Microbial translocation revisited: targeting the endotoxic potential of gut microbes in HIV-infected individuals.
AIDS
; 33(4): 645-653, 2019 03 15.
Article
en En
| MEDLINE
| ID: mdl-30531315
ABSTRACT
OBJECTIVE:
Translocation of microbial products such as lipopolysaccharides (LPS) from the gut may contribute to chronic inflammation in HIV-infected individuals. Recent studies indicate that differences in degree of acylation of gut-bacterial-derived LPS may explain variable immune effects, with hexa-acylated rather than penta-acylated LPS having proinflammatory capacity. We investigated whether the degree of acylation of gut-derived LPS associates with systemic inflammation, and the potential effect of probiotic intervention.METHODS:
Gut microbiota profiles from a probiotics intervention were investigated and validated in a cohort of HIV-infected individuals commencing antiretroviral therapy. The PiCRUSt software was used to predict overall functional capacity of the microbiota and in-house bioinformatics to distinguish between bacteria producing hexa-acylated and penta-acylated LPS. RESULTS ANDCONCLUSION:
HIV-infected individuals with the highest ratio of proinflammatory hexa-acylated LPS to noninflammatory penta-acylated LPS-producing bacteria exhibited increased levels of systemic inflammation (neopterin, Pâ<â0.001) and tryptophan catabolism (kynurenine/tryptophan ratio, Pâ=â0.01), indicating a link between proinflammatory LPS, tryptophan catabolism and inflammation. After probiotics for 8 weeks, there was a decrease in Gram-negative bacteria (Pâ=â0.01), related primarily to a reduction in bacteria producing penta-acylated LPS (Pâ=â0.01), but not hexa-acylated LPS. The reduction in Gram-negative bacteria correlated positively with decreased plasma LPS (râ=â0.72), mainly related to a reduction in bacteria producing noninflammatory penta-acylated LPS (râ=â0.58). Notably, gut bacteria producing hexa-acylated LPS were outnumbered by penta-acylated LPS with a factor of 25 in HIV-infected individuals. Further studies are warranted to determine whether microbes producing hexa-acylated LPS might be a more relevant trigger of systemic inflammation compared with plasma LPS captured by the existing limulus assay.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
Problema de salud:
2_enfermedades_transmissibles
Asunto principal:
Infecciones por VIH
/
Lipopolisacáridos
/
Traslocación Bacteriana
/
Tracto Gastrointestinal
/
Inflamación
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
AIDS
Asunto de la revista:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Año:
2019
Tipo del documento:
Article