Thinking with your Gut

There has been a lot of buzz lately about the importance of gut microbes impacting human health and immune system maturation. This has led to recent discoveries supporting the idea that gut commensals can contribute to the pathogenesis of autoimmune diseases like T1D. New methods and sequencing technologies have expanded the learning curve for researchers to analyze and interpret microbiome data, leading to the theory that there is a relationship between the ratio of bacterial composition in the gut and T1D. 

There have been many advances in data analytics, one of which is animalcules, which is useful to researchers because it enables them to analyze data at multiple levels.  They can explore large datasets and identify patterns between multiple sample groups in the phylum level, check the top abundant species in one specific sample group and see the microbiome composition at different taxon levels. 

This type of analysis is often used in diabetes research by exploring whether there is an association between a bacterial genus and glucose metabolism.

  • Trends in the data identified four microbiome markers as the primary clinical indicators of T2D: Escherichia, Veillonella, Blautia and Anaerostipes..
  • Escherichia and Veillonella both increased with disease progression. While Escherichia is associated with measures of blood glucose, Veillonella is connected to  insulin-related measures.
  • Blautia and Anaerostipes decrease with disease progression and are associated with improved beta cell function and insulin efficiency.

Bacteroides fragilis (BF), a component of the human colonic commensal microbiota, has also been widely studied to determine the influence of commensal bacteria in immune regulation.

  • Capsular polysaccharides of BF, specifically polysaccharide A (PSA), have the ability to promote immune regulation by directly acting on dendritic cells and regulatory T cells.
  • Associations have been found between a higher prevalence of Bacteroides members, including BF, to T1D disease incidence and progression in humans. 
  • There is also an increased abundance of Bacteroides members and reduction in firmicutes that precede T1D onset in children.
  • However, systemic exposure of specific Bacteroides members could cause pro-autoimmune effects under T1D susceptibility. 

Looking Forward: The development of more advanced data methods is helping researchers visualize and understand the patterns in microbial community structure and diversity. Hopefully, this will promote more valuable insights into the connection between the microbial community, phenotypes of interest and T1D.

Sources 

  • Diener, Christian, et al. “Progressive Shifts in the Gut Microbiome Reflect Prediabetes and Diabetes Development in a Treatment-Naive Mexican Cohort.” BioRxiv, Cold Spring Harbor Laboratory, 1 Jan. 2019, www.biorxiv.org/content/10.1101/710152v1.
  • Sofi, M. Hanief., et al. “Polysaccharide A-Dependent Opposing Effects of Mucosal and Systemic Exposures to Human Gut Commensal Bacteroides Fragilis in Type 1 Diabetes.” BioRxiv, Cold Spring Harbor Laboratory, 1 Jan. 2019, www.biorxiv.org/content/10.1101/492579v3.
  • Zhao, Yue, et al. “Animalcules: Interactive Microbiome Analytics and Visualization in R.” BioRxiv, Cold Spring Harbor Laboratory, 1 Jan. 2020, www.biorxiv.org/content/10.1101/2020.05.29.123760v1.

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