Preterm infant gut microbiota, antibiotic effects

Dysbiotic colonization of the preterm infant gut microbiota may have lifelong effects on host health. The normal progression of colonization of preterm infants is a patterned, yet chaotic, process, and thought to be chiefly driven by host factors. While preterm infants almost universally receive early and often repeated and/or prolonged intravenous antibiotic therapy, it remains unclear if and how specific antibiotics alter the developmental progression of the gut microbiota in this population. By analyzing 401 fecal samples from 84 longitudinally-sampled preterm infants, we demonstrate that meropenem, cefotaxime, and ticarcillin-clavulanate significantly reduce species richness during their administration, and significantly enrich or deplete specific bacterial species and antibiotic resistance (AR) genes. In contrast, vancomycin and gentamicin, the antibiotics most commonly administered to preterm infants, have non-uniform effects on species richness. We show this response is predictable with 85% accuracy based on the relative abundance of only two bacterial species and two AR genes before treatment. To more fully investigate the role of the gut-associated resistome in response to specific antibiotics, we performed functional metagenomic selections for resistance to 16 clinically relevant antibiotics from a set of 21 preterm infants’ gut microbiota. Of the 794 AR genes identified, 79% had not previously been classified as providing any resistance phenotype. Combined with deep shotgun sequencing of all 401 fecal samples, we find that multidrug resistant Escherichia, Klebsiella, and Enterobacter species, which are commonly associated with nosocomial infections, dominate the preterm infant gut microbiota. We show that AR genes that are enriched following specific antibiotic treatments are generally unique to the specific treatment and highly correlated (p<0.001) with the abundance of a single species. The most notable exception includes ticarcillin-clavulanate and ampicillin, both of which enrich a large number of overlapping AR genes, and are highly correlated with Klebsiella pneumoniae species in the preterm infant gut microbiota. In addition to AR genes relevant to specific antibiotics likely providing a protective function, we show that all antibiotic treatments also result in widespread collateral microbiome impact through enrichment of AR genes with no known direct activity against the specific antibiotic treatment.

Classified as human gut / stool mixed assays of infant / toddler by sonnet_x2 with confidence 0.78. Assay mixed.

• host run.host_tax_id · “9606”
• body site study.title · “preterm infant gut microbiota”
• life stage study.title · “preterm infant gut microbiota”
• life stage study.description · “84 longitudinally-sampled preterm infants”

982 runs over 403 samples · mean 0.43 Gbp per run (median 0.10 Gbp, total 423.76 Gbp; 982 runs with a base count) · layout PAIRED 581, SINGLE 401 · platform ILLUMINA 982 · models Illumina HiSeq 2500 (804), NextSeq 500 (178) · 41% of runs with a Sandpiper profile · first public 2016-05-05

Gibson MK first · Wang B · Ahmadi S · Burnham CA · Tarr PI · Warner BB · Dantas G last · Thänert R first · Thänert A · Ou J · Bajinting A · Burnham CD · Engelstad HJ · Tecos ME · Ndao IM · Hall-Moore C · Rouggly-Nickless C · Carl MA · Rubin DC · Davidson NO · Warner BW last · Pärnänen KMM first · Hultman J · Markkanen M · Satokari R · Rautava S · Lamendella R · Wright J · McLimans CJ · Kelleher SL · Virta MP last · Zeng S first · Patangia D · Almeida A · Zhou Z · Mu D · Paul Ross R · Stanton C · Wang S last · Casaburi G first · Wei J · Kazi S · Liu J · Wang K · Tao GZ · Lin PY · Dunn JCY · Henrick BM · Frese SA · Sylvester KG last · Stebliankin V first · Sazal M · Valdes C · Mathee K · Narasimhan G last · Lugli GA first · Mancabelli L · Milani C · Fontana F · Tarracchini C · Alessandri G · van Sinderen D · Turroni F · Ventura M last · Li S · Ying J · Wang H · Qu Y · Niu X · Xu X first · Feng Q · Zhang T · Gao Y · Cheng Q · Zhang W · Wu Q · Xu K · Li Y · Nguyen N · Taft DH · Mills DA · Lemay DG · Zhu W · Mao S · Zhang A · He W first · Russel J · Klincke F · Nesme J · Sørensen SJ last · Zhang L · Yuan Y · Tian M · Zhou M · Hu Y · Huang J · Zou R · Zhao F · Su X · Liu Q · He Y · Feng J · Huang W · Luo Y · Shen W · Valguarnera E first · Tung J · Pak JJ · Russell SK · Hecht DW · Schwartz DJ · Wardenburg JB last · Bücking R first · Pasquali G · Löber U · Buss C · Viemann D · Jarquín-Díaz VH · Forslund-Startceva SK last

PRJNA301903.csv.gz (15.6 KB) · parquet (91.9 KB) — all 403 samples, every field with route and confidence · PRJNA301903_determinations.csv.gz (48.3 KB) — 5,908 evidence rows