Latent tuberculosis infection (LTBI) in people living with HIV (PLHIV) raises the annual risk of tuberculosis reactivation by approximately 3%–16%. This study evaluates how LTBI shapes gut microbial composition, predicted microbial function, and immune‑metabolic interactions in ART‑naive individuals across HIV and TB disease states.
The authors performed integrated cross‑sectional analyses and exploratory longitudinal follow‑up to compare the gut microbiome and host immune‑metabolic parameters across defined groups: HIV‑LTBI‑, HIV‑LTBI+, HIV+LTBI‑, HIV+LTBI+, and HIV+TB+. Analyses included taxonomic profiling, predicted functional pathway inference, short‑chain fatty acid (SCFA) measurements, and correlation networks linking microbial taxa with immune markers.
Within the overall dysbiotic context associated with HIV infection, LTBI was associated with a distinct gut microbial and immune‑metabolic profile rather than simply amplifying HIV‑related dysbiosis. Individuals with both HIV and LTBI (HIV+LTBI+) exhibited alpha diversity measures comparable to HIV‑negative groups, yet their microbial community composition formed a separate cluster. A notable community‑level change was a reduced Firmicutes/Bacteroidota ratio in HIV+LTBI+ participants.
Co‑occurrence network analysis showed a densely connected microbiome in HIV+LTBI+ individuals but with greater vulnerability to loss of hub nodes, indicating a configuration that could be functionally sensitive to perturbations.
Compared with HIV+LTBI‑ individuals, the HIV+LTBI+ group demonstrated depletion of butyrate‑producing Firmicutes. Concurrently, there was enrichment of amplicon sequence variants (ASVs) assigned to Megasphaera, Prevotella, Bifidobacterium, and Streptococcus. These taxonomic shifts suggest altered fermentation capacity and potential effects on mucosal immune interactions, given the known roles of butyrate producers in maintaining gut barrier function and modulating inflammation.
Predictive functional profiling indicated reduced pathways for aromatic amino acid metabolism in HIV+LTBI+ samples. Despite the loss of many butyrate‑producing taxa, fecal propionate concentrations were maintained in HIV+LTBI+ individuals. The combination of taxonomic depletion of butyrate producers and preserved propionate suggests a shift in SCFA ecology rather than a uniform loss of SCFA production.
Staged correlation analyses across the HIV and TB disease spectrum revealed progressive remodeling of host–microbiome associations. Specific findings included correlations between Prevotella ASVs and immune markers such as PD‑1+CD8+ T cells and plasma IP‑10. In the HIV+TB+ group, measures of gut and systemic inflammation—calprotectin and sCD14—were increased and there were weakened associations among butyrate‑associated taxa and host markers. These patterns indicate shifting microbe–host interaction networks with advancing mycobacterial disease.
In exploratory longitudinal analyses of individuals initiating ART, the microbiome did not revert to a composition resembling HIV‑negative participants. Instead, post‑ART microbiomes remained closer to the baseline HIV+LTBI+ profile. Furthermore, the degree of microbiome divergence and patterns in SCFA profiles after ART were associated with the CD4/CD8 ratio rather than absolute CD4 count, implicating immune reconstitution dynamics in shaping microbiome recovery.
These results identify LTBI as an important modifier of gut microbiome composition and immune‑metabolic interactions in PLHIV. The distinct taxonomic, functional, and network features associated with HIV+LTBI+ may have relevance for susceptibility to reactivation and progression to active TB. The authors propose this framework to guide future longitudinal studies that directly investigate microbiome trajectories preceding TB reactivation and to explore whether microbiome‑targeted interventions could modify risk.
The abstract summarizes cross‑sectional findings and exploratory longitudinal observations; detailed methods, sample sizes, statistical parameters, and full data were not reported in the provided source excerpt. Specific numeric effect sizes, confidence intervals, and exact participant numbers by group were not available in the abstract text provided here.