Author
Listed:
- Eran Blacher
(Weizmann Institute of Science)
- Stavros Bashiardes
(Weizmann Institute of Science)
- Hagit Shapiro
(Weizmann Institute of Science)
- Daphna Rothschild
(Weizmann Institute of Science
Weizmann Institute of Science)
- Uria Mor
(Weizmann Institute of Science)
- Mally Dori-Bachash
(Weizmann Institute of Science)
- Christian Kleimeyer
(Weizmann Institute of Science)
- Claudia Moresi
(Weizmann Institute of Science)
- Yotam Harnik
(Weizmann Institute of Science)
- Maya Zur
(Weizmann Institute of Science)
- Michal Zabari
(Hadassah-Hebrew University Medical Center)
- Rotem Ben-Zeev Brik
(Weizmann Institute of Science)
- Denise Kviatcovsky
(Weizmann Institute of Science)
- Niv Zmora
(Weizmann Institute of Science)
- Yotam Cohen
(Weizmann Institute of Science)
- Noam Bar
(Weizmann Institute of Science
Weizmann Institute of Science)
- Izhak Levi
(Weizmann Institute of Science
Weizmann Institute of Science)
- Nira Amar
(Weizmann Institute of Science)
- Tevie Mehlman
(Weizmann Institute of Science)
- Alexander Brandis
(Weizmann Institute of Science)
- Inbal Biton
(Weizmann Institute of Science)
- Yael Kuperman
(Weizmann Institute of Science)
- Michael Tsoory
(Weizmann Institute of Science)
- Leenor Alfahel
(Ben-Gurion University of the Negev)
- Alon Harmelin
(Weizmann Institute of Science)
- Michal Schwartz
(Weizmann Institute of Science)
- Adrian Israelson
(Ben-Gurion University of the Negev)
- Liisa Arike
(University of Gothenburg)
- Malin E. V. Johansson
(University of Gothenburg)
- Gunnar C. Hansson
(University of Gothenburg)
- Marc Gotkine
(Hadassah-Hebrew University Medical Center)
- Eran Segal
(Weizmann Institute of Science
Weizmann Institute of Science)
- Eran Elinav
(Weizmann Institute of Science
Division of Cancer-Microbiome Research, DKFZ)
Abstract
Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disorder, in which the clinical manifestations may be influenced by genetic and unknown environmental factors. Here we show that ALS-prone Sod1 transgenic (Sod1-Tg) mice have a pre-symptomatic, vivarium-dependent dysbiosis and altered metabolite configuration, coupled with an exacerbated disease under germ-free conditions or after treatment with broad-spectrum antibiotics. We correlate eleven distinct commensal bacteria at our vivarium with the severity of ALS in mice, and by their individual supplementation into antibiotic-treated Sod1-Tg mice we demonstrate that Akkermansia muciniphila (AM) ameliorates whereas Ruminococcus torques and Parabacteroides distasonis exacerbate the symptoms of ALS. Furthermore, Sod1-Tg mice that are administered AM are found to accumulate AM-associated nicotinamide in the central nervous system, and systemic supplementation of nicotinamide improves motor symptoms and gene expression patterns in the spinal cord of Sod1-Tg mice. In humans, we identify distinct microbiome and metabolite configurations—including reduced levels of nicotinamide systemically and in the cerebrospinal fluid—in a small preliminary study that compares patients with ALS with household controls. We suggest that environmentally driven microbiome–brain interactions may modulate ALS in mice, and we call for similar investigations in the human form of the disease.
Suggested Citation
Eran Blacher & Stavros Bashiardes & Hagit Shapiro & Daphna Rothschild & Uria Mor & Mally Dori-Bachash & Christian Kleimeyer & Claudia Moresi & Yotam Harnik & Maya Zur & Michal Zabari & Rotem Ben-Zeev , 2019.
"Potential roles of gut microbiome and metabolites in modulating ALS in mice,"
Nature, Nature, vol. 572(7770), pages 474-480, August.
Handle:
RePEc:nat:nature:v:572:y:2019:i:7770:d:10.1038_s41586-019-1443-5
DOI: 10.1038/s41586-019-1443-5
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Cited by:
- Felipe Papa Pellizoni & Aline Zazeri Leite & Nathália de Campos Rodrigues & Marcelo Jordão Ubaiz & Marina Ignácio Gonzaga & Nauyta Naomi Campos Takaoka & Vânia Sammartino Mariano & Wellington Pine Omo, 2021.
"Detection of Dysbiosis and Increased Intestinal Permeability in Brazilian Patients with Relapsing–Remitting Multiple Sclerosis,"
IJERPH, MDPI, vol. 18(9), pages 1-17, April.
- Monica Lopes-Ferreira & Adolfo Luis Almeida Maleski & Leticia Balan-Lima & Jefferson Thiago Gonçalves Bernardo & Lucas Marques Hipolito & Ana Carolina Seni-Silva & Joao Batista-Filho & Maria Alice Pim, 2022.
"Impact of Pesticides on Human Health in the Last Six Years in Brazil,"
IJERPH, MDPI, vol. 19(6), pages 1-19, March.
- Jiezhou Pan & Guidong Gong & Qin Wang & Jiaojiao Shang & Yunxiang He & Chelsea Catania & Dan Birnbaum & Yifei Li & Zhijun Jia & Yaoyao Zhang & Neel S. Joshi & Junling Guo, 2022.
"A single-cell nanocoating of probiotics for enhanced amelioration of antibiotic-associated diarrhea,"
Nature Communications, Nature, vol. 13(1), pages 1-11, December.
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