Elevated inflammatory fecal immune factors in men who have sex with men with HIV associate with microbiome composition and gut barrier function

Abstract

IntroductionPeople living with HIV infection (PLWH) exhibit elevated levels of gastrointestinal inflammation. Potential causes of this inflammation include HIV infection and associated immune dysfunction, sexual behaviors among men who have sex with men (MSM) and gut microbiome composition.MethodsTo better understand the etiology of gastrointestinal inflammation we examined levels of 28 fecal soluble immune factors (sIFs) and the fecal microbiome in well-defined cohorts of HIV seronegative MSM (MSM-SN), MSM with untreated HIV infection (MSM-HIV) and MSM with HIV on anti-retroviral treatment (MSMART). Additionally, fecal solutes from these participants were used to stimulate T-84 colonic epithelial cells to assess barrier function.ResultsBoth MSM cohorts with HIV had elevated levels of fecal calprotectin, a clinically relevant marker of GI inflammation, and nine inflammatory fecal sIFs (GM-CSF, ICAM-1, IL-1β, IL-12/23, IL-15, IL-16, TNF-β, VCAM-1, and VEGF). Interestingly, four sIFs (GM-CSF, ICAM-1, IL-7 and IL-12/23) were significantly elevated in MSM-SN compared to seronegative male non-MSM. Conversely, IL-22 and IL-13, cytokines beneficial to gut health, were decreased in all MSM with HIV and MSM-SN respectively. Importantly, all of these sIFs significantly correlated with calprotectin, suggesting they play a role in GI inflammation. Principal coordinate analysis revealed clustering of fecal sIFs by MSM status and significant associations with microbiome composition. Additionally, fecal solutes from participants in the MSM-HIV cohort significantly decreased colonic transcellular fluid transport in vitro, compared to non-MSM-SN, and this decrease associated with overall sIF composition and increased concentrations of eight inflammatory sIFs in participants with HIV. Lastly, elevated levels of plasma, sCD14 and sCD163, directly correlated with decreased transcellular transport and microbiome composition respectively, indicating that sIFs and the gut microbiome are associated with, and potentially contribute to, bacterial translocation.ConclusionTaken together, these data demonstrate that inflammatory sIFs are elevated in MSM, regardless of HIV infection status, and are associated with the gut microbiome and intestinal barrier function.

Gut microbiome dysbiosis in men who have sex with men increases HIV infection risk through immunity homeostasis alteration

“…Moreover, our results prompted that MSM behavior could alter human immunity response through gut microbiome dysbiosis, this might be the potential mechanism of T-cell phenotype alteration and bioenergy metabolism disorder in the MSM population ( Kruize et al., 2020 ). A recent study demonstrated that gut microbiome in MSM was associated with elevated inflammatory factors, which also supported our conclusion ( Littlefield et al., 2022 ). Different from meta-analysis, our study systematically retrieved HIV and MSM-associated gut microbiome changes from available studies and focused on the influence of these gut microbiomes on human immunity by bioinformatic technology.…”

Immune activation and inflammation in lactating women on combination antiretroviral therapy: role of gut dysfunction and gut microbiota imbalance

“…Subgroups with elevated fecal calprotectin levels included women with third-trimester CD4+ T-lymphocyte counts <350 cells/µL consistent with findings from previous studies ( 35 , 36 ). Other studies in HIV-infected individuals described similar ( 37 , 38 ) or elevated fecal calprotectin levels ( 8 , 9 ), most likely depending on the degree of gut mucosal damage and immune dysfunction despite taking cART ( 39 ). In our study, above normal median fecal calprotectin levels were observed in HIV-infected cART-experienced individuals, in agreement with studies in cART-naïve Italians ( 40 , 41 ).…”

“…The fecal calprotectin levels are thus a useful marker of gut inflammation and an indirect marker of intestinal permeability ( 7 ). Faecal calprotectin levels have been reported to be higher in the HIV-infected population even if on cART compared with that in HIV-uninfected peers ( 8 , 9 ). Despite these studies, the influence of gut inflammation on microbial translocation and systemic inflammation is still insufficiently understood.…”

Gut resistome linked to Sexual Preference and HIV infection

“…Recent studies have shown that gut microbiome of MSM is altered independently of HIV-1 infection status, showing higher levels of gastrointestinal in ammation 29 and contributing to an increased risk of HIV-1 infection 30 . On the other hand, Prevotella enriched enterotype in other populations has shown contradictory health effects being related to anti-in ammatory effects of diet 31 and lower risk of infection and mortality in critical care patients 32 but also to different in ammatory conditions 33,34 .…”