Effects of Probiotics Supplementation on CRP, IL-6, and Length of ICU Stay in Traumatic Brain Injuries and Multiple Trauma Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Table 1

Characteristics of the included studies.

Author, year	Country	Participants (intervention, control)	Age (intervention, control, yrs.)	Duration (days)	Intervention (probiotic strains)	Outcome
Kotzampassi et al., 2006	Greece	35, 30	(52.9 ± 19, 55.9 ± 18)	15	Synbiotic (contains a combination of 1011 CFU of each of four probiotics; Pediococcus pentoseceus, Leuconostoc mesenteroides, L. paracaseissp, and L. plantarum, as well as 2.5 g each of inulin, oat bran, pectin, and resistant starch)	(i) Synbiotic group compared with the control group: no significant changes in mortality; (ii) Synbiotic group compared with the control group: significant changes in CRP (until 15 day), TNF-a (until 7 day), IL-6 (until 15 day) significant changes days of stay in the ICU. Synbiotic-treated group: significantly reduced in mortality
Spindler-Vesel et al., 2007	England	26, 26	48 (29.5–60), 41 (26–54)	7	Synbiotic (contains a combination of 10^10Pediococcus pentosaceus, 10^10Lactococcus raffinolactis, 10^10Lactobacillus paracasei subsp. paracasei, 10^10Lactobacillus plantarum, and 2.5 g of each of the following 4 fibers: β glucan, inulin, pectin, and resistant starch per sachet)	(i) Synbiotic group compared with the control group: no significant changes in CRP and stay in ICU days
Giamarellos-Bourboulis et al., 2009	Greece	36, 36	(52.9, 55.9)	15	Synbiotic 2000Forte	(i) Significant changes in CRP were observed between the two groups
Tan et al., 2011	China	26, 26	(40.5 ± 13.0, 40.8 ± 12.8)	21	Probiotic (included 0.5 × 10^8Bifidobacterium longum, 0.5 × 10^7Lactobacillus bulgaricus, and 0.5 × 10^7Streptococcus thermophiles)	(i) Probiotics significantly increased in IL-12p70 and IFNγ compared with controls; (ii) Probiotics significantly decreased in IL-4, IL-10, IL-6 and CRP compared with controls
Habib et al., 2020	Egypt	32, 33	(39.08 ± 7.11, 39.88 ± 7.90)	9.46	Probiotic (Lacteol Forte® sachet)	(i) Probiotic group compared with the control group: no significant changes in mortality and days of stay in the ICU
Wan et al., 2020	China	38, 38	(35.97 ± 13.12, 38.65 ± 11.26)	15	Probiotic (Bifidobacterium longum, Lactobacillus bulgaricus, and Enterococcus faecalis >1.010^7 CFU)	(i) Probiotic group compared with the control group: no significant changes in mortality; (ii) Significant changes in days of stay in the ICU; (iii) IL-6, IL-10, TNF-a, and CRP at 7 and 15 days were significantly decreased
Brenner et al., 2020	The United States	16, 15	(37.9 ± 38.5, 36.7 ± 6.2)	56	L. reuteri DSM 17938 drops, 100 million CFU	(i) Probiotic group compared with the control group: no significant changes in CRP, IL-1α, IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, TNFα, and IFNγ

CRP, C-reactive protein; ICU, intensive care unit; IL, interleukin; TNF-a, tumor necrosis factor-alpha; CFU, colony forming unit; IFNγ; interferon gamma.