Disturbance of the human gut microbiota in patients with Myotonic Dystrophy type 1

Abstract

Myotonic dystrophy type 1 (DM1) is a rare autosomal dominant genetic disorder. Although DM1 is primarily characterized by progressive muscular weakness, it exhibits many multisystemic manifestations, such as cognitive deficits, cardiac conduction abnormalities, and cataracts, as well as endocrine and reproductive issues. Additionally, the gastrointestinal (GI) tract is frequently affected, encompassing the entire digestive tract. However, the underlying causes of these GI symptoms remain uncertain, whether it is biomechanical problems of the intestine, involvement of bacterial communities, or both. The primary objective of this study is to investigate the structural changes in the gut microbiome of DM1 patients. To achieve this purpose, 35 patients with DM1 were recruited from the DM-Scope registry of the neuromuscular clinic in the Saguenay-Lac-St-Jean region of the province of Québec, Canada. Stool samples from these 35 patients, including 15 paired samples with family members living with them as controls, were collected. Subsequently, these samples were sequenced by 16S MiSeq and were analyzed with DADA2 to generate taxonomic signatures. Our analysis revealed that the DM1 status correlated with changes in gut bacterial community. Notably, there were differences in the relative abundance of Bacteroidota, Euryarchaeota, Fusobacteriota, and Cyanobacteria Phyla compared to healthy controls. However, no significant shift in gut microbiome community structure was observed between DM1 phenotypes. These findings provide valuable insights into how the gut bacterial community, in conjunction with biomechanical factors, could potentially influence the gastrointestinal tract of DM1 patients.

Keywords: Bacterial communities; DM1; Gastrointestinal symptoms; Gut microbiota; Microbiome; Myotonic Dystrophy type 1.

Graphical abstract

Fig. 1

Bacterial relative abundance at the phylum and genus level in all 35 DM1 patients and 15 controls. a) At the phylum level based on their status. b) At the phylum level for various phenotypes of DM1. c) At the genus level based on their status. d) At the genus level for various phenotypes of DM1. “Pediatrics” includes congenital, childhood and juvenile onset, while “Adult”, and late onset were classified as “Adult”.

Fig. 2

a) The prevalence of bacteria at the phylum level in the gut microbiome of paired DM1 patients compared to their control samples. (* P value of lower than 0.05). b) P value of different taxa calculated by ANCOM-BC analysis in the paired samples analysis.

Fig. 3

Alpha-diversity analysis (Shannon, Simpson, and Chao1) in this study. a) Comparing the alpha diversity of all 15 DM1 samples with 15 healthy controls using Paired-sample Wilcoxon test (P ≥ 0.05). On the right-hand side, each line is related to each paired sample including one DM1 patient and one control. In blue, controls and in yellow, patients with DM1. b) phenotypic subgroups of all 35 DM1 patients. In blue, Pediatrics and in red, Adults.

Fig. 4

PCoAs of beta-diversity between paired samples in the study representing the significance difference for DM1 patients and controls. (a) PCoA based on weighted UniFrac (P ≤ 0.05, R² =0.08) and (b) unweighted UniFrac. In red, controls and in blue, patients with DM1.

Fig. 5

Shared and unique ASVs among both status of samples (a) as well as the various phenotypes of DM1 compared to controls(b).

Fig. 6

ANCOM differential abundance analysis. a) ANCOM volcano plot. Volcano plot representing the Log2-transformed fold change (Log2FC, x-axis) of ASV table at the genus level in DM1 patients compared to paired controls in relation to their p value (neglogQval, y-axis). A positive x-axis means a species is abundant in DM1 groups and a negative x-axis value means a species is abundant in control samples. b) Bar graph demonstrating the most significantly differed genera with higher and lower abundance in DM1 and healthy control population.