Gut Microbiota and Fecal Metabolites Associated With Neurocognitive Impairment in HIV-Infected Population

Abstract

Gut microbiota dysbiosis has been associated with many neurological diseases. However, how microbiota composition and metabolism relate to neurocognitive impairment (NCI) in HIV-infected individuals is largely unknown. In this study, a total of 102 HIV infected participants were classified into two groups—those with NCI and those without—using the global deficit score (GDS). Fecal samples were collected from the participants for 16S rRNA gene sequencing and untargeted metabolomics. The plasma level of 25 hydroxy-vitamin D (25(OH)D) was also evaluated. Although α-diversity and β-diversity were comparable, the HIV patients with NCI were significantly different from those without NCI in terms of abundance of several gut microbiota. The decreased abundance of butyrate-producing bacteria (BPB) and increased abundance of Klebsiella were related with NCI and carotid intima-media thickness (CIMT). Significant differences in fecal metabolites were also found between individuals with versus without NCI, including increased bile acids and bioactive lipids, decreased vitamin D, terpenoids, and resolvin D1 in the NCI group. Furthermore, the perturbed metabolic profile was closely related to BPB and Klebsiella. In addition, a low level of vitamin D was associated with NCI and CIMT. Both fecal and plasma vitamin D were positively correlated with BPB. Our results show that BPB and Klebsiella and the associated metabolites are associated with NCI in people with HIV. In addition, vitamin D, both in feces and blood, was associated with NCI and BPB, suggesting a protective effect of vitamin D on NCI.

Research Progress in the Epidemiology of HIV/AIDS in China

“…The same group also performed 16S rRNA gene sequencing and untargeted metabolomics on fecal samples of PLWH with or without neurocognitive impairment (NCI). The results show that the decreased abundance of butyrate-producing bacteria, the increased abundance of Klebsiella, and the associated metabolites were associated with NCI in PLWH ( 65 ).…”

“…Very recently, Ding et al conducted a case-control study using untargeted metabolomics to characterize the key metabolites and metabolic pathways associated with HIV infection and multiple NCDs, focusing on identifying the common metabolic pathways underlying them (64). They found that PLWH presented widespread alterations in cellular metabolism versus HIV-negative individuals, and glycerophospholipid metabolism emerged as the potential common metabolic pathway underlying NCDs in treated HIV infection; followed by d-glutamine and d-glutamate, and alanine, aspartate and glutamate metabolism.…”

“…For example, Jiang et al found that more MSM self-tested for HIV (52.1% vs. 41.6%) but fewer MSM used facility-based HIV testing (42.9% vs. 54.1%) during COVID-19 measures compared to before COVID-19 measures (68). Furthermore, as compared to PLWH in other countries and the general population in most parts of the world, PLWH in China reported a relatively low willingness to receive the COVID-19 vaccination (69). The internet and social media as well as interpersonal communications may be major sources of influence on PLWH's perceptions and willingness to receive COVID-19 vaccination, which have important implications for immunization programs targeting PLWH.…”

Altered gut microbiota is associated with different immunologic responses to antiretroviral therapy in HIV‐infected men who have sex with men

“…[22][23][24] However, previous studies mainly focused on comparing the gut microbiota between HIVinfected and HIV-uninfected heterosexual individuals and have not considered the immunologic response among PLHIV on ART. [25][26][27][28] In many settings, men who have sex with men (MSM) account for the majority of HIV/AIDS cases. 29 However, the role of microbiota in immune reconstitution for HIV-infected MSM is still understudied.…”

Differential Gut Microbiota Compositions Related With the Severity of Major Depressive Disorder

“…Gut microbiota plays an important role in maintaining the host’s health, and many researchers pay attention to the cross talk between the gut and brain ( Han et al., 2020 ; Qiao et al., 2020 ; Kovács et al., 2021 ; Khoshkam et al., 2021 ). Mounting evidence shows that gut microbiota can affect the host’s brain functions and behaviors via the “microbiota–gut–brain” axis ( Chen et al., 2021 ; Rajput et al., 2021 ; Ding et al., 2021 ; Dong et al., 2021 ). In our previous work, we found significant differences in gut microbiota compositions between MDD patients and healthy controls (HC) ( Chen et al., 2020 ; Bai et al., 2021 ), and these differences were specifically relative to bipolar disorder and schizophrenia ( Zheng et al., 2019 ; Zheng et al., 2020 ).…”