Table 2.

Signature Pathways Altered Between the Drug-User and Non-User Cohorts based on the significant DE genes. Pathway enrichments were assessed using the Laboratory of Immunopathogenesis and Bioinformatics resource, DAVID. Only Pathway associations with a p-value < 0.05 and an FDR < 10% were considered statistically noteworthy

Top Canonical Pathways associated with DE genes	FDR (%)	p-value
METFORMIN
Extracellular Exosome	6.2	2.5 × 10–3
LPS/IL-1 Mediated Inhibition of RXR Function	8.1	1.1 × 10–3
Histamine Biosynthesis	8.1	2.0 × 10–3
Protein Digestion	8.5	2.8 × 10–4
NSAIDS
Antiviral Defense	2 × 10–2	5.6 × 10–7
Cell Division and Chromosome Partitioning	9.8 × 10–2	6.6 × 10–6
type I interferon signaling pathway	0.16	3.2 × 10–6
Inhibition of Viral Genome Replication	2.2	3.5 × 10–5
Innate Immunity	5.7	4.7 × 10–4
STATIN
Antigen Presentation Pathway	1 × 10–3	1.5 × 10–7
Interferon-gamma-mediated signaling pathway	1.9 × 10–3	2.9 × 10–8
Regulation of interleukin-10 secretion	5.1 × 10–3	2 × 10–9
OX40 Signaling Pathway	8.7 × 10–3	5.2 × 10–6
Regulation of interleukin-4 production	1 × 10–2	7.8 × 10–9
B Cell Development	1.5 × 10–2	1.2 × 10–5
Cdc42 Signaling	3.4 × 10–2	5.7 × 10–5
Nur77 Signaling in T Lymphocytes	3.4 × 10–2	5.7 × 10–5
Th1 and Th2 Activation Pathway	4.3 × 10–2	8.7 × 10–5
Dendritic Cell Maturation	4.6 × 10–2	1 × 10–4
iCOS-iCOSL Signaling in T Helper Cells	0.17	5.1 × 10–4
CD28 Signaling in T Helper Cells	0.19	6.3 × 10–4
Phagosome Maturation	0.26	8.7 × 10–4
PKCtheta Signaling in T Lymphocytes	0.3	1.1 × 10–3
Role of NFAT in Regulation of the Immune Response	0.46	1.7 × 10–3
Role of JAK family kinases in IL-6-type Cytokine Signaling	7.1	3.1 × 10–2