Fecal microbiota transplantation in HIV: A pilot placebo-controlled study

Sergio Serrano-Villar; Alba Talavera-Rodríguez; María José Gosalbes; Nadia Madrid; José A. Pérez-Molina; Ryan J. Elliott; Beatriz Navia; Val F. Lanza; Alejandro Vallejo; Majdi Osman; Fernando Dronda; Shrish Budree; Javier Zamora; Carolina Gutiérrez; Mónica Manzano; María Jesús Vivancos; Raquel Ron; Javier Martínez-Sanz; Sabina Herrera; Uxua Ansa; Andrés Moya; Santiago Moreno

doi:10.1038/s41467-021-21472-1

Fecal microbiota transplantation in HIV: A pilot placebo-controlled study

Sergio Serrano-Villar^*, Alba Talavera-Rodríguez, María José Gosalbes, Nadia Madrid, José A. Pérez-Molina, Ryan J. Elliott, Beatriz Navia, Val F. Lanza, Alejandro Vallejo, Majdi Osman, Fernando Dronda, Shrish Budree, Javier Zamora, Carolina Gutiérrez, Mónica Manzano, María Jesús Vivancos, Raquel Ron, Javier Martínez-Sanz, Sabina Herrera, Uxua AnsaAndrés Moya, Santiago Moreno

^*Corresponding author for this work

Metabolism and Systems Science

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Abstract

Changes in the microbiota have been linked to persistent inflammation during treated HIV infection. In this pilot double-blind study, we study 30 HIV-infected subjects on antiretroviral therapy (ART) with a CD4/CD8 ratio < 1 randomized to either weekly fecal microbiota capsules or placebo for 8 weeks. Stool donors were rationally selected based on their microbiota signatures. We report that fecal microbiota transplantation (FMT) is safe, not related to severe adverse events, and attenuates HIV-associated dysbiosis. FMT elicits changes in gut microbiota structure, including significant increases in alpha diversity, and a mild and transient engraftment of donor’s microbiota during the treatment period. The greater engraftment seems to be achieved by recent antibiotic use before FMT. The Lachnospiraceae and Ruminococcaceae families, which are typically depleted in people with HIV, are the taxa more robustly engrafted across time-points. In exploratory analyses, we describe a significant amelioration in the FMT group in intestinal fatty acid-binding protein (IFABP), a biomarker of intestinal damage that independently predicts mortality. Gut microbiota manipulation using a non-invasive and safe strategy of FMT delivery is feasible and deserves further investigation. Trial number: NCT03008941.

Original language	English
Article number	1139
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-21472-1
Publication status	Published - 18 Feb 2021

Bibliographical note

Funding Information:
We thank all the study participants who contributed to this work, subjects who helped to disseminate the crowdfunding campaign to raise funds for this project, those who altruistically contributed with donations, as well as the clinical research staff who made this research possible. We especially thank Laura Luna and María Helena Álvarez for their technical support throughout the study. This work was supported by the Instituto de Salud Carlos III (Plan Estatal de I + D + i 2013–2016, project PI18/00154, a Gilead Fellowship (GLD16-00030), the SPANISH AIDS Research Network RD16/0025/ 0001project), and co-financed by the European Development Regional Fund ‘A way to achieve Europe’ (ERDF). The present investigation was also funded by the Instituto de Salud Carlos III and the Fundación Asociación Española contra el Cáncer within the ERANET TRANSCAN-2 program, grant number AC17/00022, a crowdfunding project from the precipita platform of the Fundación Española para la Ciencia y la Tecnología (FECYT) and a restricted grant from Finch Therapeutics. The SEIMC-GESIDA Foundation supported this study with safety and data monitoring (GESIDA 9116). The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Funding Information:
Outside the submitted work, S.S.-V. reports personal fees from ViiV Healthcare, Janssen Cilag, Gilead Sciences, and MSD as well as non-financial support from ViiV Healthcare and Gilead Sciences and research grants from MSD and Gilead Sciences. J.M.-S. reports non-financial support from ViiV Healthcare, Gilead Sciences, and Jannsen Cilag. J.P. reports grants, personal fees and non-financial support from ViiV Healthcare; grants, personal fees, and non-financial support from Gilead Sciences; grants, personal fees, and non-financial support from Janssen Cilag; personal fees from MSD; and personal fees from Abbvie. F.D. reports personal fees from Gilead. J.M.S. reports personal fees from ViiV Healthcare, Janssen Cilag, and Gilead Sciences. MJ.V. reports personal fees from Gilead Sciences, non-financial support from ViiV Healthcare, and Gilead Sciences, and grants from ViiV Healthcare. S.M. reports personal fees and non-financial from ViiV Healthcare, Janssen, Gilead Sciences, and MSD, as well as grants from MSD, ViiV Healthcare, and Gilead Sciences. S.B. and M.O. work for OpenBiome. R.E. was an employee at OpenBiome during the conduct of this study. A.T.-R., M.J.G., N.M., B.N., V.L., A.V., J.Z., C.G., M.M., R.R., S.H., U.A., and A.M. report no conflicts of interest.

Publisher Copyright:
© 2021, The Author(s).

ASJC Scopus subject areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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Cite this

Serrano-Villar, S., Talavera-Rodríguez, A., Gosalbes, M. J., Madrid, N., Pérez-Molina, J. A., Elliott, R. J., Navia, B., Lanza, V. F., Vallejo, A., Osman, M., Dronda, F., Budree, S., Zamora, J., Gutiérrez, C., Manzano, M., Vivancos, M. J., Ron, R., Martínez-Sanz, J., Herrera, S., ... Moreno, S. (2021). Fecal microbiota transplantation in HIV: A pilot placebo-controlled study. Nature Communications, 12(1), Article 1139. https://doi.org/10.1038/s41467-021-21472-1

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title = "Fecal microbiota transplantation in HIV: A pilot placebo-controlled study",

abstract = "Changes in the microbiota have been linked to persistent inflammation during treated HIV infection. In this pilot double-blind study, we study 30 HIV-infected subjects on antiretroviral therapy (ART) with a CD4/CD8 ratio < 1 randomized to either weekly fecal microbiota capsules or placebo for 8 weeks. Stool donors were rationally selected based on their microbiota signatures. We report that fecal microbiota transplantation (FMT) is safe, not related to severe adverse events, and attenuates HIV-associated dysbiosis. FMT elicits changes in gut microbiota structure, including significant increases in alpha diversity, and a mild and transient engraftment of donor{\textquoteright}s microbiota during the treatment period. The greater engraftment seems to be achieved by recent antibiotic use before FMT. The Lachnospiraceae and Ruminococcaceae families, which are typically depleted in people with HIV, are the taxa more robustly engrafted across time-points. In exploratory analyses, we describe a significant amelioration in the FMT group in intestinal fatty acid-binding protein (IFABP), a biomarker of intestinal damage that independently predicts mortality. Gut microbiota manipulation using a non-invasive and safe strategy of FMT delivery is feasible and deserves further investigation. Trial number: NCT03008941.",

author = "Sergio Serrano-Villar and Alba Talavera-Rodr{\'i}guez and Gosalbes, {Mar{\'i}a Jos{\'e}} and Nadia Madrid and P{\'e}rez-Molina, {Jos{\'e} A.} and Elliott, {Ryan J.} and Beatriz Navia and Lanza, {Val F.} and Alejandro Vallejo and Majdi Osman and Fernando Dronda and Shrish Budree and Javier Zamora and Carolina Guti{\'e}rrez and M{\'o}nica Manzano and Vivancos, {Mar{\'i}a Jes{\'u}s} and Raquel Ron and Javier Mart{\'i}nez-Sanz and Sabina Herrera and Uxua Ansa and Andr{\'e}s Moya and Santiago Moreno",

note = "Funding Information: We thank all the study participants who contributed to this work, subjects who helped to disseminate the crowdfunding campaign to raise funds for this project, those who altruistically contributed with donations, as well as the clinical research staff who made this research possible. We especially thank Laura Luna and Mar{\'i}a Helena {\'A}lvarez for their technical support throughout the study. This work was supported by the Instituto de Salud Carlos III (Plan Estatal de I + D + i 2013–2016, project PI18/00154, a Gilead Fellowship (GLD16-00030), the SPANISH AIDS Research Network RD16/0025/ 0001project), and co-financed by the European Development Regional Fund {\textquoteleft}A way to achieve Europe{\textquoteright} (ERDF). The present investigation was also funded by the Instituto de Salud Carlos III and the Fundaci{\'o}n Asociaci{\'o}n Espa{\~n}ola contra el C{\'a}ncer within the ERANET TRANSCAN-2 program, grant number AC17/00022, a crowdfunding project from the precipita platform of the Fundaci{\'o}n Espa{\~n}ola para la Ciencia y la Tecnolog{\'i}a (FECYT) and a restricted grant from Finch Therapeutics. The SEIMC-GESIDA Foundation supported this study with safety and data monitoring (GESIDA 9116). The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Funding Information: Outside the submitted work, S.S.-V. reports personal fees from ViiV Healthcare, Janssen Cilag, Gilead Sciences, and MSD as well as non-financial support from ViiV Healthcare and Gilead Sciences and research grants from MSD and Gilead Sciences. J.M.-S. reports non-financial support from ViiV Healthcare, Gilead Sciences, and Jannsen Cilag. J.P. reports grants, personal fees and non-financial support from ViiV Healthcare; grants, personal fees, and non-financial support from Gilead Sciences; grants, personal fees, and non-financial support from Janssen Cilag; personal fees from MSD; and personal fees from Abbvie. F.D. reports personal fees from Gilead. J.M.S. reports personal fees from ViiV Healthcare, Janssen Cilag, and Gilead Sciences. MJ.V. reports personal fees from Gilead Sciences, non-financial support from ViiV Healthcare, and Gilead Sciences, and grants from ViiV Healthcare. S.M. reports personal fees and non-financial from ViiV Healthcare, Janssen, Gilead Sciences, and MSD, as well as grants from MSD, ViiV Healthcare, and Gilead Sciences. S.B. and M.O. work for OpenBiome. R.E. was an employee at OpenBiome during the conduct of this study. A.T.-R., M.J.G., N.M., B.N., V.L., A.V., J.Z., C.G., M.M., R.R., S.H., U.A., and A.M. report no conflicts of interest. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = feb,

day = "18",

doi = "10.1038/s41467-021-21472-1",

language = "English",

volume = "12",

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Serrano-Villar, S, Talavera-Rodríguez, A, Gosalbes, MJ, Madrid, N, Pérez-Molina, JA, Elliott, RJ, Navia, B, Lanza, VF, Vallejo, A, Osman, M, Dronda, F, Budree, S, Zamora, J, Gutiérrez, C, Manzano, M, Vivancos, MJ, Ron, R, Martínez-Sanz, J, Herrera, S, Ansa, U, Moya, A & Moreno, S 2021, 'Fecal microbiota transplantation in HIV: A pilot placebo-controlled study', Nature Communications, vol. 12, no. 1, 1139. https://doi.org/10.1038/s41467-021-21472-1

TY - JOUR

T1 - Fecal microbiota transplantation in HIV

T2 - A pilot placebo-controlled study

AU - Serrano-Villar, Sergio

AU - Talavera-Rodríguez, Alba

AU - Gosalbes, María José

AU - Madrid, Nadia

AU - Pérez-Molina, José A.

AU - Elliott, Ryan J.

AU - Navia, Beatriz

AU - Lanza, Val F.

AU - Vallejo, Alejandro

AU - Osman, Majdi

AU - Dronda, Fernando

AU - Budree, Shrish

AU - Zamora, Javier

AU - Gutiérrez, Carolina

AU - Manzano, Mónica

AU - Vivancos, María Jesús

AU - Ron, Raquel

AU - Martínez-Sanz, Javier

AU - Herrera, Sabina

AU - Ansa, Uxua

AU - Moya, Andrés

AU - Moreno, Santiago

N1 - Funding Information: We thank all the study participants who contributed to this work, subjects who helped to disseminate the crowdfunding campaign to raise funds for this project, those who altruistically contributed with donations, as well as the clinical research staff who made this research possible. We especially thank Laura Luna and María Helena Álvarez for their technical support throughout the study. This work was supported by the Instituto de Salud Carlos III (Plan Estatal de I + D + i 2013–2016, project PI18/00154, a Gilead Fellowship (GLD16-00030), the SPANISH AIDS Research Network RD16/0025/ 0001project), and co-financed by the European Development Regional Fund ‘A way to achieve Europe’ (ERDF). The present investigation was also funded by the Instituto de Salud Carlos III and the Fundación Asociación Española contra el Cáncer within the ERANET TRANSCAN-2 program, grant number AC17/00022, a crowdfunding project from the precipita platform of the Fundación Española para la Ciencia y la Tecnología (FECYT) and a restricted grant from Finch Therapeutics. The SEIMC-GESIDA Foundation supported this study with safety and data monitoring (GESIDA 9116). The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Funding Information: Outside the submitted work, S.S.-V. reports personal fees from ViiV Healthcare, Janssen Cilag, Gilead Sciences, and MSD as well as non-financial support from ViiV Healthcare and Gilead Sciences and research grants from MSD and Gilead Sciences. J.M.-S. reports non-financial support from ViiV Healthcare, Gilead Sciences, and Jannsen Cilag. J.P. reports grants, personal fees and non-financial support from ViiV Healthcare; grants, personal fees, and non-financial support from Gilead Sciences; grants, personal fees, and non-financial support from Janssen Cilag; personal fees from MSD; and personal fees from Abbvie. F.D. reports personal fees from Gilead. J.M.S. reports personal fees from ViiV Healthcare, Janssen Cilag, and Gilead Sciences. MJ.V. reports personal fees from Gilead Sciences, non-financial support from ViiV Healthcare, and Gilead Sciences, and grants from ViiV Healthcare. S.M. reports personal fees and non-financial from ViiV Healthcare, Janssen, Gilead Sciences, and MSD, as well as grants from MSD, ViiV Healthcare, and Gilead Sciences. S.B. and M.O. work for OpenBiome. R.E. was an employee at OpenBiome during the conduct of this study. A.T.-R., M.J.G., N.M., B.N., V.L., A.V., J.Z., C.G., M.M., R.R., S.H., U.A., and A.M. report no conflicts of interest. Publisher Copyright: © 2021, The Author(s).

PY - 2021/2/18

Y1 - 2021/2/18

N2 - Changes in the microbiota have been linked to persistent inflammation during treated HIV infection. In this pilot double-blind study, we study 30 HIV-infected subjects on antiretroviral therapy (ART) with a CD4/CD8 ratio < 1 randomized to either weekly fecal microbiota capsules or placebo for 8 weeks. Stool donors were rationally selected based on their microbiota signatures. We report that fecal microbiota transplantation (FMT) is safe, not related to severe adverse events, and attenuates HIV-associated dysbiosis. FMT elicits changes in gut microbiota structure, including significant increases in alpha diversity, and a mild and transient engraftment of donor’s microbiota during the treatment period. The greater engraftment seems to be achieved by recent antibiotic use before FMT. The Lachnospiraceae and Ruminococcaceae families, which are typically depleted in people with HIV, are the taxa more robustly engrafted across time-points. In exploratory analyses, we describe a significant amelioration in the FMT group in intestinal fatty acid-binding protein (IFABP), a biomarker of intestinal damage that independently predicts mortality. Gut microbiota manipulation using a non-invasive and safe strategy of FMT delivery is feasible and deserves further investigation. Trial number: NCT03008941.

AB - Changes in the microbiota have been linked to persistent inflammation during treated HIV infection. In this pilot double-blind study, we study 30 HIV-infected subjects on antiretroviral therapy (ART) with a CD4/CD8 ratio < 1 randomized to either weekly fecal microbiota capsules or placebo for 8 weeks. Stool donors were rationally selected based on their microbiota signatures. We report that fecal microbiota transplantation (FMT) is safe, not related to severe adverse events, and attenuates HIV-associated dysbiosis. FMT elicits changes in gut microbiota structure, including significant increases in alpha diversity, and a mild and transient engraftment of donor’s microbiota during the treatment period. The greater engraftment seems to be achieved by recent antibiotic use before FMT. The Lachnospiraceae and Ruminococcaceae families, which are typically depleted in people with HIV, are the taxa more robustly engrafted across time-points. In exploratory analyses, we describe a significant amelioration in the FMT group in intestinal fatty acid-binding protein (IFABP), a biomarker of intestinal damage that independently predicts mortality. Gut microbiota manipulation using a non-invasive and safe strategy of FMT delivery is feasible and deserves further investigation. Trial number: NCT03008941.

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U2 - 10.1038/s41467-021-21472-1

DO - 10.1038/s41467-021-21472-1

M3 - Article

C2 - 33602945

AN - SCOPUS:85101278889

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

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M1 - 1139

ER -

Fecal microbiota transplantation in HIV: A pilot placebo-controlled study

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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