Probiotic/prebiotic supplementation of antiretrovirals improves gastrointestinal immunity in SIV-infected macaques

Klatt, Nichole R.; Canary, Lauren; Sun, Xiaoyong; Vinton, Carol L.; Funderburg, Nicholas T.; Morcock, David R.; Quiñones, Mariam; Deming, Clay; Perkins, Molly R.; Hazuda, Daria J.; Miller, Michael D.; Lederman, Michael M.; Segre, Julie; Lifson, Jeffrey D.; Haddad, Elias K.; Estes, Jacob D.; Brenchley, Jason M.

doi:10.1172/jci66227

Cited by 115 publications

(151 citation statements)

References 24 publications

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“…In addition to direct binding of microbial products with sevelamer, such strategies should alleviate gastrointestinal tract inflammation and damage; reduce the microbial burden, thus enhancing gastrointestinal immune function; and increase reconstitution of mucosal CD4 + T cells, potentially having a beneficial impact on morbidity and mortality. These strategies may include administration of antibiotics, antiinflammatory drugs, or synbiotic-probiotic supplementation of antiretroviral treatment (27). Clinical trials assessing each of these strategies are underway.…”

Section: Figurementioning

confidence: 99%

Early microbial translocation blockade reduces SIV-mediated inflammation and viral replication

Kristoff¹,

Haret-Richter²,

Ma³

et al. 2014

J. Clin. Invest.

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Damage to the intestinal mucosa results in the translocation of microbes from the intestinal lumen into the circulation. Microbial translocation has been proposed to trigger immune activation, inflammation, and coagulopathy, all of which are key factors that drive HIV disease progression and non-HIV comorbidities; however, direct proof of a causal link is still lacking. Here, we have demonstrated that treatment of acutely SIV-infected pigtailed macaques with the drug sevelamer, which binds microbial lipopolysaccharide in the gut, dramatically reduces immune activation and inflammation and slightly reduces viral replication. Furthermore, sevelamer administration reduced coagulation biomarkers, confirming the contribution of microbial translocation in the development of cardiovascular comorbidities in SIV-infected nonhuman primates. Together, our data suggest that early control of microbial translocation may improve the outcome of HIV infection and limit noninfectious comorbidities associated with AIDS.

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Section: Figurementioning

confidence: 99%

Early microbial translocation blockade reduces SIV-mediated inflammation and viral replication

Kristoff¹,

Haret-Richter²,

Ma³

et al. 2014

J. Clin. Invest.

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“…ϩ T cell restoration in the GI tract after probiotic therapy or therapy with probiotics supplemented with interleukin-21 (IL-21) (15,16). In HIV-infected individuals, probiotics have been shown to decrease inflammation and microbial translocation (17,18).…”

mentioning

confidence: 99%

Effects of Fecal Microbial Transplantation on Microbiome and Immunity in Simian Immunodeficiency Virus-Infected Macaques

Hensley-McBain

Zevin

Manuzak

et al. 2016

J Virol

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An altered intestinal microbiome during chronic human immunodeficiency virus (HIV) infection is associated with mucosal dysfunction, inflammation, and disease progression. We performed a preclinical evaluation of the safety and efficacy of fecal microbiota transplantation (FMT) as a potential therapeutic in HIV-infected individuals. Antiretroviral-treated, chronically simian immunodeficiency virus (SIV)-infected rhesus macaques received antibiotics followed by FMT. The greatest microbiota shift was observed after antibiotic treatment. The bacterial community composition at 2 weeks post-FMT resembled the pre-FMT community structure, although differences in the abundances of minor bacterial populations remained. Immunologically, we observed significant increases in the number of peripheral Th17 and Th22 cells and reduced CD4؉ T cell activation in gastrointestinal tissues post-FMT. Importantly, the transplant was well tolerated with no negative clinical side effects. Although this pilot study did not control for the differential contributions of antibiotic treatment and FMT to the observed results, the data suggest that FMT may have beneficial effects that should be further evaluated in larger studies. IMPORTANCE Due to the immunodeficiency and chronic inflammation that occurs during HIV infection, determination of the safety of FMT is crucial to prevent deleterious consequences if it is to be used as a treatment in the future. Here we used the macaque model of HIV infection and performed FMT on six chronically SIV-infected rhesus macaques on antiretroviral treatment. In addition toproviding a preclinical demonstration of the safety of FMT in primates infected with a lentivirus, this study provided a unique opportunity to examine the relationships between alterations to the microbiome and immunological parameters. In this study, we found increased numbers of Th17 and Th22 cells as well as decreased activation of CD4 ؉ T cells post-FMT, and these changes correlated most strongly across all sampling time points with lower-abundance taxonomic groups and other taxonomic groups in the colon. Overall, these data provide evidence that changes in the microbiome, particularly in terms of diversity and changes in minor populations, can enhance immunity and do not have adverse consequences.A ntiretroviral treatment (ART) has substantially decreased the progression to AIDS in human immunodeficiency virus (HIV)-infected individuals. However, despite the ability to suppress viremia, HIV-infected individuals in whom the infection is suppressed by ART have increased rates of morbidity and mortality compared to those of uninfected individuals (1). One mechanism underlying the increased mortality is dysfunction of the gastrointestinal (GI) tract, which is associated with inflammation during HIV infection. Several lines of evidence support the role of GI dysfunction in HIV-related disease, including (i) a consistent association between mortality in HIV-infected individuals and markers of microbial translocation and gut epithe...

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“…Las células mononucleares de sangre periférica (PBMC) tratadas con Lactobacillus sakei y Escherichia coli Nissle aumentan la expresión de CD69 y CD25 y de citoquinas proinflamatorias como iL-1β, iL-6, TNF-α y GM-CSF en comparación con PBMC tratados únicamente con lipopolisacáridos (LPS) 28 . Asimismo, algunas especies de probióticos mejoran la actividad de los linfocitos Th17 e inducen una respuesta tipo Th1, favoreciendo la inmunidad celular 29 . No obstante, se ha demostrado que el uso de probióticos puede aumentar la frecuencia de LT reguladores e inducir la producción de iL-10 30 , además de regular negativamente la secreción de citoquinas proinflamatorias en PBMC de pacientes con colitis ulcerativa y síndrome de fatiga crónica 31 .…”

Section: Modulación De La Respuesta Inmuneunclassified

“…Por otra parte, el impacto potencial de la terapia simbiótica en la infección por el vih-1 se ha demostrado en modelos animales de macacos infectados con el virus de la inmunodeficiencia simiana, un virus homólogo del vih-1. En este modelo se observó que en los animales tratados con simbióticos (vSL#3 e inulina) hubo una disminución en la expresión de CD38 y hLA-DR en LT comparado con el placebo, además de un incremento en la expresión de genes relacionados con células presentadoras de antígeno y en la actividad polifuncional de los linfocitos Th17, lo que sugiere un rol importante en el restablecimiento del GALT 29 . Finalmente, en la Tabla 1 se resumen los ensayos clínicos más importantes reportados a la fecha relacionados con el impacto que tiene la suplementación con prebióticos y probióti-cos o simbióticos en la evolución clínica de los .…”

Section: Efectos De Los Probióticos Prebióticos Y Terapia Simbióticaunclassified

Efecto de la terapia con probióticos/prebióticos sobre la reconstitución del tejido linfoide asociado a la mucosa gastrointestinal durante la infección por el virus de la inmunodeficiencia humana-1

et al. 2017

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Probiotic/prebiotic supplementation of antiretrovirals improves gastrointestinal immunity in SIV-infected macaques

Cited by 115 publications

References 24 publications

Early microbial translocation blockade reduces SIV-mediated inflammation and viral replication

Early microbial translocation blockade reduces SIV-mediated inflammation and viral replication

Effects of Fecal Microbial Transplantation on Microbiome and Immunity in Simian Immunodeficiency Virus-Infected Macaques

Efecto de la terapia con probióticos/prebióticos sobre la reconstitución del tejido linfoide asociado a la mucosa gastrointestinal durante la infección por el virus de la inmunodeficiencia humana-1

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