Gut Microbe Case study - Transcriptomics, 16S, Immune deficiency (IMD) Signaling Pathway

The gut microbiota can affect the symptoms of intellectual disability (ID) and autism spectrum disorder (ASD) diseases. Loss of function mutations in histone demethylases KDM5A, KDM5B, or KDM5C are found in patients with ID and ASD. However, the molecular mechanisms that regulate host-commensal microbiota homeostasis in normal and disease states remain largely unknown. Drosophila is a widely accepted model for studying behavior.

This study used Drosophila melanogaster as a model organism to investigate the mechanistic contribution of KDM5 to social behavior by regulating the gut microbiome composition. Research strategy major workflows include:

A: EXPERIMENTAL MODEL AND SUBJECT DETAILS

B: METHOD DESCRIPTION

C: IMMUNE DEFICIENT PATHWAY

D: MICROBIOME, QUANTIFICATION, TRANSCRIPTOMICS

E: SOCIAL BEHAVIOR

• Reducing KDM5 causes intestinal barrier dysfunction and changes in social behavior that correlates with compositional changes in the gut microbiota.

• Therapeutic alteration of the dysbiotic microbiota through antibiotic administration or feeding with a probiotic Lactobacillus strain partially rescues the behavioral, lifespan, and cellular phenotypes observed in kdm5-deficient flies.

• KDM5 demethylase activity was found to transcriptionally regulate component genes of the immune deficiency (IMD) signaling pathway and gut-microbiome-brain function.

This research suggests that modification of the gut microbiome can serve as a clinical therapeutic approach for ID and ASD patients with aberrant IMD signaling.

Primary reference, (Chen et al., 2019)

Chen, K., Luan, X., Liu, Q., Wang, J., Chang, X., Snijders, A. M., Mao, J. H., Secombe, J., Dan, Z., Chen, J. H., Wang, Z., Dong, X., Qiu, C., Chang, X., Zhang, D., Celniker, S. E., & Liu, X. (2019). Drosophila histone demethylase KDM5 regulates social behavior through immune control and gut microbiota maintenance. Cell Host & Microbe, 25(4), 537–552.e8. https://doi.org/10.1016/J.CHOM.2019.02.003

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