Effects of probiotics on serum levels of Th1/Th2 cytokine and clinical outcomes in severe traumatic brain-injured patients: a prospective randomized pilot study.

INTRODUCTION: Traumatic brain injury (TBI) is associated with a profound immunological dysfunction manifested by a severe shift from T-helper type 1 (Th1) to T-helper type 2 (Th2) response. This predisposes patients to infections, sepsis, and adverse outcomes. Probiotic bacteria have been shown to balance the Th1/Th2 cytokines in allergic murine models and patients. For the present study, we hypothesized that the enteral administration of probiotics would adjust the Th1/Th2 imbalance and improve clinical outcomes in TBI patients. METHODS: We designed a prospective, randomized, single-blind study. Patients with severe TBI and Glasgow Coma Scale scores between 5 and 8 were included, resulting in 26 patients in the control group and 26 patients in the probiotic group. All patients received enteral nutrition via a nasogastric tube within 24 to 48 hours following admission. In addition, the probiotic group received 109 bacteria of viable probiotics per day for 21 days. The associated serum levels of Th1/Th2 cytokines, Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores, nosocomial infections, length of ICU stay, and 28-day mortality rate were studied. RESULTS: The patients responded to viable probiotics, and showed a significantly higher increase in serum IL-12p70 and IFNγ levels while also experiencing a dramatic decrease in IL-4 and IL-10 concentrations. APACHE II and SOFA scores were not significantly affected by probiotic treatment. Patients in the probiotic group experienced a decreased incidence of nosocomial infections towards the end of the study. Shorter ICU stays were also observed among patients treated with probiotic therapy. However, the 28-day mortality rate was unaffected. CONCLUSIONS: The present study showed that daily prophylactic administration of probiotics could attenuate the deviated Th1/Th2 response induced by severe TBI, and could result in a decreased nosocomial infection rate, especially in the late period. TRIAL REGISTRATION: ChiCTR-TRC-10000835.

Enteral nutrition in patients with severe traumatic brain injury: reasons for intolerance and medical management.

Approximately, 50% of patients with severe traumatic brain injury (TBI) exhibit intolerance to enteral nutrition (EN). This intolerance hampers the survival and rehabilitation of this subpopulation to a great extent, and poses various difficulties for clinicians due to its complex underlying mechanisms. This review discusses the possible reasons for intolerance to EN following severe TBI, current trends in medical management, as well as other related issues that are experienced by many clinicians.

Da-Cheng-Qi Decoction () Combined with Lactobacillus Acidophilus Improves Gastrointestinal Function of Traumatic Brain-Injured Model Mice.

OBJECTIVE: To investigate the effects of Da-Cheng-Qi Decoction (DCQD, ) combined with Lactobacillus acidophilus (LA) on the recovery of gastrointestinal (GI) function in traumatic brain-injured (TBI) mice. METHODS: A total of 150 male C57BL/6 mice were randomly divided into sham-injury, normal saline (NS), DCQD (0.4 mL/day), LA (⩾1 × 1010 cfu/day LA), DCQD+LA (LA administration at the same dosage after 4 h of feeding DCQD), and ½ DCQD+LA groups (LA administration at the same dosage after 4 h of feeding ½ DCQD dose) by a random number table, 5-8 mice in each group. The sever TBI model was constructed according to Feeney's enhanced gravitational forces of free falling. On days 1, 3, and 7 post-TBI, plasma diamine oxidase (DAO) and D-lactic acid levels were assessed by enzyme-linked immunosorbent assay (ELISA). Occludin expression in the intestinal epithelium was assessed by Western blot analysis. Transmission electron microscopy (TEM) was used to observe the morphological changes in the network structure of interstitial cells of Cajal (ICC) and change of enteric nervous system-ICC-smooth muscle cell (ENS-ICC-SMC). Immunofluorescence staining was used to detect changes in the network structure of the ICC. RESULTS: Compared with the NS group, occludin expression in the DCQD+LA group significantly increased on Day 1, 3, and 7 post-TBI (P<0.05 or P<0.01). The concentration of DAO significantly decreased in the LA, DCQD, and DCQD+LA groups on Day 3 and 7, whilst the D-lactate concentrations in the LA and ½ DCQD+LA groups decreased on Day 1 and 3 post-injury (P<0.05 or P<0.01). The NS group experienced a great damage on the ENS-ICC-SMC network morphology and ICC network structure, and all treatment groups had some improvements, among which the DCQD+LA group presented relatively intact network morphology. CONCLUSIONS: DCQD combined with LA treatment could effectively repair the intestinal mucosal barrier and improve GI motility in mice after TBI. The combination of DCQD and LA was more effective than their respective monotherapies.

[Heterogeneity changes in secretion ability of monocyte/macrophage and its significance after trauma hemorrhage in rat].

OBJECTIVE: To investigate the relationship between the heterogeneity in secretion ability of monocyte (Mo)/macrophage and the immune dysfunction after severe trauma. METHODS: Twenty-four healthy Wistar rats were randomly divided into normal control group and trauma hemorrhage 1, 4 and 7 days groups. The contents of interleukin-6 (IL-6) and IL-10 secretion of Mo/macrophage from different anatomical regions were determined by radioimmunoassay. RESULTS: (1)In normal rats, the ability to secrete IL-6 and IL-10 was different among alveolar macrophages (AM), peritoneal macrophages (PM) and Mo. PM showed the highest ability to secrete IL-10 while Mo had the highest ability to secrete IL-6. (2)After trauma hemorrhage, the secretion of IL-6 and IL-10 by AM were increased dramatically. On the contrary, the secretion of IL-6 by PM was declined from the 1st day to the 4th day, then increased even over that of the normal control group on the 7th day. However, the secretion of IL-10 by PM was significantly elevated on the 1st day after trauma hemorrhage, peaking on the 4th day, and only slight lowering was found on the 7th day. The secretion of IL-6 by Mo was declined gradually all the time, reaching the lowest point on the 7th day. On the contrary, the secretion of IL-10 by Mo was increasing, reaching its peak on the 7th day. CONCLUSION: The heterogeneity of secretion ability of Mo/macrophage obtained from different anatomical regions is present under normal condition, and is more obvious following a severe injury. This change may play an important role in the immune dysfunction and the development of complications after trauma.

Identification of synthetic peptides that inhibit lipopolysaccharide (LPS) binding to myeloid differentiation protein-2 (MD-2).

Many studies have suggested that the synergic effect of myeloid differential protein-2 (MD-2) on bacterial lipopolysaccharide (LPS) stimulation of toll-like receptor 4 (TLR4) may be a critical step during the LPS-TLR4 response signaling pathway. We performed a bioinformatic analysis on the MD-2 protein and identified the amino acid sequence NH2-FSKGKYKCV-COOH (K128-132) as a possible key sequence involved in the binding between MD-2 and LPS. We then screened a random phage display peptide library using this sequence as bait in order to identify antagonistic peptides. After 3 rounds of selection, 3 positive clones were identified. All 3 peptides were shown to inhibit, in a dose-dependent manner the production of tumor necrosis factor-α and interleukin-6 in human U937 and THP-1 cell lines as well as human peripheral blood monocytes stimulated by LPS. Only 2 of the 3 peptides were able to bind MD-2 directly as shown by sulfo-SBED biotin label transfer experiments. BALB/C mice were used to estimate the protection of these peptides from LPS challenge, and 2 of the 3 peptides (Lys-Thr-Val-Pro-Asp-Asn-His and Ile-Gly-Lys-Phe-Leu-Tyr-Arg) reduced mortality of the challenged mice from 100% to 53.8%. This study has demonstrated that interfering with the binding between MD-2 and LPS might be a potential therapeutic strategy for treating LPS-induced sepsis, and in doing so has identified 2 potential peptide candidates.

Increased gut absorptive capacity in rats with severe head injury after feeding with probiotics.

OBJECTIVE: The absorptive capacity of the gut is decreased after severe head injury (SHI), and this may be related to poor recovery. Probiotics may be a promising approach to improving gut absorption. The aim of this study was to investigate the effect of probiotics on gut absorptive capacity (GAC) after SHI. METHODS: A rat model in which SHI was induced by air percussion was used. One hundred fourteen Sprague-Dawley rats were randomized into three groups: SHI followed by standard enteral nutrition (group A); SHI followed by standard enteral nutrition plus probiotics (group B); and standard chow diet ad libitum (group C, sham-operated). The enteral diets were infused for 14 d after SHI. RESULTS: SHI induced weight loss and decreased the serum concentration of D-xylose and the apparent protein digestibility. Probiotics significantly improved GAC after SHI. Apparent protein digestibility and the concentration of D-xylose were lower in group A than in B or C after 14 d. The rats receiving probiotics showed less weight loss than group A. SHI induced intestinal flora dysfunction and a decrease in villus height and surface area. Digestive enzyme activities and gut motion were also depressed significantly, and these changes were closely related to the decrease in GAC. Probiotics increased villus height and surface area; Escherichia coli counts decreased significantly, and anaerobic counts increased. CONCLUSION: Probiotics improve the GAC after SHI, perhaps because of enhanced villus surface area, and correction of intestinal flora dysfunction.