Is gut microbiota of patients with ALS different from that of healthy individuals?

Abstract

Background/aim: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Several studies have shown that alterations of microbiota increase the risk of neurodegenerative disorders. We aimed to reveal whether there is a difference in the gut microbiota of patients with ALS.

Materials and methods: The participants are divided into three groups. Group 1 comprised patients with ALS. Healthy family members living in the same house of the patients formed Group 2. Lastly, sex- and age-matched healthy people were included in Group 3. Fecal samples were collected in 15-mL falcon tubes and stored at -80 °C. Genomic DNA isolation was performed on samples. Bacterial primers selected from the 16S rRNA region for the bacterial genome and ITS1 and ITS4 (internal transcribed spacer) were used for the identification of DNA. Next generation sequence analysis (NGS) and taxonomic analyses were performed at the level of bacterial phylum, class, order, family, genus, and species. Alpha and beta diversity indexes were used. The linear discriminant analysis (LDA) effect size method (LEfSe) was applied to identify a microbial taxon specific to ALS disease.

Results: The relative abundances of the Succinivibrionaceae and Lachnospiraceae families were significantly lower in patients. The dominant families among patients were Streptococcaceae and Ruminococcaceae, while the dominant families among healthy controls were Bacteroidaceae and Succinivibrionaceae. The LEfSe analysis revealed that four families (Atopobiaceae, Actinomycetaceae, Erysipelatoclostridiaceae, Peptococcacceae) differed significantly between the patients and healthy controls (LDA values> 2.5, p < 0.05).

Conclusion: Comparison with family members living in the same house is the strength of this study. We found that there were changes in the microbiota of the patients, consistent with the literature. Studies that analyze the composition of the gut microbiota in the predisease period may be needed to understand whether dysbiosis is caused by the mechanisms inherent in the disease or whether it is dysbiosis that initiates the disease.

Keywords: ALS; Amyotrophic lateral sclerosis; gut microbiota; neurodegenerative diseases; pathogenesis of ALS.

Figure 1

Relative abundances of phylum-level taxa in groups.

Figure 2

Relative abundances of class-level taxa in groups.

Figure 3

Relative abundances of order-level taxa in groups.

Figure 4

Relative abundances of family-level taxa in groups.

Figure 5

Relative abundances of genus-level taxa in groups.

Figure 6

LDA score and cladogram. The cladogram results of LEfSe analysis show taxonomic clades that are differential in abundance, where different circles from the inside to the outside represent different classification levels from domain to species and the larger size of the nodes reflects higher relative abundance. The biomarkers are colored in red and green depending on the group. The bar chart shows the biomarkers with differential abundance between the groups and larger than the preset value (LDA score > 4, p < 0.05). The LDA score indicates the extent to which the corresponding group is affected by the differential microbes.

Figure 7

Firmicutes and Bacteroidetes levels of the participants.