Introduction: Sepsis, a life-threatening condition caused by the body's extreme response to infection, remains a significant challenge in medical practice due to its high mortality rate and complex treatment dynamics. Antibiotic therapy is a cornerstone in the management of sepsis, yet responses to these treatments can vary dramatically among patients. Recent research suggests that the gut microbiome, the diverse community of microorganisms residing in the human gastrointestinal tract, plays a crucial role in modulating the body's response to antibiotics. This study aims to investigate the impact of the gut microbiome on the effectiveness of antibiotic treatment in sepsis patients, providing insights into potential predictive markers and therapeutic targets for improving clinical outcomes.
Methods: This prospective study was conducted over a period of 18 months at a tertiary care hospital. A total of 200 sepsis patients admitted to the intensive care unit (ICU) were enrolled in the study. The sample comprised 110 males and 90 females, with a mean age of 58 years (range: 22-85 years). Inclusion criteria were a confirmed diagnosis of sepsis according to the Sepsis-3 criteria, and patients had not received any antibiotic treatment within the two weeks prior to enrollment. Patients with a history of chronic gastrointestinal diseases, recent surgery, or immunocompromised status were excluded.
Stool samples were collected from all patients within 24 hours of ICU admission, before the initiation of antibiotic therapy. DNA was extracted from the stool samples and sequenced using 16S rRNA gene sequencing to characterize the gut microbiome composition. Antibiotic response was evaluated based on clinical outcomes, including the resolution of sepsis symptoms, reduction in inflammatory markers (CRP, IL-6), and mortality rates at 28 days post-treatment. Statistical analyses were performed to identify correlations between gut microbiome diversity and treatment outcomes.
Results: The analysis revealed significant variability in the gut microbiome composition among sepsis patients. Patients who responded positively to antibiotic treatment (n=120) exhibited a higher diversity of gut microbiota compared to non-responders (n=80). Specifically, responders had a mean Shannon diversity index of 4.5, while non-responders had a mean index of 3.2 (p<0.01). The relative abundance of specific bacterial taxa also differed significantly between the two groups. Responders showed higher levels of Bacteroides and Faecalibacterium, with mean counts of 15,000 and 12,000 per gram of stool respectively, compared to non-responders who had mean counts of 8,000 and 5,000 per gram (p<0.05).
Inflammatory markers were markedly reduced in the responder group. The mean CRP level in responders decreased from 150 mg/L at admission to 45 mg/L on day 7, whereas in non-responders, the mean CRP level only decreased from 160 mg/L to 120 mg/L (p<0.01). Similarly, IL-6 levels dropped from a mean of 300 pg/mL to 80 pg/mL in responders, compared to a decrease from 310 pg/mL to 210 pg/mL in non-responders (p<0.01). The 28-day mortality rate was significantly lower in the responder group (15%) compared to the non-responder group (35%) (p<0.01).
Conclusion: The findings of this study underscore the significant impact of the gut microbiome on the response to antibiotic treatment in sepsis patients. A diverse gut microbiome appears to be associated with better clinical outcomes, including more effective resolution of sepsis symptoms, greater reduction in inflammatory markers, and lower mortality rates. These results suggest that gut microbiome profiling could serve as a valuable tool in predicting antibiotic treatment efficacy and tailoring personalized therapeutic strategies for sepsis patients. Further research is warranted to explore the mechanisms underlying these associations and to develop microbiome-targeted interventions that could enhance treatment outcomes in sepsis.
Keywords: Sepsis, Gut Microbiome, Antibiotic Treatment, Treatment Response, Inflammatory Markers, Microbiome D