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In a recent study published in the journal Nature Medicine, researchers at the University of Calgary analyzed the dynamics of fecal microbiota and conducted single-cell profiling of inflammatory responses and systemic immunity to determine associations between gut microbiome dysbiosis and an increased risk of nosocomial infections.

Study: Dysbiosis of a microbiota–immune metasystem in critical illness is associated with nosocomial infections. Image Credit: nobeastsofierce / Shutterstock

Background

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Nosocomial or hospital-acquired infections are highly prevalent in critically ill patients on life support and admitted to intensive care units (ICUs). Apart from the increased risk of nosocomial infections due to invasive medical devices such as endotracheal tubes and intravascular and bladder catheters, the weakening of the patients’ adaptive and innate immunity is also thought to make critically ill patients susceptible to infections from pathogens that rarely infect healthy individuals.

Studies from animal models and humans have revealed that the gut microbiome plays a significant role in the maintenance of immunity, not in the gut alone but also systemically. Gut microbiome dysbiosis in hospitalized patients and those admitted to ICUs has also been associated with a higher probability of infections and adverse outcomes. While the increased abundance of pathobionts in the gut could explain some of the infections, infections are also caused by microbes other than the typical pathobionts found in the gut, indicating that other mechanisms are involved in increasing the risk of infections in critically ill, hospitalized patients.

About the study

In the present study, the researchers used a multi-omics approach to analyze the fecal microbiota of a prospective, longitudinal cohort of 51 adults who were critically ill and admitted to surgical, neurological, medical, and trauma ICUs. Only patients newly admitted and who required mechanical ventilation in the ICU for at least three days were enrolled in the study.

Patients who had been at the hospital for more than two days at any time in the three months leading up to the ICU admission were excluded from the study to avoid confounding results. Patients who were immunocompromised, or had been on antibiotic treatment during the three days leading up to the ICU admission, or had a gastrointestinal malignancy or inflammatory bowel disease, or were not expected to survive more than three days at the time of the ICU admission were also not included in the study.

Rectal swabs were used to study the fecal microbiome composition using amplicon sequencing of the 16s ribosomal ribonucleic acid (rRNA) gene. The swab samples were obtained on the day the patients were admitted to the ICU and then on the third- and seventh days post-admission.

Additionally, mass cytometry was used to conduct single-cell analysis to understand the changing adaptive and innate immunity in patients who were critically ill. Furthermore, the role of specific immune system defects associated with a metasystem dysbiosis related to Enterobacteriaceae enrichment in increasing the risk of fungal and bacterial nosocomial infections was also examined using dimensionality reduction analysis.

Results

The results revealed that systemic immunity and the gut microbiome form an integrated metasystem, and dysbiosis in the gut results in host defense impairments, increasing the risk of hospital-acquired infections. Furthermore, the increase of Enterobacteriaceae in the gut was linked to elevated systemic inflammatory responses and dysregulated responses by myeloid cells. Although the impact of Enterobacteriaceae abundance on adaptive immunity was lower, the innate immune responses against microbes were seen to be impaired with an increase in immature and hypofunctional neutrophils and an elevated risk of fungal and bacterial infections.

The authors believe that the reduced impact of the gut microbiome dysbiosis on the adaptive immune responses might be because the study only focused on the first week of ICU admission. However, continued gut microbiome dysbiosis could result in dysregulations of the adaptive immune responses during the course of ICU admission, as shown by other studies that reported apoptosis of lymphocytes and increased risk of organ dysfunction and nosocomial infections.

These findings have important implications in preventing adverse outcomes in critically ill patients hospitalized or admitted to ICUs, as nosocomial infections are one of the primary causes of prolonged hospitalizations and even mortality. Targeting the correction of the immune-microbiome metasystem dysbiosis in patients admitted to ICUs could reduce the susceptibility to nosocomial infections and improve overall outcomes.

Conclusions

Overall, the findings reported that the increased risk of nosocomial infections in critically ill patients admitted to ICUs is associated with the dysbiosis of the metasystem comprising the gut microbiome and systemic immune responses. Furthermore, during the early stages of ICU admission, the gut microbiome imbalance with enrichment of Enterobacteriaceae seems to impact the innate immune responses and not adaptive immunity significantly. However, with prolonged dysbiosis, the adaptive immune responses could also be affected.

Written by

Dr. Chinta Sidharthan

Chinta Sidharthan is a writer based in Bangalore, India. Her academic background is in evolutionary biology and genetics, and she has extensive experience in scientific research, teaching, science writing, and herpetology. Chinta holds a Ph.D. in evolutionary biology from the Indian Institute of Science and is passionate about science education, writing, animals, wildlife, and conservation. For her doctoral research, she explored the origins and diversification of blindsnakes in India, as a part of which she did extensive fieldwork in the jungles of southern India. She has received the Canadian Governor General’s bronze medal and Bangalore University gold medal for academic excellence and published her research in high-impact journals.