Impact Of Administration Of Probiotics On Gut Microbiota And Clinical Outcomes In Critically Ill Patients

[Background]Gut exerts considerable immune function depending on the microbiota, intestinal barrier and intestinal immune system. The gut microbiota is a complicated ecosystem that consists of a vast number of microorganisms and relates closely to the host’s maturation, growing up, nutrition metabolism and aging. During critical illness and following medical interventions, the composition and phenotype of intestinal micro-organisms suffer tremendous alteration, leaving the host susceptible to opportunistic pathogens and lead to SIRS and MODS.In short, the disturbance of microbiota leads to the "undrained abscess", indicating complications and poor progronstic.Probiotics are live microorganisms that when administered in adequate amounts confer a health benefit on the host. They inhibit the potential pathogenic micrograms and help to maintain the stability of gut microbiota through enhancement of barrier function, immunomodulation, secretion bacteriocin, competition for nutrients and binding sites. In addition, the abuse of antibiotics and subsequent resistance highlight the probiotics since they avoid the risk of resistance and secondary infection. There is a strong scientific rationale for the use of probiotics in the intensive care units (ICUs) setting and available results turned out promising. This deserves further research and application. Above all, we conducted the study concerning the effect of adiminstraion of probiotics on the gut microbiota and clinical outcomes in critically ill patients.[Objective]1. To investigate the effect of probiotic on primary clinical outcomes and clinical manifestation in medical critically ill patients.2. To quantify specific groups of bacteria in human feces in order to investigate ef-fect of probiotic on gut microbiota in critically ill patients.3. To evaluate the intestinal epithelium barrier function during critical illness and identify whether probiotics help to restore the barrier function.4. To evaluate effect of probiotics on attenuating inflammation and immunomodula- tion during the course of the disease in critically ill patients.[Methods]1. A single-blind, randomized controlled trial was performed in a respiratory inten-sive care units (RICUs). Patients allocated to the intervention group received enterally or orally administered probiotics Clostridium butyricum until death or discharge.2. Stool and blood samples were collected on the 1st day and 15th day of administra-tion. Total bacterial DNA was extracted from stool samples, followed by Realtime-qPCR to quantify specific groups of bacteria. The serum level of DAO、 LPS、TNF-a and IL-10 was determined by ELISA assay.3. During the follow up, primary clinical outcomes (mortality, nosocomial infection rate, length of stay, length of antibiotic use) and clinical manifestations (adverse effect of gastric intestinal tract and fever day) were recorded.[Results]1. Sixty-one patients were enrolled in the study and 28 patients were randomly as-signed to intervention group receiving probiotics thrice daily during their stay in the RICUs. No difference of crude mortality was observed between the interven-tion and controlled groups (21.21% vs 21.43%, p=0.98). Other primary outcomes were also unaffected by the treatment.2. The occurance of contisapation was significantly reduced in intervention group compared with the controlled group (17.86% vs 42.42%, p=0.04). The overall ratio of gastrointestinal adverse effect was not improved by probiotics. In addition, the fever day (%length of stay) was reduced by intervention compared with con-trolled group (4.85% vs12.94%, p=0.00).3. There was no difference of baseline gut bateria between two groups. Bacteroides yielded a significantly decrease after probiotic intervention (Am=-0.69, p=0.048), while Escherichia coli and Enterococcus showed a tendency to decrease in the in-tervention group (Δm=-0.65, p=0.08; Δm=-0.52, p=0.22) compared to controlled group on the 15th day. No obvious fluctuation of Bifidobacterium and Lactobacil-lus was observed by the intervention.4. DAO, the indicator of intestinal epithelium barrier function was significantly el-evated in both controlled and intervention group (β1=66.18, p<0.01; (32=70.43, p<0.01). The damage was not attenuated by probiotics.5. Serum LPS significantly decreased in the intervention group (β2=-39.18, p=0.002) while the concentration remained relatively stable in the controlled group. There was a significant increase in the level of IL-10 in both groups and the increase was not influenced by probiotics (β1=87.85, p=0.01; 02=58.96, p=0.03).The level of TNF-a showed no change along with time or intervention.[Conclusion]1. Our study failed to show beneficial effect of probiotics on primary clinical out-comes in medical critically ill patients. Further study is needed to assess the effi-cacy of probiotics. Administration of probiotics is effective in reducing occurance of constipation but lack of efficacy in the overall gastric intestinal tract disorders.2. The administration of probiotics for 14 days significantly decreased Bacteroides, while potential pathogenics such as Escherichia coli、Enterococcus tended to be inhibited. It sounds promising and intriguing but the exact role probiotics plays in medical critically patients was doultful.3. The intestinal epithelium tend to be breached by pathophysiologic change and medical intervention. The probiotics shows no effect on attenuating the damage but reduce the LPS concentration, indicating that probiotics help to ease the bur-den of Gm-bacteria originated from gut. The detailed mechanism deserves further research4. Even though there is a strong scientific rationale for the use of probiotics in the ICUs, the exact state of gut microbiota and benefits of probiotics need to be fur-ther assessed in spite of confounding factors in clinical setting.