TY - JOUR
T1 - Oral and Stool Microbiome Coalescence and Its Association With Antibiotic Exposure in Acute Leukemia Patients
AU - Franklin, Samantha
AU - Aitken, Samuel L.
AU - Shi, Yushi
AU - Sahasrabhojane, Pranoti V.
AU - Robinson, Sarah
AU - Peterson, Christine B.
AU - Daver, Naval
AU - Ajami, Nadim A.
AU - Kontoyiannis, Dimitrios P.
AU - Shelburne, Samuel A.
AU - Galloway-Peña, Jessica
N1 - Publisher Copyright:
Copyright © 2022 Franklin, Aitken, Shi, Sahasrabhojane, Robinson, Peterson, Daver, Ajami, Kontoyiannis, Shelburne and Galloway-Peña.
PY - 2022/3/31
Y1 - 2022/3/31
N2 - Failure to maintain segregation of oral and gut microbial communities has been linked to several diseases. We sought to characterize oral-fecal microbiome community coalescence, ectopic extension of oral bacteria, clinical variables contributing to this phenomenon, and associated infectious consequences by analyzing the 16S rRNA V4 sequences of longitudinal fecal (n=551) and oral (n=737) samples from 97 patients with acute myeloid leukemia (AML) receiving induction chemotherapy (IC). Clustering observed in permutation based multivariate analysis of variance (PERMANOVA) of Bray-Curtis dissimilarity and PCoA plot of UniFrac distances between intra-patient longitudinal oral-stool sample pairs suggested potential oral-stool microbial community coalescence. Bray-Curtis dissimilarities and UniFrac distances were used to create an objective definition of microbial community coalescence. We determined that only 23 of the 92 patients exhibited oral-stool community coalescence. This was validated through a linear mixed model which determined that patients who experienced coalescence had an increased proportion of shared to unique OTUs between their oral-stool sample pairs over time compared to non-coalesced patients. Evaluation of longitudinal microbial characteristics revealed that patients who experienced coalescence had increased stool abundance of Streptococcus and Stenotrophomonas compared to non-coalesced patients. When treated as a time-varying covariate, each additional day of linezolid (HR 1.15, 95% CI 1.06 – 1.24, P <0.001), meropenem (HR 1.13, 95% CI 1.05 – 1.21, P = 0.001), metronidazole (HR 1.13, 95% CI 1.05 – 1.21, P = 0.001), and cefepime (HR 1.10, 95% CI 1.01 – 1.18, P = 0.021) increased the hazard of oral-stool microbial community coalescence. Levofloxacin receipt was associated with a lower risk of microbiome community coalescence (HR 0.75, 95% CI 0.61 – 0.93, P = 0.009). By the time of neutrophil recovery, the relative abundance of Bacteroidia (P<0.001), Fusobacteria (P=0.012), and Clostridia (P=0.013) in the stool were significantly lower in patients with oral-gut community coalescence. Exhibiting oral-stool community coalescence was associated with the occurrence of infections prior to neutrophil recovery (P=0.002), as well as infections during the 90 days post neutrophil recovery (P=0.027). This work elucidates specific antimicrobial effects on microbial ecology and furthers the understanding of oral/intestinal microbial biogeography and its implications for adverse clinical outcomes.
AB - Failure to maintain segregation of oral and gut microbial communities has been linked to several diseases. We sought to characterize oral-fecal microbiome community coalescence, ectopic extension of oral bacteria, clinical variables contributing to this phenomenon, and associated infectious consequences by analyzing the 16S rRNA V4 sequences of longitudinal fecal (n=551) and oral (n=737) samples from 97 patients with acute myeloid leukemia (AML) receiving induction chemotherapy (IC). Clustering observed in permutation based multivariate analysis of variance (PERMANOVA) of Bray-Curtis dissimilarity and PCoA plot of UniFrac distances between intra-patient longitudinal oral-stool sample pairs suggested potential oral-stool microbial community coalescence. Bray-Curtis dissimilarities and UniFrac distances were used to create an objective definition of microbial community coalescence. We determined that only 23 of the 92 patients exhibited oral-stool community coalescence. This was validated through a linear mixed model which determined that patients who experienced coalescence had an increased proportion of shared to unique OTUs between their oral-stool sample pairs over time compared to non-coalesced patients. Evaluation of longitudinal microbial characteristics revealed that patients who experienced coalescence had increased stool abundance of Streptococcus and Stenotrophomonas compared to non-coalesced patients. When treated as a time-varying covariate, each additional day of linezolid (HR 1.15, 95% CI 1.06 – 1.24, P <0.001), meropenem (HR 1.13, 95% CI 1.05 – 1.21, P = 0.001), metronidazole (HR 1.13, 95% CI 1.05 – 1.21, P = 0.001), and cefepime (HR 1.10, 95% CI 1.01 – 1.18, P = 0.021) increased the hazard of oral-stool microbial community coalescence. Levofloxacin receipt was associated with a lower risk of microbiome community coalescence (HR 0.75, 95% CI 0.61 – 0.93, P = 0.009). By the time of neutrophil recovery, the relative abundance of Bacteroidia (P<0.001), Fusobacteria (P=0.012), and Clostridia (P=0.013) in the stool were significantly lower in patients with oral-gut community coalescence. Exhibiting oral-stool community coalescence was associated with the occurrence of infections prior to neutrophil recovery (P=0.002), as well as infections during the 90 days post neutrophil recovery (P=0.027). This work elucidates specific antimicrobial effects on microbial ecology and furthers the understanding of oral/intestinal microbial biogeography and its implications for adverse clinical outcomes.
KW - antimicrobials
KW - coalescence
KW - leukemia
KW - microbiome
KW - oralization
UR - http://www.scopus.com/inward/record.url?scp=85128411185&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85128411185&partnerID=8YFLogxK
U2 - 10.3389/fcimb.2022.848580
DO - 10.3389/fcimb.2022.848580
M3 - Article
C2 - 35433514
AN - SCOPUS:85128411185
SN - 2235-2988
VL - 12
JO - Frontiers in Cellular and Infection Microbiology
JF - Frontiers in Cellular and Infection Microbiology
M1 - 848580
ER -