The altered metabolites contributed by dysbiosis of gut microbiota are associated with microbial translocation and immune activation during HIV infection

Abstract

BackgroundThe immune activation caused by microbial translocation has been considered to be a major driver of HIV infection progression. The dysbiosis of gut microbiota has been demonstrated in HIV infection, but the interplay between gut microbiota and its metabolites in the pathogenesis of HIV is seldom reported.MethodsWe conducted a case-controlled study including 41 AIDS patients, 39 pre-AIDS patients and 34 healthy controls. Both AIDS group and pre-AIDS group were divided according to clinical manifestations and CD4 + T cell count. We collected stool samples for 16S rDNA sequencing and untargeted metabolomics analysis, and examined immune activation and microbial translocation for blood samples.ResultsThe pre-AIDS and AIDS groups had higher levels of microbial translocation and immune activation. There were significant differences in gut microbiota and metabolites at different stages of HIV infection. Higher abundances of pathogenic bacteria or opportunistic pathogen, as well as lower abundances of butyrate-producing bacteria and bacteria with anti-inflammatory potential were associated with HIV severity. The metabolism of tryptophan was disordered after HIV infection. Lower level of anti-inflammatory metabolites and phosphonoacetate, and higher level of phenylethylamine and polyamines were observed in HIV infection. And microbial metabolic pathways related to altered metabolites differed. Moreover, disrupted metabolites contributed by altered microbiota were found to be correlated to microbial translocation and immune activation.ConclusionsMetabolites caused by dysbiosis of gut microbiota and related metabolic function are correlated to immune activation and microbial translocation, suggesting that the effect of microbiota on metabolites is related to intestinal barrier disruption in HIV infection.

Dysbiosis of gut microbiota and metabolites during AIDS: implications for CD4+ T cell reduction and immune activation

“…There is increasing evidence that HIV infection is associated with gut microbiota dysbiosis [31][32][33][34][35][36]. Our previous research, based on a small population, confirmed that changes in gut microbiota diversity are related to HIV infection, particularly during the AIDS stage [37]. Here, with the largest horizontal study to date, we have further substantiated that the AIDS stage is associated with more severe gut microbiota dysbiosis.…”

Alterations in the Gut Microbiome Composition of People Living with HIV in the Asia–Pacific Region: A Systematic Review

“…The methodological characteristics of the studies are summarized in Table 1 . Geographically, most of the studies were conducted in China, accounting for 10 out of the 15 studies [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ], while the remaining studies were divided as follows: three were from Japan [ 32 , 33 , 34 ], one was from Thailand [ 35 ], and one was from Australia [ 36 ]. Study designs comprised eight cross-sectional studies [ 23 , 24 , 25 , 26 , 28 , 31 , 35 , 36 ], six prospective cohort studies [ 22 , 29 , 30 , 32 , 33 , 34 ], and one case–control study [ 27 ].…”

“…Geographically, most of the studies were conducted in China, accounting for 10 out of the 15 studies [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ], while the remaining studies were divided as follows: three were from Japan [ 32 , 33 , 34 ], one was from Thailand [ 35 ], and one was from Australia [ 36 ]. Study designs comprised eight cross-sectional studies [ 23 , 24 , 25 , 26 , 28 , 31 , 35 , 36 ], six prospective cohort studies [ 22 , 29 , 30 , 32 , 33 , 34 ], and one case–control study [ 27 ]. However, two of the prospective cohort studies only employed a cross-sectional approach to describing the gut microbiomes of their participants and did not include a longitudinal analysis or a comparison of microbiome changes or associations [ 22 , 29 ].…”

“…All studies used stool or fecal samples for gut microbiome analyses. Similarly, all studies performed metagenomics analyses using next-generation sequencing, but there were some differences in the amplified regions: 13 studies used the 16s rRNA V3–V4 regions [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 32 , 33 , 34 , 35 , 36 ], one study used 16s rRNA V1–V3 hypervariable regions [ 31 ], and one study utilized the 16s rDNA V4 region [ 22 ]. Regarding inclusion criteria, all studies included participants confirmed to have HIV infection with a further assessment of their clinical status based on their CD4 count, HIV viral load, and/or the presence of other comorbidities.…”

Neutralizing gut-derived lipopolysaccharide as a novel therapeutic strategy for severe leptospirosis

“…More importantly, from a translational perspective, our findings suggest that the increased risk of death in severe leptospirosis can be reduced by LPS neutralization combined with anti- Leptospira therapy. In fact, gut microbiota dysbiosis in COVID-19 patients or HIV infection is also associated with microbial translocation, LPS biosynthesis, and an expansion of Proteobacteria [61, 62]. The application of LPS antagonist therapies, whether microbial or pharmaceutical, may be a viable precision-medicine strategy to increase the survival rate of patients with severe leptospirosis or other gut-damaging infections by protecting against the spread of LPS in the bloodstream.…”