Study Probes Gut Microbiome Alterations, Probiotics in ALS Patients

The gut microbiome in people with amyotrophic lateral sclerosis (ALS) is altered compared to healthy people, which includes an imbalance in potentially protective microbial groups and others with pro-inflammatory activity, a study found. 

Also, while taking probiotic supplements over six months influenced the gut microbiome in patients, it did not affect disease progression. 

The study, “A prospective longitudinal study on the microbiota composition in amyotrophic lateral sclerosis,” was published in the journal BMC Medicine.

There is emerging evidence that the composition of the microbes in the gut (microbiome) affects the risk and severity of some neurodegenerative diseases, as in Parkinson’s disease and Alzheimer’s disease. 

Studies have shown an altered gut microbiome in animal models of ALS. However, the few preliminary studies that have analyzed the composition of the fecal microbiome in people with ALS have been inconclusive. 

In this study, researchers at the University of Bologna and University of Piemonte Orientale in Italy, along with collaborators at the company Biolab Research, designed a study to investigate the gut microbiome in ALS patients and the impact of probiotic supplementation on the gut microbiome and ALS progression.

The team enrolled 28 male and 22 female ALS patients age 18 to 75, along with 50 age and sex-matched control subjects. The control participants lived in the same area and ate the same types of foods. They had similar body-mass-index, did not use medicines that might affect results for four weeks prior, and had no serious diseases. 

Before the study (baseline), all patients underwent a clinical evaluation, including the ALS Functional Rating Scale-Revised (ALSFRS-R) score as well as lung function tests. Patients were followed for six months, which included monthly monitoring for disease severity. 

Stool samples were collected at home at baseline, after three and six months, and from controls at the beginning of the study (baseline). Microbes were identified by genetic analysis. 

At baseline, the microbial profile of stool samples from patients and controls was analyzed. No clear grouping of diseased and control profiles could be observed.

To quantify the main microbial groups, a genetic analysis technique called quantitative PCR, which can measure the amount of DNA in a given sample, was used. Compared to controls, a significantly lower amount of the bacteria Clostridium as well as yeasts, and significantly higher numbers of Escherichia coli (E. coli) and Enterobacteriaceae bacteria, were detected in ALS patients. 

Also, ALS patients with a greater amount of yeasts scored higher (better) on ALS and lung function tests. No correlation was found between the numbers of microbes and body-mass-index. 

A more comprehensive DNA sequencing method known as next-generation sequencing was used to analyze the whole microbiome. 

Two groups of bacteria called Bacteroidetes and Firmicutes, which represented up to 45% of microbes, were found in both groups. A higher percentage of the bacteria groups Actinobacteria and Verrucomicrobia were detected in the ALS group compared to controls, although the difference was not statistically significant. 

In contrast, members of a group of bacteria called Cyanobacteria were significantly higher (0.3%) in the ALS group than the control group (0.2%). 

“These data support the hypothesis that Cyanobacteria play a fundamental role in the pathogenesis of neurodegenerative diseases and particularly of ALS,” the researchers wrote.

Additional bacteria more abundant in ALS patients included Lactobacillus, Citrobacter, Coprococcus, and Ruminiclostridium. 

The abundance of species (diversity) was higher in controls than in ALS patients with low ALSFRS-R scores. An alternate method to measure diversity also found differences between patients and controls, as well as differences between high- and low-functioning patients. 

To evaluate the effect of probiotic supplementation, patients were divided into two groups. One group received a daily probiotic supplement for six months while the remaining patients received a placebo for three months, followed by the daily supplement for an additional three months. 

The supplement contained Streptococcus thermophilus, Lactobacillus fermentum, Lactobacillus delbrueckii subsp. delbrueckii, Lactobacillus plantarum, and Lactobacillus salivarius.

The results showed no substantial alterations in the gut microbiome associated with probiotic supplementation, except for bacteria in the Rikenellaceae family, which is one of the most represented microbial families in the gut belonging to the Bacteroidales group. 

These microbes significantly increased with the probiotic treatment, particularly in those who received the supplement for the entire six months. 

The abundance of Cyanobacteria decreased over time in both the placebo and probiotic groups, although not significantly.

While supplementation influenced the composition of the gut microbiome, it did not alter the biodiversity to control levels or affect the progression of the disease as measure by ALSFRS-R. 

“The results that we obtained…show that ALS is associated [with] variations in some gut microbial components with respect to controls also in patients with low disability and full vital functions,” the researchers wrote.

“Interestingly, an unbalance between potentially protective microbial groups, such as members of Bacteroidales, and [others] with potential neurotoxic or pro-inflammatory activity, such as Cyanobacteria, has been shown,” they continued.

“Our study poses the bases for larger clinical studies to characterize the [microbiome] changes as a novel ALS biomarker and to test new microbial strategy to ameliorate the health status of the gut,” they concluded.