The effects of prebiotics on microbial dysbiosis, butyrate production and immunity in HIV-infected subjects

Abstract

Altered interactions between the gut mucosa and bacteria during HIV infection seem to contribute to chronic immune dysfunction. A deeper understanding of how nutritional interventions could ameliorate gut dysbiosis is needed. Forty-four subjects, including 12 HIV viremic untreated (VU) patients, 23 antiretroviral therapy-treated (ART) virally suppressed patients (15 immunological responders and 8 non-responders) and 9 HIV controls (HIV), were blindly randomized to receive either prebiotics (scGOS/lcFOS/glutamine) or placebo (34/10) over 6 weeks in this pilot study. We assessed fecal microbiota composition using deep 16S rRNA gene sequencing and several immunological and genetic markers involved in HIV immunopathogenesis. The short dietary supplementation attenuated HIV-associated dysbiosis, which was most apparent in VU individuals but less so in ART subjects, whose gut microbiota was found more resilient. This compositional shift was not observed in the placebo arm. Significantly, declines in indirect markers of bacterial translocation and T-cell activation, improvement of thymic output, and changes in butyrate production were observed. Increases in the abundance of Faecalibacterium and Lachnospira strongly correlated with moderate but significant increases of butyrate production and amelioration of the inflammatory biomarkers soluble CD14 and high-sensitivity C-reactive protein, especially among VU. Hence, the bacterial butyrate synthesis pathway holds promise as a viable target for interventions.

Anaerobic Bacterial Fermentation Products Increase Tuberculosis Risk in Antiretroviral-Drug-Treated HIV Patients

“…The source of butyrate in the blood of the longitudinal cohort is currently unclear. Since gut and vaginal microbiomes also have HIV associated dysbiosis with epithelial dysfunction (Borgdorff et al, 2016; Serrano-Villar et al, 2016) non-pulmonary sources may contribute to the HIV associated SCFA elevation in the blood. Additionally, the BAL studies are cross sectional.…”

“…An assessment of the contribution of bacterial SCFA production to local immune suppression will require placebo-controlled randomized clinical trials using SCFA as a measurable outcome. If anaerobically-produced SCFA are immune-compromising, then antibiotic or prebiotic treatments that reduce SCFA (Serrano-Villar et al, 2016) might improve immune response.…”

The immune response to Prevotella bacteria in chronic inflammatory disease

“…). A recent interventional study administering prebiotics to HIV patients found that short dietary supplementation attenuated gut dysbiosis and systemic inflammation . However, longitudinal studies in humans and experimental work in mice are needed to delineate a causal relationship between HIV‐induced Prevotella ‐rich dysbiosis, inflammation and adverse disease outcomes.…”

Ranitidine and finasteride inhibit the synthesis and release of trimethylamine N-oxide and mitigates its cardiovascular and renal damage through modulating gut microbiota

“…High-throughput sequencing analysis of the 16S gene in the microbial genome revealed that there were significant increases in the quantities of microbes in the families g_Helicobacter, f_Desulfovibrionaceae, Mucispirillum_schaedleri_ASF457, and g_Blautia in the faeces of mice treated with ranitidine and finasteride, whereas the relative abundances of microbes in the families Enterobacter_sp_.IPC1-8 and g_Bacteroides were significantly reduced. The prevalence of corresponding metabolic pathways, such as nucleotide and cofactor and vitamin metabolismwere significantly increased, whereas those of metabolic signalling pathways related to glycan biosynthesis and metabolism and cardiovascular diseases were significantly reduced.It is known that Blautia can proliferate under the stimulation of prebiotics and is a typical beneficial bacteria [27,28]. Serrano-Villar S et al found that Blautia was significantly increased in the gut microbiota when normal individuals consumed probiotics [27].…”