Infants younger than 90 days with late-onset sepsis display disturbances of the microbiome-immunity interplay
Objective To provide exploratory microbiome data of infants < 90 days of age with suspected late-onset sepsis and evaluate distinct immunological and gut microbial specificities. We hypothesized that previously healthy infants < 3 months of age with sepsis have a yet undefined immunological predisposition relating to specific signatures of the gut microbiome. Methods We performed an exploratory single center study between January 1st, 2019 and July 1st 2021. Routine diagnostics included conventional culture (blood, cerebrospinal fluid, urine), PCR and inflammatory markers in infants < 90 days of age with suspected sepsis. We additionally analyzed lymphocyte subsets including CD4+ CD25+ forkhead box protein (FoxP3)+ Tregs and performed 16S rRNA sequencing of stool samples, both compared to age-matched healthy controls. Results A convenience sample cohort of n= 51 infants with suspected sepsis was enrolled. Invasive bacterial infection (IBI) was diagnosed in n= 24 (47.1%) patients and viral infection in n= 13 (25.5%) whereas in 14 cases the cause of fever remained undetermined. When compared to healthy controls, the gut microbiome of infants with suspected sepsis was characterized by significant differences in the gut microbial composition such as a decreased abundance of actinobacteria due to less depicted Bifidobacterium spp. and an increase of Bacteroida spp. We observed that certain correlations of the microbiome – immunity interplay were abolished in infants with sepsis such as the negative correlation between B. longum and CD4-positive cells and the positive correlation between B. longum abundance and T-Reg frequency while other specific interactions of the microbiome – immune interplay remained unaffected. Conclusion Our exploratory data indicate specific signatures of the gut microbial composition as well as disturbances in the microbiome – immunity interplay in infants with suspected late-onset sepsis which may represent a predisposition for early infection in infants < 3 months of age.