Alterations in nasal microbiota of patients with amyotrophic lateral sclerosis

Abstract

Background: Links between alterations in gut microbiota composition and amyotrophic lateral sclerosis (ALS) have previously been reported. This study aimed to examine the microbiota in the nasal cavity of ALS. Methods: Sixty-six ALS patients and 40 healthy caregivers who live in close proximity with patients were enrolled. High throughput metagenomic sequencing of the 16S ribosomal deoxyribonucleic acid (rDNA) gene V3–V4 region of nasal microbiota was used to characterize the alpha and beta diversity and relative abundance of bacterial taxa, predict function, and conduct correlation analysis between specific taxa and clinical features. Results: The nasal microbiome of ALS patients showed lower alpha diversity than that of corresponding healthy family members. Genera Gaiella, Sphingomonas, Polaribacter_1, Lachnospiraceae_NK4A136_group, Klebsiella, and Alistipes were differentially enriched in ALS patients compared to controls. Nasal microbiota composition in ALS patients significantly differed from that in healthy subjects (unweighted UniFrac P = 0.001), while LEfSe analysis indicated that Bacteroidetes and Firmicutes dominated healthy nasal communities at the phylum level, whereas Actinobacteria was the predominant phylum and Thermoleophilia was the predominant class in ALS patients. Genus Faecalibacterium and Alistipes were positively correlated with ALS functional rating scale revised (ALSFRS-R; r s = 0.349, P = 0.020 and r s = 0.393, P = 0.008), while Prevotella-9 and Bacteroides operational taxonomic units (OTUs) were positively associated with lung function (FVC) in ALS patients (r s = 0.304, P = 0.045, and r s = 0.300, P = 0.048, respectively). Prevotella-1 was positively correlated with white blood cell counts (WBC, r s = 0.347, P = 0.021), neutrophil percentage (Neu%, r s = 0.428, P = 0.004), and neutrophil-to-lymphocyte ratio (NLR, r s = 0.411, P = 0.006), but negatively correlated with lymphocyte percentage (Lym%, r s = –0.408, P = 0.006). In contrast, Streptococcus was negatively associated with Neu% (r s = –0.445, P = 0.003) and NLR (r s = –0.436, P = 0.003), while positively associated with Lym% (r s = 0.437, P = 0.003). No significant differences in nasal microbiota richness and evenness were detected among the severe and mild ALS patients. Conclusions: ALS is accompanied by altered nasal microbial community composition and diversity. The findings presented here highlight the need to understand how dysbiosis of nasal microbiota may contribute to the development of ALS.

Gut-Modulating Agents and Amyotrophic Lateral Sclerosis: Current Evidence and Future Perspectives

“…All currently published oral and fecal microbiome studies performed on human ALS patients are summarized in Table 1 . It is important to note that evidence of dysbiosis and microbial translocation has also been found in other primary samples and/or tissues [ 42 , 43 , 44 ]. For example, in a recently published study by Liu et al [ 42 ], nasal swabs collected from 66 ALS patients and 40 healthy caregivers differed significantly in microbial composition and diversity.…”

“…It is important to note that evidence of dysbiosis and microbial translocation has also been found in other primary samples and/or tissues [ 42 , 43 , 44 ]. For example, in a recently published study by Liu et al [ 42 ], nasal swabs collected from 66 ALS patients and 40 healthy caregivers differed significantly in microbial composition and diversity. At the phylum level, Bacteroidetes and Firmicutes were substantially increased in healthy nasal communities, while Actinobacteria dominated the nasal microbiota of ALS patients.…”

“…At the phylum level, Bacteroidetes and Firmicutes were substantially increased in healthy nasal communities, while Actinobacteria dominated the nasal microbiota of ALS patients. Specific genera like Gaiella , Sphingomonas , Lachnospiraceae , and Klebsiella were all found to be significant predictors of ALS [ 42 ]. Faecalibacterium and Alistipes were also notably enriched in ALS patients and positively correlated with ALSFRS-R scores [ 42 ].…”

“…Specific genera like Gaiella , Sphingomonas , Lachnospiraceae , and Klebsiella were all found to be significant predictors of ALS [ 42 ]. Faecalibacterium and Alistipes were also notably enriched in ALS patients and positively correlated with ALSFRS-R scores [ 42 ]. Further profiling and correlation analyses linked several changes to the nasal microbiota with ALS-related immune dysregulation and metabolic dysfunction.…”