Skip to main content

Association of early dietary fiber intake and mortality in septic patients with mechanical ventilation based on MIMIC IV 2.1 database: a cohort study



Whether early dietary fiber intake in septic patients is associated with a better clinical prognosis remains unclear, especially the time and the amount. Therefore, we assessed the association between early dietary fiber intake and clinical outcomes in septic patients by examining an extensive database.


We conducted a retrospective cohort study using data from the MIMIC IV 2.1 database, focusing on consecutive septic patients requiring mechanical ventilation in medical or mixed medical-surgical ICUs. We collected patient demographics and nutritional data. Dietary fiber amounts were calculated according to enteral nutrition instructions from manufacturers within the first 72 h after admission. After adjusting for covariates, we employed restricted cubic spline (RCS) regression to investigate the relationship between fiber intake (FI) and 28-day mortality. Patients were categorized into three groups based on their fiber index (FI) within 72 h of admission: low fiber index (LFI) group when FI was < 3 g/(%), medium fiber index (MFI) group when FI ranged from 3 to 35 g(%), and high fiber index (HFI) group when FI ≥ 35 g(%). Univariate and multivariate Cox proportional hazards regression models were utilized to assess the association between early FI and 28-day mortality. We ultimately employed Kaplan–Meier (KM) curves and log-rank test visually represent the association between FI and 90-day mortality. The second outcomes include ICU-acquired infections and the hospital and ICU death, length of hospital and ICU stay, and length of mechanical ventilation.


Among 1057 subjects, 562 (53.2%) were male, with a median age of 64.8 years (IQR 53.4–75.2). We observed a J-shaped relationship between FI and 28-day mortality. The MFI group exhibited the lowest 28-day mortality [adjusted HR 0.64 (0.45–0.91), p = 0.013] and the lowest rate of hospital mortality [adjusted OR 0.60 (0.39–0.93), p = 0.022], with no statistically significant differences noted in the HFI group when compared to the LFI group. Similar patterns were observed for 60-day and 90-day mortality. However, no statistically significant differences were observed in other secondary outcomes after adjusting for covariates.


Early medium fiber index intake improved 28-day mortality and lower hospital mortality in septic M/SICU patients on mechanical ventilation.

Peer Review reports


The dietary fiber (DF) required by critically ill patients remains unknown, including when and the amount. Studies have shown DF can reduce diarrhea [1,2,3,4,5], improve intestinal motility [6], and also with safety and tolerability profile in hemodynamically stable critically ill patients, though rare studies reported [7] the fatal complications. The current Clinical Nutrition guidelines [8, 9] for critical illness have no explicit recommendation about DF use, and there are no recommendations about using nutritional formulas containing DF or supplements for DF at the early stage of sepsis.

Sepsis is one of the most common illnesses in the ICU, with its leading cause of morbidity and mortality worldwide [10] and one of the most costly diseases [11]. Early enteral nutrition for critical patients is vital in maintaining gut function. Widely published literature has presented DFs' indirect anti-inflammatory effects in healthy and hospitalized patients [2, 12], and a few reports have reported the effects of probiotics or synbiotics in critical patients [13, 14]. However, little was known about DF in septic patients, especially the association between the amount of early DF intake and the clinical outcomes.

Differing opinions on DF and its impact on mortality and other clinical outcomes can be attributed to variations in DF type, quantity, and duration of DF used [14,15,16]. Studies in critical care patients have examined DF from various sources, including symbiotic, enteral nutritional formula, and DF supplements. Our study specifically focused on soluble DF from enteral nutritional formulas, as it provided a consistent amount. Notably, Fu et al. [17]. Found that higher fiber intake, as measured by the Fiber Index (FI), was associated with increased production of short-chain fatty acids (SCAFs) and was well-tolerated by critical patients within 72 h of ICU admission.

Therefore, the objective of this study was to evaluate whether DF intake 72 h after admission had a relationship between the amount (measure by FI) and clinical outcomes.



Patients were eligible for analysis as below: 1. Critically ill adults meet the criteria of sepsis 3.0 definition [18], the clinical criteria is as below: suspected or documented infection and an acute increase of ≥ 2 SOFA points (a proxy for organ dysfunction) [18]; 2. Be in hospital and be in ICU for the first time; 3. ICU stay lasting ≥ 5 days; 4. Receipt of invasive mechanical ventilation initiated within 48 h of ICU admission; 5. Absence of gastrointestinal bleeding; 6. Receiving nutrition support, either enteral nutrition [EN] OR EN plus parenteral nutrition [PN]); 7. Nutritional variables are consecutive. Patients with missing weight, height, or caloric intake data were excluded, as shown in Fig. 1 in the flowchart (Fig. 1).

Fig. 1
figure 1

Flowchart of the study

Baseline characteristics include age, gender, Body Mass Index (BMI), Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score II(SASPII), Charlson Comorbidity Index (CCI), number of antibiotics within 72 h, norepinephrine equivalents within 72 h, proton pump inhibitors or H2 receptor antagonists within 72 h.

Nutrition data

The calculation of energy intake encompasses both non-nutritional and nutritional sources, including substances like propofol, glucose infusions, enteral nutrition formulas, and parenteral nutrition. The target energy was determined by considering corrected ideal body weight, age, and gender (the target energy is based on the calculation of the fiber index) [19, 20]. Feeding route, whether early enteral nutrition (feeding within 48 h of admit to ICU), energy achievement (the ratio of actual energy to target energy), actual non-nutrition energy, enteral nutrition energy, protein, fiber intake and FI were collected.

Fiber index and formula

We checked the DF amount from the database of enteral nutrition instructions from different manufacturers (as shown in sTable1.xlsx). The amount of fiber consumed depends on total caloric consumption, so the relative consumption of fiber was a calorie-corrected “fiber index” [17]. We use FI [17] as fiber intake over the 72 h divided by the percentage of target energy received, the calculation formula is as follows:


Patients were stratified into three groups based on their 72-h Fiber Index (FI). Using Restricted Cubic Spline (RCS) regression analysis, we identified the lowest hazard ratio (HR) when the FI ranged from 3 to 35 g/(%). Accordingly, we established cutoff values of 3 and 35 (see Fig. 2). These categories were defined as follows: the Low Fiber Index (LFI) group for FI < 3 g/(%) (including FI = 0), the Medium Fiber Index (MFI) group for FI ranging between 3 and 35 g/(%), and the High Fiber Index (HFI) group for FI ≥ 35 g/(%).

Fig. 2
figure 2

Relationship between FI and 28-day mortality. Model adjusted for age, BMI, SOFA, SAPS II, CCI, vasoactive agents, norepinephrine equivalents, feeding route and early enteral nutrition

Outcome data

We designated the first 72 h following admission to the ICU as the ‘early’ phase. We assessed patient mortality at four time points: 28 days, 60 days, 90 days, and one year after admission. Hospital/ICU mortality was defined as the occurrence of death within the hospital or ICU setting. Length of ICU/hospital defined as the duration of the patient’s stay in either the ICU or the hospital. The following formula of Norepinephrine equivalents in ICU settings (all in mcg/kg/min, except vasopressin in units/min): Norepinephrine equivalents = norepinephrine + epinephrine + phenylephrine/10 + dopamine/100 + metaraminol/8 + vasopressin*2.5 + angiotensin II*10 [21]. Lastly, the length of mechanical ventilation represented the duration of invasive mechanical ventilation. Infection complications were defined as follows: (1) Ventilator-associated pneumonia was defined as a new pneumonia that develops after 48 h of endotracheal intubation [22, 23]. The data was extracted from the patient’s diagnosis according to the ICD-9 code (ICD-9 99731 Ventilator associated pneumonia). (2) Clostridium difficile infection was defined as infection by Clostridium difficile. The data was extracted from the patient’s diagnosis according to the ICD-9 and ICD10 code (ICD-9 00845, ICD10 A047, A0471, A0472 Intestinal infection due to Clostridium difficile). (3) Early-onset nosocomial infection was defined as an infection occurring within 48 to 120 h after admission, involving different microorganisms than those present at the time of admission, we extracted from the microorganism information to identify the new different microorganism. The same way to identify late-onset nosocomial infection, which are characterized by the emergence of new microorganisms after 120 h of admission [24].

Study description

A retrospective cohort study was conducted among all consecutive, septic, invasive mechanically ventilated patients in a mixed medical-surgical or medical ICU from MIMIC IV 2.1 database.

Data collection

Data for this study were sourced from the Multiparameter Intelligent Monitoring in Intensive Care IV 2.1 database, with data extraction carried out using PostgreSQL v11.5.

Statistical analysis

Demographic variables and nutritional data for the initial 72 h were compared among groups. Continuous variables are presented as either mean ± standard deviation (SD) or median (interquartile range, IQR) and were assessed for group differences using one-way ANOVA, with multiple comparisons conducted using the SNK method. Categorical variables are presented as counts or percentages and were compared among groups using the chi-squared test.

We conducted Restricted Cubic Spline (RCS) regression analysis with four knots placed at the 5th, 35th, 65th, and 95th percentiles of FI, adjusting for variables in model 1. This analysis aimed to evaluate nonlinearity and explore the dose–response relationship between FI and HR of 28-day mortality. Our findings revealed that the FI range of 3 ~ 35 g/(%) was associated with the lowest hazard ratio (HR), leading us to select 3 and 35 as the cutoff values, as depicted in Fig. 2.

Univariate and multivariate Cox proportional hazards regression models were use to evaluate the relationship between early FI and the primary outcomes. Model 1 underwent full adjustment, including confounders such as age, BMI, SOFA, SAPS II, CCI, vasoactive agents, norepinephrine equivalents, feeding route, and early enteral nutrition and actual energy intake. Survival analysis was performed using Kaplan–Meier (KM) curves and the log-rank test. Second outcomes were assessed by multivariate cox regression analysis, multivariate logistic regression analysis, and multivariate linear regression analysis.

We employed multivariate regression to elucidate the association between FI and 28-day mortality. The model included factors meeting two criteria: (1) statistical significance with a p-value < 0.05 in univariate regression analysis, and (2) clinical relevance to the outcome.

To robust of our findings, we performed subgroup analyses, potential modifications of the relationship between FI and 28-day mortality were assessed, including the following variables: age (< 65,65 ~ 80 and ≥ 80 years), BMI (< 18.5, 18.5 ~ 25, 25 ~ 30, and ≥ 30 kg/m2), SOFA score (< 6 vs. ≥ 6), feeding route(EN vs. EN + PN), vasoactive agents used(NO vs. Yes), number of antibiotics (< 3 vs. ≥ 3).

All analyses were conducted using the statistical software packages R (, The R Foundation) and Free Statistics Software version 1.7, with significance defined as p < 0.05.


Patients’ characteristics and 72 h nutrition data

As depicted in Fig. 1, a total of 1057 subjects were included in the final analysis. None of the subjects received fibrin supplements or probiotics while in the ICU. Among these 1057 subjects, 562 (53.169%) were male, with a median age of 64.8 (IQR 53.4, 75.2) years. There were no statistically significant differences among the groups with respect to age, BMI, SASPII, CCI, the number of antibiotics administered, or the use of PPI or H2RA medications. However, there was variation in sex distribution among the groups. The MFI group had a higher proportion of female subjects, while the HFI group had a higher proportion of male subjects. Notably, the SOFA score was higher in the LFI group compared to the other groups (p = 0.046). Additionally, the HFI group had the highest number of patients who did not require vasoactive agents [LFI vs. MFI vs. HFI: 182 (27.786%) vs. 67 (34.536%) vs. 80 (38.462%), p = 0.008], as well as the highest norepinephrine equivalents (see Table 1).

Table 1 Baseline demographic and clinical characteristics among groups

Regarding nutritional variables over the initial 72 h, several notable differences showed among the groups. The LFI group had the highest prevalence of patients receiving enteral nutrition plus parenteral nutrition (EN + PN) as their feeding route [LFI vs. MFI vs. HFI: 62 (9.466%) vs. 7 (3.608%) vs. 9 (4.327%), p = 0.004]. Conversely, the HFI group exhibited the highest proportion of patients receiving early enteral nutrition (EEN) [LFI vs. MFI vs. HFI: 211 (32.214%) vs. 102 (52.577%) vs. 167 (80.288%), p < 0.001]. Additionally, the HFI group demonstrated the highest energy intake within the initial 72 h [LFI vs. MFI vs. HFI: 0.2 (IQR: 0.1, 0.4) vs. 0.2 (IQR: 0.2, 0.4) vs. 0.4 (IQR: 0.2, 0.5), p < 0.001], as well as the highest actual enteral nutrition energy intake during the same period [LFI vs. MFI vs. HFI: 0.0 (IQR: 0.0, 776.4) vs. 363.9 (IQR: 197.7, 866.9) vs. 1578.0 (IQR: 841.8, 2394.0), p < 0.001]. Furthermore, the HFI group exhibited the highest actual protein intake [LFI vs. MFI vs. HFI: 0.0 (IQR: 0.0, 41.2) vs. 19.6 (IQR: 10.1, 42.4) vs. 79.9 (IQR: 41.7, 117.4), p < 0.001]. Moreover, the HFI group exhibited the highest actual fiber intake [LFI vs. MFI vs. HFI: 0.0 (IQR: 0.0, 0.0) vs. 3.9 (IQR: 2.4, 7.1) vs. 21.6 (IQR: 11.8, 31.8), p < 0.001], and the highest Fiber Index (FI) [LFI vs. MFI vs. HFI: 0.0 (IQR: 0.0, 0.0) vs. 17.4 (IQR: 10.2, 27.3) vs. 55.5 (IQR: 42.7, 68.5), p < 0.001] (see Table 2).

Table 2 Baseline nutritic characteristics within 72 h in ICU among groups

Primary outcome

Univariate Cox proportional hazards analysis identified several factors significantly affecting 28-day mortality, including age, BMI, SOFA, SAPS II, CCI, vasoactive agents administered, average norepinephrine equivalents, and actual energy intake within 72 h. Specifically, the MFI group exhibited a HR of 0.63 with a 95% CI of (0.45 ~ 0.89) compared to the LFI group (Table 3). After adjusting for covariates, the results for 28-day mortality consistently revealed the lowest HR of 0.64 with a 95% CI of (0.45 ~ 0.91) compared to the LFI group, but the HFI group showed no statists different compared to the LFI group. Similar outcomes remained in 60 and 90-day mortality in MFI group (See Table 4).

Table 3 Univariate Cox regression models for 28- day mortality
Table 4 Primary and second outcomes

Log-rank test and Kaplan–Meier (KM) curves showed notable distinctions among three groups, with the MFI group demonstrating the highest survival rate compared to the other groups (p = 0.025) (see Fig. 3).

Fig. 3
figure 3

Kaplan–Meier survival curves for 90-day survival among groups

Secondary outcomes and subgroup analysis

Compared to the LFI group, the MFI group exhibited the lowest hospital mortality following covariate adjustment, with an odds ratio (OR) of 0.62 (95% CI: 0.4 ~ 0.95, p = 0.028), while no statistically significant differences were observed in ICU mortality, length of hospital/ICU stay, duration of mechanical ventilation, incidences of ventilator-associated pneumonia, nosocomial infections, or Clostridium difficile infection, as presented in Table 4. Subgroup analysis, conducted without detecting any interactions between subgroups, consistently indicated the lowest 28-day mortality in the MFI group, as demonstrated in Supplementary sTable 2.


We analyzed 1057 septic patients receiving mechanical ventilation in the MICU or mixed ICU. We identified a J-shaped association between FI and 28-day mortality, with the lowest mortality observed within the 3 ~ 35 g/(%) FI range. The MFI group demonstrated significantly lower mortality rates at 28, 60, and 90 days, as well as in-hospital mortality when compared to the LFI group. Conversely, the HFI group showed no statistically significant differences in comparison to the LFI group. These trends persisted after adjusting for covariates. Nevertheless, no significant associations were found between FI and ICU mortality, length of hospital/ICU stay, or the risk of hospital-acquired infections, even after controlling for confounding factors.

In our study, it was found that 92.62% of mechanically ventilated septic patients received nutritional support via enteral nutrition, with the highest proportion observed in the MFI and HFI groups, significantly surpassing that of the LFI group. Additionally, the HFI group had the highest proportion of early (within 48 h) initiation of enteral nutrition at 80.288%, followed by the MFI group (52.577), while the LFI group had the lowest proportion (32.214%). This observation may be attributed to the more severe condition of the LFI group, as evidenced by higher SOFA scores and greater use of vasoactive agents (higher norepinephrine equivalents) within the first 72 h. Furthermore, we also observed that within the MFI group, the actual energy intake, protein intake, dietary fiber intake, dietary fiber index, and energy achievement percentage within the initial 72 h were the highest among the three groups.

Early enteral nutrition may potentially reduce the mortality rate in critically ill patients, and nutritional guidelines recommend early enteral nutrition for hemodynamically stable patients [8]. However, recent clinical research has yielded conflicting results regarding whether early enteral nutrition reduces mortality in critically ill patients, largely attributed to the risk of overfeeding when initiated prematurely [25,26,27]. In our study, the poorer prognosis in HFI group may be attributed to the reasons as follows: firstly, patients with a high fiber index were always associated with the adverse risks of overfeeding at the early stage. Secondly, high fiber itself may lead to feeding intolerance [28, 29] during the early stage.

In our study, we observed a positive correlation between dietary fiber intake and energy intake. Therefore, we calculated the dietary fiber index as a relative dose. Furthermore, in our multivariate analysis, we included actual energy intake as a confounding variable to adjust the model. Remarkably, our results remained consistent. This indicates that early dietary fiber intake (calculated using the dietary fiber index) independently influences the 28-day mortality rate in sepsis.

Dietary fiber (DF) comprises carbohydrates with degrees of polymerization (DP) ranging from 3 to 9, remaining undigested by the intestine while conferring physiological health benefits [30]. DF is commonly incorporated into enteral formulas and supplements to enhance intestinal motility and alleviate diarrhea in critically ill patients. Furthermore, research has indicated additional advantages [31] when DF is administered alone or as part of synbiotics to critically ill patients or animals, although limited investigations have focused on septic ICU patients. In septic animal experiments, high doses of DF administered before modeling not only mitigated the inflammatory response [32,33,34,35] but also decreased endotoxin-induced intestinal permeability [36, 37] and improved the survival of sepsis models [38]. Conversely, varying results have been reported in clinical studies [39, 40].

DF can improve mortality in critical patients depends on the dose [33] and timing [41] of DF administration. However, some studies have shown different outcomes. For example, a study involving mechanically ventilated septic patients receiving mixed DF for six days did not affect mortality or hospital stay [5]. In a randomized trial of 72 mechanically ventilated septic patients, one group received daily synbiotics (including galactooligosaccharides 10 g/day as prebiotics) starting from ICU admission, while the other received a placebo. Results showed significant differences in bacteremia incidence and 4-week mortality between the groups, with lower VAP incidence in the synbiotic group [14]. Knight et al. conducted a prospective, randomised, double blind, placebo controlled tria with 259 critically ill patients receiving mechanical ventilation for 48 h or longer, randomly assigning them to receive synbiotics (Betaglucan, Inulin, Pectin and Resistant starch (2.5 g of each) as prebiotics) or a placebo(cellulose). They found no differences in VAP incidence, VAP rate, or in-hospital mortality between the groups [42]. A smaller-scale study by Seifi et al. administered synbiotics (prebiotics: fructooligosaccharides) for 14 days to critically ill patients, resulting in reduced NLR and serum endotoxin levels but no differences in ICU outcomes [43]. Regarding VAP prevention, meta-analyses have shown mixed results. Some favor synbiotics over probiotics [12], while others suggest mixed probiotics are effective [13]. A meta-analysis by Liu et al. [33] found DF reduced C-reactive protein and hospital stay but had improved effects on ventilation duration and mortality only in the subgroup fed ≥ 20 g/d of DF. Although DF has been linked to reduced C. difficile infections in non-severe disease [44] and in animal study [45], however, our study did not find this association in critically ill septic patients. Our study found that early and medium dietary fiber intake can improve the mortality rate of septic patients. However, the specific types and dosages of dietary fiber require further confirmation through well-designed randomized controlled trials.

Strengths and limitations

To the best of our knowledge, this is the first study to explore the relationship between DF and 28-day mortality, and identify the optimal amount of DF in mechanically ventilated patients with sepsis, especially in the early stages of sepsis. Current dietary fiber recommendations continue to rely on daily energy consumption [46]. Given the restricted energy intake during the early stages [47] of the highly catabolic phase of sepsis [48], coupled with variations in DF intake due to trophic and target feeding, we utilized the FI [17] as an indicator of early DF intake. This approach mitigates the impact of inconsistent energy intake, standardizes individual energy consumption, and enables somewhat meaningful comparisons. Additionally, we accounted for non-nutrient energy sources, such as dextrose and propofol. Furthermore, we adjusted more confounders such as age, BMI, SOFA, SAPSII, CCI, vasoactive agents, norepinephrine equivalents, feeding route, early enteral nutrition and actual energy intake. This study has limitations. We couldn’t access data on potential adverse effects of DF intake due to database constraints. Additionally, the effect of different kind of DF in the formula was not evaluated. Moreover, this is a retrospective study with numerous confounding factors, so more rigorously designed RCT studies are needed to confirm the impact of specific dietary fiber on clinical outcomes in early septic patients.

In conclusion, this retrospective cohort study found early (within 72 h of admission) optimal fiber intake (measured by FI, FI range from 3 to 35 g/(%)) can improve 28-day mortality in septic patients with invasive mechanical ventilation in the MICU or S/MICU.

Availability of data and materials

The data analyzed was obtained from the Medical Information Mart for Intensive Care IV (MIMIC-IV) Clinical Database; the following licenses/restrictions apply: To access the data, you must be a credentialed user, complete the required training (CITI Data or Specimens Only Research) and sign the data use agreement for the project. Requests to access these datasets should be directed to PhysioNet,;



Intensive care unit


Surgical/Medical Intensive care unit

MIMIC-IV Database:

Medical Information Mart for Intensive Care IV (MIMIC-IV) Clinical Database


Dietary fiber


Fiber index


Short-chain fatty acid


Enteral nutrition


Parenteral nutrition


Ventilator-associated pneumonia


Body Mass Index


Sequential Organ Failure Assessment


Simplified Acute Physiology Score II


Charlson comorbidity index


Proton pump inhibitors


H2 receptor antagonists


  1. Reis AM dos, Fruchtenicht AV, Loss SH, Moreira LF. Use of dietary fibers in enteral nutrition of critically ill patients: a systematic review. Rev Bras Ter Intensiva. 2018;30(3):358–65. Cited 2022 Nov 30. Available from:

  2. Hajipour A, Afsharfar M, Jonoush M, Ahmadzadeh M, Gholamalizadeh M, Hassanpour Ardekanizadeh N, et al. The effects of dietary fiber on common complications in critically ill patients; with a special focus on viral infections; a systematic reveiw. Immun Inflamm Dis. 2022;10(5):e613. Available from: Cited 2022 Nov 30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Chittawatanarat K, Pokawinpudisnun P, Polbhakdee Y. Mixed fibers diet in surgical ICU septic patients. Asia Pac J Clin Nutr. 2010;19:458–64.

    PubMed  Google Scholar 

  4. Schultz AA, Ashby-Hughes B, Taylor R, Gillis DE, Wilkins M. Effects of pectin on diarrhea in critically ill tube-fed patients receiving antibiotics. Am J Crit Care. 2000;9:403–11.

    Article  PubMed  CAS  Google Scholar 

  5. Majid HA, Emery PW, Whelan K. Faecal microbiota and short-chain fatty acids in patients receiving enteral nutrition with standard or fructo-oligosaccharides and fibre-enriched formulas. J Hum Nutr Diet. 2011;24:260–8. Available from:

    Article  PubMed  CAS  Google Scholar 

  6. Chen T, Ma Y, Xu L, Sun C, Xu H, Zhu J. Soluble dietary fiber reduces feeding intolerance in severe acute pancreatitis: a randomized study. J Parente Enteral Nutr. 2021;45:125–35. Available from: Cited 2022 Jul 17.

    Article  CAS  Google Scholar 

  7. Scaife CL, Saffle JR, Morris SE. Intestinal obstruction secondary to enteral feedings in burn trauma patients. J Trauma. 1999;47:859. Available from:

    Article  PubMed  CAS  Google Scholar 

  8. Compher C, Bingham AL, McCall M, Patel J, Rice TW, Braunschweig C, et al. Guidelines for the provision of nutrition support therapy in the adult critically ill patient: The American Society for Parenteral and Enteral Nutrition. J Parenter Enteral Nutr. 2022;46:12–41. Available from: Cited 2022 Aug 17.

    Article  CAS  Google Scholar 

  9. Green CH, Busch RA, Patel JJ. Fiber in the ICU: Should it Be a Regular Part of Feeding? Curr Gastroenterol Rep. 2021;23:14. Available from:

    Article  PubMed  Google Scholar 

  10. Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study. Lancet. 2020;395:200–11. Available from: Cited 2022 Nov 10.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Buchman TG, Simpson SQ, Sciarretta KL, Finne KP, Sowers N, Collier M, et al. Sepsis among medicare beneficiaries. Crit Care Med. 2020;48:276–88. Available from: Cited 2022 Nov 10.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Li C, Liu L, Gao Z, Zhang J, Chen H, Ma S, et al. Synbiotic therapy prevents nosocomial infection in critically ill adult patients: a systematic review and network meta-analysis of randomized controlled trials based on a Bayesian framework. Front Med. 2021;8:693188. Available from: Cited 2022 Dec 2.

    Article  Google Scholar 

  13. Li C, Lu F, Chen J, Ma J, Xu N. Probiotic supplementation prevents the development of ventilator-associated pneumonia for mechanically ventilated ICU patients: a systematic review and network meta-analysis of randomized controlled trials. Front Nutr. 2022;9:919156. Available from:

    Article  PubMed  PubMed Central  Google Scholar 

  14. Shimizu K, Yamada T, Ogura H, Mohri T, Kiguchi T, Fujimi S, et al. Synbiotics modulate gut microbiota and reduce enteritis and ventilator-associated pneumonia in patients with sepsis: a randomized controlled trial. Crit Care. 2018;22:239.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kotzampassi K, Giamarellos-Bourboulis EJ, Voudouris A, Kazamias P, Eleftheriadis E. (Synbiotic 2000Forte®) in critically Ill trauma patients: early results of a randomized controlled trial. World J Surg. 2006;30:1848–55. Available from:

    Article  PubMed  Google Scholar 

  16. Tuncay P, Arpaci F, Doganay M, Erdem D, Sahna A, Ergun H, et al. Use of standard enteral formula versus enteric formula with prebiotic content in nutrition therapy: A randomized controlled study among neuro-critical care patients. Clin Nutr ESPEN. 2018;25:26–36. Available from:

    Article  Google Scholar 

  17. Fu Y, Moscoso DI, Porter J, Krishnareddy S, Abrams JA, Seres D, et al. Relationship between dietary fiber intake and short-chain fatty acid-producing bacteria during critical illness: a prospective cohort study. J Parenter Enter Nutr. 2020;44:463–71.

    Article  CAS  Google Scholar 

  18. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315:801.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Jolliet P, Pichard C, Biolo G, Chioléro R, Grimble G, Leverve X, et al. Enteral nutrition in intensive care patients: a practical approach. Intensive Care Med. 1998;24:848–59. Available from:

    Article  PubMed  CAS  Google Scholar 

  20. Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, et al. Early versus Late Parenteral Nutrition in Critically Ill Adults. N Engl J Med. 2011;365:506–17.

  21. Goradia S, Sardaneh AA, Narayan SW, Penm J, Patanwala AE. Vasopressor dose equivalence: A scoping review and suggested formula. J Crit Care. 2021;61:233–40. Available from: Cited 2023 May 18.

    Article  PubMed  CAS  Google Scholar 

  22. Modi AR, Kovacs CS. Hospital-acquired and ventilator-associated pneumonia: Diagnosis, management, and prevention. Cleve Clin J Med. 2020;87:633–9. Available from:

    Article  PubMed  Google Scholar 

  23. Torres A, Niederman MS, Chastre J, Ewig S, Fernandez-Vandellos P, Hanberger H, et al. International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia. Eur Respir J. 2017;50:1700582. Available from:

    Article  PubMed  Google Scholar 

  24. Johnstone J, Meade M, Lauzier F, Marshall J, Duan E, Dionne J, et al. Effect of probiotics on incident ventilator-associated pneumonia in critically Ill patients. JAMA. 2021;326:1024. Available from:

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Reignier J, Plantefeve G, Mira J-P, Argaud L, Asfar P, Aissaoui N, et al. Low versus standard calorie and protein feeding in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3). Lancet Respir Med. 2023;11:602–12. Available from: Cited 2023 Sep 27.

    Article  PubMed  CAS  Google Scholar 

  26. Matejovic M, Huet O, Dams K, Elke G, Vaquerizo Alonso C, Csomos A, et al. Medical nutrition therapy and clinical outcomes in critically ill adults: a European multinational, prospective observational cohort study (EuroPN). Crit Care. 2022;26:143. Available from: Cited 2022 Aug 5.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Pardo E, Lescot T, Preiser J-C, Massanet P, Pons A, Jaber S, et al. Association between early nutrition support and 28-day mortality in critically ill patients: the FRANS prospective nutrition cohort study. Crit Care. 2023;27:7. Available from: Cited 2023 Sep 27.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Ford AL, Nagulesapillai V, Piano A, Auger J, Girard S-A, Christman M, et al. Microbiota stability and gastrointestinal tolerance in response to a high-protein diet with and without a prebiotic, probiotic, and synbiotic: a randomized, double-blind, placebo-controlled trial in older women. J Acad Nutri Diet. 2020;120:500-516.e10. Available from:

    Article  Google Scholar 

  29. Majid HA, Cole J, Emery PW, Whelan K. Additional oligofructose/inulin does not increase faecal bifidobacteria in critically ill patients receiving enteral nutrition: A randomised controlled trial. Clin Nutr. 2014;33(6):966-72.

  30. Howlett John F, Betteridge Victoria A, Champ M, Craig Stuart AS, Meheust A, Jones JM. The definition of dietary fiber – discussions at the Ninth Vahouny Fiber Symposium: building scientific agreement. Food Nutri Res. 2010;54:5750. Available from: Cited 2022 Dec 1.

    Article  Google Scholar 

  31. Haghighat N, Mohammadshahi M, Shayanpour S, Haghighizadeh MH. Effects of synbiotics and probiotics supplementation on serum levels of endotoxin, heat shock protein 70 antibodies and inflammatory markers in hemodialysis patients: a randomized double-blinded controlled trial. Probiotics Antimicrob Proteins. 2020;12:144–51. Available from:

    Article  PubMed  CAS  Google Scholar 

  32. Wang H, He C, Liu Y, Zhao H, Long L, Gai X, et al. Soluble dietary fiber protects intestinal mucosal barrier by improving intestinal flora in a murine model of sepsis. Biomed Pharmacother. 2020;129:110343. Available from: Cited 2022 Oct 2.

    Article  PubMed  CAS  Google Scholar 

  33. Liu T, Wang C, Wang Y, Wang L, Ojo O, Feng Q, et al. Effect of dietary fiber on gut barrier function, gut microbiota, short-chain fatty acids, inflammation, and clinical outcomes in critically ill patients: A systematic review and meta-analysis. J Parenter Enteral Nutr. 2022;46:997–1010.

    Article  CAS  Google Scholar 

  34. Di Caro V, Cummings JL, Alcamo AM, Piganelli JD, Clark RSB, Morowitz MJ, et al. Dietary cellulose supplementation modulates the immune response in a murine endotoxemia model. Shock. 2019;51:526–34. Available from: Cited 2022 Nov 11.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Zhang Y, Dong A, Xie K, Yu Y. Dietary supplementation with high fiber alleviates oxidative stress and inflammatory responses caused by severe sepsis in mice without altering microbiome diversity. Front Physiol. 2019;9:1929. Available from: Cited 2022 Oct 2.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Di Caro V, Alcamo AM, Cummings JL, Clark RSB, Novak EA, Mollen KP, et al. Effect of dietary cellulose supplementation on gut barrier function and apoptosis in a murine model of endotoxemia. PLoS One. 2019;14:e0224838. Available from: Cited 2022 Oct 2.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Asahara T, Takahashi A, Yuki N, Kaji R, Takahashi T, Nomoto K. Protective Effect of a Synbiotic against Multidrug-Resistant Acinetobacter baumannii in a Murine Infection Model. Antimicrob Agents Chemother. 2016;60:3041–50. Available from:

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Napier BA, Andres-Terre M, Massis LM, Hryckowian AJ, Higginbottom SK, Cumnock K, et al. Western diet regulates immune status and the response to LPS-driven sepsis independent of diet-associated microbiome. Proc Natl Acad Sci USA. 2019;116:3688–94. Available from: Cited 2022 Oct 2.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Jain PK, McNaught CE, Anderson ADG, MacFie J, Mitchell CJ. Influence of synbiotic containing Lactobacillus acidophilus La5, Bifidobacterium lactis Bb 12, Streptococcus thermophilus, Lactobacillus bulgaricus and oligofructose on gut barrier function and sepsis in critically ill patients: a randomised controlled trial. Clin Nutr. 2004;23:467–75. Available from:

    Article  PubMed  Google Scholar 

  40. Spapen H, Diltoer M, van Malderen C, Opdenacker G, Suys E, Huyghens L. Soluble fiber reduces the incidence of diarrhea in septic patients receiving total enteral nutrition: a prospective, double-blind, randomized, and controlled trial. Clin Nutr. 2001;20:301–5.

    Article  PubMed  CAS  Google Scholar 

  41. Caparrós T, Lopez J, Grau T. Early enteral nutrition in critically III patients with a high-protein diet enriched with arginine, fiber, and antioxidants compared with a standard high-protein diet. The effect on nosocomial infections and outcome. JPEN J Parenter Enteral Nutr. 2001;25:299–309.

    Article  PubMed  Google Scholar 

  42. Knight DJW, Gardiner D, Banks A, Snape SE, Weston VC, Bengmark S, et al. Effect of synbiotic therapy on the incidence of ventilator associated pneumonia in critically ill patients: a randomised, double-blind, placebo-controlled trial. Intensive Care Med. 2009;35:854–61. Available from:

    Article  PubMed  Google Scholar 

  43. Seifi N, Sedaghat A, Nematy M, Khadem-Rezaiyan M, Shirazinezhad R, Ranjbar G, et al. Effects of synbiotic supplementation on the serum endotoxin level, inflammatory status, and clinical outcomes of adult patients with critical illness: A randomized controlled trial. Nut in Clin Prac. 2022;37:451–8.

    Article  CAS  Google Scholar 

  44. Sethi A, Eggers S, Mares J, Christensen K, Gangnon R, Suen G, et al. 2582. The association between dietary fiber and diet and gut colonization with clostridium difficile. Open Forum Infect Dis. 2019;6:S897–S897. Available from: Cited 2022 Nov 10.

    Article  PubMed Central  Google Scholar 

  45. Schnizlein MK, Vendrov KC, Edwards SJ, Martens EC, Young VB. Dietary Xanthan Gum Alters Antibiotic Efficacy against the Murine Gut Microbiota and Attenuates Clostridioides difficile Colonization. mSphere. 2020;5:e00708-19. Available from:

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Venegas-Borsellino C, Kwon M. Impact of Soluble Fiber in the Microbiome and Outcomes in Critically Ill Patients. Curr Nutr Rep. 2019;8:347–55. Available from: Cited 2022 Aug 17.

    Article  PubMed  Google Scholar 

  47. Patel JJ, Rice T, Heyland DK. Safety and outcomes of early enteral nutrition in circulatory shock. J Parenter Enteral Nutri. 2020;44:779–84. Available from:

    Article  Google Scholar 

  48. O’Keefe SJD. The Need to Reassess Dietary Fiber Requirements in Healthy and Critically Ill Patients. Gastroenterol Clin North Am. 2018;47:219–29. Available from: Cited 2022 Dec 1.

    Article  PubMed  PubMed Central  Google Scholar 

Download references


We thank the Free Statistics team for providing technical assistance and valuable data analysis and visualization tools. We thank Dr. Qilin Yang (The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China), Dr. Jie Liu (Department of Vascular and Endovascular Surgery, Chinese PLA General Hospital, Beijing, China) for their help in the review and comments regarding the manuscript. In addition, Xiaoyan Wang especially wishes to thank all members of the team of Clinical Scientists who have given her powerful spiritual support and encouragement.


The authors declare that they have no funding.

Author information

Authors and Affiliations



Xiaoyan Wang and Shuchuan Miao participated in the design of research schemes, extracted and analyzed the data, and wrote the main manuscript text. Qilin Yang reviewed the manuscript and provided statistical technical support. Hongliang extracted data, and Yuanwei Yang collated the data. De jiao Meng participated in the design of research schemes. All authors contributed to the article and approved the submitted version.

Corresponding author

Correspondence to Shuchuan Miao.

Ethics declarations

Ethics approval and consent to participate

The studies involving human participants were reviewed and approved by the Massachusetts Institute of Technology and Beth Israel Deaconess Medical Center. This study did not require informed consent for participation following the national legislation and institutional requirements.

Consent for publication

Non applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1: sTable 1.

Specifications and nutrients in MIMIC IV 2.1 Database.

Additional file 2:

sTable. Subgroup analysis of 28-day mortality.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, X., Miao, S., Yang, Y. et al. Association of early dietary fiber intake and mortality in septic patients with mechanical ventilation based on MIMIC IV 2.1 database: a cohort study. Nutr J 23, 1 (2024).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: