Abstract Body

Background:

The microbiome-gut-brain axis interplay is a major player in regulating the CNS status. In a substudy from the BCN02 trial, pro-inflammatory microbial signatures were identified as potential predictors of immune-mediated HIV-1 control in the absence of ART. Assessments from a BCN02 substudy investigating the CNS safety of using the histone deacetylase inhibitor romidepsin (RMD) showed no significant changes in neurocognitive and functional outcomes over the intervention. Here, we investigated possible interactions between the gut microbiota and CNS status in the BCN02 HIV vaccine strategy.

Methods:

Associations between microbial abundance (shotgun metagenomics), global neurocognitive functioning (NPZ-6) and functional outcomes (CNS-related symptoms, emotional status, daily functioning, and quality of life) were assessed in 2 subgroups from the BCN02 trial (intervention scheme shown in Figure): (i) HIV-1 viremic controllers and non-controllers (C-NC, n=11) and (ii) intervention and non-intervention (I-NI, n=16) at different timepoints (Figure). Spearman’s correlations and BH-adjusted p-values (≤0.05) were measured by R/rcorr. Gut microbiota profiling in subjects with lower (NPZ-6< -0.5; n=3) and higher (NPZ-6 >-0.5; n=15) global neurocognitive functioning at pre-RMD was performed using R/phyloseq.

Results:

In the C-NC subgroup, Clostridiales, Methanosphaera stadtmanae and Methanobrevibacter unclassified positively correlated with NPZ-6. Such associations were also observed in the I-NI subgroup, in which methanogenic archaea (Methanosphaera and Methanobrevibacter) as well as short fatty acids (SCFAs)-producing bacterial genera (Megasphaera and Phascolarctobacterium) positively correlated with NPZ-6. Bacteria associated with CNS disorders in previous reports, including Sutterella and Desulfovibrio spp. positively correlated with emotional status (depression, anxiety and perceived stress) and negatively with quality of life and NPZ-6. No discernable longitudinal trends were observed in the 2 subgroups. The gut microbiota of subjects with lower NPZ-6 was enriched in brain disorder-associated bacteria and related functions such as S. wadsworthensis and D. desulfuricans (α< 0.05,LDA >2.0) and 1,2-propanediol degradation pathway.

Conclusions:

Neurocognitive functioning positively associates with anti-inflammatory gut methanogenic archaea and SCFAs-producing bacteria in a HIV cure strategy. CNS disruption-associated bacteria are increased in individuals with lower global neurocognitive functioning.

BCN02 intervention scheme