Progression and survival of patients with motor neuron disease relative to their fecal microbiota

Abstract

Gut microbiota studies have been well-investigated for neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease, however, fewer studies have comprehensively examined the gut microbiome in Motor Neuron Disease (MND), with none examining its impact on disease prognosis. Here, we investigate MND prognosis and the fecal microbiota, using 16S rRNA case–control data from 100 individuals with extensive medical histories and metabolic measurements. We contrast the composition and diversity of fecal microbiome signatures from 49 MND and 51 healthy controls by combining current gold-standard 16S microbiome pipelines. Using stringent quality control thresholds, we conducted qualitative assessment approaches including; direct comparison of taxa, PICRUSt2 predicted metagenomics, Shannon and Chao1-index and Firmicutes/Bacteroidetes ratio. We show that the fecal microbiome of patients with MND is not significantly different from that of healthy controls that were matched by age, sex, and BMI, however there are distinct differences in Beta-diversity in some patients with MND. Weight, BMI, and metabolic and clinical features of disease in patients with MND were not related to the composition of their fecal microbiome, however, we observe a greater risk for earlier death in patients with MND with increased richness and diversity of the microbiome, and in those with greater Firmicutes to Bacteroidetes ratio. This was independent of anthropometric, metabolic, or clinical features of disease, and warrants support for further gut microbiota studies in MND. Given the disease heterogeneity in MND, and complexity of the gut microbiota, large studies are necessary to determine the detailed role of the gut microbiota and MND prognosis.

Keywords:

• Motor Neuron Disease
• fecal microbiota
• disease progression
• survival
• metabolism

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Acknowledgements

The authors thank all patients with MND and healthy control individuals who participated in this study.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Data availability

The 16S data will be deposited in dbGAP.

Additional information

Funding

This research was supported by a Motor Neurone Disease Research Institute of Australia Cunningham Family MND Research Grant (FJS, PAM, RDH, STN), the National Health and Medical Research Council [1078901, 1113400 to NRW, 1121962 to FCG] and a UQ Early Career Research Grant (STN). The authors acknowledge the valuable funding of Wesley Medical Research [Project No. 2016-32]. STN is supported by the Scott Sullivan Fellowship (MND and Me Foundation, Royal Brisbane and Women’s Hospital Foundation, and the Queensland Brain Institute) and the Australian Institute for Bioengineering and Nanotechnology at the University of Queensland.