Preventive effect of probiotics on infections following colorectal cancer surgery: An umbrella meta-analysis

Table 1 Characteristics of the included studies

Ref.	Country	Number of included studies	Sample size	Supplementation time	Type of supplementation	Risk of bias tool, No. of high quality/total studies	Percentage of high-quality studies (%)	Investigated outcomes	Quality
Zeng et al[32], 2021	China	19	1975	Preoperative	Multi-strain Probiotics and synbiotics	Cochrane, 19/19	100	Total infections, UTIs, bacteremia, sepsis, SSIs, pneumonia, central line infection, peritoneal infection, intra-abdominal infection	High
Amitay et al[25], 2020	Germany	11	NR	Preoperative	Multi-strain Probiotics and synbiotics	NHBLI tool, 1/11	9	Total infections, sepsis	High
Rueda-Robles et al[43], 2022	Brazil	13	1535	Pre- and postoperative	Multi-strain Probiotics and synbiotics	Joanna Briggs Institute’s critical assessment tools, 2/13	15	Sepsis, SSIs, pneumonia, intra-abdominal infection	High
Ye et al[31], 2023	China	16	1798	Preoperative	Multi-strain Probiotics and synbiotics	Jadad, 16/16	100	SSIs, pneumonia	High
He et al[29], 2013	China	6	361	Preoperative	Multi-strain Probiotics and synbiotics	Jadad, 5/6	83	Total infections, sepsis, SSIs, pneumonia, peritoneal infection, abdominal infection	High
An et al[26], 2022	Korea	20	1763	Preoperative	Multi-strain Probiotics and synbiotics	Cochrane, 6/20	30	UTIs, bacteremia, SSIs, pneumonia	High
de Andrade Calaça et al[28], 2017	Brazil	7	821	Pre- and postoperative	Multi-strain Probiotics	NR	NR	Total infections, Bacteremia, SSIs	Moderate
Chen et al[27], 2020	China	6	803	Preoperative	Multi-strain Probiotics	Jadad, 6/6	100	Total infections, UTIs, sepsis, SSIs, pneumonia, central line infection	Moderate
Persson et al[30], 2024	Brazil	10	1276	Pre- and postoperative	Multi-strain Probiotics	NR	NR	UTIs, SSIs, pneumonia	Moderate
Ouyang et al[19], 2019	China	13	1186	Pre- and postoperative	Multi-strain Probiotics	Cochrane, 11/13	84	Total infections, UTIs, SSIs, pneumonia	Moderate
Chen et al[3], 2024	China	10	NR	Preoperative	Multi-strain Probiotics	Cochrane, 2/10	20	SSIs	Moderate

NR: Not reported; UTIs: Urinary tract infections; SSIs: Surgical site infection.

Table 2 Overall and stratified analyses for the impacts of probiotics on post-surgical infections in patients undergoing colorectal cancer surgery

		Subgroups	Studies	Relative risk (95%CI)	I2 (%)	P value	Publication bias
Total infections		Overall	6	0.40 (0.31-0.51)	56.1	0.04	0.31
	Supplementation type	Multi-strain Probiotics	3	0.50 (0.41-0.61)	0.0	0.39
		Multi-strain Probiotics and synbiotics	3	0.31 (0.25-0.40)	0.0	0.56
	Intervention time	Preoperative	4	0.31 (0.25-0.40)	0.0	0.77
		Pre- and postoperative	2	0.52 (0.42-0.64)	0.0	0.85
	Country	China	4	0.37 (0.26-0.52)	59.6	0.06
		Other countries	2	0.44 (0.29-0.68)	59.7	0.11
	Quality of studies	High	3	0.31 (0.25-0.40)	0.0	0.56
		Moderate	3	0.50 (0.41-0.61)	0.0	0.39
Urinary tract infections		Overall	5	0.44 (0.31-0.61)	0.0	0.66	0.009
	Supplementation type	Multi-strain Probiotics	3	0.43 (0.27-0.69)	16.2	0.30
		Multi-strain Probiotics and synbiotics	2	0.44 (0.26-0.74)	0.0	0.86
	Intervention time	Preoperative	3	0.38 (0.25-0.59)	0.0	0.57
		Pre- and postoperative	2	0.52 (0.32-0.86)	0.0	0.49
	Country	China	3	0.43 (0.27-0.59)	16.4	0.30
		Other countries	2	0.45 (0.27-0.75)	0.0	0.89
	Quality of studies	High	2	0.44 (0.26-0.74)	0.0	0.86
		Moderate	3	0.43 (0.27-0.69)	16.2	0.30
Bacteremia		Overall	3	0.41 (0.30-0.56)	0.0	0.91	0.80
	Supplementation type	Multi-strain Probiotics	1	0.40 (0.26-0.62)	-	-
		Multi-strain Probiotics and synbiotics	2	0.42 (0.27-0.67)	0.0	0.70
	Intervention time	Preoperative	2	0.42 (0.27-0.67)	0.0	0.70
		Pre- and postoperative	1	0.40 (0.26-0.62)	-	-
	Country	China	1	0.37 (0.16-0.86)	-	-
		Other countries		0.42 (0.30-0.59)	0.0	0.74
	Quality of studies	High	2	0.42 (0.27-0.67)	0.0	0.70
		Moderate	1	0.40 (0.26-0.62)	-	-
Sepsis		Overall	5	0.35 (0.25-0.44)	0.0	0.90	0.87
	Supplementation type	Multi-strain Probiotics	1	0.28 (0.17-0.47)	-	-
		Multi-strain Probiotics and synbiotics	4	0.35 (0.25-0.50)	0.0	0.92
	Intervention time	Preoperative	4	0.31 (0.23-0.43)	0.0	0.92
		Pre- and postoperative	1	0.41 (0.22-0.78)	-	-
	Country	China	3	0.31 (0.21-0.46)	0.0	0.78
		Other countries	2	0.35 (0.23-0.53)	0.0	0.52
	Quality of studies	High	4	0.35 (0.25-0.50)	0.0	0.92
		Moderate	1	0.28 (0.17-0.47)	-	-
Surgical site infection		Overall	10	0.56 (0.49-0.63)	0.0	0.71	0.94
	Supplementation type	Multi-strain Probiotics	5	0.56 (0.45-0.70)	0.0	0.70
		Multi-strain Probiotics and synbiotics	5	0.56 (0.47-0.66)	5.8	0.37
	Intervention time	Preoperative	6	0.55 (0.47-0.65)	3.2	0.39
		Pre- and postoperative	4	0.56 (0.44-0.71)	0.0	0.78
	Country	China	6	0.53 (0.44-0.63)	0.0	0.59
		Other countries	4	0.60 (0.49-0.73)	0.0	0.64
	Quality of studies	High	5	0.56 (0.47-0.66)	5.8	0.37
		Moderate	5	0.56 (0.45-0.70)	0.0	0.73
Pneumonia		Overall	8	0.38 (0.30-0.48)	0.0	0.89	0.74
	Supplementation type	Multi-strain Probiotics	3	0.61 (0.55-0.67)	5.1	0.34
		Multi-strain Probiotics and synbiotics	5	0.36 (0.26-0.49)	0.0	0.97
	Intervention time	Preoperative	5	0.35 (0.26-0.48)	0.0	0.98
		Pre- and postoperative	3	0.42 (0.29-0.62)	0.0	0.37
	Country	China	5	0.39 (0.29-0.59)	0.0	0.65
		Other countries	3	0.36 (0.25-0.53)	0.0	0.82
	Quality of studies	High	5	0.36 (0.26-0.49)	0.0	0.97
		Moderate	3	0.41 (0.28-0.60)	5.1	0.34
Central line infection		Overall	2	0.34 (0.14-0.81)	11.1	0.28	-
Peritoneal infection		Overall	2	0.42 (0.18-1.01)	0.0	0.89	-
Intra-abdominal infection		Overall	3	0.51 (0.25-1.04)	0.0	0.45	0.50
	Supplementation type	Multi-strain Probiotics and synbiotics	3	0.51 (0.25-1.04)	0.0	0.45
	Intervention time	Preoperative	2	0.78 (0.28-2.02)	0.0	0.55
		Pre- and postoperative	1	0.35 (0.13-0.97)	-	-
	Country	China	2	0.78 (0.28-2.02)	0.0	0.55
		Other countries	1	0.35 (0.13-0.97)	-	-
	Quality of studies	High	3	0.51 (0.25-1.04)	0.0	0.45

Table 3 Strength of evidence according to the GRADE

Outcome	No. of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Relative risk (95%CI)	Quality	Importance
Total infections	6 studies	Meta-analysis of RCTs	No serious	Serious2	No serious	No serious	None	0.40 (0.31-0.51)	Moderate (+)(+)(+)	Critical
Urinary tract infections	5 studies	Meta-analysis of RCTs	Serious1	No serious	No serious	No serious	None	0.44 (0.31-0.61)	Moderate (+)(+)(+)	Important
Bacteremia	3 studies	Meta-analysis of RCTs	No serious	No serious	No serious	No serious	None	0.41 (0.30-0.56)	High (+)(+)(+)(+)	Important
Sepsis	5 studies	Meta-analysis of RCTs	No serious	No serious	No serious	No serious	None	0.35 (0.25-0.44)	High (+)(+)(+)(+)	Critical
Surgical site infection	10 studies	Meta-analysis of RCTs	No serious	No serious	No serious	No serious	None	0.56 (0.49-0.63)	High (+)(+)(+)(+)	Critical
Pneumonia	8 studies	Meta-analysis of RCTs	No serious	No serious	No serious	No serious	None	0.38 (0.30-0.48)	High (+)(+)(+)(+)	Critical
Central line infection	2 studies	Meta-analysis of RCTs	No serious	No serious	No serious	Serious3	None	0.34 (0.14-0.81)	Moderate (+)(+)(+)	Critical
Peritoneal infection	2 studies	Meta-analysis of RCTs	No serious	No serious	No serious	Serious3	None	0.42 (0.18-1.01)	Moderate (+)(+)(+)	Critical
Intra-abdominal infection	3 studies	Meta-analysis of RCTs	No serious	No serious	No serious	Serious3	None	0.51 (0.25-1.04)	Moderate (+)(+)(+)	Critical

¹Significant publication bias.

²Significant heterogeneity.

³CI include null effect or include appreciable harm or benefit.

RR: Relative risk; RCTs: Randomized clinical trials.