Background: The gut is considered an important target organ of injury after severe insult such as sepsis, trauma, and shock. The impact of bacterial translocation or mesenteric lymph on systemic inflammatory response and multiple organ damage has been investigated in animals, but dynamic changes in the gut flora and environment have not been fully clarified in critically ill patients. In the present study, we quantitatively evaluated changes in the gut microflora and environment in patients with severe systemic inflammatory response syndrome (SIRS). Methods: Twenty-five patients with severe SIRS, who fulfilled the criteria for SIRS, had a serum CRP level >10 mg/dL, and were treated in the intensive care unit for more than 2 days, were included in our study. SIRS was a result of sepsis in 18 patients, trauma in 6, and burn in 1. A fecal sample was used for quantitative evaluation of microflora (bacterial counts of 10 key groups including Bifidobacterium and Lactobacillus) by plate or tube technique and of the gut environment (pH and 9 organic acids by high speed liquid chromatography). Data obtained from patients were compared with corresponding data from healthy volunteers. Results: Analysis of fecal flora confirmed that patients with severe SIRS had significantly lower total anaerobic bacterial counts (especially 2–4 log fewer “beneficial” Bifidobacterium and Lactobacillus) and 2 log higher “pathogenic” Staphylococcus and Pseudomonas group counts than those of healthy volunteers. Concentrations of total organic acids (especially “beneficial” short-chain fatty acids such as acetic acid, propionic acid, and butyric acid) in the feces were significantly decreased in the patients, whereas pH was markedly increased. Conclusions: The gut flora and environment are significantly altered in patients with severe SIRS. Abnormal gut flora and environment may affect systemic inflammatory response after severe insult.

Commensal microbiota deteriorate in critically ill patients. The preventive effects of probiotic/synbiotic therapy on microbiota and septic complications have not been thoroughly clarified in patients with sepsis. The objective of this study was to evaluate whether synbiotics have effects on gut microbiota and reduce complications in mechanically ventilated patients with sepsis. Sepsis patients who were mechanically ventilated in the intensive care unit (ICU) were included in this randomized controlled study. Patients receiving daily synbiotics (Bifidobacterium breve strain Yakult, Lactobacillus casei strain Shirota, and galactooligosaccharides) initiated within 3 days after admission (the Synbiotics group) were compared with patients who did not receive synbiotics (the No-Synbiotics group). The primary outcome was infectious complications including enteritis, ventilator-associated pneumonia (VAP), and bacteremia within 4 weeks from admission. The secondary outcomes included mortality within 4 weeks, fecal bacterial counts, and organic acid concentration. Enteritis was defined as the acute onset of continuous liquid stools for more than 12 h. Seventy-two patients completed this trial; 35 patients received synbiotics and 37 patients did not receive synbiotics. The incidence of enteritis was significantly lower in the Synbiotics than the No-Synbiotics group (6.3% vs. 27.0%; p < 0.05). The incidence of VAP was also significantly lower in the Synbiotics than the No-Synbiotics group (14.3% vs. 48.6%; p < 0.05). The incidence of bacteremia and mortality did not differ significantly between the two groups. In the analysis of fecal bacteria, the number of Bifidobacterium and Lactobacillus in the Synbiotics group was significantly higher than that in the No-Synbiotics group. In the analysis of fecal organic acids, total organic acid concentration, especially the amounts of acetate, were significantly greater in the Synbiotics group than in the No-Synbiotics group at the first week (p < 0.05). Prophylactic synbiotics could modulate the gut microbiota and environment and may have preventive effects on the incidence of enteritis and VAP in patients with sepsis. UMIN, R000007633 . Registered on 29 September 2011.

Background Metagenomic analysis targeting the 16S rRNA gene has made it possible to characterize the vast array of microorganisms contained in the gut. Aim The purpose of this study was to evaluate how gut microbiota change in intensive care unit (ICU) patients in the acute phase after admission. Methods This prospective observational cohort study investigated 12 patients admitted to a single ICU of a large urban tertiary referral hospital. All patients were mechanically ventilated on admission. Fecal samples were collected from patients on days 1–2, 2–4, 5–8, and 7–10 after admission. DNA was extracted from fecal samples, and 16S rRNA deep sequencing was performed to monitor gut changes. Results Bacteria belonging to the phyla Firmicutes or Bacteroidetes were predominant in each sample. We observed serial dynamic changes in the percentages of Bacteroidetes and Firmicutes that were significantly altered during study period (p < 0.05). A ratio of Bacteroidetes to Firmicutes (B/F ratio) of >10 was seen in four of the six patients who died, whereas a B/F ratio of 10 or <0.10. There was a statistical difference in the B/F ratio between the dead patients and survivors (p = 0.022). Conclusions Dynamic changes in gut microbiota at the phylum level of ICU patients during the acute phase were identified by high-throughput DNA sequencing. An extreme imbalance in gut microbiota may be associated with prognosis in critically ill patients.

Background Gut under severe insult is considered to have an important role in promoting infection and multiple organ dysfunction syndrome from the viewpoint of altered intestinal epithelium, immune system and commensal bacteria. There are few reports, however, about the relationship between gut flora and septic complications. Methods We analyzed gut flora in patients with systemic inflammatory response syndrome (SIRS) and evaluated key bacteria and their cutoff values for infectious complications and mortality by using classification and regression trees (CART). Eighty-one SIRS patients with a serum C-reactive protein level higher than 10 mg/dL treated in the intensive care unit (ICU) for more than 2 days were included for the study. We quantitatively evaluated nine types of bacteria in fecal samples by plate or tube technique. Two hundred seventy-one samples were analyzed using CART and logistic regression. Results The dominant factors for complication of enteritis were the minimum number of total obligate anaerobes and the maximum number of Staphylococcus and Enterococcus. The dominant factors for complication of bacteremia were the minimum numbers of total obligate anaerobes and total facultative anaerobes. The dominant factors for mortality were the numbers of total obligate anaerobes and total facultative anaerobes and age. Conclusions A decrease in total obligate anaerobes and an increase in pathogenic bacteria in the gut are associated with septic complications and mortality in patients with SIRS. The altered gut flora may be a potential prognostic marker in SIRS patients.

The gut is an important target organ for stress caused by severe insults such as sepsis, trauma, burn, shock, bleeding and infection. Severe insult to the gut is considered to have an important role in promoting infectious complications and multiple organ dysfunction syndrome. These are sequelae of interactions between deteriorated intestinal epithelium, the immune system and commensal bacteria. The gut is the “motor” of multiple organ failure, and now it is recognized that gut dysfunction is a causative factor in disease progression. The gut flora and environment are significantly altered in critically ill patients, and the number of obligate anaerobes is associated with prognosis. Synbiotic therapy is a combination of probiotics and prebiotics. Probiotic, prebiotic and synbiotic treatment has been shown to be a promising therapy to maintain and repair the gut microbiota and gut environment. In the critically ill, such as major abdominal surgery, trauma and ICU patients, synbiotic therapy has been shown to significantly reduce septic complications. Further basic and clinical research would clarify the underlying mechanisms of the therapeutic effect of probiotic/synbiotic treatment and define the appropriate conditions for use.