Subsystems and pathways enriched or decreased within (A) Colon muscosa-associate microbiome, and (B) Fecal microbiome after induction of colitis in Control-DSS and ATB-DSS.

<p>Subsystems or pathways overrepresented in the ATB-DSS (Control-DSS) fecal or colon mucosa samples have a positive (negative) difference between mean proportions and are indicated by white (black) color. 10 mice per group.</p

Relative abundances of bacterial phyla in fecal samples collected before induction of colitis.

<p>Antepartum antibiotic exposure significantly decreased Firmicutes and Proteobacteria but increased Bacteroidetes population. 10 mice per group.</p

Antepartum Antibiotic Treatment Increases Offspring Susceptibility to Experimental Colitis: A Role of the Gut Microbiota

<div><p>Background and aims</p><p>Postnatal maturation of the immune system is largely driven by exposure to microbes, and thus the nature of intestinal colonization may be associated with development of childhood diseases that may persist into adulthood. We investigated whether antepartum antibiotic (ATB) therapy can increase offspring susceptibility to experimental colitis through alteration of the gut microbiota.</p><p>Methods</p><p>Pregnant C57Bl/6 mice were treated with cefazolin at 160 mg/kg body weight or with saline starting six days before due date. At 7 weeks, fecal samples were collected from male offspring after which they received 4% dextran sulfate sodium (DSS) in drinking water for 5 days. Disease activity index, histology, colonic IL-6, IL-1β and serum C-reactive protein (CRP) were determined. The V3-V4 region of colonic and fecal bacterial 16S rRNA was sequenced. Alpha-, beta-diversity and differences at the phylum and genus levels were determined, while functional pathways of classified bacteria were predicted.</p><p>Results</p><p>ATB influenced fecal bacterial composition and hence bacterial functional pathways before induction of colitis. After induction of colitis, ATB increased onset of clinical disease, histologic score, and colonic IL-6. In addition, ATB decreased fecal microbial richness, changed fecal and colon microbial composition, which was accompanied by a modification of microbial functional pathways. Also, several taxa were associated with ATB at lower taxonomical levels.</p><p>Conclusions</p><p>The results support the hypothesis that antepartum antibiotics modulate offspring intestinal bacterial colonization and increase susceptibility to develop colonic inflammation in a murine model of colitis, and may guide future interventions to restore physiologic intestinal colonization in offspring born by antibiotic-exposed mothers.</p></div

Partial least square discriminant analysis (PLS-DA) of bacterial communities comparing taxa that were associated with the Control-DSS or ATB-DSS treatments in the A) Colon mucosa, and B) Feces.

<p>All taxa are colored based on the phyla to which they belong and sized based on their relative abundance. Some sequences could only be affiliated to phylum (p.), class (c.), order (o.), or family (f.) levels. Specific taxa were positively or negatively associated with each treatment group, which may be an indicator of shifts in the physiological or metabolic processes that may be influenced by the taxa. 10 mice per group.</p

Rarefaction analysis on Chao 1, a measure of species richness based on operational taxonomic unit (OTU), following DSS treatment for the Control-DSS and ATB-DSS mice colon mucosa-associated (A) and fecal microbiota (B) Control-DSS and ATB-DSS had similar richness in the colon mucosa-associated microbiota; however, ATB-DSS had a lower fecal richness compared to the Control-DSS.

<p>10 mice per group.</p

Partial least square discriminant analysis (PLS-DA) of bacterial communities comparing taxa that were associated with the Control or ATB treatments in the fecal samples collected before induction of colitis.

<p>All taxa are coloured based on the phyla to which they belong and sized based on their relative abundance. Some sequences could only be affiliated to phylum (p.), class (c.), order (o.), or family (f.) levels. Specific taxa were positively or negatively associated with each treatment group, which may be an indicator of shifts in the physiological or metabolic processes that may be influenced by the taxa. 10 mice per group.</p

Subsystems and pathways enriched or decreased within fecal microbiome from Control and ATB groups before induction of colitis.

<p>Corrected <i>P</i> values were calculated using the Storey false discover rate (FDR) correction. Subsystems or pathways overrepresented in the ATB (Control) fecal samples have a positive (negative) difference between mean proportions and are indicated by white (black) color. 10 mice per group.</p

Principle coordinate analysis (PCoA) of (A) Unweighted (<i>P</i> = 0.0001) and (B) Weighted (<i>P</i> = 0.0001) UniFrac distances in fecal microbiota after induction of colitis.

<p>Fecal samples clustered according to the treatment and the mother (<i>P</i> = 0.001) further influenced the clustering. The <i>P</i> values were determined using PERMANOVA. 10 mice per group (two samples were excluded due to very low sequencing depth). Control-DSS-M1 and Control-DSS-M2 shows mice in the control group but from two different mothers; ATB-DSS-M1 and ATB-DSS-M2 shows mice in the ATB (antibiotic) group but from two different mothers.</p

Principle coordinate analysis (PCoA) of (A) Unweighted (<i>P</i> = 0.0004) and (B) Weighted (<i>P</i> = 0.06) UniFrac distances in colon mucosa-associated microbiota (MAM) after induction of colitis.

<p>Colonic samples clustered according to the treatment. The clustering was further influenced by the mother (<i>P</i> < 0.001) especially in unweighted ATB-DSS (<i>P</i> = 0.009). The <i>P</i> values were determined using PERMANOVA. 10 mice per group. Control-DSS-M1 and Control-DSS-M2 shows mice in the control group but from two different mothers; ATB-DSS-M1 and ATB-DSS-M2 shows mice in the ATB (antibiotic) group but from two different mothers.</p

Relative abundances of bacterial phyla after induction of colitis in the colon mucosa (A) and in the feces (B).

<p>No significant difference was observed in the abundant phyla between the treatment groups. 10 mice per group.</p