Extended Data Fig. 2: Characterization of the gut microbiome in an Israeli cohort of PLWH by shotgun metagenomic sequencing.

(a) Differential species abundance between untreated PLWH and HC, controlling for mode of transmission. Wald test with FDR correction (DESeq2). Dashed lines: p adjusted of 0.05. Differentially abundant species are shown in color according to disease status; black, non-differentially abundant species. (b) Differential species abundance between PLWH on ART and HC, controlling for mode of transmission. Wald test with FDR correction (DESeq2). Dashed lines: p adjusted of 0.05. Differentially abundant species are shown in color according to disease status; black, non-differentially abundant species. (c–d) Alpha diversity analysis comparing untreated PLWH, PLWH on ART, and HC, as shown in Fig. 2a and Fig. 2c, was repeated after excluding individuals with MSM behavior. Two-sided Mann-Whitney test (p = 0.0165). (c) Simpson’s diversity index comparing untreated PLWH (n = 46) and HC (n = 20); values are plotted as mean ± SEM. (d) Simpson’s diversity index comparing PLWH on ART (n = 42) and HC (n = 20); values are plotted as mean ± SEM. (e) Linear model showing the association between CD4⁺ T cell counts and blood CRP levels in PLWH (simple linear regression, p < 0.019). (f) Pairwise comparison of the Simpson’s index between untreated PLWH and PLWH on ART (n = 55/group). Wilcoxon matched-pairs signed rank test. Plotted values represent mean ± SEM. (g) PCoA of pairwise comparison between untreated PLWH and PLWH on ART. PERMANOVA. (h) Pairwise comparison of differential species abundance between untreated PLWH and PLWH on ART, controlling for patientID. Wald test with FDR correction (DESeq2). Dashed lines: p adjusted of 0.05. Differentially abundant species are shown in color according to the group of PLWH; black, non-differentially abundant species. For pairwise comparisons, the first blood and stool sample collected before initiation of ART and the last blood and stool sample collected during ART were compared. (i–j) Differential viral species abundance between (i) untreated PLWH and (j) PLWH on ART compared to HC, controlling for mode of transmission. Wald test with FDR correction (DESeq2). Differentially abundant viral species are colored according to disease status; non-significant species are shown in black. * p < 0.05; ART, antiretroviral treatment; HC, healthy controls; PCoA, principal coordinate analysis; PC, principal component; PLWH, people living with human immunodeficiency virus; Padj, adjusted P value.