Abstract
BackgroundA connection between amyotrophic lateral sclerosis (ALS) and alteredgut microbiota composition has previously been reported in animal models. Thiswork is the first prospective longitudinal study addressing the microbiotacomposition in ALS patients and the impact of a probiotic supplementation on thegut microbiota and disease progression.MethodsFifty patients and 50 matched controls were enrolled. The microbialprofile of stool samples from patients and controls was analyzed viaPCR-Denaturing Gradient Gel Electrophoresis, and the main microbial groupsquantified via qPCR. The whole microbiota was then analyzed via next generationsequencing after amplification of the V3–V4 region of 16S rDNA. Patients werethen randomized to receive probiotic treatment or placebo and followed up for6 months with ALSFRS-R, BMI, and FVC%.ResultsThe results demonstrate that the gut microbiota of ALS patients ischaracterized by some differences with respect to controls, regardless of thedisability degree. Moreover, the gut microbiota composition changes during thecourse of the disease as demonstrated by the significant decrease in the numberof observed operational taxonomic unit during the follow-up. Interestingly, anunbalance between potentially protective microbial groups, such asBacteroidetes, and other with potential neurotoxic or pro-inflammatory activity,such as Cyanobacteria, has been shown. The 6-month probiotic treatmentinfluenced the gut microbial composition; however, it did not bring thebiodiversity of intestinal microbiota of patients closer to that of controlsubjects and no influence on the progression of the disease measured by ALSFRS-Rwas demonstrated.ConclusionsOur study poses the bases for larger clinical studies tocharacterize the microbiota changes as a novel ALS biomarker and to test newmicrobial strategy to ameliorate the health status of the gut.Trial registrationCE 107/14, approved by the Ethics Committee of the “Maggiore dellaCarità” University Hospital, Italy.
Highlights
A connection between amyotrophic lateral sclerosis (ALS) and altered gut microbiota composition has previously been reported in animal models
ALS is familial in the 10% of cases with a Mendelian pattern of inheritance while in the remaining sporadic cases a multifactorial origin is supposed in which several predisposing genes interact with environmental factors in manifesting the disease [1]
Within Clostridiaceae, the significantly lower amount of Clostridiaceae 1, including some ambiguous taxa belonging to this family, as well as Clostridium cluster I in ALS patients is in agreement with the results previously reported by Rowin et al [13]
Summary
A connection between amyotrophic lateral sclerosis (ALS) and altered gut microbiota composition has previously been reported in animal models. ALS is familial in the 10% of cases with a Mendelian pattern of inheritance while in the remaining sporadic cases a multifactorial origin is supposed in which several predisposing genes interact with environmental factors in manifesting the disease [1]. Imbalance in the gut microbiota composition may be one of the environmental factors contributing to the development of ALS. The composition of the intestinal microbiota is gaining importance in human health studies since there is increasing evidence that its alteration plays a role in disease etiology. It has been hypothesized that the intestinal microbiota can represent an epigenetic entity that interacts with environmental factors in determining pathogenic influence on the central nervous system (CNS) [2]
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