A prospective longitudinal study on the microbiota composition in amyotrophic lateral sclerosis

Abstract Background A connection between amyotrophic lateral sclerosis (ALS) and altered gut microbiota composition has previously been reported in animal models. This work is the first prospective longitudinal study addressing the microbiota composition in ALS patients and the impact of a probiotic...

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Main Authors: Diana Di Gioia, Nicole Bozzi Cionci, Loredana Baffoni, Angela Amoruso, Marco Pane, Luca Mogna, Francesca Gaggìa, Maria Ausiliatrice Lucenti, Enrica Bersano, Roberto Cantello, Fabiola De Marchi, Letizia Mazzini
Format: Article
Language:English
Published: BMC 2020-06-01
Series:BMC Medicine
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Online Access:http://link.springer.com/article/10.1186/s12916-020-01607-9
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author Diana Di Gioia
Nicole Bozzi Cionci
Loredana Baffoni
Angela Amoruso
Marco Pane
Luca Mogna
Francesca Gaggìa
Maria Ausiliatrice Lucenti
Enrica Bersano
Roberto Cantello
Fabiola De Marchi
Letizia Mazzini
author_facet Diana Di Gioia
Nicole Bozzi Cionci
Loredana Baffoni
Angela Amoruso
Marco Pane
Luca Mogna
Francesca Gaggìa
Maria Ausiliatrice Lucenti
Enrica Bersano
Roberto Cantello
Fabiola De Marchi
Letizia Mazzini
author_sort Diana Di Gioia
collection DOAJ
description Abstract Background A connection between amyotrophic lateral sclerosis (ALS) and altered gut microbiota composition has previously been reported in animal models. This work is the first prospective longitudinal study addressing the microbiota composition in ALS patients and the impact of a probiotic supplementation on the gut microbiota and disease progression. Methods Fifty patients and 50 matched controls were enrolled. The microbial profile of stool samples from patients and controls was analyzed via PCR-Denaturing Gradient Gel Electrophoresis, and the main microbial groups quantified via qPCR. The whole microbiota was then analyzed via next generation sequencing after amplification of the V3–V4 region of 16S rDNA. Patients were then randomized to receive probiotic treatment or placebo and followed up for 6 months with ALSFRS-R, BMI, and FVC%. Results The results demonstrate that the gut microbiota of ALS patients is characterized by some differences with respect to controls, regardless of the disability degree. Moreover, the gut microbiota composition changes during the course of the disease as demonstrated by the significant decrease in the number of observed operational taxonomic unit during the follow-up. Interestingly, an unbalance between potentially protective microbial groups, such as Bacteroidetes, and other with potential neurotoxic or pro-inflammatory activity, such as Cyanobacteria, has been shown. The 6-month probiotic treatment influenced the gut microbial composition; however, it did not bring the biodiversity of intestinal microbiota of patients closer to that of control subjects and no influence on the progression of the disease measured by ALSFRS-R was demonstrated. Conclusions Our study poses the bases for larger clinical studies to characterize the microbiota changes as a novel ALS biomarker and to test new microbial strategy to ameliorate the health status of the gut. Trial registration CE 107/14, approved by the Ethics Committee of the “Maggiore della Carità” University Hospital, Italy.
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spelling doaj.art-15d36d648fc645b38d7a291dc306a1d92022-12-21T20:17:49ZengBMCBMC Medicine1741-70152020-06-0118111910.1186/s12916-020-01607-9A prospective longitudinal study on the microbiota composition in amyotrophic lateral sclerosisDiana Di Gioia0Nicole Bozzi Cionci1Loredana Baffoni2Angela Amoruso3Marco Pane4Luca Mogna5Francesca Gaggìa6Maria Ausiliatrice Lucenti7Enrica Bersano8Roberto Cantello9Fabiola De Marchi10Letizia Mazzini11Department of Agricultural and Food Sciences, University of BolognaDepartment of Agricultural and Food Sciences, University of BolognaDepartment of Agricultural and Food Sciences, University of BolognaBIOLAB RESEARCH srlBIOLAB RESEARCH srlBIOLAB RESEARCH srlDepartment of Agricultural and Food Sciences, University of BolognaDepartment of Neurology and ALS Centre, University of Piemonte Orientale, Maggiore della Carità HospitalDepartment of Neurology and ALS Centre, University of Piemonte Orientale, Maggiore della Carità HospitalDepartment of Neurology and ALS Centre, University of Piemonte Orientale, Maggiore della Carità HospitalDepartment of Neurology and ALS Centre, University of Piemonte Orientale, Maggiore della Carità HospitalDepartment of Neurology and ALS Centre, University of Piemonte Orientale, Maggiore della Carità HospitalAbstract Background A connection between amyotrophic lateral sclerosis (ALS) and altered gut microbiota composition has previously been reported in animal models. This work is the first prospective longitudinal study addressing the microbiota composition in ALS patients and the impact of a probiotic supplementation on the gut microbiota and disease progression. Methods Fifty patients and 50 matched controls were enrolled. The microbial profile of stool samples from patients and controls was analyzed via PCR-Denaturing Gradient Gel Electrophoresis, and the main microbial groups quantified via qPCR. The whole microbiota was then analyzed via next generation sequencing after amplification of the V3–V4 region of 16S rDNA. Patients were then randomized to receive probiotic treatment or placebo and followed up for 6 months with ALSFRS-R, BMI, and FVC%. Results The results demonstrate that the gut microbiota of ALS patients is characterized by some differences with respect to controls, regardless of the disability degree. Moreover, the gut microbiota composition changes during the course of the disease as demonstrated by the significant decrease in the number of observed operational taxonomic unit during the follow-up. Interestingly, an unbalance between potentially protective microbial groups, such as Bacteroidetes, and other with potential neurotoxic or pro-inflammatory activity, such as Cyanobacteria, has been shown. The 6-month probiotic treatment influenced the gut microbial composition; however, it did not bring the biodiversity of intestinal microbiota of patients closer to that of control subjects and no influence on the progression of the disease measured by ALSFRS-R was demonstrated. Conclusions Our study poses the bases for larger clinical studies to characterize the microbiota changes as a novel ALS biomarker and to test new microbial strategy to ameliorate the health status of the gut. Trial registration CE 107/14, approved by the Ethics Committee of the “Maggiore della Carità” University Hospital, Italy.http://link.springer.com/article/10.1186/s12916-020-01607-9Amyotrophic lateral sclerosisNeurodegenerationBiomarkerMicrobiota
spellingShingle Diana Di Gioia
Nicole Bozzi Cionci
Loredana Baffoni
Angela Amoruso
Marco Pane
Luca Mogna
Francesca Gaggìa
Maria Ausiliatrice Lucenti
Enrica Bersano
Roberto Cantello
Fabiola De Marchi
Letizia Mazzini
A prospective longitudinal study on the microbiota composition in amyotrophic lateral sclerosis
BMC Medicine
Amyotrophic lateral sclerosis
Neurodegeneration
Biomarker
Microbiota
title A prospective longitudinal study on the microbiota composition in amyotrophic lateral sclerosis
title_full A prospective longitudinal study on the microbiota composition in amyotrophic lateral sclerosis
title_fullStr A prospective longitudinal study on the microbiota composition in amyotrophic lateral sclerosis
title_full_unstemmed A prospective longitudinal study on the microbiota composition in amyotrophic lateral sclerosis
title_short A prospective longitudinal study on the microbiota composition in amyotrophic lateral sclerosis
title_sort prospective longitudinal study on the microbiota composition in amyotrophic lateral sclerosis
topic Amyotrophic lateral sclerosis
Neurodegeneration
Biomarker
Microbiota
url http://link.springer.com/article/10.1186/s12916-020-01607-9
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