - ↑ Serum albumin
Xiong et al. [42] Controlled clinical trial Lactobacillus plantarum Perioperative; from 3 days preoperatively to POD 7; 1 capsule/day - ↓ NLR
Lactobacillus rhamnosus - Faster serum albumin recovery
Lactobacillus acidophilus - ↓ Hospital stay/cost
Bifidobacterium animalis - ↑ QoL
- Preserved microbiota diversity (↑ diversity ↓F/B ratio)
Cao et al. [43] Randomized controlled trial Clostridium butyricum Postoperative; POD 1–21; 6 capsules twice daily - ↓ Leukocytes, neutrophils, IL-1β, IL-6, TNF-α
- Improved immune/nutritional markers
- ↑ SCFAs and beneficial microbes
Zheng et al. [10] Clinical study Bifidobacterium infantis Postoperative; initiated a few days postoperatively and continued for ~7 days; twice daily - ↓ Leukocyte counts
L. acidophilus - Improved immune/nutritional status
Enterococcus faecalis - ↓ F/B ratio (more Bacteroides, Faecalibacterium, Akkermansia, less Streptococcus)
Bacillus cereus
Niu et al. [44] Clinical study Bifidobacterium triple viable bacteria Postoperative; POD 1–7; once daily - ↓ GI symptoms (reflux, vomiting, etc.)
- ↓ CRF levels,
- Better microbial balance/ nutritional status
- ↓ Stress response
Liu et al. [45] Clinical trial B. infantis Preoperative; 5–7 days before surgery; three times daily - ↓ Systemic inflammation
L. acidophilus - ↓ Insulin resistance
E. faecalis - ↓ Infections
B. cereus - ↑ SCFA producers
(more Faecalibacterium prausnitzii, Gemmiger formicilis)
Zheng et al. [46] Clinical + animal study L. plantarum MH-301 Perioperative (exact schedule not specified); evaluated in both clinical and animal models - In rats: ↓ inflammation preserved gut barrier
L. rhamnosus LGG-18 - In patients: ↑ immune markers
L. acidophilus ↓ inflammation restored gut microbiota
B. animalis
Liu et al. [47] Randomized, double-blind, controlled trial Bifidobacterium longum Perioperative; from 7 days preoperative to POD 7 or discharge; three capsules twice daily - ↓ Infections
L. acidophilus - Faster GI recovery (flatus, bowel movement)
E. faecalis - ↓ Hospital stay
- Earlier start of adjuvant chemotherapy

RCT, randomized controlled trial; GI, gastrointestinal; POD, postoperative day; NLR, neutrophil-to-lymphocyte ratio; QoL, quality of life; F/B, Firmicutes-to-Bacteroidetes; IL, interleukin; TNF-α, tumor necrosis factor alpha; SCFA, short-chain fatty acid; CRF, corticotropin-releasing factor.

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        Postoperative gut dysbiosis and its clinical implications, with an emphasis on probiotic strategies in gastric cancer patients undergoing gastrectomy: a narrative review
        Ann Clin Nutr Metab. 2025;17(2):114-124.   Published online August 1, 2025
        DOI: https://doi.org/10.15747/ACNM.25.0023
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      Postoperative gut dysbiosis and its clinical implications, with an emphasis on probiotic strategies in gastric cancer patients undergoing gastrectomy: a narrative review
      Postoperative gut dysbiosis and its clinical implications, with an emphasis on probiotic strategies in gastric cancer patients undergoing gastrectomy: a narrative review
      Mechanism Microbial changes Key microbial taxa Metabolites/effects Clinical implications References
      Loss of gastric barrier and oralization Colonization of oral bacteria due to loss of acid barrier from hypoacidity ↑ Streptococcus - Gut microbiota oralization [4,18-21]
      ↑ Veillonella - ↑ Streptococcus-associated inflammation and gut permeability
      ↑ Prevotella - Chronic diarrhea (up to 40%)
      ↑ Oribacterium
      ↑ Mogibacterium
      Loss of beneficial gut bacteria ↑ Blautia ↓ SCFAs (e.g., butyrate) - Impaired epithelial barrier [22,23]
      ↓ Bacteroides - ↑ Inflammation in the gut
      (a key SCFA producer) - ↑ IBD and CRC risk
      Increased gut oxygenation Overgrowth of aerotolerant and facultative anaerobic bacteria ↑ Streptococcus - SIBO-like symptoms (bloating, diarrhea) [4,18,21,24]
      ↑ Enterococcus - Microbial dysbiosis
      ↑ Escherichia
      ↑ Enterobacter
      Altered bile flow and bile acid-driven dysbiosis Overgrowth of bile acid-transforming bacteria due to anatomical bile rerouting ↑ Clostridium spp. (leading to 7α-dehydroxylation) ↑ Secondary bile acids (e.g., DCA) - Genotoxicity and oxidative stress [4,24-27]
      - Activation of EGFR and Wnt oncogenic pathways
      - ↑ Risk of metachronous CRC
      CRC-associated bacterial enrichment after total gastrectomy ↑ Fusobacterium nucleatum ↑ DCA - CRC progression via inflammation and invasion [5,11,24,27,28]
      ↑ Atopobium parvulum ↑ MMP9 - Potential impairment of anastomotic healing (via collagen matrix degradation)
      ↑ Alistipes onderdonkii ↑TNF-α & IL-1β
      Study Study design Probiotic(s) used Timing & duration Key clinical outcomes
      Ye et al. [40] Meta-analysis of RCTs Various strains (not specified) Perioperative (exact duration and regimen not specified) - Faster GI recovery (earlier flatus/defecation)
      - ↓ Hospital stay
      - ↑ Albumin
      - ↓ Infections
      Park et al. [41] Double-blind RCT Saccharomyces boulardii Postoperative; POD 1–28; 250 mg twice daily - ↑ Serum albumin
      Xiong et al. [42] Controlled clinical trial Lactobacillus plantarum Perioperative; from 3 days preoperatively to POD 7; 1 capsule/day - ↓ NLR
      Lactobacillus rhamnosus - Faster serum albumin recovery
      Lactobacillus acidophilus - ↓ Hospital stay/cost
      Bifidobacterium animalis - ↑ QoL
      - Preserved microbiota diversity (↑ diversity ↓F/B ratio)
      Cao et al. [43] Randomized controlled trial Clostridium butyricum Postoperative; POD 1–21; 6 capsules twice daily - ↓ Leukocytes, neutrophils, IL-1β, IL-6, TNF-α
      - Improved immune/nutritional markers
      - ↑ SCFAs and beneficial microbes
      Zheng et al. [10] Clinical study Bifidobacterium infantis Postoperative; initiated a few days postoperatively and continued for ~7 days; twice daily - ↓ Leukocyte counts
      L. acidophilus - Improved immune/nutritional status
      Enterococcus faecalis - ↓ F/B ratio (more Bacteroides, Faecalibacterium, Akkermansia, less Streptococcus)
      Bacillus cereus
      Niu et al. [44] Clinical study Bifidobacterium triple viable bacteria Postoperative; POD 1–7; once daily - ↓ GI symptoms (reflux, vomiting, etc.)
      - ↓ CRF levels,
      - Better microbial balance/ nutritional status
      - ↓ Stress response
      Liu et al. [45] Clinical trial B. infantis Preoperative; 5–7 days before surgery; three times daily - ↓ Systemic inflammation
      L. acidophilus - ↓ Insulin resistance
      E. faecalis - ↓ Infections
      B. cereus - ↑ SCFA producers
      (more Faecalibacterium prausnitzii, Gemmiger formicilis)
      Zheng et al. [46] Clinical + animal study L. plantarum MH-301 Perioperative (exact schedule not specified); evaluated in both clinical and animal models - In rats: ↓ inflammation preserved gut barrier
      L. rhamnosus LGG-18 - In patients: ↑ immune markers
      L. acidophilus ↓ inflammation restored gut microbiota
      B. animalis
      Liu et al. [47] Randomized, double-blind, controlled trial Bifidobacterium longum Perioperative; from 7 days preoperative to POD 7 or discharge; three capsules twice daily - ↓ Infections
      L. acidophilus - Faster GI recovery (flatus, bowel movement)
      E. faecalis - ↓ Hospital stay
      - Earlier start of adjuvant chemotherapy
      Table 1. Changes in the gut microbiota and clinical implications after gastrectomy for gastric cancer

      SCFA, short-chain fatty acid; IBD, inflammatory bowel disease; CRC, colorectal cancer; SIBO, small intestinal bacterial overgrowth; DCA, deoxycholic acid; EGFR, epidermal growth factor receptor; MMP9, matrix metalloproteinase-9; TNF-α, tumor necrosis factor alpha; IL-1β, interleukin 1 beta.

      Table 2. Clinical trials of probiotics in gastrectomy for gastric cancer

      RCT, randomized controlled trial; GI, gastrointestinal; POD, postoperative day; NLR, neutrophil-to-lymphocyte ratio; QoL, quality of life; F/B, Firmicutes-to-Bacteroidetes; IL, interleukin; TNF-α, tumor necrosis factor alpha; SCFA, short-chain fatty acid; CRF, corticotropin-releasing factor.

      Table 1.

      Table 2.

      Ann Clin Nutr Metab : Annals of Clinical Nutrition and Metabolism
      © Korean Society of Surgical Metabolism and Nutrition · Korean Society for Parenteral and Enteral Nutrition
        · Asian Society of Surgical Metabolism and Nutrition · Japanese Society for Surgical Metabolism and Nutrition.
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