HIV infection results in metabolic alterations in the gut microbiota different from those induced by other diseases

Abstract

Imbalances in gut bacteria have been associated with multiple diseases. However, whether there are disease-specific changes in gut microbial metabolism remains unknown. Here, we demonstrate that human immunodeficiency virus (HIV) infection (n = 33) changes, at quantifiable levels, the metabolism of gut bacteria. These changes are different than those observed in patients with the auto-immune disease systemic lupus erythaematosus (n = 18), and Clostridium difficile-associated diarrhoea (n = 6). Using healthy controls as a baseline (n = 16), we demonstrate that a trend in the nature and directionality of the metabolic changes exists according to the type of the disease. The impact on the gut microbial activity, and thus the metabolite composition and metabolic flux of gut microbes, is therefore disease-dependent. Our data further provide experimental evidence that HIV infection drastically changed the microbial community, and the species responsible for the metabolism of 4 amino acids, in contrast to patients with the other two diseases and healthy controls. The identification in this present work of specific metabolic deficits in HIV-infected patients may define nutritional supplements to improve the health of these patients.

The gut microbiome and HIV-1 pathogenesis

“…The former was characterized by enrichment of genes involved in LPS biosynthesis, bacterial translocation and inflammation, with depletion of genes encoding factors contributing to amino acid metabolism and energy processes[49]. A recent study suggested that HIV-1 infection results in metabolic alterations associated with changes in gut microbiota that differ from those induced in other diseases[83]. This “disease-dependent” impact on gut microbial activity was most notably characterized by a bacterial community with a reduced ability to synthesize a set of specific amino acids whereas these same amino acids are metabolized by bacteria from patients with systemic lupus erythaematosus (SLE) or Clostridium difficile infection[83].…”

Probiotics Differently Affect Gut-Associated Lymphoid Tissue Indolamine-2,3-Dioxygenase mRNA and Cerebrospinal Fluid Neopterin Levels in Antiretroviral-Treated HIV-1 Infected Patients: A Pilot Study

“…Directly related to this, HIV-1 infected patients are likely to harbor enteropathogenic bacteria that can catabolize tryptophan into immunomodulatory kynourenine derivatives, known to correlate with disease progression and mucosal immune disruption [6]. Indeed, it has been recently reported that HIV-1 infection leads to a significant and distinct impact on the metabolism of the gut ecosystem compared with other diseases [7]. In the course of HIV-1 infection, the chronic immune activation—partially due to a dysfunction of the GALT—with consequent microbial translocation has been linked with an increased production of interferon (IFN) gamma and IDO activity [8,9].…”

Biomarkers of aging in HIV: inflammation and the microbiome

“…In line with this observation, researches that followed showed that the microbiota is depleted in genes belonging to main energetic processes (pyruvate metabolism, glycolysis and gluconeogenesis) and amino acid metabolism [63] which could impact on cART-mediated reconstitution of CD4+ T-cells [69]. In addition, bacterial genera enriched in HIV-infected, untreated subjects were found to encode enzymes involved in tryptophan catabolism [70,71], an independent predictor of non-AIDS comorbidities and death [52,72], thus entailing that the dysbiotic bacteria in HIV infection may directly contribute to immunoactive tryptophan catabolism in HIV and negatively impact on overall mortality [70].…”