Leaky intestine and impaired microbiome in an amyotrophic lateral sclerosis mouse model

• Published in: Physiological reports Vol. 3; no. 4; pp. e12356 - n/a
• Main Authors: Wu, Shaoping, Yi, Jianxun, Zhang, Yong‐guo, Zhou, Jingsong, Sun, Jun
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.04.2015; BlackWell Publishing Ltd
• Subjects: Amyotrophic lateral sclerosis; Animal models; Antimicrobial peptides; Atrophy; autophagy; cell biology; Digestive system; Disease; dysbiosis; E-cadherin; Epithelial cells; Epithelium; Fecal microflora; Gastrointestinal tract; Homeostasis; Immune response; Innate immunity; Intestinal microflora; intestinal permeability; Intestine; Microbial activity; microbiome; Microbiomes; Motor neurons; Movement disorders; Neurodegenerative diseases; Neurological diseases; Original Research; Paneth cells; Paralysis; Parkinson's disease; Permeability; Physiology; Respiration; signal transduction; Small intestine; Superoxide dismutase; tight junction; ZO‐1; intestinal permeability; autophagy; cell biology; signal transduction; Antimicrobial peptides; Paneth cells; ZO‐1; microbiome; tight junction; dysbiosis
• ISSN: 2051-817X; 2051-817X
• DOI: 10.14814/phy2.12356

Emerging evidence has demonstrated that intestinal homeostasis and the microbiome play essential roles in neurological diseases, such as Parkinson's disease. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons and muscle atrophy. Currently, there is no effective treatment. Most patients die within 3–5 years due to respiratory paralysis. Although the death of motor neurons is a hallmark of ALS, other organs may also contribute to the disease progression. We examined the gut of an ALS mouse model, G93A, which expresses mutant superoxide dismutase (SOD1G93A), and discovered a damaged tight junction structure and increased permeability with a significant reduction in the expression levels of tight junction protein ZO‐1 and the adherens junction protein E‐cadherin. Furthermore, our data demonstrated increased numbers of abnormal Paneth cells in the intestine of G93A mice. Paneth cells are specialized intestinal epithelial cells that can sense microbes and secrete antimicrobial peptides, thus playing key roles in host innate immune responses and shaping the gut microbiome. A decreased level of the antimicrobial peptides defensin 5 alpha was indeed found in the ALS intestine. These changes were associated with a shifted profile of the intestinal microbiome, including reduced levels of Butyrivibrio Fibrisolvens, Escherichia coli, and Fermicus, in G93A mice. The relative abundance of bacteria was shifted in G93A mice compared to wild‐type mice. Principal coordinate analysis indicated a difference in fecal microbial communities between ALS and wild‐type mice. Taken together, our study suggests a potential novel role of the intestinal epithelium and microbiome in the progression of ALS. Emerging evidence has demonstrated that intestinal homeostasis and microbiome play essential roles in neurological diseases, such as Parkinson's disease. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons and muscle atrophy. Our data provide the first evidence about leaky intestine and impaired microbiome that may play a potential role in ALS disease progression.