A randomized trial evaluating virus-specific effects of a combination probiotic in children with acute gastroenteritis

the Pediatric Emergency Research Canada Probiotic (PERC) Regimen for Outpatient Gastroenteritis Utility of Treatment (PROGUT) Trial Group

doi:10.1038/s41467-020-16308-3

A randomized trial evaluating virus-specific effects of a combination probiotic in children with acute gastroenteritis

the Pediatric Emergency Research Canada Probiotic (PERC) Regimen for Outpatient Gastroenteritis Utility of Treatment (PROGUT) Trial Group

Pediatrics

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

Abstract

Gastroenteritis accounts for nearly 500,000 deaths in children younger than 5 years annually. Although probiotics have been touted as having the potential to expedite diarrhea resolution, recent clinical trials question their effectiveness. A potential explanation is a shift in pathogens following the introduction of a rotavirus vaccine. Here, we report the results of a multi-center, double-blind trial of 816 children with acute gastroenteritis who completed follow-up and provided multiple stool specimens. Participants were randomized to receive a probiotic containing Lactobacillus rhamnosus and Lactobacillushelveticus or placebo. We report no virus-specific beneficial effects attributable to the probiotic, either in reducing clinical symptoms or viral nucleic acid clearance from stool specimens collected up to 28 days following enrollment. We provide pathophysiological and microbiologic evidence to support the clinical findings and conclude that our data do not support routine probiotic administration to children with acute gastroenteritis, regardless of the infecting virus.

Original language	English (US)
Article number	2533
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-16308-3
State	Published - Dec 1 2020

Bibliographical note

Funding Information:
We thank the participants and their families for trusting us to conduct this trial; the trial investigators and support staff across all sites for their commitment to the successful and diligent conduct of the trial; the site coordinators, including Marie-Christine Auclair, R.N., B.Sc.N., Zach Cantor, B.A., Kamary Coriolano Da Silva, Ph.D., Dale Dalgleish, B.H. Sc.N., Eleanor Fitzpatrick, M.N., Kelly Kim, B.Sc., B.A., Maggie Rumantir, M.D., Judy Sweeney, R.N., B.Sc.N., and Avery Yandt, B.Sc., B.A., for trial coordination; the staff of Lallemand Health Solutions, Calgary Laboratory Services, Alberta Health Services, Research Pharmacy, Provincial Laboratory for Public Health, Edmonton and Calgary, Alberta, for supporting the conduct of this trial; the emergency department physicians, nurses, and ancillary staff at all trial sites; the Pediatric Emergency Medicine Research Associates’ Program at Alberta Children’s Hospital, the Students Undertaking a Pediatric Program of Research Training program at the Children’s Hospital of Eastern Ontario, and the staff of the Pediatric Research Academic Initiative in SickKids Emergency program at the Hospital for Sick Children, for identifying potentially eligible trial participants; and Dr. Marie Louie (Calgary) for building the connections that made the microbiologic investigations possible. No compensation for the assistance provided by any aforementioned persons was provided. This study was supported by the Canadian Institutes of Health Research (grants 286384 and 325412), the Alberta Children’s Hospital Foundation Professorship in Child Health and Wellness (to Dr. Freedman), a grant from the Alberta Children’s Hospital Foundation to the Pediatric Emergency Medicine Research Associates’ Program, Calgary Laboratory Services (in kind), Provincial Laboratory for Public Health–Alberta Public Laboratories, Luminex, and Copan Italia. P.M.S. is the recipient of a Canada Research Chair in Gastrointestinal Disease.

Funding Information:
None of the authors have any potential or perceived conflicts of interest to declare. The study sponsors played no role in study design, conduct, data acquisition, analysis, manuscript preparation or the decision to submit the manuscript for publication. Dr. Stephen Freedman provides consulting services to Takeda Pharmaceuticals Inc. and was an invited speaker at the 10th Probiotics, Prebiotics and New Foods, Nutraceuticals and Botanicals for Nutrition and Human and Microbiota Health. PMS serves on advisory boards for Antibe Therapeutics, Cargill and Nestle-Gerber. He has received honoraria from Abbott Nutrition for speaking at continuing medical education activities and received research support from Lallemand Human Nutrition for a postdoctoral fellow award through a Mitacs Accelerates Internship.

Publisher Copyright:
© 2020, The Author(s).

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SDG 3 Good Health and Well-being

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10.1038/s41467-020-16308-3

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A randomized trial evaluating virus-specific effects of a combination probiotic in children with acute gastroenteritis. / the Pediatric Emergency Research Canada Probiotic (PERC) Regimen for Outpatient Gastroenteritis Utility of Treatment (PROGUT) Trial Group.
In: Nature communications, Vol. 11, No. 1, 2533, 01.12.2020.

Research output: Contribution to journal › Article › peer-review

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title = "A randomized trial evaluating virus-specific effects of a combination probiotic in children with acute gastroenteritis",

abstract = "Gastroenteritis accounts for nearly 500,000 deaths in children younger than 5 years annually. Although probiotics have been touted as having the potential to expedite diarrhea resolution, recent clinical trials question their effectiveness. A potential explanation is a shift in pathogens following the introduction of a rotavirus vaccine. Here, we report the results of a multi-center, double-blind trial of 816 children with acute gastroenteritis who completed follow-up and provided multiple stool specimens. Participants were randomized to receive a probiotic containing Lactobacillus rhamnosus and Lactobacillushelveticus or placebo. We report no virus-specific beneficial effects attributable to the probiotic, either in reducing clinical symptoms or viral nucleic acid clearance from stool specimens collected up to 28 days following enrollment. We provide pathophysiological and microbiologic evidence to support the clinical findings and conclude that our data do not support routine probiotic administration to children with acute gastroenteritis, regardless of the infecting virus.",

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note = "Funding Information: We thank the participants and their families for trusting us to conduct this trial; the trial investigators and support staff across all sites for their commitment to the successful and diligent conduct of the trial; the site coordinators, including Marie-Christine Auclair, R.N., B.Sc.N., Zach Cantor, B.A., Kamary Coriolano Da Silva, Ph.D., Dale Dalgleish, B.H. Sc.N., Eleanor Fitzpatrick, M.N., Kelly Kim, B.Sc., B.A., Maggie Rumantir, M.D., Judy Sweeney, R.N., B.Sc.N., and Avery Yandt, B.Sc., B.A., for trial coordination; the staff of Lallemand Health Solutions, Calgary Laboratory Services, Alberta Health Services, Research Pharmacy, Provincial Laboratory for Public Health, Edmonton and Calgary, Alberta, for supporting the conduct of this trial; the emergency department physicians, nurses, and ancillary staff at all trial sites; the Pediatric Emergency Medicine Research Associates{\textquoteright} Program at Alberta Children{\textquoteright}s Hospital, the Students Undertaking a Pediatric Program of Research Training program at the Children{\textquoteright}s Hospital of Eastern Ontario, and the staff of the Pediatric Research Academic Initiative in SickKids Emergency program at the Hospital for Sick Children, for identifying potentially eligible trial participants; and Dr. Marie Louie (Calgary) for building the connections that made the microbiologic investigations possible. No compensation for the assistance provided by any aforementioned persons was provided. This study was supported by the Canadian Institutes of Health Research (grants 286384 and 325412), the Alberta Children{\textquoteright}s Hospital Foundation Professorship in Child Health and Wellness (to Dr. Freedman), a grant from the Alberta Children{\textquoteright}s Hospital Foundation to the Pediatric Emergency Medicine Research Associates{\textquoteright} Program, Calgary Laboratory Services (in kind), Provincial Laboratory for Public Health–Alberta Public Laboratories, Luminex, and Copan Italia. P.M.S. is the recipient of a Canada Research Chair in Gastrointestinal Disease. Funding Information: None of the authors have any potential or perceived conflicts of interest to declare. The study sponsors played no role in study design, conduct, data acquisition, analysis, manuscript preparation or the decision to submit the manuscript for publication. Dr. Stephen Freedman provides consulting services to Takeda Pharmaceuticals Inc. and was an invited speaker at the 10th Probiotics, Prebiotics and New Foods, Nutraceuticals and Botanicals for Nutrition and Human and Microbiota Health. PMS serves on advisory boards for Antibe Therapeutics, Cargill and Nestle-Gerber. He has received honoraria from Abbott Nutrition for speaking at continuing medical education activities and received research support from Lallemand Human Nutrition for a postdoctoral fellow award through a Mitacs Accelerates Internship. Publisher Copyright: {\textcopyright} 2020, The Author(s).",

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doi = "10.1038/s41467-020-16308-3",

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AU - the Pediatric Emergency Research Canada Probiotic (PERC) Regimen for Outpatient Gastroenteritis Utility of Treatment (PROGUT) Trial Group

AU - Freedman, Stephen B.

AU - Xie, Jianling

AU - Nettel-Aguirre, Alberto

AU - Pang, Xiao Li

AU - Chui, Linda

AU - Williamson-Urquhart, Sarah

AU - Schnadower, David

AU - Schuh, Suzanne

AU - Sherman, Philip M.

AU - Lee, Bonita

AU - Gouin, Serge

AU - Farion, Ken J.

AU - Poonai, Naveen

AU - Hurley, Katrina F.

AU - Qiu, Yuanyuan

AU - Ghandi, Binal

AU - Lloyd, Colin

AU - Finkelstein, Yaron

AU - Freedman, Stephen B.

AU - Xie, Jianling

AU - Chui, Linda

AU - Williamson-Urquhart, Sarah

AU - Schnadower, David

AU - Schuh, Suzanne

AU - Gouin, Serge

AU - Farion, Ken J.

AU - Poonai, Naveen

AU - Hurley, Katrina F.

AU - Qiu, Yuanyuan

AU - Ghandi, Binal

AU - Lloyd, Colin

AU - Willan, Andrew R.

AU - Goeree, Ron

AU - Johnson, David W.

AU - Black, Karen

AU - Gorelick, Marc H.

N1 - Funding Information: We thank the participants and their families for trusting us to conduct this trial; the trial investigators and support staff across all sites for their commitment to the successful and diligent conduct of the trial; the site coordinators, including Marie-Christine Auclair, R.N., B.Sc.N., Zach Cantor, B.A., Kamary Coriolano Da Silva, Ph.D., Dale Dalgleish, B.H. Sc.N., Eleanor Fitzpatrick, M.N., Kelly Kim, B.Sc., B.A., Maggie Rumantir, M.D., Judy Sweeney, R.N., B.Sc.N., and Avery Yandt, B.Sc., B.A., for trial coordination; the staff of Lallemand Health Solutions, Calgary Laboratory Services, Alberta Health Services, Research Pharmacy, Provincial Laboratory for Public Health, Edmonton and Calgary, Alberta, for supporting the conduct of this trial; the emergency department physicians, nurses, and ancillary staff at all trial sites; the Pediatric Emergency Medicine Research Associates’ Program at Alberta Children’s Hospital, the Students Undertaking a Pediatric Program of Research Training program at the Children’s Hospital of Eastern Ontario, and the staff of the Pediatric Research Academic Initiative in SickKids Emergency program at the Hospital for Sick Children, for identifying potentially eligible trial participants; and Dr. Marie Louie (Calgary) for building the connections that made the microbiologic investigations possible. No compensation for the assistance provided by any aforementioned persons was provided. This study was supported by the Canadian Institutes of Health Research (grants 286384 and 325412), the Alberta Children’s Hospital Foundation Professorship in Child Health and Wellness (to Dr. Freedman), a grant from the Alberta Children’s Hospital Foundation to the Pediatric Emergency Medicine Research Associates’ Program, Calgary Laboratory Services (in kind), Provincial Laboratory for Public Health–Alberta Public Laboratories, Luminex, and Copan Italia. P.M.S. is the recipient of a Canada Research Chair in Gastrointestinal Disease. Funding Information: None of the authors have any potential or perceived conflicts of interest to declare. The study sponsors played no role in study design, conduct, data acquisition, analysis, manuscript preparation or the decision to submit the manuscript for publication. Dr. Stephen Freedman provides consulting services to Takeda Pharmaceuticals Inc. and was an invited speaker at the 10th Probiotics, Prebiotics and New Foods, Nutraceuticals and Botanicals for Nutrition and Human and Microbiota Health. PMS serves on advisory boards for Antibe Therapeutics, Cargill and Nestle-Gerber. He has received honoraria from Abbott Nutrition for speaking at continuing medical education activities and received research support from Lallemand Human Nutrition for a postdoctoral fellow award through a Mitacs Accelerates Internship. Publisher Copyright: © 2020, The Author(s).

PY - 2020/12/1

Y1 - 2020/12/1

N2 - Gastroenteritis accounts for nearly 500,000 deaths in children younger than 5 years annually. Although probiotics have been touted as having the potential to expedite diarrhea resolution, recent clinical trials question their effectiveness. A potential explanation is a shift in pathogens following the introduction of a rotavirus vaccine. Here, we report the results of a multi-center, double-blind trial of 816 children with acute gastroenteritis who completed follow-up and provided multiple stool specimens. Participants were randomized to receive a probiotic containing Lactobacillus rhamnosus and Lactobacillushelveticus or placebo. We report no virus-specific beneficial effects attributable to the probiotic, either in reducing clinical symptoms or viral nucleic acid clearance from stool specimens collected up to 28 days following enrollment. We provide pathophysiological and microbiologic evidence to support the clinical findings and conclude that our data do not support routine probiotic administration to children with acute gastroenteritis, regardless of the infecting virus.

AB - Gastroenteritis accounts for nearly 500,000 deaths in children younger than 5 years annually. Although probiotics have been touted as having the potential to expedite diarrhea resolution, recent clinical trials question their effectiveness. A potential explanation is a shift in pathogens following the introduction of a rotavirus vaccine. Here, we report the results of a multi-center, double-blind trial of 816 children with acute gastroenteritis who completed follow-up and provided multiple stool specimens. Participants were randomized to receive a probiotic containing Lactobacillus rhamnosus and Lactobacillushelveticus or placebo. We report no virus-specific beneficial effects attributable to the probiotic, either in reducing clinical symptoms or viral nucleic acid clearance from stool specimens collected up to 28 days following enrollment. We provide pathophysiological and microbiologic evidence to support the clinical findings and conclude that our data do not support routine probiotic administration to children with acute gastroenteritis, regardless of the infecting virus.

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A randomized trial evaluating virus-specific effects of a combination probiotic in children with acute gastroenteritis

Abstract

Bibliographical note

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