Gut microbiota in HIV–pneumonia patients is related to peripheral CD4 counts, lung microbiota, and in vitro macrophage dysfunction

Abstract

Pneumonia is common and frequently fatal in HIV-infected patients, due to rampant, systemic inflammation and failure to control microbial infection. While airway microbiota composition is related to local inflammatory response, gut microbiota has been shown to correlate with the degree of peripheral immune activation (IL6 and IP10 expression) in HIV-infected patients. We thus hypothesized that both airway and gut microbiota are perturbed in HIV-infected pneumonia patients, that the gut microbiota is related to peripheral CD4+ cell counts, and that its associated products differentially program immune cell populations necessary for controlling microbial infection in CD4-high and CD4-low patients. To assess these relationships, paired bronchoalveolar lavage and stool microbiota (bacterial and fungal) from a large cohort of Ugandan, HIV-infected patients with pneumonia were examined, and in vitro tests of the effect of gut microbiome products on macrophage effector phenotypes performed. While lower airway microbiota stratified into three compositionally distinct microbiota as previously described, these were not related to peripheral CD4 cell count. In contrast, variation in gut microbiota composition significantly related to CD4 cell count, lung microbiota composition, and patient mortality. Compared with patients with high CD4+ cell counts, those with low counts possessed more compositionally similar airway and gut microbiota, evidence of microbial translocation, and their associated gut microbiome products reduced macrophage activation and IL-10 expression and increased IL-1β expression in vitro. These findings suggest that the gut microbiome is related to CD4 status and plays a key role in modulating macrophage function, critical to microbial control in HIV-infected patients with pneumonia.Electronic supplementary materialThe online version of this article (10.1186/s40168-019-0651-4) contains supplementary material, which is available to authorized users.

Dysbiotic Fecal Microbiome in HIV-1 Infected Individuals in Ghana

“…In contrast, the relative abundance in the genera identified to be more abundant in HIV-showed a trend of positive correlation with fecal microbiome alpha diversity and CD4 counts. Enrichment of Streptococcus in fecal microbiome of HIV-1 infected individuals with low CD4 counts has been reported previously (Monaco et al, 2016;Shenoy et al, 2019). The inverse correlation of relative abundance in Gemella and Streptococcus with CD4 counts in the present study (Figure 7 and Supplementary Figures 5C, D) may imply association of these bacteria with immunosuppression (Shenoy et al, 2019;Ueberroth and Roxas, 2019).…”

“…Enrichment of Streptococcus in fecal microbiome of HIV-1 infected individuals with low CD4 counts has been reported previously ( Monaco et al., 2016 ; Shenoy et al., 2019 ). The inverse correlation of relative abundance in Gemella and Streptococcus with CD4 counts in the present study ( Figure 7 and Supplementary Figures 5C, D ) may imply association of these bacteria with immunosuppression ( Shenoy et al., 2019 ; Ueberroth and Roxas, 2019 ). Furthermore, this study showed reduction of several butyrate producing bacteria including Faecalibacterium, Butyricimonas , and other members of Ruminococcaceae , known for their role in maintenance of gut homeostasis ( Furusawa et al., 2013 ), in HIV+ as previously reported ( Dillon et al., 2017 ).…”

HIV, Sexual Orientation, and Gut Microbiome Interactions

“…Notably, these studies controlling for MSM status account for only 33% (N = 16) of the total studies (N = 48) comparing HIV+ to HIV− patients published to date [29, 50-54, 56-58, 60-64, 68, 76, 83-85, 88-100]. Several other studies variably controlled for MSM status but had no HIV-control group [15,30,32,34,38,54,66,67,69,[101][102][103][104][105][106][107][108]. Thus, the majority of published studies to date have been insufficiently controlled for the critical variable of MSM status, limiting interpretation of the data.…”

Resistance to human immunodeficiency virus infection: a rare but neglected state

“…Rocafort and coworker 148 reported that the gut microbiota signature of recently HIV‐infected patients is characterized by a depletion of representatives from Akkermansia , Anaerovibrio , Bifidobacterium , and Clostridium . Another recent study 149 performed on a cohort of HIV‐infected pneumonia patients confirmed that the gut microbiota of HIV‐infected individuals included a high relative abundance of members from Bacteroidaceae, Enterococcaceae, Enterobacteriaceae, Ruminococcaceae, and/or Prevotellaceae in association with Ruminococcaceae representatives, and was related to the patient's CD4 + cell counts; the relatively high abundance of phylum Ruminococcaceae contrasts with that observed in previous studies. Future investigation is required to investigate whether these changes are specific to HIV infection or are simply a consequence of the gut inflammation process.…”