Comparison of Continuous Feeding and Sequential Feeding on Gut Microbiota and Metabolomics in 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. 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.

Study Overview

• Status: Completed
• Conditions: Feeding Behavior
• Intervention / Treatment: Behavioral: continous feeding; Behavioral: sequential feeding

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shan Dong Province
    • Qingdao, Shan Dong Province, China, 266000
      • The Affiliated Hospital of Qingdao University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: continuous feeding; The total amount of every days' Enteral Nutritional Suspension was fed at constant speed for 24h	Behavioral: continous feeding; 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.
Experimental: sequential feeding; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Qingdao University
• Investigators: Principal Investigator: Bo Yao, phD, The affiliated hospital of Qingdao

Publications and helpful links

General Publications

• Lynch SV, Pedersen O. The Human Intestinal Microbiome in Health and Disease. N Engl J Med. 2016 Dec 15;375(24):2369-2379. doi: 10.1056/NEJMra1600266. No abstract available.
• Singer P, Blaser AR, Berger MM, Alhazzani W, Calder PC, Casaer MP, Hiesmayr M, Mayer K, Montejo JC, Pichard C, Preiser JC, van Zanten ARH, Oczkowski S, Szczeklik W, Bischoff SC. ESPEN guideline on clinical nutrition in the intensive care unit. Clin Nutr. 2019 Feb;38(1):48-79. doi: 10.1016/j.clnu.2018.08.037. Epub 2018 Sep 29.
• McClave SA, Taylor BE, Martindale RG, Warren MM, Johnson DR, Braunschweig C, McCarthy MS, Davanos E, Rice TW, Cresci GA, Gervasio JM, Sacks GS, Roberts PR, Compher C; Society of Critical Care Medicine; American Society for Parenteral and Enteral Nutrition. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr. 2016 Feb;40(2):159-211. doi: 10.1177/0148607115621863. No abstract available. Erratum In: JPEN J Parenter Enteral Nutr. 2016 Nov;40(8):1200.
• McDonald D, Ackermann G, Khailova L, Baird C, Heyland D, Kozar R, Lemieux M, Derenski K, King J, Vis-Kampen C, Knight R, Wischmeyer PE. Extreme Dysbiosis of the Microbiome in Critical Illness. mSphere. 2016 Aug 31;1(4):e00199-16. doi: 10.1128/mSphere.00199-16. eCollection 2016 Jul-Aug.
• Kaczmarek JL, Thompson SV, Holscher HD. Complex interactions of circadian rhythms, eating behaviors, and the gastrointestinal microbiota and their potential impact on health. Nutr Rev. 2017 Sep 1;75(9):673-682. doi: 10.1093/nutrit/nux036.

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2020
• Primary Completion (Actual): June 28, 2022
• Study Completion (Actual): June 28, 2022

Study Registration Dates

• First Submitted: June 21, 2020
• First Submitted That Met QC Criteria: June 21, 2020
• First Posted (Actual): June 23, 2020

Study Record Updates

• Last Update Posted (Actual): November 14, 2022
• Last Update Submitted That Met QC Criteria: November 9, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: QYFYKYLL761311920

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: connect to corresponding author by email after paper publication
• IPD Sharing Time Frame: connect to corresponding author by email after paper publication
• IPD Sharing Access Criteria: by appropriate reasons
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No