Effects of probiotic treatment on the prognosis of patients with sepsis: a systematic review

doi:10.5847/wjem.j.1920-8642.2025.018

Abstract

Abstract:

BACKGROUND Sepsis, a common acute and critical disease, leads to 11 million deaths annually worldwide. Probiotics are living microorganisms that are beneficial to the host and may benefit sepsis outcomes, but their effects are still inconclusive. This study aimed to evaluate the overall effect of probiotics on the prognosis of patients with sepsis.

DATA RESOURCES: We searched several sources for published/presented studies, including PubMed, EMBASE, Web of Science, the Cochrane Library and the US National Library of Medicine Clinical Trials Register (www.clinicaltrials.gov) updated through July 30, 2023, to identify all relevant randomized controlled trials (RCTs) or observational studies that assessed the effectiveness of probiotics or synbiotics in patients with sepsis and reported mortality. We focused primarily on mortality during the study period and analyzed secondary outcomes, including 28-day mortality, in-intensive care unit (ICU) mortality and other outcomes.

RESULTS: Data from 405 patients in five RCTs and 108 patients in one cohort study were included in the analysis. The overall quality of the studies was satisfactory, but clinical heterogeneity existed. All adult studies reported a tendency for probiotics to reduce the mortality of patients with sepsis, and most studies reported a decreasing trend in the incidence of infectious complications, length of ICU stay and duration of antibiotic use. There was only one RCT involving children.

CONCLUSION: Probiotics show promise for improving the prognosis of patients with sepsis, including reducing mortality and the incidence of infectious complications, particularly in adult patients. Despite the limited number of studies, especially in children, these findings will be encouraging for clinical practice in the treatment of sepsis and suggest that gut microbiota-targeted therapy may improve the prognosis of patients with sepsis.

Key words: Sepsis, Probiotics, Synbiotics, Mortality, Gut microbiota

Chao Gong, Shengyong Xu, Youlong Pan, Shigong Guo, Joseph Harold Walline, Xue Wang, Xin Lu, Shiyuan Yu, Mubing Qin, Huadong Zhu, Yanxia Gao, Yi Li. Effects of probiotic treatment on the prognosis of patients with sepsis: a systematic review[J]. World Journal of Emergency Medicine, 2025, 16(1): 18-27.

Figures/Tables 4

Figure 1.

Table 1.

Summary characteristics of the five RCTs and one cohort study evaluating probiotics in patients with sepsis

Study	Population				Control	Intervention
Study	Inclusion criteria	Intervention /control	Male/female	Median or mean age	Control	Intervention	Probiotic strains	Dose	Duration
Barraud et al^[17] 2010	Adult patients with severe sepsis mechanically ventilated for a period of more than 48 h	52/49	41/60	60.75 years	EN+placebo	EN+probiotics	Mainly L. rhamnosus GG (but also L. casei, L. acidophilus, and B. bifidum)	2×10¹⁰ CFU of probiotics, QD	The entire period of mechanical ventilation until successful weaning (≤28 d)
Shimizu et al^[18] 2018	Patients with sepsis older than 16 years and mechanically ventilated within 3 d after admission to ICU	35/37	47/25	74.00 years	EN using a standard polymeric diet	A standard polymeric diet+ synbiotics	B. breve strain+ L. casei strain	6 × 10⁸ CFU of probiotics +10 g of prebiotics (galactooligosaccharides), QD	The period from the beginning of enteral nutrition to the beginning of oral intake
Angurana et al^[16] 2018	Children aged 3 months to 12 years old with severe sepsis	50/50	60/40	3.65 years	Routine and standard treatment +placebo	Routine and standard treatment+ probiotics	L. paracasei DSM 24734 + L. plantarum DSM 24730 + L. acidophilus DSM 24735 + L. delbrueckii subsp. bulgaricus DSM 24734 + B. longum DSM 24736 + B. infantis DSM 24737 + B. breve DSM 24732 + S. thermophilus DSM 24731	450×10¹⁰CFU viable lyophilized bacteria, BID	7 d
Chávez-Íñiguez et al^[29] 2023	Adult patients with sepsis-induced AKI (≥18 years old)	48/44	45/47	56.90 years	Placebo	Synbiotics	S. thermophilus + L. acidophilus+ B. longum	90 ×10¹⁰ CFU of probiotics + 600 mg of prebiotics (agave inulin), QD	7 d
Mahmoodpoor et al^[19] 2023	Critically ill patients diagnosed with sepsis and fed enterally (18-70 years old)	20/20	23/17	59.23 years	Routine and standard treatment + placebo	Routine and standard treatment+ probiotics	L. species (casei, acidophilus, rhamnosus, bulgaricus) + B. species (breve, longum) + S. thermophilus	10¹⁰ of probiotics, BID	10 d
Xie et al^[15] 2023^*	Senile patients with sepsis (age ≥60 years old)	58/50	61/47	71.90 years	EEN	EEN + probiotics	B. longum + L. acidophilus + Enterococcus faecalis	≥1.89×10⁶ CFU of living bacteria, TID	14 d

Table 1.

Table 2.

Figure 2.

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Study	Mortality, n (%)								Infectious complications, n (%)						Other outcomes, day, mean±SD
	Mortality during the study period		28-day mortality		In-ICU mortality		90-day mortality		VAP		Enteritis (or diarrhea)		Bacteremia		Length of ICU stay		Antibiotics duration
	I	C	I	C	I	C	I	C	I	C	I	C	I	C	I	C	I	C
Barraud et al^[17] 2010	13 (25.0)	20 (40.8)	9 (17.3)	18 (36.7)	10 (19.2)	18 (36.7)	13 (25.0)	20 (40.8)	15 (28.8)	7 (14.2)	29 (55.7)	25 (51.0)	0 (0)	8 (16.3)	18.4±10.6	19.7±16.2	NR	NR
Shimizu et al^[18] 2018	3 (8.6)	4 (10.8)	3 (8.6)	4 (10.8)	NR	NR	NR	NR	5 (14.3)	18 (48.6)	2 (6.3)	10 (27.0)	5 (14.3)	5 (13.5)	26.6±23.2^b	30.1±21.6^b	15.1±12.4^b	18.7±13.9^b
Angurana et al^[16] 2018	6 (12)	5 (10)	6 (12)	5 (10)	NR	NR	NR	NR	3 (6)	2 (4)	NR	NR	2 (4)	5 (10)	7.2±5.3^b	8.6±3.8^b	7.9±4.6^b	8.4±2.3^b
Chávez-Íñiguez et al^[29] 2023	18 (37)	27 (61)	13 (27)^a	17 (38)^a	NR	NR	18 (37.5)^a	24 (54.6)^a	NR	NR	6 (12.5)	9 (20.5)	NR	NR	NR	NR	NR	NR
Mahmoodpoor et al^[19] 2023	4 (20)	6 (30)	NR	NR	4 (20)	6 (30)	NR	NR	NR	NR	0 (0)	7 (35)	NR	NR	12.0±2.8^b	13.7±4.4^b	NR	NR
Xie et al^[15] 2023*	1 (1.72)	4 (8)	1 (1.72)	4 (8)	NR	NR	NR	NR	NR	NR	NR	NR	NR	NR	NR	NR	NR	NR

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