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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. 6 — For Spinal-Onset ALS, Gut-Dysbiosis May Drive Microbial Translocation to Blood, Leading to Increased Disease Severity, whereas for Bulbar-Onset ALS, Oral-Dysbiosis May Drive Microbial Translocation to Blood, Leading to Increased Disease Severity. A Blood lipopolysaccharide-binding protein (LBP) levels in mg/L as a marker for microbial translocation to the blood. Results represent both ALS patients (spinal- and bulbar-onset ALS patients combined) or spinal- and bulbar-onset ALS patients quantified separately. Both spinal- and bulbar-onset ALS patients displayed significant increases in blood LBP levels, with bulbar-onset ALS patients showing significantly higher levels than spinal-onset ALS patients. B Linear regression analysis comparing blood LBP levels and ALSFRS-R score for all ALS patients combined (left), spinal-onset ALS patients only (middle), and bulbar-onset ALS patients only (right). Spinal-onset ALS patients shown in red, bulbar-onset ALS patients shown in blue. In both spinal- and bulbar-onset ALS patients, higher blood LBP levels (greater microbial translocation to the blood) were strongly associated with lower ALSFRS-R score (greater ALS severity). C Linear regression analyses comparing fecal F/B ratio and blood LBP levels (left) and oral F/B ratio and blood LBP levels (right) in spinal-onset ALS patients. In spinal-onset ALS patients, fecal F/B ratio showed strong correlations with blood LBP levels, but oral F/B ratio showed poor correlations with blood LBP levels. In spinal-onset ALS patients, higher fecal F/B ratio (greater gut-dysbiosis) was strongly associated with greater blood LBP levels (greater microbial translocation to the blood). D Linear regression analyses comparing fecal F/B ratio and blood LBP levels (left) and oral F/B ratio and blood LBP levels (right) in bulbar-onset ALS patients. In bulbar-onset ALS patients, oral F/B ratio showed strong correlations with blood LBP levels, but fecal F/B ratio showed poor correlations with blood LBP levels. In bulbar-onset ALS patients, lower oral F/B ratio (greater oral-dysbiosis) was strongly associated with greater blood LBP levels (greater microbial translocation to the blood). Statistics: In panel A, contrasts between control and ALS patients (combined) utilized Mann–Whitney test, while contrasts between control, spinal-onset ALS, and bulbar-onset ALS utilized Kruskal–Wallis test with Dunn’s post-hoc test. Values represent sample median with interquartile range. For panels B-D, statistical significance was established using linear regression analysis and Spearman’s correlation coefficient (r) test. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001