Crohn’s disease (CD) is a chronic inflammatory disease of the intestinal mucosa which can occur discontinuously throughout the entire digestive tract. Its pathogenesis is still poorly understood (1, 2). In China, the morbidity and prevalence of CD are increasing constantly, which leads to a heavy economic and social burden (3). Although the innovation and application of series of new drugs has greatly improved the therapeutic effect (4), complications such as intestinal bleeding, obstruction, fistula, perforation, abscess still occur (5, 6), these patients as well as those who respond poorly to conservative treatment may require surgery (7, 8).

During the natural course of CD, the nutritional condition and the diet are important in the etiology of CD, particularly in regions where the rising prevalence rate has paralleled changes in eating habits and food industrialization (9, 10). High prevalence of malnutrition and micronutrient deficiencies were observed in patients with CD and constitutes a challenging issue for patients who require surgery (9). While malnutrition was confirmed to be an independent prognostic factor for increased risk of post-operative complications after abdominal surgery, which contributes to approximate 20–40% of surgical complication rates (11, 12). In this regards, early diagnosis of malnutrition is extremely important since pre-operative nutritional intervention may contribute to lower post-surgical complication and mortality rates (13–15). However, until now, there is few evidence directly linking nutritional status to post-operative complications in CD patients. Evidence that supports the effectiveness of nutritional support for patients with CD during peri-operative period, and whether it can contribute to lower post-operative complication incidence rate is scant (11, 16). Thus, we selected scored Patient-Generated Subjective Global Assessment (PG-SGA score) as a validated tool to screen patients’ immune-nutritional status (17, 18), and we selected the comprehensive complication index (CCI) to quantify the post-operative complications within 30 days.

Furthermore, several strategies were adopted to establish a standard clinical protocol of pre-operative enteral nutrition (EN): including patient nutrition education programs, dietary instruction, partial enteral nutrition (PEN), exclusive enteral nutrition (EEN), and total parenteral nutrition (TPN), which can significantly reduce the effects of catabolism (19). Our primary hypothesis was that pre-operative EN would increase pre-operative immune-nutritional status and reduce 30-day post-operative complications, as measured using the CCI. The objective of this study is to evaluate whether the nutritional status could predict post-operative complications in CD patients and the benefit of EN on the nutritional status and preventing post-operative complications of CD patients.

Despite the advent of medicine, a huge step forward for patients with CD, leading to a rapid response and huge remission of disease. However, complications such as intestinal bleeding, intestinal obstruction, fistula, perforation, abscess still exist (5–7). In such kind of occasion, surgery is still the recommended treatment (7). Therefore, it is crucial to enhance the outcome by optimizing perioperative management. Pre-operative malnutrition has been shown to be associated with increased risk of post-operative complications and increased LOS after abdominal surgery (12, 23, 24). Factors such as nausea, vomiting, abdominal pain, and diarrhea reducing oral food intake contribute to malnutrition in CD patients (25, 26). Furthermore, medications such as glucocorticoids often reduce phosphorus, zinc, and calcium absorption and may lead to osteoporosis (17). Although several studies demonstrated improved disease activity and prolonged time to relapse following nutritional support (27, 28), the efficacy and protocol of nutritional support has not been fully clarified.

Consistent with previous findings, pre-operative nutritional optimization was recommended in CD patients with poor nutritional status to minimize post-operative complications (23, 29). In our study, patients with lower nutritional status and higher inflammatory level are related with post-operative complications in quantity and severity. Furthermore, the pre-operative nutritional status may also have impact on post-operative recovery of gastrointestinal function. Prolonged post-operative ileus and delay in recovery of the gastrointestinal function were commonly observed in non-nutritional group, leading to a longer LOS directly. Meanwhile, malnutrition will also increase the rate of emergency surgery, staged surgery, and diversion. The difference of surgical strategy was done for the reason leading to the surgical difficulty such as severe intra-abdominal adhesions, tissue edema, complete intestinal obstruction, or severe fistula, which indicates that successful pre-operative nutritional support could decrease the occurrence of complications during the course CD and reduce intra-abdominal inflammation.

In recent studies, diet appears to play an important role in disease pathogenesis (23, 24, 30, 31). Recent studies have shown that EEN can induce remission and mucosal healing (32, 33). So far, nutritional support, including dietary and EN is likely to play an important role during the treatment of CD. But few evidence support the effectiveness of EN. Furthermore, the evidence to support the interplay between nutritional status and post-operative complications is still lacking. Based on our results, a specific nutritional strategy may be able to play a pivotal role in improving immune-nutritional status and preventing post-operative complications of CD patients. The pre-operative EN was found to significantly improve the nutritional status scored by PG-SGA assessment and reduce the inflammatory response according to CDAI score. Meanwhile, improvements in level of serum albumin concentration, pre-albumin concentration, and TLC were also mentioned. The TLC indicates the immunological status of patient, which is also one of the important components of PNI score. Various studies have indicated that T lymphocytes affected by the systemic inflammatory response play an important role in the depression of innate cellular immunity of intestinal inflammation in cancer patients and found PNI an independent prognostic indicator in predicting post-operative complication (34, 35). Accompany with the significant decrease of inflammatory indicators such as WBC and CRP, our results indicated the beneficial effect of this new kind of comprehensive nutritional strategy in alleviating nutritional status and intestinal inflammation in CD patients.

Micronutrient status is also impacted by inflammatory severity and disease location, which may reduce surface area for absorption (36). The level of serum microelement may also be affected by some medicines (36). Weisshof et al. indicated that these micronutrients lead to deleterious downstream effects such as impaired immune response within the gut, and inflammation because of increased production of reactive oxygen species (37). In this study, we monitored important nutrients such as folate, 25-OH-vit D, calcium, potassium, magnesium, and phosphorus which were determined to be frequently suboptimal in patient with CD (38, 39). The statistic between two groups indicated that micronutrients supplementary play an important role in treatment of CD patients whose micronutrient intake from dietary was suboptimal.

This study is, to the best of our knowledge, the first study focusing on the application of EN on post-operative outcomes of CD patients. We used PSM for potential imbalances between groups, which confirmed the robustness of our conclusions. On account of CCI, we can quantify the post-operative complication more precisely with the application of such a comprehensive and sensitive measure. Regular follow-up consultation no longer than 3 or 6 months and weekly self-reporting was executed in our program since compliance is often limited for the strategy of dietary, EEN, PEN. In light of these design considerations, we believe that our results contribute new evidence for the role of nutritional support in CD patients who are candidates for surgical treatment.

Our result should be considered with some limitations. Groups were not balanced at baseline for age and ASA scores at first, however, our analyses were adjusted for these potential confounders. There was a considerable rate of missing data for PG-SGA score, CDAI index as a result of missing follow-up consultations. These missing data were handled with multiple imputation to reduce the risk of attrition bias. And the self-reporting database such as dietary compliance might be subject to reporting bias. Last but not least, this is a retrospective observational study which outcomes might be influenced by our local experience, a multi-center prospective study is excepted.

In conclusion, pre-operative nutritional status is correlated with post-operative outcomes while EN plays a positive role in preventing the post-operative complications. EN is a useful method for improving the pre-operative nutritional status and reducing the post-operative adverse events for CD patients undergoing surgery.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by the Ethics Committee of Shanghai Ruijin Hospital. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

ZH, TJ, YJ, and QJ: conceptualization. TJ, YJ, and QJ: writing—original draft. ZH, MZ, AF, and YS: review and editing. SX: supervision. All authors read and agreed to the published version of the manuscript.