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Critically ill patients admitted to the intensive care unit (ICU) frequently present with gastrointestinal dysfunction and are at elevated risk of malnutrition. Gastrointestinal dysfunction is correlated with adverse clinical outcomes, including prolonged mechanical ventilation duration, extended ICU length of stay, and increased 90-day mortality.
In critically ill ICU patients, severe gut microbiota dysbiosis and intestinal barrier impairment may occur due to the burden of primary critical illnesses, as well as the administration of proton pump inhibitors and antibiotics. This cascade contributes to a high prevalence of gastrointestinal dysfunction, alongside profound gut-derived systemic inflammatory responses and organ damage. Given the pivotal role of gut microbiota in maintaining intestinal homeostasis, fecal microbiota transplantation (FMT) holds promise as a novel therapeutic strategy for enteral feeding intolerance secondary to gastrointestinal dysfunction in critically ill ICU patients.
This study intends to deliver FMT via a nasojejunal tube to critically ill patients with gastrointestinal dysfunction admitted to the ICU. Its objectives are to evaluate the intervention's effects on gastrointestinal function recovery and the alleviation of enteral feeding intolerance, while also assessing its impacts on intestinal barrier function, gut microbiota composition and metabolic profiles, serum metabolite signatures, immune-inflammatory responses (including lymphocyte subsets, cytokines, C-reactive protein, and procalcitonin), ICU delirium, ICU sleep quality, and clinical outcomes (encompassing ICU mortality, in-hospital mortality, 28-day all-cause mortality, 90-day all-cause mortality, 90-day readmission rate, and 90-day incidence of secondary infections).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control group | No Intervention | Patients received standard ICU care. | |
| FMT intervention group | Experimental | Patients received FMT via a nasojejunal tube in addition to standard ICU care. Specifically, 50-100 mL of intestinal microbiota suspension was administered daily via the nasojejunal tube between 11:00 and 13:00 for three consecutive days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fecal microbiota transplantation (FMT) | Other | Patients received FMT via a nasojejunal tube in addition to standard ICU care. Specifically, 50-100 mL of intestinal microbiota suspension was administered daily via the nasojejunal tube between 11:00 and 13:00 for three consecutive days. |
| Measure | Description | Time Frame |
|---|---|---|
| Enteral nutrition FI improvement rate | 24, 48, 72, 96, and 120 hours after study enrollment |
| Measure | Description | Time Frame |
|---|---|---|
| Gut microbiota composition as well as α and β diversity measured from rectal swabs by 16S rRNA gene sequencing | 24-0 hours and 120 hours after study enrollment | |
| Fecal metabolite profile (by untargeted LC-MS) from rectal swabs | 24-0 hours and 120 hours after study enrollment |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jiancheng Zhang | Contact | +86-13554105815 | zhjcheng1@126.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Union Hospital, Tongji Medical College, Huazhong University of Science and Technology | Wuhan | Hubei | 460022 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27459152 | Background | Uhde M, Ajamian M, Caio G, De Giorgio R, Indart A, Green PH, Verna EC, Volta U, Alaedini A. Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease. Gut. 2016 Dec;65(12):1930-1937. doi: 10.1136/gutjnl-2016-311964. Epub 2016 Jul 25. | |
| 36397118 | Background |
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|
| Serum metabolite profile (by untargeted LC-MS) | 24-0 hours and 120 hours after study enrollment |
| Serum level of citrulline | 0, 24, 48, 72, 96, and 120 hours after study enrollment |
| APACHE II score | 0, 24, 48, 72, 96, and 120 hours after study enrollment |
| SOFA score | 0, 24, 48, 72, 96, and 120 hours after study enrollment |
| Cumulative intravenous dose of vasopressor agents (including norepinephrine, epinephrine, dobutamine, etc.) | 0, 24, 48, 72, 96, and 120 hours after study enrollment |
| Serum level of C-reactive protein | 0, 24, 48, 72, 96, and 120 hours after study enrollment |
| Serum level of procalcitonin | 0, 24, 48, 72, 96, and 120 hours after study enrollment |
| Peripheral blood level of cytokines (including IL-6, IL-17, TNF-α, IL-10, IL-1β, etc.) | 0 and 120 hours after study enrollment |
| Peripheral blood lymphocyte subsets (including CD4+ T, CD8+ T, B lymphocytes, NK cells, etc.) | 0, 24, 48, 72, 96, and 120 hours after study enrollment |
| ICU mortality | Within 28 days after study enrollment |
| In-hospital mortality | Within 60 days after study enrollment |
| 28-day all-cause mortality | Within 28 days after study enrollment |
| 90-day all-cause mortality | Within 90 days after study enrollment |
| 90-day readmission rate | Within 90 days after study enrollment |
| 90-day secondary infection rate | Within 90 days after study enrollment |
| Heming N, Carlier R, Prigent H, Mekki A, Jousset C, Lofaso F, Ambrosi X, Bounab R, Maxime V, Mansart A, Crenn P, Moine P, Foltzer F, Cuenoud B, Konz T, Corthesy J, Beaumont M, Hartweg M, Roessle C, Preiser JC, Breuille D, Annane D. Effect of an enteral amino acid blend on muscle and gut functionality in critically ill patients: a proof-of-concept randomized controlled trial. Crit Care. 2022 Nov 17;26(1):358. doi: 10.1186/s13054-022-04232-5. |
| 21400011 | Background | Piton G, Manzon C, Cypriani B, Carbonnel F, Capellier G. Acute intestinal failure in critically ill patients: is plasma citrulline the right marker? Intensive Care Med. 2011 Jun;37(6):911-7. doi: 10.1007/s00134-011-2172-x. Epub 2011 Mar 12. |
| 38717124 | Background | Yadegar A, Bar-Yoseph H, Monaghan TM, Pakpour S, Severino A, Kuijper EJ, Smits WK, Terveer EM, Neupane S, Nabavi-Rad A, Sadeghi J, Cammarota G, Ianiro G, Nap-Hill E, Leung D, Wong K, Kao D. Fecal microbiota transplantation: current challenges and future landscapes. Clin Microbiol Rev. 2024 Jun 13;37(2):e0006022. doi: 10.1128/cmr.00060-22. Epub 2024 May 8. |
| 29432297 | Background | McClave SA, Patel J, Bhutiani N. Should fecal microbial transplantation be used in the ICU? Curr Opin Crit Care. 2018 Apr;24(2):105-111. doi: 10.1097/MCC.0000000000000489. |
| 36009962 | Background | Beyi AF, Wannemuehler M, Plummer PJ. Impacts of Gut Microbiota on the Immune System and Fecal Microbiota Transplantation as a Re-Emerging Therapy for Autoimmune Diseases. Antibiotics (Basel). 2022 Aug 12;11(8):1093. doi: 10.3390/antibiotics11081093. |
| 33239790 | Background | Schluter J, Peled JU, Taylor BP, Markey KA, Smith M, Taur Y, Niehus R, Staffas A, Dai A, Fontana E, Amoretti LA, Wright RJ, Morjaria S, Fenelus M, Pessin MS, Chao NJ, Lew M, Bohannon L, Bush A, Sung AD, Hohl TM, Perales MA, van den Brink MRM, Xavier JB. The gut microbiota is associated with immune cell dynamics in humans. Nature. 2020 Dec;588(7837):303-307. doi: 10.1038/s41586-020-2971-8. Epub 2020 Nov 25. |
| 35472097 | Background | Arunachala Murthy T, Chapple LS, Lange K, Marathe CS, Horowitz M, Peake SL, Chapman MJ. Gastrointestinal dysfunction during enteral nutrition delivery in intensive care unit (ICU) patients: Risk factors, natural history, and clinical implications. A post-hoc analysis of The Augmented versus Routine approach to Giving Energy Trial (TARGET). Am J Clin Nutr. 2022 Aug 4;116(2):589-598. doi: 10.1093/ajcn/nqac113. |
| 17663503 | Background | Deane A, Chapman MJ, Fraser RJ, Bryant LK, Burgstad C, Nguyen NQ. Mechanisms underlying feed intolerance in the critically ill: implications for treatment. World J Gastroenterol. 2007 Aug 7;13(29):3909-17. doi: 10.3748/wjg.v13.i29.3909. |
| 17095943 | Background | Nguyen NQ, Fraser RJ, Chapman MJ, Bryant LK, Holloway RH, Vozzo R, Wishart J, Feinle-Bisset C, Horowitz M. Feed intolerance in critical illness is associated with increased basal and nutrient-stimulated plasma cholecystokinin concentrations. Crit Care Med. 2007 Jan;35(1):82-8. doi: 10.1097/01.CCM.0000250317.10791.6C. |
| ID | Term |
|---|---|
| D000069467 | Fecal Microbiota Transplantation |
| ID | Term |
|---|---|
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
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