Study Title:

Probiotics Boost Infection-Fighting Immunity Following Traumatic Brain Injury

Study Abstract

Traumatic brain injury (TBI) is associated with a profound immunological dysfunction manifested by a severe shift from T helper 1 (Th1) to 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 this study, we hypothesized that the enteral administration of probiotics would adjust the Th1/Th2 imbalance and improve clinical outcomes in TBI patients.

We designed a prospective, randomized, single-blind study. Patients with severe TBI and Glasgow Coma Scale (GCS) 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 (EN) via nasogastric tube within 24-48 hours following admission. In addition, the probiotics 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 intensive care unit (ICU) stay, as well as 28-day mortality rate were studied.

The patients responded to viable probiotics, and showed a significantly higher increase in serum IL-12p70 and IFN-gammalevels 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.

This study showed that daily prophylactic administration of probiotics could attenuate the deviated Th1/Th2 response induced by severe TBI, and result in a decreased nosocomial infection rate, especially in the late period.

From press release:
Traumatic brain injury is associated with a profound suppression of the patient's ability to fight infection. At the same time the patient also often suffers hyper-inflammation, due to the brain releasing glucocorticoids in response to the injury. New research published in BioMed Central's open access journal Critical Care shows that including probiotics with nutrients, supplied via the patient's feeding tube, increased interferon levels, reduced the number of infections, and even reduced the amount of time patients spent in intensive care.

In a small scale trial, based at North Sichuan Medical College and Hospital in China, 52 patients who had suffered traumatic brain injuries, and who were being treated in the intensive care unit (ICU), were either treated as usual or had their nutrition supplemented with probiotics.

Suppression of the immune system can be measured by an alteration of helper T-cells (Th) from Th1, which stimulate the action of macrophages to fight infection, to Th2. Th2 cells recruit B-cells which in turn are involved in antibody production. This switch from Th1 to Th2 leaves patients vulnerable to infections including ventilator-associated pneumonia and sepsis. Researchers involved in this trial monitored the TH1/Th2 switch by measuring levels of the Th1-associated signaling molecules (cytokines) IL-12 and interferon gamma (IFNy).

No differences were found between the groups of patients when they began the trial, and throughout the study all the patients had lower levels of IL-12 and IFN? than uninjured healthy controls. However by day 15 the patients who received the probiotics had significantly higher levels of both IL-12 and IFNy than the control patients. They also showed a decrease in the Th2-associated factors IL-4 and IL-10.

Prof Jing-Ci Zhu, the supervisor of this study from the Third Military Medical University School of Nursing in China, explained, "Probiotic treatment appeared to swing the Th1/Th2 balance back towards normality and, in our study, had beneficial effects. Possibly due to the small size of our study there was no significant difference in the number of infections between the groups (9 for the probiotic group, 16 for the control patients). However probiotic therapy reduced the number of infections occurring after seven days, reduced the number of different antibiotics needed to treat infections, and shortened the length of time the patients were required to stay in ICU."

Study Information

Min Tan, Jing-Ci Zhu, Jiang Du, Li-Mei Zhang, Hua-Hua Yin
Effects of probiotics on serum levels of Th1/Th2-cytokine and clinical outcomes in severe traumatic brain-injured patients: a prospective randomized pilot study
Critical Care
2011 December
North Sichuan Medical College and Hospital in China

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