Katharine Nicholson1, Kjetil Bjornevik2, Galeb Abu-Ali3,4, James Chan5, Marianna Cortese2, Brixhilda Dedi1, Maryangel Jeon1, Ramnik Xavier4,6,7, Curtis Huttenhower3,4, Alberto Ascherio2,8,9, James D Berry1. 1. Sean M. Healey and AMG Center for ALS, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. 2. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 3. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 4. Broad Institute of MIT and Harvard, Cambridge, MA, USA. 5. Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA. 6. Gastrointestinal Unit, Center for the Study of Inflammatory Bowel Disease, and Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. 7. Center for Microbiome Informatics and Therapeutics, MIT, Cambridge, MA, USA. 8. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 9. Channing Division of Network Medicine, Brigham and Women's Hospital and, Harvard Medical School, Boston, MA, USA.
Abstract
OBJECTIVE: To characterize the gut microbiota in people with amyotrophic lateral sclerosis (ALS) relative to controls and to test the hypothesis that butyrate-producing bacteria are less abundant in the gastrointestinal tracts of people with ALS (PALS). Methods: We conducted a case-control study at Massachusetts General Hospital to compare the gut microbiota in people with ALS to that in controls. Metagenomic shotgun sequencing was performed on DNA extracted from stool samples of 66 people with ALS (PALS), 61 healthy controls (HC), and 12 neurodegenerative controls (NDC). Taxonomic metagenomic profiles were analyzed for shifts in the microbial community structure between the comparator groups using per-feature univariate and multivariate association tests. Results: The relative abundance of the dominant butyrate-producing bacteria Eubacterium rectale and Roseburia intestinalis was significantly lower in ALS patients compared to HC. Adjustment for age, sex, and constipation did not materially change the results. The total abundance of 8 dominant species capable of producing butyrate was also significantly lower in ALS compared to HC (p < 0.001). Conclusions: The levels of several butyrate-producing bacteria, which are important for gut integrity and regulation of inflammation, were lower in people with ALS compared to controls. These findings lend support to the inference that the gut microbiota could be a risk factor for ALS. Further investigations are warranted, preferably earlier in the disease with corresponding dietary collection and a longitudinal design.
OBJECTIVE: To characterize the gut microbiota in people with amyotrophic lateral sclerosis (ALS) relative to controls and to test the hypothesis that butyrate-producing bacteria are less abundant in the gastrointestinal tracts of people with ALS (PALS). Methods: We conducted a case-control study at Massachusetts General Hospital to compare the gut microbiota in people with ALS to that in controls. Metagenomic shotgun sequencing was performed on DNA extracted from stool samples of 66 people with ALS (PALS), 61 healthy controls (HC), and 12 neurodegenerative controls (NDC). Taxonomic metagenomic profiles were analyzed for shifts in the microbial community structure between the comparator groups using per-feature univariate and multivariate association tests. Results: The relative abundance of the dominant butyrate-producing bacteria Eubacterium rectale and Roseburia intestinalis was significantly lower in ALSpatients compared to HC. Adjustment for age, sex, and constipation did not materially change the results. The total abundance of 8 dominant species capable of producing butyrate was also significantly lower in ALS compared to HC (p < 0.001). Conclusions: The levels of several butyrate-producing bacteria, which are important for gut integrity and regulation of inflammation, were lower in people with ALS compared to controls. These findings lend support to the inference that the gut microbiota could be a risk factor for ALS. Further investigations are warranted, preferably earlier in the disease with corresponding dietary collection and a longitudinal design.
Entities:
Keywords:
Amyotrophic lateral sclerosis; gut microbiota; risk factors
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