The study reports on the gut microbiome and immune response in hospital-acquired infections

In a recent study published in the journal Nature medicineResearchers at the University of Calgary analyzed the dynamics of fecal microbiota and performed single-cell profiling of systemic inflammatory and immune responses to determine associations between gut microbial dysbacteriosis and increased risk of nosocomial infection.

background

Nosocomial or acquired infections are most common in critically ill patients on life support and admitted to intensive care units (ICUs). Aside from the increased risk of nosocomial infections due to invasive medical devices such as endotracheal tubes, endovascular catheters, and bladders, impairment of patients’ innate and adaptive immunity is also thought to render critically ill patients vulnerable to infection from pathogens that rarely infect healthy subjects. individual.

Studies from animal models and humans have revealed that the gut microbiome plays an important role in maintaining immunity, not only in the gut but also systemically. Dysbacteriosis of the intestinal microbiome in hospitalized patients and those admitted to intensive care units has also been associated with a higher likelihood of infection and adverse outcomes. While increased abundance of pathogens in the gut could explain some infections, infection is also induced by microbes other than typical pathogens residing in the gut, suggesting that other mechanisms are involved in the increased risk of infection in critically ill patients. and patients in the hospital. .

about studying

In this study, the researchers used a multifaceted approach to analyze the fecal microbiota of a prospective longitudinal cohort of 51 critically ill adults admitted to surgical, neurological, medical, and trauma intensive care units. Newly admitted patients who required mechanical ventilation in the intensive care unit for at least three days were enrolled in the study.

Patients who were hospitalized for more than two days at any time in the three months preceding ICU admission were excluded from the study to avoid confounding results. Patients who are immunocompromised, who were receiving antibiotic treatment during the three days prior to admission to the ICU, have malignancy of the gastrointestinal tract or inflammatory bowel disease, or were not expected to live more than three days at the time of Admission to the intensive care unit. It was also not included in the study.

Rectal swabs were used to study the composition of the fecal microbiome using amplicon sequencing of the rRNA gene. Swab samples were obtained on the day patients were admitted to the intensive care unit and then on days three and seven after admission.

In addition, cytometry was used to perform single cell analysis to understand altered adaptive and innate immunity in critically ill patients. Furthermore, the role of specific immune system defects associated with genetic dysbiosis related to the enrichment of intestinal bacteria in increasing the risk of fungal and bacterial infections in nosocomial settings was also examined using a dimensional reduction analysis.

results

The results revealed that systemic immunity and the gut microbiome constitute a complementary integrated system, and that gut dysbiosis results in impaired host defense, which increases the risk of nosocomial-acquired infections. Moreover, the increase of Enterobacteriaceae in the intestine was associated with elevated systemic inflammatory responses and dysregulated responses by myeloid cells. Although the effect of Enterobacteriaceae abundance on adaptive immunity was less, innate immune responses against microbes were observed to be disrupted with increased immature, functional neutrophils and increased risk of fungal and bacterial infections.

The authors believe that the reduced impact of gut microbiome disruption on adaptive immune responses may be because the study focused only on the first week of ICU admission. However, persistent dysregulation of the gut microbiome can lead to abnormalities in adaptive immune responses during ICU admission, as shown in other studies reporting lymphocyte apoptosis and increased risk of organ dysfunction and nosocomial infections.

These findings have important implications for preventing adverse outcomes in critically ill patients hospitalized or admitted to intensive care units, as nosocomial infections are a major cause of prolonged hospitalizations and even deaths. Targeting correction of cellular dysplasia of the immune microbiome in patients admitted to intensive care units can reduce exposure to nosocomial infections and improve overall outcomes.

conclusions

Overall, the results reported that an increased risk of nosocomial infection in critically ill patients admitted to intensive care units is associated with dysregulation of the genetic system involving the gut microbiome and systemic immune responses. Furthermore, during the early stages of ICU admission, an imbalance of the gut microbiome with enrichment of intestinal bacteria appears to affect innate immune responses rather than adaptive immunity significantly. However, with prolonged dysbacteriosis, adaptive immune responses can also be affected.