Gut barrier dysfunction and multidrug-resistant bacterial translocation in adult critical illness: Mechanistic insights from a systematic review

Table 1 Characteristics of included clinical studies evaluating gut barrier dysfunction and multidrug-resistant bacterial translocation in critically ill adults

Ref.	Country	Study design	ICU population	Organism/focus	Key findings
Thom et al[22], 2010	United States	Observational cohort	ICU patients	Acinetobacter baumannii	Identical strains detected in GI colonization and bloodstream infection
Jung et al[20], 2010	South Korea	Cohort	ICU patients	MDR Acinetobacter baumannii	Colonization associated with increased risk of bacteraemia
Giannella et al[17], 2014	Italy	Prospective multicentre cohort	Rectal carriers	CRKP	Rectal colonization strongly predicted subsequent bacteraemia
Giacobbe et al[19], 2017	Italy	Multicentre retrospective cohort	Colonized patients	CRKP	Prior infections predicted CRKP bacteraemia
Freedberg et al[11], 2018	United States	Prospective observational study	ICU patients	Gastrointestinal microbiome colonization	GI pathogen colonization at ICU admission associated with subsequent infection and mortality
Amberpet et al[21], 2018	India	Prospective study	Pediatric ICU patients	Vancomycin-resistant enterococci	Intestinal colonization identified as a major risk factor for MDR transmission
Zaborin et al[12], 2014	United States	Microbiome observational study	Critically ill patients	Gut pathogen communities	Ultra-low-diversity gut microbiota associated with pathogen domination during critical illness
Silago et al[29], 2020	Tanzania	Observational cohort	Critical care patients	MDR Gram-negative bacteria	Colonization and environmental contamination contributed to bacteraemia
Padar et al[31], 2021	Estonia	Prospective ICU study	ICU patients	Citrulline/I-FABP	Biomarkers reflected intestinal injury in critical illness
Reintam Blaser et al[33], 2021	Multicentre Europe	Prospective observational study	Critically ill patients	GI dysfunction	Developed gastrointestinal dysfunction scoring system
Chu et al[16], 2022	China	Prospective cohort	ICU patients	CRE	Rectal colonization significantly associated with bloodstream infection
Garcia et al[13], 2022	Spain	Prospective cohort	ICU patients	MDR bacteria/microbiome	Gut microbiome disruption associated with MDR colonization
Mu et al[23], 2022	China	Molecular cohort study	Septic patients	Gut–blood pathogen concordance	Bloodstream pathogens genetically matched gut strains
Falcone et al[41], 2022	Italy	Observational cohort	Severe COVID-19 ICU patients	MDR Klebsiella pneumoniae	Hypervirulent MDR strains spread in ICU population
Baek et al[14], 2023	South Korea	Microbiome analysis	ICU patients	CRE	Dysbiosis associated with CRE colonization
Casale et al[40], 2023	Italy	Cohort study	Hospitalized COVID-19 ICU patients	Carbapenem-resistant organisms	Colonization increased mortality and infection risk
Onuk et al[34], 2023	Turkey	Prospective cohort	ICU patients	Citrulline/I-FABP	Biomarkers correlated with gastrointestinal dysfunction
Tyszko et al[35], 2023	Poland	Observational study	Septic ICU patients	Citrulline/I-FABP	Biomarkers predicted gastrointestinal failure
Molinari et al[25], 2025	International multicentre	Prospective observational study	Septic shock patients	Endotoxin activity	Higher endotoxin activity associated with organ failure and mortality
Yang et al[15], 2025	China	Microbiome study	ICU patients	CRKP	Microbiome diversity associated with colonization resistance
Favier et al[18], 2026	Argentina	Prospective surveillance study	ICU patients	Carbapenem-resistant Enterobacterales	Rectal and extra-rectal colonization predicted subsequent infection
Fang et al[28], 2025	China	Molecular epidemiological study	Hospitalized patients	CRKP	Colonizing and bloodstream isolates showed plasmid and genotypic concordance
Nguyen et al[37], 2025	France	Prospective clinical study	Septic/peritonitis patients	Endotoxin burden/HDL	HDL levels associated with reduced endotoxin burden in sepsis
Lyu et al[27], 2026	China	Prospective cohort	ICU patients	CRE	Genotypic concordance between colonizing and infecting strains

ICU: Intensive care units; ESBL: Extended-spectrum beta-lactamase; GI: Gastrointestinal; MDR: Multidrug-resistant; CRKP: Carbapenem-resistant Klebsiella pneumoniae; I-FABP: Intestinal fatty acid-binding protein; HDL: High-density lipoprotein; CRE: Carbapenem-resistant Enterobacteriaceae; COVID-19: Coronavirus disease 2019.

Table 2 Clinical studies evaluating the association between intestinal colonization and subsequent bloodstream infection in critically ill patients

Ref.	Country	Study design			Population		Pathogen		Colonization site		Progression to infection		Key finding
Thom et al[22], 2010	United States	Observational study			ICU patients		Acinetobacter baumannii		GI tract		Identical strains detected		GI colonization matched bloodstream isolates
Jung et al[20], 2010	South Korea	Cohort			ICU patients		MDR Acinetobacter baumannii		Gastrointestinal tract		Increased risk of bacteraemia		Colonization independently predicted bloodstream infection
Giannella et al[17], 2014	Italy	Prospective multicentre cohort			ICU patients with rectal colonization		CRKP		Rectal		Approximately 20%-40% bacteraemia		Rectal carriage strongly predicted CRKP bloodstream infection
Giacobbe et al[19], 2017	Italy	Multicentre retrospective cohort			Colonized patients		CRKP		Rectal		Increased bacteraemia risk		Previous infections predicted CRKP bacteraemia
Freedberg et al[11], 2018	United States	Prospective observational study			ICU patients		MDR gut pathogens		Gastrointestinal microbiome		Increased infection and mortality risk		GI pathogen colonization at ICU admission predicted adverse outcomes
Amberpet et al[21], 2018	India	Prospective study			Pediatric ICU patients		Vancomycin-resistant enterococci		Intestinal tract		Increased colonization risk		Intestinal colonization facilitated MDR persistence and transmission
Silago et al[29], 2020	Tanzania	Observational cohort			Critical care patients		MDR Gram-negative bacteria		GI/environmental		Transmission linked to bacteraemia		Colonization and cross-transmission contributed to infection
Chu et al[16], 2022	China	Prospective cohort			ICU patients		CRE		Rectal		Approximately 15%-30% progression		Colonization associated with subsequent infection
Mu et al[23], 2022	China	Molecular cohort			Septic ICU patients		Various pathogens		Gut microbiome		High strain concordance		Bloodstream pathogens genetically matched gut strains
Casale et al[40], 2023	Italy	Cohort study			COVID-19 ICU patients		Carbapenem-resistant organisms		Gastrointestinal/respiratory		Increased mortality and infection risk		Colonization associated with superinfection and adverse outcomes
Fang et al[28], 2025	China	Molecular epidemiological study			Hospitalized patients		CRKP		Gastrointestinal tract		Genotypic concordance observed		Colonizing and infecting strains shared homologous resistance plasmids
Lyu et al[27], 2026	China		Prospective cohort	ICU patients		CRE		Rectal		Significant progression observed		Colonizing and infecting isolates showed genotypic concordance
Favier et al[18], 2026	Argentina		Prospective surveillance study	ICU patients		Carbapenem-resistant Enterobacterales		Rectal and extra-rectal		Increased infection risk		Surveillance cultures predicted subsequent CRE infection

ICU: Intensive care units; COVID-19: Coronavirus disease 2019; GI: Gastrointestinal; MDR: Multidrug-resistant; CRKP: Carbapenem-resistant Klebsiella pneumoniae; CRE: Carbapenem-resistant Enterobacteriaceae.

Table 3 Biomarker and microbiome evidence associated with intestinal barrier dysfunction in critically ill patients

Ref.	Country	Study design	Population	Biomarker/method	Key findings	Clinical implication
Wijnands et al[9], 2015	Netherlands	Review/clinical synthesis	Sepsis patients	Citrulline metabolism	Reduced citrulline associated with enterocyte dysfunction	Marker of intestinal barrier injury
Blaser et al[10], 2019	Europe	Observational clinical study	Critically ill patients	Citrulline, I-FABP	Low citrulline and elevated I-FABP associated with GI dysfunction	Biomarkers of mucosal injury
Padar et al[31], 2021	Estonia	Prospective ICU study	ICU patients	Citrulline, I-FABP	Dynamic changes correlated with enteral nutrition and gut injury	Monitoring intestinal function
Reintam Blaser et al[33], 2021	Multicentre Europe	Prospective multicentre study	Critically ill patients	GI Dysfunction Score	Developed standardized scoring for GI dysfunction	Clinical assessment tool
Garcia et al[13], 2022	Spain	Prospective cohort	ICU patients	Gut microbiome sequencing	Reduced diversity associated with MDR colonization and infection	Dysbiosis associated with increased infection risk
Onuk et al[34], 2023	Turkey	Prospective cohort	ICU patients	Citrulline, I-FABP, gastric ultrasound	Biomarkers correlated with gastrointestinal injury	Early detection of GI dysfunction
Tyszko et al[35], 2023	Poland	Observational cohort	Septic ICU patients	Citrulline, I-FABP	Biomarkers associated with severity of gastrointestinal injury	Prognostic markers
Baek et al[14], 2023	South Korea	Microbiome analysis	ICU patients	Microbiome sequencing	CRE colonization associated with microbiome disruption	Loss of colonization resistance
Yang et al[15], 2025	China	Microbiome study	ICU patients	Microbiome diversity analysis	Preserved microbiome diversity associated with reduced CRKP colonization	Microbiome-mediated resistance

I-FABP: Intestinal fatty acid-binding protein; GI: Gastrointestinal; ICU: Intensive care units; MDR: Multidrug-resistant; CRE: Carbapenem-resistant Enterobacteriaceae; CRKP: Carbapenem-resistant Klebsiella pneumoniae.