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. Author manuscript; available in PMC: 2024 Apr 30.
Published in final edited form as: Nat Microbiol. 2023 Oct 16;8(11):2033–2049. doi: 10.1038/s41564-023-01493-w

Figure 2: Lactulose use is associated with increased Bifidobacteria species abundance and reduced VRE abundance in the absence of systemic antibiotic use.

Figure 2:

(A) Relative abundance by shotgun taxonomy of one sample per subject is shown (n = 22 healthy donors, 262 patients with liver disease). The sample with highest Bifidobacteria abundance for each subject was analyzed. Samples were arranged first by whether they were obtained without lactulose (left) or within 7 days after lactulose administration (right) and then by decreasing Bifidobacterium relative abundance. Among the Bifidobacteriaceae family, a small number of non-Bifidobacteria members are part of the Actinobacteria phylum and are also shown in shades of purple. The antibiotic resistance (vanA) gene was queried and colored based on expression level normalized to gene length (RPKM). Cumulative oral lactulose dose (grams) for 7 days prior to sample collection is shown. Rifaximin, broad-spectrum antibiotics, proton pump inhibitors (PPI), and alternative laxatives exposure prior to sample collection is shown. Red = treatment was administered within 7 days prior to the sample being collected; green = treatment not given in this period. The chronicity of liver disease and whether a patient had clinically significant portal hypertension (green = no, red = yes) at time of consent is shown. Stool consistency was categorized as either liquid (yellow), semi-formed (turquoise), or formed (royal blue) for each sample. (B) Relative abundances of Bifidobacteria, Enterococcus, and Proteobacteria were quantified for samples from patients that were not exposed to antibiotics (including rifaximin) in the 7 preceding days. Samples were stratified based on lactulose exposure. One sample per patient was analyzed, and each dot represents a single value (n=47 (lactulose exposure), n=70 (no lactulose exposure). Median and interquartile range are indicated by the horizontal line and box, respectively. The lower vertical line depicts Q1 – 1.5*IQR and the upper vertical line depicts Q3 + 1.5*IQR. Statistical comparisons between groups were analyzed using a two-tailed Wilcoxon rank sum test. P-values are adjusted for multiple comparisons using the Benjamini-Hochberg procedure and represented as: *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001.