Comparison of Continuous Feeding and Sequential Feeding on Gut Microbiota and Metabolomics in Critically Ill Patients

Study Overview
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Brief Summary
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Continuous feeding is the most popular enteral feeding mode in the ICU because of its lower nursing burden and theoretically better intestinal toleration. However, continuous feeding is nonphysiological. We proposed a feeding mode called sequential feeding, as it utilizes a combination of continuous feeding in the beginning, time-restricted feeding in the second stage, and oral feeding at last. The gut microbiota plays a critical role in human health due to its many useful functions. Not only dietary structure but also eating mode (eating time for example) influenced the gut microbiota in a healthy population. Therefore, we think this new feeding mode, sequential feeding, also has different influences on gut microbiota and metabolomics in critically ill patients compared to continuous feeding.

Detailed Description
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Nutrition is an important part of therapy for critically ill patients. Continuous feeding is the most popular enteral feeding mode in the ICU because of its lower nursing burden and theoretically better intestinal toleration. However, continuous feeding is nonphysiological. In our opinion, feeding mode should be changed according to gastrointestinal function and disease progression; one singe feeding mode is not always suitable for critically ill patients. We proposed a feeding mode called sequential feeding, as it utilizes a combination of continuous feeding in the beginning, time-restricted feeding in the second stage, and oral feeding at last. The gut microbiota plays a critical role in human health due to its many useful functions, such as metabolism, vitamin metabolism, and maintenance of the intestinal barrier and immune system. Not only dietary structure but also eating mode (eating time for example) influenced the gut microbiota in a healthy population. Therefore, we think this new feeding mode, sequential feeding, also has different influences on gut microbiota and metabolomics in critically ill patients compared to continuous feeding.

Official Title
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Comparison of Continuous Feeding and Sequential Feeding on Gut Microbiota and Metabolomics in Critically Ill Patients

Conditions
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Feeding Behavior

Intervention / Treatment
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* Behavioral: continous feeding
* Behavioral: sequential feeding


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ●Patients newly admitted to the ICU and fed through gastric tubes Exclusion Criteria: Patients with the ability to eat orally at admission Patients with diabetes or gastrointestinal disease Patients who are unable to tolerate enteral feeding An estimated feeding time of less than 7 days

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: continuous feeding<br>The total amount of every days' Enteral Nutritional Suspension was fed at constant speed for 24h | Behavioral: continous feeding<br>* At the beginning, all the patients received continuous feeding. After achieving ≥80% of the nutrition target calories (25-30 kcal/kg/d) through continuous feeding, the patients were randomly assigned into the sequential feeding (SF) group or the continuous feeding (CF) group with a random number table. Patients in the CF group received continuous feeding with constant velocity by enteral feeding pump over one day.<br>|
| Experimental: sequential feeding<br>This feeding mode utilizes a combination of continuous feeding in the beginning, time-restricted feeding in the second stage and oral feeding in the last stage | Behavioral: sequential feeding<br>* At the beginning, all the patients received continuous feeding. After achieving ≥80% of the nutrition target calories (25-30 kcal/kg/d) through continuous feeding, the patients were randomly assigned into the sequential feeding (SF) group or the continuous feeding (CF) group with a random number table. In the SF group, continuous feeding was changed into time-restricted feeding. The total daily dosage of enteral nutrition was equally distributed during three time periods at 7-9:00, 11-13:00 and 17-19:00. Other times of the day were fasting times. Enteral nutritional suspension in each time period was administered at a uniform rate within two hours by an enteral feeding pump.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Shannon index | Shannon index is a paramater of α diversity in gut microbiota Full-length 16S rRNA gene sequencing analysis using QIIME software | at the time point of 7th feeding day after achieving ≥80% of the nutrition target calories | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| bacteria bundance | It is a paramater of amount of bactera by Full-length 16S rRNA gene sequencing analysis using QIIME software | at the time point of 7th feeding day after achieving ≥80% of the nutrition target calories | 
| numbers of compounds | it is a paramater by untargeted metabolomics analysis | at the time point of 7th feeding day after achieving ≥80% of the nutrition target calories |