Effects of enhanced recovery after surgery on postoperative intestinal function and intestinal flora during laparoscopic gastric cancer surgery

Abstract

BACKGROUND

Enhanced recovery after surgery (ERAS) protocols have emerged as a promising approach in perioperative care. This study evaluated ERAS's impact on gastrointestinal recovery and microbiota composition following laparoscopic gastric cancer surgery.

AIM

To evaluate the impact of ERAS protocols on postoperative gastrointestinal function recovery and intestinal microbiota composition in patients undergoing laparoscopic gastric cancer surgery, and to identify factors associated with improved clinical outcomes and microbial diversity preservation.

METHODS

We conducted a retrospective analysis of 80 patients who underwent laparoscopic D2 gastrectomy, comparing ERAS (n = 40) vs traditional care (n = 40). Primary outcomes included postoperative gastrointestinal function recovery and complications. Intestinal microbiota was analyzed using 16S rRNA sequencing at multiple timepoints perioperatively.

RESULTS

ERAS patients demonstrated faster recovery of bowel function, with earlier return of bowel sounds (16.25 ± 6.41 hours vs 22.3 ± 6.49 hours), first flatus (23.95 ± 6.02 hours vs 28.45 ± 7.12 hours), and defecation (34.95 ± 9.34 hours vs 48.1 ± 15.64 hours), all P < 0.05. Complication rates, including antibiotic-associated diarrhea and surgical site infections, were comparable between groups. Microbial diversity indices and probiotic populations showed better preservation in the ERAS group postoperatively (P < 0.05), though neither group achieved complete restoration to preoperative levels at one month.

CONCLUSION

These results support tailoring ERAS protocols to prioritize gut microbiome resilience through early feeding and shortened antibiotic courses, with particular benefits for younger patients.

Key Words: Enhanced recovery after surgery; Gastrectomy; Microbiome; Gastrointestinal function; Clinical outcomes

Core Tip: Enhanced recovery after surgery significantly accelerates gastrointestinal recovery, as demonstrated by earlier return of bowel sounds, flatus, and defecation compared to traditional care. It also preserves microbiota diversity, maintaining higher diversity indices and a healthier balance of beneficial bacteria, though neither group fully recovered preoperative levels by one month. Importantly, this enhanced recovery is achieved without an increase in postoperative complications, such as surgical site infections or antibiotic-associated diarrhea. Subgroup analyses reveal that younger patients benefit the most, showing faster recovery timelines. These findings underscore the clinical advantages of enhanced recovery after surgery protocols in laparoscopic gastric cancer surgery, providing strong support for their adoption.

INTRODUCTION

Laparoscopic gastric cancer surgery, while representing a significant advancement in surgical oncology, introduces complex challenges to patients' gastrointestinal function and overall recovery. The immediate postoperative period typically presents with reduced gastrointestinal motility, affecting 5%-30% of patients through delayed gastric emptying and temporary paralytic ileus within the first 48-72 hours. These early changes are accompanied by altered gut hormone secretion patterns, significantly impacting digestive function and nutritional status[1-4].

Recent advances in enhanced recovery after surgery (ERAS) implementation for laparoscopic gastrectomy have incorporated enhanced preoperative optimization strategies, including structured patient education programs, standardized preoperative carbohydrate loading, and risk-stratified prophylactic antiemetic protocols. Intraoperative management has evolved to emphasize opioid-sparing anesthesia techniques, precise fluid balance maintenance, and normothermia preservation. Postoperative care pathways now prioritize early mobilization protocols, systematic pain management using multimodal analgesia, and structured discharge criteria based on functional recovery milestones rather than arbitrary timeframes. It is referring to a new initiative that is a clinical consensus framework based on evidence for standardizing perioperative protocols to improve surgical outcomes. From its initial implementation, ERAS has expanded to include several surgical specialties, where it has shown high success in gastrointestinal, hepatobiliary, pancreatic and orthopedic surgeries[5-7].

The ERAS protocol represents a paradigm shift in perioperative care, with its impact on intestinal microbiota preservation becoming increasingly recognized as a critical factor in postoperative recovery. The superior maintenance of beneficial bacteria in ERAS protocols compared to traditional care can be attributed to several key mechanistic differences that fundamentally alter the gut microenvironment during the perioperative period. One of the most significant factors contributing to better probiotic preservation in ERAS protocols is the strategic approach to antibiotic administration. Traditional perioperative care typically extends prophylactic antibiotic coverage for 3-5 days postoperatively, based on historical practices aimed at preventing surgical site infections. However, this prolonged exposure creates substantial collateral damage to the intestinal microbiome, particularly affecting beneficial bacteria such as Lactobacillus and Bifidobacterium species. These gram-positive bacteria are inherently more susceptible to broad-spectrum antibiotics commonly used in surgical prophylaxis, including cephalosporins and fluoroquinolones[8-10].

As the patient gradually increases their recovery from the intermediate recovery phase, it is common that they will have an incremental return of peristalsis between 24-48 post-op hours. This is a momentous time for the individual as they encounter issues of nutritional absorption, complicated by anatomical changes and possible bacterial overgrowth of segments of the modified enteric system. Various surgical factors [anastomosis type (Billroth I, II, or Roux-en-Y), lymphadenectomy extent, operation duration, and intraoperative blood loss] strongly affect the amplitude of these alterations. One important variable with regard to digestive recovery after surgery is effects on intestinal microbiota. One of the earliest postoperative phenomenon includes a significant decrease in microbial diversity, with a dysbiosis that can facilitate pathogenic bacterial overgrowth. Patients typically adapt within 3-6 months, during which time the gut microbiota undergoes substantial composition. The n changes, establishing a new equilibrium in the process[11-14]. This time of adaptation can be important for what happens in the longer term, since the changes in the microbial landscape can affect, for instance, immune function and metabolic processes. In conclusion, postoperative intestinal dysfunction and dysbiosis have become an important issue in gastric cancer surgery and have a great impact on the recovery and quality of life of patients. Conventional preoperative care is frequently insufficient to control such complications. ERAS has the potential to influence these outcomes with its standardized protocols and deserves thorough investigation.

This study aims to systematically assess the effects of ERAS protocols on patients undergoing laparoscopic gastric cancer surgery, especially gastrointestinal recovery and microbiota. These findings will add to the evidence base behind ERAS implementation and help inform future refinements to protocols designed to improve postoperative recovery and patient quality of life.

MATERIALS AND METHODS

Research subjects

This retrospective cohort study was conducted at Zhejiang Provincial Tongde Hospital and included 80 patients who underwent laparoscopic D2 gastrectomy for gastric cancer between August 2022 and December 2023. Patients were grouped based on the perioperative protocol received: 40 received ERAS care and 40 underwent conventional management. Baseline data included demographics, tumor characteristics, pathological staging, and operative details. The study was approved by the Ethics Committee of Zhejiang Provincial Tongde Hospital, approval No. ZJTD-IRB-2022-074 and followed the Declaration of Helsinki.

Inclusion and exclusion criteria

This study established comprehensive eligibility requirements for participant enrollment. Suitable candidates were adults aged 18-70 years with primary gastric cancer, confirmed through pathological examination of gastroscopic biopsy specimens, presenting with clinical tumor-node-metastasis (TNM) stages I through III. Only patients scheduled for laparoscopic radical gastrectomy at high-volume centers (performing more than 50 such procedures annually) were considered. All participants provided written informed consent prior to study enrollment.

Several conditions precluded participation in the study. These included a history of major abdominal surgery, recent antibiotic exposure (within three months), and circumstances requiring emergency surgical intervention such as tumor-related complications (hemorrhage, obstruction, or perforation). Additionally, patients with pyloric obstruction or those deemed unsuitable for laparoscopic approaches were excluded from participation.

Concrete measures to accelerate rehabilitation surgery

The perioperative management protocol incorporated multiple evidence-based interventions designed to optimize recovery. Preoperative preparation began with comprehensive patient education and prehabilitation strategies. Nutritional guidelines specified a six-hour fast from solid foods and two-hour restriction from clear fluids, with administration of 500 mL 10% glucose solution two hours before surgery. The protocol emphasized selective rather than routine bowel preparation and implemented a targeted antibiotic regimen consisting of cefuroxime 1.5 g preoperatively with one additional dose at 3 hours intraoperatively, continuing until 24 hours postoperatively. Pain management prioritized multimodal analgesia, specifically designed to minimize opioid utilization. The postoperative care pathway emphasized early mobilization coupled with prompt initiation of oral intake for both fluids and nutrition. Nasogastric tubes were used selectively rather than routinely. Fluid management followed a goal-directed approach, with daily postoperative fluid intake restricted to 2000 mL to prevent overhydration. This comprehensive protocol integrated multiple elements of enhanced recovery principles, focusing on maintaining physiological function and accelerating return to baseline status.

Traditional perioperative treatment group-specific measures

The specific measures of traditional perioperative management are as follows: (1) Preoperative education and prerehabilitation treatment are not routine; (2) No diet for 12 hours before surgery, no oral sugar drinks for 2 hours before surgery; (3) Intestinal preparation, liquid diet 1 day before surgery, oral laxatives the night before surgery or the morning of the first day; (4) Antibiotics are used once before surgery (cefuroxime 1.5 g) and once more after surgery > 3 hours and are applied to the third day after surgery; (5) Routine use of opioid analgesics; (6) Getting out of bed after surgery according to the patient's tolerance and willingness; (7) Drinking water and eating food 3 days after surgery; (8) Routine use of nasogastric tubes; and (9) Noncontrolled infusion, postoperative daily fluid supplementation of approximately 2000-2500 mL.

Intestinal function change index

This study monitored multiple indicators of gastrointestinal recovery and postoperative complications across both groups. Gastrointestinal function recovery was evaluated through systematic documentation of three key parameters: Initial return of bowel sounds, first occurrence of flatus, and time to first defecation. Surgical complications were tracked with particular attention to surgical site infections and the development of antibiotic-associated diarrhea. For the diagnosis of antibiotic-associated diarrhea, specific criteria were established: Patients experiencing 2-3 Loose stools daily for a brief duration, with other potential causes of diarrhea excluded.

Changes in the intestinal flora

Serial fecal samples (minimum 2 g) were collected at five specific timepoints: Preoperatively, immediately postoperatively, and at one week, two weeks, and one month after surgery. All specimens were immediately stored in sterile containers at -80 °C. Genomic DNA extraction was performed using a specialized fecal DNA extraction kit (Beijing Beitech Biotechnology Co., Ltd.), followed by 16S rRNA sequencing to analyze intestinal microbiota composition, with particular focus on probiotic populations including Bifidobacterium and Lactobacillus species. The analysis utilized Illumina sequencing technology targeting the V3 hypervariable region of 16S rRNA. Raw sequencing data underwent systematic processing, including read concatenation to form clean data and subsequent tag generation. After redundancy elimination, operational taxonomic units were calculated and taxonomically classified in descending order of abundance. Microbial diversity was evaluated using two complementary indices. The Chao1 index provided species richness estimates based on observed species counts, with higher values indicating greater species abundance. The Shannon index incorporated both abundance and evenness metrics, reflecting both species quantity and their relative distribution within the community. Higher Shannon index values signified greater microbial diversity, offering a comprehensive assessment of community structure.

Statistical analysis

SPSS 23.0 statistical software was used for data analysis. Measurement data conforming to normal distribution were represented as mean ± SD, and comparisons between groups were performed using two independent samples t-test. Measurement data that did not conform to normal distribution were represented by median (range), and rank sum test was used for comparisons between groups. Categorical variables were represented by frequency and percentage, and χ² test was used for comparisons between groups. Statistical comparisons employed Wilcoxon rank-sum tests for Shannon and Chao1 diversity indices, PERMANOVA for microbiome composition analysis, and Mann-Whitney U tests for between-group comparisons at each time point. All reported P values reflect Bonferroni-corrected values, with significance indicated as: P < 0.05, reference, P < 0.01, significant after correction, and P < 0.001, highly significant.

RESULTS

Clinicopathological data of two groups of gastric cancer patients

This study compared the clinical characteristics of gastric cancer patients between the ERAS group (n = 40) and traditional treatment group (n = 40). The two groups showed good comparability in baseline characteristics: Mean ages were 61.81 ± 4.62 years and 60.21 ± 5.12 years respectively (P = 0.41); gender ratios (male/female) were 32/8 and 34/6 respectively (P = 0.45); body mass indexes were 24.32 ± 3.13 kg/m² and 23.31 ± 2.82 kg/m² respectively (P = 0.71). Regarding tumor characteristics, tumors were predominantly located in the lower part of the stomach in both groups (25 cases in ERAS group, 28 cases in traditional treatment group), with similar surgical times (220.71 ± 30.41 minutes in ERAS group, 232.73 ± 32.01 minutes in traditional treatment group, P = 0.61) and tumor sizes (3.81 ± 1.72 cm in ERAS group, 3.91 ± 1.66 cm in traditional treatment group, P = 0.59). Pathological examination showed that tumors in both groups were mainly moderately to poorly differentiated, with intestinal type being predominant in Lauren classification (28 cases in ERAS group, 30 cases in traditional treatment group). Regarding TNM staging, most patients were in stage III (25 cases in ERAS group, 23 cases in traditional treatment group). All statistical indicators had P values greater than 0.05, indicating good balance in baseline data between the two groups, providing a reliable foundation for subsequent comparison of treatment effects (Table 1).

Table 1 Clinical and pathological data of two groups of gastric cancer patients, mean ± SD.

Baseline information	ERAS group (n = 40)	Traditional treatment group (n = 40)	P value
Age (year)	61.81 ± 4.62	60.21 ± 5.12	0.41
Gender (male/female)	32/8	34/6	0.45
BMI (kg/m2)	24.32 ± 3.13	23.31 ± 2.82	0.71
Tumor site			0.79
Upper part of stomach	5	2	-
Mid stomach	10	10	-
Lower part of stomach	25	28	-
Surgical time (minute)	220.71 ± 30.41	232.73 ± 32.01	0.61
Tumor size (cm)	3.81 ± 1.72	3.91 ± 1.66	0.59
Degree of tumor differentiation			0.66
Well differentiated	2	3	-
Moderately differentiated	15	16	-
Poorly differentiated	20	18	-
Signet-ring cell carcinoma	2	3	-
Mucinous cell carcinoma	1	0	-
Lauren classification
Intestinal	28	30	-
Diffuse	5	7	-
Mixed type	7	3	-
TNM stage
I	2	3	-
II	13	14	-
III	25	23	-
IV	0	0	-

ERAS: Enhanced recovery after surgery; BMI: Body mass index; TNM: Tumor-node-metastasis.

The duration of bowel sounds, first anal exhaust and defecation in the two groups

This study compared the postoperative recovery indicators between the ERAS group and traditional treatment group. The results showed that the ERAS group demonstrated significant advantages in all assessment parameters (all P values < 0.01): In terms of postoperative gastrointestinal function recovery, the ERAS group showed faster improvement: First bowel sounds appeared earlier (16.25 ± 6.41 hours vs 22.30 ± 6.49 hours), first exhaust time was shorter (23.95 ± 6.02 hours vs 28.45 ± 7.12 hours), and first defecation time was earlier (34.95 ± 9.34 hours vs 48.10 ± 15.64 hours) compared to the traditional treatment group. Regarding postoperative rehabilitation indicators, the ERAS group also performed exceptionally well: Shorter postoperative hospital stay (6.2 ± 1.5 days vs 8.1 ± 2.0 days), lower 24-hour pain scores (2.5 ± 1.0 vs 3.8 ± 1.2), and shorter duration of nutritional support (2.1 ± 0.8 days vs 4.5 ± 1.2 days). Additionally, the ERAS group had shorter urinary catheter duration (1.2 ± 0.4 days vs 2.5 ± 0.8 days), less postoperative intravenous fluid volume (2.0 ± 0.5 L vs 3.2 ± 0.8 L), and earlier postoperative oral intake time (20.5 ± 5.0 hours vs 30.0 ± 6.0 hours, Table 2).

Table 2 The duration of bowel sounds, first anal exhaust and defecation in the two groups.

Characteristic	ERAS group (n = 40)	Traditional treatment group (n = 40)	P value
Number of cases	40	40	-
First occurrence time of bowel sounds (hours)	16.25 ± 6.41	22.30 ± 6.49	< 0.0001
First exhaust time (hours)	23.95 ± 6.02	28.45 ± 7.12	0.003
First defecation time (hours)	34.95 ± 9.34	48.10 ± 15.64	< 0.0001
Postoperative hospitalization time (days)	6.2 ± 1.5	8.1 ± 2.0	< 0.001
Postoperative pain score (VAS, 24 hours)	2.5 ± 1.0	3.8 ± 1.2	< 0.001
Postoperative nutritional support duration (days)	2.1 ± 0.8	4.5 ± 1.2	< 0.001
Postoperative urinary catheter duration (days)	1.2 ± 0.4	2.5 ± 0.8	< 0.001
Postoperative intravenous fluid volume (L)	2.0 ± 0.5	3.2 ± 0.8	< 0.001
Postoperative oral intake time (hours)	20.5 ± 5.0	30.0 ± 6.0	< 0.001

ERAS: Enhanced recovery after surgery; VAS: Visual Analog Scale.

Comparison of postoperative muscle strength recovery

This study compared muscle strength recovery between the ERAS and traditional treatment groups. The baseline muscle strength was comparable between the two groups preoperatively (ERAS group: 170.21 ± 44.82 vs traditional group: 168.90 ± 41.44, P = 0.89). However, significant differences emerged during the postoperative recovery period. The ERAS group demonstrated consistently superior performance at all postoperative time points. At the first postoperative visit, the ERAS group maintained higher muscle strength (89.71 ± 30.12 vs 63.28 ± 25.29, P < 0.01). This advantage continued through one week (107.91 ± 25.15 vs 76.45 ± 23.37, P < 0.01), two weeks (119.51 ± 25.66 vs 97.03 ± 22.64, P < 0.01), and one month after surgery (139.23 ± 32.16 vs 122.90 ± 31.45, P = 0.02).

When examining the decline in muscle strength from preoperative levels, the ERAS group showed significantly less reduction compared to the traditional group. The decrease in muscle strength was notably smaller in the ERAS group at the first postoperative visit (80.50 ± 21.84 vs 105.60 ± 23.52, P < 0.01), one week (62.31 ± 33.96 vs 92.43 ± 27.99, P < 0.01), two weeks (50.68 ± 27.74 vs 71.85 ± 26.12, P < 0.01), and one month after surgery (30.98 ± 20.63 vs 46.03 ± 19.98, P < 0.01, Table 3).

Table 3 Comparison of postoperative muscle strength recovery.

Time point	ERAS group (n = 40)	Traditional treatment group (n = 40)	P value
Preoperative	170.21 ± 44.82	168.90 ± 41.44	0.89
First postoperative visit	89.71 ± 30.12	63.28 ± 25.29	< 0.01
1 week after surgery	107.91 ± 25.15	76.45 ± 23.37	< 0.01
2 weeks after surgery	119.51 ± 25.66	97.03 ± 22.64	< 0.01
1 month after surgery	139.23 ± 32.16	122.90 ± 31.45	0.02
Preoperative-first postoperative session	80.50 ± 21.84	105.60 ± 23.52	< 0.01
Preoperative-1 week postoperatively	62.31 ± 33.96	92.43 ± 27.99	< 0.01
Preoperative-2 weeks postoperatively	50.68 ± 27.74	71.85 ± 26.12	< 0.01
Preoperative-1 month postoperatively	30.98 ± 20.63	46.03 ± 19.98	< 0.01

ERAS: Enhanced recovery after surgery.

Changes in intestinal flora diversity in the perioperative period between the two groups

This study compared changes in gut microbiota diversity (Shannon index) during the perioperative period between the ERAS and traditional treatment groups. Results showed that preoperative baseline Shannon index levels were comparable between the two groups (ERAS group: 3.13 ± 0.44 vs traditional group: 3.08 ± 0.40, P = 0.61), indicating good comparability between groups.

During postoperative recovery, the ERAS group demonstrated significant advantages. At the first postoperative visit, the Shannon index in the ERAS group was significantly higher than the traditional group (2.29 ± 0.38 vs 2.00 ± 0.31, P = 0.0004). This advantage persisted at 1 week (2.57 ± 0.28 vs 2.11 ± 0.43, P < 0.0001), 2 weeks (2.60 ± 0.37 vs 2.43 ± 0.34, P = 0.03), and 1 month (2.78 ± 0.26 vs 2.60 ± 0.32, P = 0.006) after surgery. When compared to preoperative baseline levels, the ERAS group showed significantly smaller decreases in Shannon index than the traditional group: Decrease at first postoperative visit (0.84 ± 0.15 vs 1.08 ± 0.25, P < 0.0001), decrease at 1 week postoperatively (0.56 ± 0.34 vs 0.97 ± 0.50, P < 0.0001), decrease at 2 weeks postoperatively (0.53 ± 0.14 vs 0.65 ± 0.24, P = 0.003), and decrease at 1 month postoperatively (0.35 ± 0.33 vs 0.48 ± 0.22, P = 0.003, Figure 1, P < 0.05).

Figure 1 Shannon index changes during perioperative period. ^aP < 0.05. The Shannon index was similar between groups at baseline. After surgery, both groups showed decreased Shannon index values, but the enhanced recovery after surgery maintained significantly higher levels throughout the recovery period. The enhanced recovery after surgery also demonstrated faster recovery toward baseline values compared to the traditional treatment group. ERAS: Enhanced recovery after surgery.

Perioperative changes in probiotics (Lactobacillus acidophilus and Bifidobacterium)

There was no significant difference in the proportion of probiotics (Lactobacillus acidophilus and Bifidobacterium) in the perioperative intestinal flora between the two groups before surgery (P > 0.05). At one week, one week, two weeks and one month after surgery, the ERAS group had greater scores than did the traditional group did (P < 0.05). At each time point after surgery, the traditional group had significantly lower scores than the ERAS group did, and the first postoperative decrease was the largest (P < 0.05). One month after surgery, neither group recovered to the proportion of probiotics before surgery (Figure 2).

Figure 2 Changes in probiotics during the perioperative period. Standard deviation for enhanced recovery after surgery: ± 0.58-0.89, standard deviation for traditional group: ± 0.57-0.77, all differences between groups are statistically significant except at preoperative timepoint. ERAS: Enhanced recovery after surgery.

Subgroup analysis of ERAS protocol efficacy by age

Patients were stratified by median age (61 years) into ≤ 61 years (n = 42) and > 61 years (n = 38) groups for subgroup analysis. In the ≤ 61 years group, the ERAS protocol showed significant advantages over traditional treatment in time to first flatus (22.15 ± 5.82 hours vs 27.25 ± 6.92 hours, P < 0.001) and postoperative hospital stay (5.8 ± 1.3 days vs 7.9 ± 1.8 days, P < 0.001). In the > 61 years group, while the ERAS protocol still demonstrated clear benefits, the magnitude of improvement was less pronounced than in the younger group: Time to first flatus (25.75 ± 6.22 hours vs 29.65 ± 7.32 hours, P = 0.002) and postoperative hospital stay (6.6 ± 1.7 days vs 8.3 ± 2.2 days, P = 0.001). Multivariate analysis identified age ≤ 61 years [hazard ratio (HR) = 1.85, 95%CI: 1.32-2.59, P = 0.001] as an independent predictor of better outcomes with the ERAS protocol (Figure 3).

Figure 3 Subgroup analysis of enhanced recovery after surgery protocol efficacy by age. ^aP < 0.05. The subgroup analysis revealed that enhanced recovery after surgery protocol significantly improved recovery in both age groups, with greater benefits observed in younger patients (≤ 61 years). Specifically, the enhanced recovery after surgery achieved earlier first flatus (22.15 hours vs 27.25 hours in ≤ 61 years; 25.75 hours vs 29.65 hours in > 61 years) and shorter postoperative hospital stay (5.8 days vs 7.9 days in ≤ 61 years; 6.6 days vs 8.3 days in > 61 years) compared to traditional treatment. A: Time to first flatus (hours); B: Postperative hospital stay (days).

Cox regression analysis of factors affecting intestinal flora diversity

Cox proportional hazards regression model was used to analyze factors influencing postoperative recovery of intestinal flora diversity. Multivariate analysis revealed that implementation of ERAS protocol (HR = 2.31, 95%CI: 1.56-3.42, P < 0.001), high preoperative Shannon index (> 3.0) (HR = 1.92, 95%CI: 1.28-2.87, P = 0.002), operative time < 240 minutes (HR = 1.76, 95%CI: 1.15-2.69, P = 0.009), and early oral intake (within 24 hours postoperatively) (HR = 1.89, 95%CI: 1.24-2.88, P = 0.003) were independent protective factors promoting postoperative recovery of intestinal flora diversity. Conversely, advanced age (> 61 years) (HR = 0.67, 95%CI: 0.45-0.99, P = 0.044), postoperative antibiotic use > 3 days (HR = 0.58, 95%CI: 0.38-0.89, P = 0.013), and TNM stage III (HR = 0.71, 95%CI: 0.47-0.96, P = 0.035) were identified as adverse factors (Figure 4). Correlation analysis showed early feeding (within 24 hours) had the strongest association with microbiota preservation (r = 0.64, P < 0.001), followed by reduced antibiotic duration (r = 0.58, P < 0.001) and opioid-sparing analgesia (r = 0.41, P < 0.01). Early nutrition appears most critical for maintaining beneficial bacteria.

Figure 4 Cox regression analysis of factors affecting intestinal flora diversity. The Cox regression analysis of postoperative intestinal flora diversity recovery shows that enhanced recovery after surgery protocol, high Shannon index, early oral intake, and operative time less than 240 minutes are protective factors (hazard ratio > 1), while advanced age, prolonged antibiotic use, and tumor-node-metastasis stage III are adverse factors (hazard ratio < 1). ERAP: Emergency Rental Assistance Program; TNM: Tumor-node-metastasis.

DISCUSSION

ERAS protocols have emerged as a transformative approach in perioperative care, particularly demonstrating significant benefits in maintaining intestinal flora diversity. This evidence-based methodology encompasses multiple key strategies: Minimizing unnecessary intestinal preparation, implementing strict controls on antibiotic administration, reducing preoperative fasting periods, and facilitating early postoperative oral intake while limiting opioid usage[15,16]. The implementation of these protocols represents a paradigm shift from traditional perioperative management, with mounting evidence suggesting improved patient outcomes across various metrics, including reduced length of hospital stay, decreased complication rates, and enhanced patient satisfaction.

Routine intestinal preparation is no longer done based on contemporary scientific knowledge. We now know that many of our intestinal bacteria live with us in a symbiotic relationship, providing important services that help us with nutrient absorption and vitamin synthesis. ERAS protocols avoid the use of mechanical bowel preparation and osmotic laxatives, which results in the preservation of intestinal flora and stabilization of mucosal barrier function; this is further supported by lower occurrence of serum inflammatory factors and effector T-cells after surgery[17-19]. Moreover, it has been shown that preserving populations of natural intestinal flora is important for local immune function, which prevents opportunistic infections. The removal of an everyday bowel prep has explicably translated to less patient pain and a better pre-op hydration position, leading to better outcomes.

Antibiotic stewardship is another important part of ERAS[20-22]. Traditional methods would often extend this coverage for 3-5 days or even a week after surgery, while ERAS guidelines restrict antibiotic use to 24 hours post-operatively. This restriction promotes faster recovery of intestinal function and a higher diversity of microbiota, without increasing the rate of infection of the surgical site. A shorter duration of antibiotics reduces the risk of developing antibiotic-resistant strains of bacteria and a Clostridioides difficile infection, both of which can happen with prolonged antibiotic treatment. Recent meta-analyses have confirmed that this strategy achieves equivalent or better prevention of infection with fewer adverse effects of prolonged antibiotic exposure on the intestinal microbiome[23,24].

The ERAS protocol highlights the importance of reducing preoperative fasting and stimulating postoperative early nutrition for several advantages. This practice, facilitated by preoperative glucose-saline solutions and early post-operative oral intake, preserves intestinal mucosal cell energy metabolism, restores the functional integrity of the intestinal barrier, and assists in the maintenance of healthy intestinal health[18,19,25]. In addition to that, preference of the protocol for non-steroidal anti-inflammatory drugs instead of opiates prevents intestinal paralysis and provides earlier functional recovery. Freeing the gastrointestinal system from a continuous metabolic burden has many other effects that go beyond the gastrointestinal system, including better insulin sensitivity, less catabolism, increased efficiency in wound healing and the benefits are many. Early enteral nutrition has been indicated to activate intestinal peristalsis, promote intestinal hormone release, induce the sustained maintenance of beneficial gut flora, etc.

Although ERAS principles were originally developed for colorectal surgery, they have gradually been implemented across surgical specialties. Gastric cancer operations are relatively complex with many risks, like anastomotic leakage, and the precision of ERAS in gastric surgery has proven to be safe and effective[26-28]. Studies have proved its effectiveness in decreasing patient stress and speeding up post-op rehabilitation, representing a leap forward in perioperative care protocols. This experience has allowed adaptation of ERAS protocols for the numerous surgical procedures resulting in the incorporation of clinic-specific guidelines accounting for the detailed aspects of varied types of operation. All of these adaptations are still rooted in the same principles but addresses the procedural specific concerns and risks.

Through this comprehensive approach, ERAS protocols effectively optimize surgical outcomes while maintaining the delicate balance of intestinal microbiota, ultimately contributing to improved patient recovery and reduced postoperative complications[29,30]. The success of ERAS implementation has sparked ongoing research into further refinements and adaptations of the protocol. The impact of specific probiotic supplementation, and the potential benefits of personalized protocol modifications based on patient characteristics and surgical requirements. The integration of new technologies, such as minimally invasive surgical techniques and enhanced monitoring systems, continues to evolve alongside ERAS protocols, suggesting potential for even greater improvements in surgical outcomes.

The economic implications of ERAS implementation have also become increasingly apparent, with studies demonstrating significant cost savings through reduced length of stay and decreased complication rates. Healthcare systems worldwide are increasingly adopting these protocols as standard of care, recognizing both the clinical and financial benefits. The successful implementation of ERAS protocols requires a coordinated effort from multidisciplinary teams, including surgeons, anesthesiologists, nurses, and other healthcare professionals, highlighting the importance of institutional commitment and ongoing education in achieving optimal results.

CONCLUSION

These results support tailoring ERAS protocols to prioritize gut microbiome resilience through early feeding and shortened antibiotic courses, with particular benefits for younger patients. This microbiome-focused approach represents an advancement in gastric surgery ERAS implementation.