The role of gut microbiota support in the prehabilitation process for patients requiring gastrointestinal surgery

Introduction

Millions of surgeries are performed annually worldwide [1]. Each surgery induces psychological and physiological stress that can exacerbate complications, lead to organ dysfunction and dysbiosis, impair cognitive function, and cause disability [2]. Length of hospital stay remains a significant indicator of the financial burden on patients within healthcare systems, especially for planned surgeries. Many medical institutions have introduced Enhanced Recovery After Surgery (ERAS) programs aimed at improving patient outcomes while reducing costs and readmissions [3]. The ERAS protocol primarily focuses on activities determined largely by the surgeon shortly before surgery. Prehabilitation is a multidisciplinary perioperative approach centred on the patient. This process is multifaceted, with the primary goal of optimising the patient’s physiological and psychological state before, during, and after surgery. Prehabilitation programs may vary strategically but always share the same objective [4]. The aim of this review is to determine the possibilities of supporting the gut microbiota in the perioperative period for patients requiring gastrointestinal surgery.

Prehabilitation – reducing perioperative stress process

The concept of the ERAS protocol arose from the ongoing search for answers on how to care for patients to reduce surgical stress, accelerate their recovery, and minimise the risk of postoperative complications [4]. This idea has gained the approval of the world’s largest surgical societies. The protocol consists of guidelines related to preoperative education, nutritional optimisation, standardised non-opioid analgesia, balancing perioperative electrolytes and fluids, using minimally invasive surgical techniques, and promoting early mobilisation and feeding [5]. Existing research shows that properly implemented ERAS protocols are safe, reduce hospital stay and the risk of postoperative complications, and lower pain levels while significantly saving hospital costs [6]. The expert panel developing recommendations for the use of prehabilitation unanimously stated that prehabilitation should be a component of comprehensive perioperative care (Table 1) [7]. The primary goal of prehabilitation is to prepare the patient for all factors associated with the planned surgery that negatively and destructively affect homeostasis and bodily function. Given the multidimensional nature of these factors, the patient must be prepared in terms of nutritional status, physical condition, and psychological state. Such preparation requires a multimodal approach and the work of specialists in multidisciplinary teams [8]. A prehabilitation team should consist of a solid team of surgeons, anaesthesiologists, perioperative physicians, physiotherapists, dieticians, psychologists, and specially trained nurses, working in tandem to create a robust system providing support to the patient both at home, in outpatient settings, and during hospitalisation [8]. ERAS protocols, which are becoming increasingly effective, focus primarily on the intraoperative and postoperative periods. To better prepare the patient for planned surgery, which can accelerate the time of total recovery, these protocols can be supplemented with additional elements creating a prehabilitation process that begins several weeks before surgery [4]. The latest Polish recommendations for the use of prehabilitation refer to a period of 4–8 weeks before the planned surgery, depending on the stage of the disease, and risk groups for complications should be identified at the stage of initial qualification for the procedure [7]. Previous studies have limitations and are characterised by low methodological quality due to the multifactorial nature of surgical stress, as well as the heterogeneity of patient populations, interventions, and outcome measures, with a wide range of agreement [9]. Prehabilitation can take the form of classical, extended, and individualised interventions. Classical interventions should include support from a dietitian, physiotherapist, and psychologist. Extended prehabilitation additionally focuses on comorbidities, nutritional interventions, and extended diagnostics. Individualisation, depending on the type of surgery performed, allows all stages of prehabilitation to be tailored to the patient. This may include, among other things, supporting the gut microbiota, securing sperm and egg cells, and selecting appropriate exercises to accelerate post-operative recovery or improve quality of life [7].

Addressing deficiencies and improving nutritional status

Nutritional intervention in prehabilitation aims to restore energy deficits, prevent weight loss, maintain a healthy gut microbiota profile, and improve functional capacity (Figure 1) [10]. To achieve this, a normocaloric diet (25–40 kcal/kg body weight) with a protein intake of 1.2–1.8 g/kg body weight is usually sufficient [7].
Intervention should include dietary counselling, an enriched diet, oral nutritional supplements (ONS), and parenteral support if enteral feeding is not possible. According to ESPEN recommendations, the enteral route is always preferred when possible, and even if patients are on a normal diet, it is often insufficient to meet their energy needs. Therefore, it is recommended that patients receive ONS in the preoperative period, regardless of their nutritional status [11]. Nutritional intervention in the ERAS program is performed late, only in patients with malnutrition identified in screening tests after admission to the ward [12]. Perioperative nutritional optimisation reduces the risk of both infectious and non-infectious postoperative complications. It also reduces the length of hospital stay in patients undergoing surgery for gastrointestinal cancer [13]. In the prehabilitation process, assessment of nutritional status and its modification could begin as early as 8 weeks before surgery, because a 4–5 week prehabilitation process may not be sufficient to increase preoperative physiological reserves, improve the status of the gut microbiota, and reduce postoperative complications [14]. Prehabilitation allows for the optimisation of modifiable risk factors that increase the occurrence of surgical site infections [15].

The impact of gut microbiota on reducing the risk of postoperative complications

Commensal bacteria also contribute to colonisation resistance against pathogens through competitive inhibition, the production of antimicrobial peptides, and activation of the immune system (Figure 2). Significant changes in the gut microbiome can be detected within a day of changing diet [16]. Despite these constant fluctuations, the overall composition and function of the gut microbiota in healthy individuals most often returns to a stable baseline [17]. However, within just 6 hours of a major physiological injury, the gut microbiota undergoes dramatic changes in both microbial density and function, a condition termed dysbiosis [18]. For example, severe burns, including necessary surgical procedures, can result in a 90% reduction in Bacteroidetes and Firmicutes types and an increase in pathogenic Gammaproteobacteria in the intestine [18]. This bloom of pathogenic Gammaproteobacteria includes species often responsible for postoperative infections: Escherichia coli, Pseudomonas aeruginosa, and Enterococcus faecalis [19]. After burns, this observation is significant, as it has been established that the intestines are the primary source of pathogens that can cause life-threatening infections [20]. Anastomotic leakage (AL) is a significant problem in colorectal surgery, and its incidence has remained constant in recent years. In a systematic review conducted by McDermott et al., several regulated and unregulated risk factors for anastomotic leakage were identified, including male sex, smoking, obesity, alcohol, steroid and non-steroid anti-inflammatory drugs, operative time, transfusion, wound contamination, and emergency surgery [21]. Most of these factors can be influenced in the prehabilitation process. Before bowel surgeries, to reduce the risk of anastomotic leakage, oral antibiotic therapy and mechanical bowel preparation are practiced, which according to numerous studies do not bring the expected results [22]. When searching for the causes of this complication, a hypothesis emerged that the gut microbiota may influence impaired healing of the anastomosis [23]. According to numerous studies, anastomotic leakage can be influenced by gut bacteria producing collagenases such as E. faecalis and Proteus mirabilis, which degrade collagen in anastomosis tissues, inhibiting tissue regeneration and causing leakage of bowel contents into the peritoneum, resulting in peritonitis or sepsis [24, 25]. To reduce the risk of anastomotic leakage, the gut microbiota can be influenced. In studies conducted by Mathew et al., it was shown that a butyrate enema, which is a short-chain fatty acid (SCFA) produced by, among others, lactic acid bacteria, performed in rats undergoing colon transection and anastomosis increases the mechanical strength of bowel anastomoses [26]. On the other hand, modification of the gut microbiota by faecal microbiota transplantation and the administration of Parabacteroides goldsteinii via a feeding tube improved the healing process of the anastomosis in a mouse model, reducing inflammation [27]. A recent study also showed that the gut microbiota transplanted from mice on a Western-style diet to mice on a low-fat, high-fibre diet can modulate the formation and healing of anastomoses [28]. Most of the studies conducted so far have shown low microbial diversity, increased frequency of Enterobacteriaceae, and changes in their virulence as the dominant mechanism associated with the occurrence of anastomotic leakage, as well as elevated levels of Akkermansia and Bacteroides [28]. Open planned abdominal surgery more often than laparoscopic surgery results in impaired intestinal barrier function and bacterial translocation, causing sepsis [29]. Sepsis is one of the worst postoperative complications of the intestines and a major cause of death in burn patients who survive the initial injury [18]. The gut microbiota is associated with the occurrence and development of sepsis, and especially its fermentation product, particularly butyric acid, which plays a major protective role [30].

The potential of probiotics, prebiotics, and synbiotics in prehabilitation

The prehabilitation process, due to its individualised nature, can be directed towards supporting the gut microbiota, which plays a crucial role in recovery [7]. The results of human clinical studies related to the influence of perioperative modification of the gut microbiota on the postoperative period show a beneficial effect on reducing the occurrence of postoperative complications and the speed of convalescence (Table 2) [31–44].
Multi-strain probiotics can alleviate postoperative memory deficits induced by general anaesthesia and reduce inflammation associated with postoperative neurocognitive disorders [45]. A systematic review conducted by Chen et al. (2022) demonstrated a 37% reduction in the incidence of all postoperative infectious complications in colorectal cancer patients who received probiotics and synbiotics [46]. Probiotic therapy in surgical patients decreases inflammatory markers, prevents gut dysbiosis, and limits non-infectious complications [47]. Probiotics or synbiotics can prevent infections, reduce delayed gastric emptying, and shorten hospital stay and antibiotic use in patients undergoing pancreatoduodenectomy [48]. Similar effects have been observed in liver transplant recipients, where probiotics reduce the risk of postoperative infections and shorten hospital stays and antibiotic durations [49]. Supporting the gut microbiota can accelerate wound healing and improve postoperative peristalsis, reducing diarrhoea and infectious complications [50]. Perioperative administration of probiotics (Lactobacillus acidophilus, Bifidobacterium bifidum, and Streptococci) and synbiotics positively impacts intestinal motility after colorectal surgery, significantly reducing abdominal bloating and postoperative ileus [51]. Probiotic strains like L. acidophilus NCFM and L. salivarius Ls-33 can induce the expression of pain receptors, reducing normal visceral perception and increasing the pain threshold by 20% after subcutaneous morphine administration (0.1 mg/kg) [52]. Cancer therapies often induce inflammation, cognitive impairment, and diarrhoea. To mitigate these effects or enhance therapeutic efficacy, recent clinical studies focus on faecal microbiota transplantation or probiotic therapy to modulate the gut microbiota [53]. Despite promising results, further research is needed to fully understand the perioperative impact of microbiota-modulating agents. Current studies primarily focus on interventions during or immediately before surgery.

Conclusions

Prehabilitation, a relatively new concept, offers innovative perioperative care. Given the gut microbiota’s crucial role, interventions starting at the beginning of prehabilitation could significantly reduce postoperative complications, improve quality of life, and accelerate recovery. Current knowledge shows that microbiota supplement therapy in the perioperative period is mostly safe and beneficial. Tailoring interventions to individual patients requires further research considering specific procedures, intervention durations, and underlying diseases.

Funding

No external funding.

Ethical approval

Not applicable.

Conflict of interest

The authors declare no conflict of interest.

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