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. 2022 Feb 21;22:62. doi: 10.1186/s12883-022-02586-5

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 2 — Spinal-Onset ALS Patients Manifest Gut-Dysbiosis, whereas Bulbar-Onset ALS Patients Display Oral-Dysbiosis. A Left panel represents principle component analysis of gut-microbiome species taxa at the phylum level. Right panel represents the heatmap for gut-microbiome distribution at the phylum level. Data derived from 20 healthy controls (black), 24 spinal-onset ALS patients (red), and 12 bulbar-onset ALS patients (blue). Spinal-onset ALS patients formed a distinct cluster from controls and bulbar-onset ALS patients. B Left panel represents principle component analysis of oral-microbiome species taxa at the phylum level. Right panel represents the heatmap for oral-microbiome distribution at the phylum level. Bulbar-onset ALS patients formed a distinct cluster from controls and spinal-onset ALS patients. C Gut-microbiome bacterial species number measured by Operational Taxonomic Unit (OTU) Richness. Results represent both ALS (spinal- and bulbar-onset ALS combined) or spinal- and bulbar-onset ALS quantified separately. Spinal-onset ALS patients displayed a significant increase in gut bacterial species count. No significant change in bulbar-onset ALS patients. D Oral-microbiome bacterial species number measured by OTU Richness. Bulbar-onset ALS patients displayed a significant increase in oral bacterial species count. No significant change in spinal-onset ALS patients. E Gut-microbiome species evenness measured through Shannon index. Spinal-onset ALS patients displayed a significant decrease in Shannon index, suggesting reduced gut-microbiome uniformity. No significant change in bulbar-onset ALS patients. F Oral-microbiome species evenness measured through Shannon index. Bulbar-onset ALS patients displayed a significant decrease in Shannon index, suggesting reduced oral-microbiome uniformity. No significant change in spinal-onset ALS patients. Statistics: For comparisons between controls and ALS patients (combined), Mann–Whitney test was utilized. For contrasts between control, spinal-onset ALS, and bulbar-onset ALS, Kruskal–Wallis test with Dunn’s post-hoc multiple comparisons test was utilized. Values represent sample median with interquartile range. Clustering was performed based on Bray Similarity matrix. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001