Gut Bacteria Metabolism Impacts Immune Recovery in HIV-infected Individuals

Abstract

While changes in gut microbial populations have been described in human immuno-deficiency virus (HIV)-infected patients undergoing antiretroviral therapy (ART), the mechanisms underlying the contributions of gut bacteria and their molecular agents (metabolites and proteins) to immune recovery remain unexplored. To study this, we examined the active fraction of the gut microbiome, through examining protein synthesis and accumulation of metabolites inside gut bacteria and in the bloodstream, in 8 healthy controls and 29 HIV-infected individuals (6 being longitudinally studied). We found that HIV infection is associated to dramatic changes in the active set of gut bacteria simultaneously altering the metabolic outcomes. Effects were accentuated among immunological ART responders, regardless diet, subject characteristics, clinical variables other than immune recovery, the duration and type of ART and sexual preferences. The effect was found at quantitative levels of several molecular agents and active bacteria which were herein identified and whose abundance correlated with HIV immune pathogenesis markers. Although, we cannot rule out the possibility that some changes are partially a random consequence of the disease status, our data suggest that most likely reduced inflammation and immune recovery is a joint solution orchestrated by both the active fraction of the gut microbiota and the host.

The genital tract and rectal microbiomes: their role in HIV susceptibility and prevention in women

“…Several studies have suggested that HIV alters the microbiome . In addition to differences in species composition, altered bacterial metabolic activity has been noted in HIV infection . However, recent studies have suggested that at least some of the differences between the gut microbiota of HIV‐positive and HIV‐negative individuals may be linked to sexual preference , leaving an open question as to how HIV infection impacts the microbial composition of the gut, and in turn how this impacts its interaction with the host immune system (also greatly impacted by HIV).…”

Phenotyping of gut microbiota: Focus on capillary electrophoresis

“…We know now that a large proportion of the bacteria colonizing a person's colon are dead, dormant or inactive and that only a minor fraction works actively . To differentiate between bacteria that are alive from which are dead, dormant or inactive, we need to extract the RNA, transform it into cDNA by reverse transcription, and then sequence the 16S rRNA molecule .…”

“…When a multiplatform analysis is under consideration, one of the first questions to answer is whether the analytical platform can introduce bias in the outcomes. Regarding the series of principal component analysis (PCA) scatter plots obtained from a set of metabolites that fulfilled the filtering criteria , it was recently found that the clustering of the metabolome samples from patient's colon with human immuno‐deficiency virus (HIV) infection, systemic lupus erythaematosus and infectious diarrhea caused by Clostridium difficile , is highly similar among the separation techniques. Therefore, in metabolomics fingerprinting no bias should be directly associated with the analytical platform.…”

“…Nowadays, it involves the computational analysis of thousands of signals that can provide a global overview of an organism in real time. Moreover, thanks to this approach, it is possible to elucidate complex pathways and networks that are impaired under specific disease states . In a broad sense, the metabolome is the downstream product of the biochemical pathways that are a direct consequence of the relationships between genetic expression, protein synthesis and enzyme activity .…”

Capillary electrophoresis mass spectrometry based metabolomics

“…While Fuji [138] used the uniqueness of CE-MS to identify metabolites in brain tissue specific to Schizophrenia. The remainder of Table 3 lists publications related to lifestyle; alcohol intake [125], physical activity [150]], microbiome [142,145,147] and to various diseases; eye disease [140,141], inborn errors of metabolism [143], kidney disease [144], diabetes [139], metabolic syndrome [149], osteoporosis [129] and encephalopathy [148]. These publications represent a variety of subjects and sample types [serum plasma, cultured cells, PBMCs, tissue] that are amendable to CE-MS metabolomics profiling, specifically, polar hydrophilic metabolites found in critical pathways such as amino acid metabolism, central energy metabolism, inflammation, stress oxidative pathways, glycolysis, cancer metabolism, and lipid transportation.…”