Probiotic effects on immunity and microbiome in HIV-1 discordant patients

Some HIV-1 infected patients are unable to completely recover normal CD4+ T-cell (CD4+) counts after achieving HIV-1 suppression with combined Antiretroviral Therapy (cART), hence being classified as immuno-discordant. The human microbiome plays a crucial role in maintaining immune homeostasis and i...

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Autores: Blázquez-Bondia, Carlos|||0000-0001-8409-008X, Parera, Mariona|||0000-0002-0756-8307, Català-Moll, Francesc|||0000-0002-2354-8648, Casadellà, Maria|||0000-0002-4115-2305, Elizalde-Torrent, Aleix|||0000-0001-7405-777X, Aguiló, Meritxell|||0000-0001-5367-8737, Espadaler Mazo, Jordi|||0000-0002-0128-8363, Santos, José Ramon, Paredes, Roger|||0000-0002-6553-691X, Noguera-Julian, Marc|||0000-0002-6194-1395
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:281731
Acceso en línea:https://ddd.uab.cat/record/281731
https://dx.doi.org/urn:doi:10.3389/fimmu.2022.1066036
Access Level:acceso abierto
Palabra clave:HIV
Immune reconstitution
Prebiotics
Probiotics
Synbiotics
id ES_bdb2bb8f5510e677a3efdca725423629
oai_identifier_str oai:ddd.uab.cat:281731
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Probiotic effects on immunity and microbiome in HIV-1 discordant patients
title Probiotic effects on immunity and microbiome in HIV-1 discordant patients
spellingShingle Probiotic effects on immunity and microbiome in HIV-1 discordant patients
Blázquez-Bondia, Carlos|||0000-0001-8409-008X
HIV
Immune reconstitution
Prebiotics
Probiotics
Synbiotics
title_short Probiotic effects on immunity and microbiome in HIV-1 discordant patients
title_full Probiotic effects on immunity and microbiome in HIV-1 discordant patients
title_fullStr Probiotic effects on immunity and microbiome in HIV-1 discordant patients
title_full_unstemmed Probiotic effects on immunity and microbiome in HIV-1 discordant patients
title_sort Probiotic effects on immunity and microbiome in HIV-1 discordant patients
dc.creator.none.fl_str_mv Blázquez-Bondia, Carlos|||0000-0001-8409-008X
Parera, Mariona|||0000-0002-0756-8307
Català-Moll, Francesc|||0000-0002-2354-8648
Casadellà, Maria|||0000-0002-4115-2305
Elizalde-Torrent, Aleix|||0000-0001-7405-777X
Aguiló, Meritxell|||0000-0001-5367-8737
Espadaler Mazo, Jordi|||0000-0002-0128-8363
Santos, José Ramon
Paredes, Roger|||0000-0002-6553-691X
Noguera-Julian, Marc|||0000-0002-6194-1395
author Blázquez-Bondia, Carlos|||0000-0001-8409-008X
author_facet Blázquez-Bondia, Carlos|||0000-0001-8409-008X
Parera, Mariona|||0000-0002-0756-8307
Català-Moll, Francesc|||0000-0002-2354-8648
Casadellà, Maria|||0000-0002-4115-2305
Elizalde-Torrent, Aleix|||0000-0001-7405-777X
Aguiló, Meritxell|||0000-0001-5367-8737
Espadaler Mazo, Jordi|||0000-0002-0128-8363
Santos, José Ramon
Paredes, Roger|||0000-0002-6553-691X
Noguera-Julian, Marc|||0000-0002-6194-1395
author_role author
author2 Parera, Mariona|||0000-0002-0756-8307
Català-Moll, Francesc|||0000-0002-2354-8648
Casadellà, Maria|||0000-0002-4115-2305
Elizalde-Torrent, Aleix|||0000-0001-7405-777X
Aguiló, Meritxell|||0000-0001-5367-8737
Espadaler Mazo, Jordi|||0000-0002-0128-8363
Santos, José Ramon
Paredes, Roger|||0000-0002-6553-691X
Noguera-Julian, Marc|||0000-0002-6194-1395
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv HIV
Immune reconstitution
Prebiotics
Probiotics
Synbiotics
topic HIV
Immune reconstitution
Prebiotics
Probiotics
Synbiotics
description Some HIV-1 infected patients are unable to completely recover normal CD4+ T-cell (CD4+) counts after achieving HIV-1 suppression with combined Antiretroviral Therapy (cART), hence being classified as immuno-discordant. The human microbiome plays a crucial role in maintaining immune homeostasis and is a potential target towards immune reconstitution. RECOVER (NCT03542786) was a double-blind placebo-controlled clinical trial designed to evaluate if the novel probiotic i3.1 (AB-Biotics, Sant Cugat del Vallès, Spain) was able to improve immune reconstitution in HIV-1 infected immuno-discordant patients with stable cART and CD4+ counts <500 cells/mm3. The mixture consisted of two strains of L. plantarum and one of P. acidilactici, given with or without a fiber-based prebiotic. 71 patients were randomized 1:2:2 to Placebo, Probiotic or probiotic + prebiotic (Synbiotic), and were followed over 6 months + 3-month washout period, in which changes on systemic immune status and gut microbiome were evaluated. Primary endpoints were safety and tolerability of the investigational product. Secondary endpoints were changes on CD4+ and CD8+ T-cell (CD8+) counts, inflammation markers and faecal microbiome structure, defined by alpha diversity (Gene Richness), beta diversity (Bray-Curtis) and functional profile. Comparisons across/within groups were performed using standard/paired Wilcoxon test, respectively. Adverse event (AE) incidence was similar among groups (53%, 33%, and 55% in the Placebo, Probiotic and Synbiotic groups, respectively, the most common being grade 1 digestive AEs: flatulence, bloating and diarrhoea. Two grade 3 AEs were reported, all in the Synbiotic group: abdominal distension (possibly related) and malignant lung neoplasm (unrelated), and 1 grade 4 AE in the Placebo: hepatocarcinoma (unrelated). Synbiotic exposure was associated with a higher increase in CD4+/CD8+ T-cell (CD4/CD8) ratio at 6 months vs baseline (median=0.76(IQR=0.51) vs 0.72(0. 45), median change= 0.04(IQR=0.19), p = 0.03). At month 9, the Synbiotic group had a significant increase in CD4/CD8 ratio (0.827(0.55) vs 0.825(0.53), median change = 0.04(IQR=0.15), p= 0.02) relative to baseline, and higher CD4+ counts (447 (157) vs. 342(73) counts/ml, p = 0.03), and lower sCD14 values (2.16(0.67) vs 3.18(0.8), p = 0.008) than Placebo. No effect in immune parameters was observed in the Probiotic arm. None of the two interventions modified microbial gene richness (alpha diversity). However, intervention as categorical variable was associated with slight but significant effect on Bray-Curtis distance variance (Adonis R2 = 0.02, p = 0.005). Additionally, at month 6, Synbiotic intervention was associated with lower pathway abundances vs Placebo of Assimilatory Sulphate Reduction (8.79·10 -6 (1.25·10 -5) vs. 1.61·10 -5 (2.77·10 -5), p = 0.03) and biosynthesis of methionine (2.3·10 -5 (3.17·10 -5) vs. 4·10 -5 (5.66·10 -5), p = 0.03) and cysteine (1.83·10 -5 (2.56·10 -5) vs. 3.3·10 -5 (4.62·10 -5), p = 0.03). At month 6, probiotic detection in faeces was associated with significant decreases in C Reactive Protein (CRP) vs baseline (11.1(22) vs. 19.2(66), median change= -2.7 (13.2) ug/ml, p = 0.04) and lower IL-6 values (0.58(1.13) vs. 1.17(1.59) ug/ml, p = 0.02) when compared with samples with no detectable probiotic. No detection of the probiotic was associated with higher CD4/CD8 ratio at month 6 vs baseline (0.718(0.57) vs. 0.58(0.4), median change = 0.4(0.2), p = 0.02). After washout, probiotic non-detection was also associated with a significant increase in CD4+ counts (457(153) vs. 416(142), median change = 45(75), counts/ml, p = 0.005) and CD4/CD8 ratio (0.67(0.5) vs 0.59(0.49), median change = 0.04 (0.18), p = 0.02). A synbiotic intervention with L. plantarum and P. acidilactici was safe and led to small increases in CD4/CD8 ratio and minor reductions in sCD14 of uncertain clinical significance. A probiotic with the same composition was also safe but did not achieve any impact on immune parameters or faecal microbiome composition.
publishDate 2022
dc.date.none.fl_str_mv 2
2022-01-01
2022
2022-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/281731
https://dx.doi.org/urn:doi:10.3389/fimmu.2022.1066036
url https://ddd.uab.cat/record/281731
https://dx.doi.org/urn:doi:10.3389/fimmu.2022.1066036
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Probiotic effects on immunity and microbiome in HIV-1 discordant patientsBlázquez-Bondia, Carlos|||0000-0001-8409-008XParera, Mariona|||0000-0002-0756-8307Català-Moll, Francesc|||0000-0002-2354-8648Casadellà, Maria|||0000-0002-4115-2305Elizalde-Torrent, Aleix|||0000-0001-7405-777XAguiló, Meritxell|||0000-0001-5367-8737Espadaler Mazo, Jordi|||0000-0002-0128-8363Santos, José RamonParedes, Roger|||0000-0002-6553-691XNoguera-Julian, Marc|||0000-0002-6194-1395HIVImmune reconstitutionPrebioticsProbioticsSynbioticsSome HIV-1 infected patients are unable to completely recover normal CD4+ T-cell (CD4+) counts after achieving HIV-1 suppression with combined Antiretroviral Therapy (cART), hence being classified as immuno-discordant. The human microbiome plays a crucial role in maintaining immune homeostasis and is a potential target towards immune reconstitution. RECOVER (NCT03542786) was a double-blind placebo-controlled clinical trial designed to evaluate if the novel probiotic i3.1 (AB-Biotics, Sant Cugat del Vallès, Spain) was able to improve immune reconstitution in HIV-1 infected immuno-discordant patients with stable cART and CD4+ counts <500 cells/mm3. The mixture consisted of two strains of L. plantarum and one of P. acidilactici, given with or without a fiber-based prebiotic. 71 patients were randomized 1:2:2 to Placebo, Probiotic or probiotic + prebiotic (Synbiotic), and were followed over 6 months + 3-month washout period, in which changes on systemic immune status and gut microbiome were evaluated. Primary endpoints were safety and tolerability of the investigational product. Secondary endpoints were changes on CD4+ and CD8+ T-cell (CD8+) counts, inflammation markers and faecal microbiome structure, defined by alpha diversity (Gene Richness), beta diversity (Bray-Curtis) and functional profile. Comparisons across/within groups were performed using standard/paired Wilcoxon test, respectively. Adverse event (AE) incidence was similar among groups (53%, 33%, and 55% in the Placebo, Probiotic and Synbiotic groups, respectively, the most common being grade 1 digestive AEs: flatulence, bloating and diarrhoea. Two grade 3 AEs were reported, all in the Synbiotic group: abdominal distension (possibly related) and malignant lung neoplasm (unrelated), and 1 grade 4 AE in the Placebo: hepatocarcinoma (unrelated). Synbiotic exposure was associated with a higher increase in CD4+/CD8+ T-cell (CD4/CD8) ratio at 6 months vs baseline (median=0.76(IQR=0.51) vs 0.72(0. 45), median change= 0.04(IQR=0.19), p = 0.03). At month 9, the Synbiotic group had a significant increase in CD4/CD8 ratio (0.827(0.55) vs 0.825(0.53), median change = 0.04(IQR=0.15), p= 0.02) relative to baseline, and higher CD4+ counts (447 (157) vs. 342(73) counts/ml, p = 0.03), and lower sCD14 values (2.16(0.67) vs 3.18(0.8), p = 0.008) than Placebo. No effect in immune parameters was observed in the Probiotic arm. None of the two interventions modified microbial gene richness (alpha diversity). However, intervention as categorical variable was associated with slight but significant effect on Bray-Curtis distance variance (Adonis R2 = 0.02, p = 0.005). Additionally, at month 6, Synbiotic intervention was associated with lower pathway abundances vs Placebo of Assimilatory Sulphate Reduction (8.79·10 -6 (1.25·10 -5) vs. 1.61·10 -5 (2.77·10 -5), p = 0.03) and biosynthesis of methionine (2.3·10 -5 (3.17·10 -5) vs. 4·10 -5 (5.66·10 -5), p = 0.03) and cysteine (1.83·10 -5 (2.56·10 -5) vs. 3.3·10 -5 (4.62·10 -5), p = 0.03). At month 6, probiotic detection in faeces was associated with significant decreases in C Reactive Protein (CRP) vs baseline (11.1(22) vs. 19.2(66), median change= -2.7 (13.2) ug/ml, p = 0.04) and lower IL-6 values (0.58(1.13) vs. 1.17(1.59) ug/ml, p = 0.02) when compared with samples with no detectable probiotic. No detection of the probiotic was associated with higher CD4/CD8 ratio at month 6 vs baseline (0.718(0.57) vs. 0.58(0.4), median change = 0.4(0.2), p = 0.02). After washout, probiotic non-detection was also associated with a significant increase in CD4+ counts (457(153) vs. 416(142), median change = 45(75), counts/ml, p = 0.005) and CD4/CD8 ratio (0.67(0.5) vs 0.59(0.49), median change = 0.04 (0.18), p = 0.02). A synbiotic intervention with L. plantarum and P. acidilactici was safe and led to small increases in CD4/CD8 ratio and minor reductions in sCD14 of uncertain clinical significance. A probiotic with the same composition was also safe but did not achieve any impact on immune parameters or faecal microbiome composition.Universitat Autònoma de Barcelona 22022-01-0120222022-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/281731https://dx.doi.org/urn:doi:10.3389/fimmu.2022.1066036reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2817312026-06-06T12:50:31Z
score 15,298079

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