Butyrate Producers as Potential Next-Generation Probiotics: Safety Assessment of the Administration of <italic toggle="yes">Butyricicoccus pullicaecorum</italic> to Healthy Volunteers

ABSTRACT Advances in gut microbiota research have triggered interest in developing colon butyrate producers as niche-specific next-generation probiotics, targeted at increasing colon butyrate production and countering disease-associated microbiota alterations. Crucial steps in the development of nex...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Leen Boesmans, Mireia Valles-Colomer, Jun Wang, Venessa Eeckhaut, Gwen Falony, Richard Ducatelle, Filip Van Immerseel, Jeroen Raes, Kristin Verbeke
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Butyricicoccus pullicaecorum metabolome microbiome next-generation probiotic safety tolerance Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/844503f046b245acb23becb8fde43b6f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:844503f046b245acb23becb8fde43b6f
record_format	dspace
spelling	oai:doaj.org-article:844503f046b245acb23becb8fde43b6f2021-12-02T19:47:34ZButyrate Producers as Potential Next-Generation Probiotics: Safety Assessment of the Administration of <italic toggle="yes">Butyricicoccus pullicaecorum</italic> to Healthy Volunteers10.1128/mSystems.00094-182379-5077https://doaj.org/article/844503f046b245acb23becb8fde43b6f2018-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00094-18https://doaj.org/toc/2379-5077ABSTRACT Advances in gut microbiota research have triggered interest in developing colon butyrate producers as niche-specific next-generation probiotics, targeted at increasing colon butyrate production and countering disease-associated microbiota alterations. Crucial steps in the development of next-generation probiotics are the design of formulations with a reasonable shelf life as well as the safety demonstration of an intervention in healthy volunteers. One such potential next-generation butyrate-producing probiotic is Butyricicoccus pullicaecorum 25-3T, with demonstrated safety in in vitro as well as animal models. Here, we examined the strain’s safety, tolerability, and impact on microbiota composition and metabolic activity in healthy volunteers in a randomized, double-blind, placebo-controlled crossover study in 30 healthy volunteers. The study design consisted of two 4-week intervention periods (108 CFU B. pullicaecorum [treatment] or maltodextrin [placebo] per day) with a 3-week washout in between. We assessed adverse events, blood parameters (primary endpoints), and fecal microbiota composition and metabolite profiles (secondary endpoints). The number of reported adverse events during the B. pullicaecorum treatment was similar to that of placebo intervention, as were observed changes in blood chemistry parameters, bowel habits, and fecal calprotectin concentrations. Administration of the strain did not induce any disruptive effect in microbiota composition or metabolic activity. In this first human intervention trial with a butyrate-producing Clostridium cluster IV isolate, we demonstrated B. pullicaecorum 25-3T administration to be both safe and well tolerated by healthy participants. This safety study paves the way for the further development of the strain as a next-generation probiotic. IMPORTANCE This study is the first to determine the safety and tolerance in humans of a butyrate-producing Clostridium cluster IV next-generation probiotic. Advances in gut microbiota research have triggered interest in developing colon butyrate producers as next-generation probiotics. Butyricicoccus pullicaecorum 25-3T is one such potential probiotic, with demonstrated safety in vitro as well as in animal models. Here, we produced an encapsulated B. pullicaecorum formulation that largely preserved its viability over an 8-month storage period at 4°C. Administration of this formulation to healthy volunteers allowed us to establish the intervention as safe and well tolerated. The probiotic intervention did not cause disruptive alterations in the composition or metabolic activity of health-associated microbiota. The results presented pave the way for the exploration of the impact of the strain on microbiota alterations in a clinical setting.Leen BoesmansMireia Valles-ColomerJun WangVenessa EeckhautGwen FalonyRichard DucatelleFilip Van ImmerseelJeroen RaesKristin VerbekeAmerican Society for MicrobiologyarticleButyricicoccus pullicaecorummetabolomemicrobiomenext-generation probioticsafetytoleranceMicrobiologyQR1-502ENmSystems, Vol 3, Iss 6 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Butyricicoccus pullicaecorum metabolome microbiome next-generation probiotic safety tolerance Microbiology QR1-502
spellingShingle	Butyricicoccus pullicaecorum metabolome microbiome next-generation probiotic safety tolerance Microbiology QR1-502 Leen Boesmans Mireia Valles-Colomer Jun Wang Venessa Eeckhaut Gwen Falony Richard Ducatelle Filip Van Immerseel Jeroen Raes Kristin Verbeke Butyrate Producers as Potential Next-Generation Probiotics: Safety Assessment of the Administration of <italic toggle="yes">Butyricicoccus pullicaecorum</italic> to Healthy Volunteers
description	ABSTRACT Advances in gut microbiota research have triggered interest in developing colon butyrate producers as niche-specific next-generation probiotics, targeted at increasing colon butyrate production and countering disease-associated microbiota alterations. Crucial steps in the development of next-generation probiotics are the design of formulations with a reasonable shelf life as well as the safety demonstration of an intervention in healthy volunteers. One such potential next-generation butyrate-producing probiotic is Butyricicoccus pullicaecorum 25-3T, with demonstrated safety in in vitro as well as animal models. Here, we examined the strain’s safety, tolerability, and impact on microbiota composition and metabolic activity in healthy volunteers in a randomized, double-blind, placebo-controlled crossover study in 30 healthy volunteers. The study design consisted of two 4-week intervention periods (108 CFU B. pullicaecorum [treatment] or maltodextrin [placebo] per day) with a 3-week washout in between. We assessed adverse events, blood parameters (primary endpoints), and fecal microbiota composition and metabolite profiles (secondary endpoints). The number of reported adverse events during the B. pullicaecorum treatment was similar to that of placebo intervention, as were observed changes in blood chemistry parameters, bowel habits, and fecal calprotectin concentrations. Administration of the strain did not induce any disruptive effect in microbiota composition or metabolic activity. In this first human intervention trial with a butyrate-producing Clostridium cluster IV isolate, we demonstrated B. pullicaecorum 25-3T administration to be both safe and well tolerated by healthy participants. This safety study paves the way for the further development of the strain as a next-generation probiotic. IMPORTANCE This study is the first to determine the safety and tolerance in humans of a butyrate-producing Clostridium cluster IV next-generation probiotic. Advances in gut microbiota research have triggered interest in developing colon butyrate producers as next-generation probiotics. Butyricicoccus pullicaecorum 25-3T is one such potential probiotic, with demonstrated safety in vitro as well as in animal models. Here, we produced an encapsulated B. pullicaecorum formulation that largely preserved its viability over an 8-month storage period at 4°C. Administration of this formulation to healthy volunteers allowed us to establish the intervention as safe and well tolerated. The probiotic intervention did not cause disruptive alterations in the composition or metabolic activity of health-associated microbiota. The results presented pave the way for the exploration of the impact of the strain on microbiota alterations in a clinical setting.
format	article
author	Leen Boesmans Mireia Valles-Colomer Jun Wang Venessa Eeckhaut Gwen Falony Richard Ducatelle Filip Van Immerseel Jeroen Raes Kristin Verbeke
author_facet	Leen Boesmans Mireia Valles-Colomer Jun Wang Venessa Eeckhaut Gwen Falony Richard Ducatelle Filip Van Immerseel Jeroen Raes Kristin Verbeke
author_sort	Leen Boesmans
title	Butyrate Producers as Potential Next-Generation Probiotics: Safety Assessment of the Administration of <italic toggle="yes">Butyricicoccus pullicaecorum</italic> to Healthy Volunteers
title_short	Butyrate Producers as Potential Next-Generation Probiotics: Safety Assessment of the Administration of <italic toggle="yes">Butyricicoccus pullicaecorum</italic> to Healthy Volunteers
title_full	Butyrate Producers as Potential Next-Generation Probiotics: Safety Assessment of the Administration of <italic toggle="yes">Butyricicoccus pullicaecorum</italic> to Healthy Volunteers
title_fullStr	Butyrate Producers as Potential Next-Generation Probiotics: Safety Assessment of the Administration of <italic toggle="yes">Butyricicoccus pullicaecorum</italic> to Healthy Volunteers
title_full_unstemmed	Butyrate Producers as Potential Next-Generation Probiotics: Safety Assessment of the Administration of <italic toggle="yes">Butyricicoccus pullicaecorum</italic> to Healthy Volunteers
title_sort	butyrate producers as potential next-generation probiotics: safety assessment of the administration of <italic toggle="yes">butyricicoccus pullicaecorum</italic> to healthy volunteers
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/844503f046b245acb23becb8fde43b6f
work_keys_str_mv	AT leenboesmans butyrateproducersaspotentialnextgenerationprobioticssafetyassessmentoftheadministrationofitalictoggleyesbutyricicoccuspullicaecorumitalictohealthyvolunteers AT mireiavallescolomer butyrateproducersaspotentialnextgenerationprobioticssafetyassessmentoftheadministrationofitalictoggleyesbutyricicoccuspullicaecorumitalictohealthyvolunteers AT junwang butyrateproducersaspotentialnextgenerationprobioticssafetyassessmentoftheadministrationofitalictoggleyesbutyricicoccuspullicaecorumitalictohealthyvolunteers AT venessaeeckhaut butyrateproducersaspotentialnextgenerationprobioticssafetyassessmentoftheadministrationofitalictoggleyesbutyricicoccuspullicaecorumitalictohealthyvolunteers AT gwenfalony butyrateproducersaspotentialnextgenerationprobioticssafetyassessmentoftheadministrationofitalictoggleyesbutyricicoccuspullicaecorumitalictohealthyvolunteers AT richardducatelle butyrateproducersaspotentialnextgenerationprobioticssafetyassessmentoftheadministrationofitalictoggleyesbutyricicoccuspullicaecorumitalictohealthyvolunteers AT filipvanimmerseel butyrateproducersaspotentialnextgenerationprobioticssafetyassessmentoftheadministrationofitalictoggleyesbutyricicoccuspullicaecorumitalictohealthyvolunteers AT jeroenraes butyrateproducersaspotentialnextgenerationprobioticssafetyassessmentoftheadministrationofitalictoggleyesbutyricicoccuspullicaecorumitalictohealthyvolunteers AT kristinverbeke butyrateproducersaspotentialnextgenerationprobioticssafetyassessmentoftheadministrationofitalictoggleyesbutyricicoccuspullicaecorumitalictohealthyvolunteers
_version_	1718375971437936640

Butyrate Producers as Potential Next-Generation Probiotics: Safety Assessment of the Administration of <italic toggle="yes">Butyricicoccus pullicaecorum</italic> to Healthy Volunteers

Ejemplares similares