Gut dysbiosis and its treatment in patients with critical illness

Abstract

The gut is a target organ that functions as the "motor" of critical illness. In patients with critical illness, the disrupted gut microbiota following infection and injury could cause diarrhea, pneumonia, and systemic inflammation. For maintaining the gut microbiota, therapeutic approaches are required to modulate host responses and prevent systemic inflammation. Probiotics and synbiotics could maintain the gut microbiota and decrease not only the incidence of diarrhea but also that of ventilator-associated pneumonia. The effects of probiotics/synbiotics differ with the type of bacteria and disease severity. Adverse effects of probiotics have been reported; therefore, the selection of safe and effective probiotics/synbiotics is warranted. Refractory diarrhea with prolonged dysbiosis may require a novel intestinal therapy, such as fecal microbiota transplantation, to alleviate gut dysbiosis.

Keywords: ICU; critically ill; dysbiosis; gut; microbiota.

FIGURE 1

The concept of injury‐induced imbalances in the immune system. The host immune response induces inflammation following injury; this is known as Systemic Inflammatory Response Syndrome (SIRS). The immunosuppression coincidentally begins at the onset of inflammation; this is known as compensatory anti‐inflammatory response (CARS). If the SIRS and CARS state is prolonged, it progresses to a state known as multiple organ dysfunction syndrome (MODS). Progressive immunosuppression is known as Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PIICS). This pro‐inflammatory state is mainly driven by macrophages, neutrophils, and regulatory T cells (cited and edited from reference [1]).

FIGURE 2

(A) Altered gut microbiota in ICU patients. Serial changes in the average proportions of genera in patients' fecal microbiota. Commensal bacteria (e.g., Bacteroidetes, Prevotella) decreased, whereas opportunistic bacteria (e.g., Enterococcus, Corynebacterium) increased (edited from reference [16]). (B) Serial changes in the fecal microbiota of ICU patients. The genera Blautia, Faecalibacterium, and Clostridium serially decreased in the fecal microbiota. On the other hand, the genus Enterococcus increased. An asterisk (*) indicates significant differences between the groups (cited and edited from reference [16]).

FIGURE 3

Pattern classification by fecal gram staining. If phagocytosed bacteria are detected, antibiotics can be administered in accordance with phagocytosed bacteria. If there are no phagocytosed bacteria, the Gram staining patterns are classified into three types with bacteria. In the diverse pattern, many types of bacteria cover the field. In the single pattern, a few types of bacteria predominantly cover the field. In the depleted pattern, most bacteria are depleted in the field. The dysbiosis progresses from a diverse pattern to a single pattern and from a single pattern to a depleted pattern.

FIGURE 4

Potential infection prevention mechanism of probiotics/synbiotics. (Left) Severe injury deteriorates the gut microbiota and results in the progression of dysbiosis, thereby causing systemic inflammation, pneumonia, and multiple organ dysfunction syndrome. (Right) Probiotics/synbiotics could improve the gut microbiota and prevent infectious complications. SCFA, short‐chain fatty acids.