75 8.5 Experiment Results

Introduction

This section pertains to results of the primary study by Li et al (2020), The gut microbiota regulates autism-like behavior by mediating vitamin B6 homeostasis in EphB6-deficient mice. 

Social Tests

The preliminary social tests showed that knockout mice spent more time self-grooming than the wild type mice. This was associated with stereotyped autism patients that displayed social deficits.

• In the marble burying test, the knockout mice buried as many marbles as the wild type mice
• The knockout mice spent less time sniffing at the partition, regardless of whether a familiar or novel mouse was placed in the cage
• During the three chambered-social approach task, the knockout mice spent similar amounts of time with the inanimate object and showed less preference for the social mouse. The wild-type mice spent more time with the social mouse

ASD can often be accompanied with symptoms such as hyperactivity, anxiety and intellectual disability; this study tested for these symptoms. Collectively, the results showed that the deletion of EphB6 in mice resulted in autism-like behavior, including stereotyped behavior and social deficits, accompanied by anxiety-like behavior, but did not result in any evidence of intellectual disability (Li et al, 2020).

Fecal Transplants

During the fecal transplants, The C57BL/6J mice that were gastrically perfused with the fecal microbiota from the Knockout mice displayed increased self-grooming and partially decreased social behavior compared to the control mice. Furthermore, transplanting fecal microbiota from the wild type mice into the Knockout mice showed an increase in Defferribacteres within the transplanted Knockout mice. Additional analysis showed that these transplanted knockout mice exhibited increased social behavior and a decreased tendency of self-grooming (Li et al., 2020).

Vitamin B₆ Homeostasis regulated Social Behavior in Knockout Mice

The metabolites in the prefrontal cortex showed significant differences between the two groups of mice

• They detected levels of vitamin B₆ in the feces, blood, and prefrontal cortex of mice and found that the EphB6-deficient mice presented increased fecal levels of pyridoxine (PN), decreased plasma levels of both pyridoxamine (PM) and pyridoxal-5 -phosphate (PLP) in the prefrontal cortex
• One week after knockout, the knockout mice transplanted with wildtype fecal microbiota inversely exhibited decreased levels of PN, while having increased levels of PM and PLP
  

  

Chapter Summary

• The deletion of EPHB6 lead to autism-like behavior and gut microbial disturbance in mice
• The transplantation of the fecal microbiota from the EphB6-deficient mice caused autism-like behavior.
• Transplantation of the fecal microbiota from wild-type mice improved autism-like behavior in adult EphB6-deficient mice
• Gut microbiota-mediated vitamin B6 homeostasis regulates social behavior, dopamine levels and the E/I balance in EphB6-deficient mice