Changes in intestinal microbiota in HIV-1-infected subjects following cART initiation: influence of CD4+ T cell count

Ji, Yongjia; Zhang, Fengdi; Zhang, Renfang; Shen, Yinzhong; Liu, Li; Wang, Jiangrong; Yang, Junyang; Tang, Qi; Xun, Jingna; Qi, Tangkai; Wang, Zhenyan; Song, Wei; Tang, Yang; Chen, Jun; Lu, Hongzhou

doi:10.1038/s41426-018-0117-y

Cited by 43 publications

(60 citation statements)

References 38 publications

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“…MDC has emerged as novel modulator of lung inflammation in mice 48 and an inflammatory marker to assess the severity of atopic dermatitis in children and infants 49 . More recently, the increased levels of MDC in HIV-infected adults have also been reported 50 . This suggests the potential inflammatory role of MDC in HIV-infected children, however the level of MDC normalizes after initiation of ART.…”

Section: Discussionmentioning

confidence: 87%

High Abundance of genus Prevotella in the gut of perinatally HIV-infected children is associated with IP-10 levels despite therapy

Kaur

Shet

Rajnala

et al. 2018

Sci Rep

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Perinatal HIV infection is characterized by faster HIV disease progression and higher initial rate of HIV replication compared to adults. While antiretroviral therapy (ART) has greatly reduced HIV replication to undetectable levels, there is persistent elevated inflammation associated with HIV disease progression. Alteration of gut microbiota is associated with increased inflammation in chronic adult HIV infection. Here, we aim to study the gut microbiome and its role in inflammation in treated and untreated HIV-infected children. Examination of fecal microbiota revealed that perinatally infected children living with HIV had significantly higher levels of genus Prevotella that persisted despite ART. These children also had higher levels of soluble CD14 (sCD14), a marker of microbial translocation, and IP-10 despite therapy. The Prevotella positively correlated with IP-10 levels in both treated and untreated HIV-infected children, while genus Prevotella and species Prevotella copri was inversely associated with CD4 count. Relative abundance of genus Prevotella and species Prevotella copri showed positive correlation with sCD14 in ART-suppressed perinatally HIV-infected children. Our study suggests that gut microbiota may serve as one of the driving forces behind the persistent inflammation in children despite ART. Reshaping of microbiota using probiotics may be recommended as an adjunctive therapy along with ART.

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Section: Discussionmentioning

confidence: 87%

High Abundance of genus Prevotella in the gut of perinatally HIV-infected children is associated with IP-10 levels despite therapy

Kaur

Shet

Rajnala

et al. 2018

Sci Rep

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“…It is important to mention that the effect of cART introduction in the modulation of gut microbiota is not completely understood. However, very recently Ji et al showed that this modulation after cART was differentially correlated with the immune status, especially in patients with CD4 + T cell counts>300/mm 3 ( 92 ). In these patients it was shown that the alpha diversity was correlated with CD4 + T cell counts, but the specific role of cART in increasing microbial diversity is still controversial ( 78 , 92 , 93 ).…”

Section: Sources Of Immune Activation and Insulin Resistance In Hiv Pmentioning

confidence: 99%

“…However, very recently Ji et al showed that this modulation after cART was differentially correlated with the immune status, especially in patients with CD4 + T cell counts>300/mm 3 ( 92 ). In these patients it was shown that the alpha diversity was correlated with CD4 + T cell counts, but the specific role of cART in increasing microbial diversity is still controversial ( 78 , 92 , 93 ). This correlation may explain the conflicting results in previous studies investigating alpha diversity in intestinal microbiota in HIV patients ( 93 – 96 ), indicating that this diversity is consequence of the immune status of the subjects.…”

Section: Sources Of Immune Activation and Insulin Resistance In Hiv Pmentioning

confidence: 99%

Insulin Resistance in HIV-Patients: Causes and Consequences

et al. 2018

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Here we review how immune activation and insulin resistance contribute to the metabolic alterations observed in HIV-infected patients, and how these alterations increase the risk of developing CVD. The introduction and evolution of antiretroviral drugs over the past 25 years has completely changed the clinical prognosis of HIV-infected patients. The deaths of these individuals are now related to atherosclerotic CVDs, rather than from the viral infection itself. However, HIV infection, cART, and intestinal microbiota are associated with immune activation and insulin resistance, which can lead to the development of a variety of diseases and disorders, especially with regards to CVDs. The increase in LPS and proinflammatory cytokines circulating levels and intracellular mechanisms activate serine kinases, resulting in insulin receptor substrate-1 (IRS-1) serine phosphorylation and consequently a down regulation in insulin signaling. While lifestyle modifications and pharmaceutical interventions can be employed to treat these altered metabolic functions, the mechanisms involved in the development of these chronic complications remain largely unresolved. The elucidation and understanding of these mechanisms will give rise to new classes of drugs that will further improve the quality of life of HIV-infected patients, over the age of 50.

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“…However, these studies did not consider the immune response to ART and implement few in China [7]. Recently, several studies reported that gut microbiota was associated with CD4 recovery in HIV-infected patients [8][9][10]. The microbiome of chronic HIV infected individuals were studied in China, however, these patients had heterogeneous HIV progression and immune response to ART [11,12].…”

Section: Introductionmentioning

confidence: 99%

Altered gut microbiota correlate with different immune response to HAART in HIV-infected individuals

Xie

Sun

et al. 2020

Preprint

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Background: Although gut microbiota dysbiosis has recently been reported in HIV infected individuals, the relationship between the gut microbiota and immune activation in patients with a different immune response to highly active antiretroviral therapy (HAART) is still not well understood. Gut microbiota and immune activation were studied in 36 non-HIV-infected subjects (Health Control) and 58 HIV-infected individuals which included 28 immunological responders (IR) and 30 immunological non-responders (INR) (≥500 and <200 CD4+ T-cell counts/µl after 2 years of HIV-1 viral suppression respectively) without comorbidities. Results: Metagenome sequencing revealed that the gut microbiota dysbiosis could not be recovered completely in HIV-infected immunological responders and immunological non-responders although with long-term suppressive antiretroviral treatment. At the 97% similarity level, Fusobacterium, Ruminococcus_gnavus and Megamonas were more abundant, whereas Faecalibacterium, Alistipes, Bifidobacterium, Eubacteriumrectale and Roseburia were more depleted in the IR and INR groups than that in the health control. Ruminococcaceae and Alistipes were positively correlated with nadir and current CD4+ T-cell counts, but negatively correlated with CD8+CD57+ T-cell counts. Inflammation markers and translocation biomarkers (LPS) levels were positively correlated with the abundance of genus Ruminococcus and Fusobacterium, but were negatively correlated with the genus Faecalibacterium. The relative abundances of Escherichia-Shigella and Blautia were significantly higher in the IR than that in the INR group. Escherichia-Shigella were negatively correlated with the CD4/CD8 ratio but positively correlated with the amount of CD8+CD57+ T-cells. Roseburia and Blautia were negatively associated with nadir CD4+ T-cell and positively associated with CD8+CD57+ T-cell counts. Conclusions: Gut microbiota dysbiosis may be one of the factors contributing to different immune response to HAART. Fusobacterium, Alistipes, Ruminococcaceae, Faecalibacterium, Escherichia-Shigella, Roseburia and Blautia maybe the major genus contributed to different immune response in immunodiscordant and immunoconcordant patients on long-term suppressive ART. Blautia and Roseburia might be associated with treatment outcome.

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Changes in intestinal microbiota in HIV-1-infected subjects following cART initiation: influence of CD4+ T cell count

Cited by 43 publications

References 38 publications

High Abundance of genus Prevotella in the gut of perinatally HIV-infected children is associated with IP-10 levels despite therapy

High Abundance of genus Prevotella in the gut of perinatally HIV-infected children is associated with IP-10 levels despite therapy

Insulin Resistance in HIV-Patients: Causes and Consequences

Altered gut microbiota correlate with different immune response to HAART in HIV-infected individuals

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