Supplier-origin gut microbiomes affect host body weight and select autism-related behaviors

Gut Microbes. 2024 Jan-Dec;16(1):2385524. doi: 10.1080/19490976.2024.2385524. Epub 2024 Aug 6.

Abstract

Autism spectrum disorders (ASD) are complex human neurodiversities increasing in prevalence within the human population. In search of therapeutics to improve quality-of-life for ASD patients, the gut microbiome (GM) has become a promising target as a growing body of work supports roles for the complex community of microorganisms in influencing host behavior via the gut-brain-axis. However, whether naturally-occurring microbial diversity within the host GM affects these behaviors is often overlooked. Here, we applied a model of population-level differences in the GM to a classic ASD model - the BTBR T+ Itpr3tf/J mouse - to assess how complex GMs affect host behavior. Leveraging the naturally occurring differences between supplier-origin GMs, our data demonstrate that differing, complex GMs selectively effect host ASD-related behavior - especially neonatal ultrasonic communication - and reveal a male-specific effect on behavior not typically observed in this strain. We then identified that the body weight of BTBR mice is influenced by the postnatal GM which was potentially mediated by microbiome-dependent effects on energy harvest in the gut. These data provide insight into how variability within the GM affects host behavior and growth, thereby emphasizing the need to incorporate microbial diversity within the host GM as an experimental factor in biomedical research.

Keywords: ASD; BTBR; Envigo; The Jackson Laboratory; growth; gut-brain-axis; microbiome; supplier-origin GM.

MeSH terms

  • Animals
  • Autism Spectrum Disorder* / microbiology
  • Autistic Disorder / microbiology
  • Autistic Disorder / psychology
  • Bacteria / classification
  • Bacteria / genetics
  • Bacteria / isolation & purification
  • Behavior, Animal*
  • Body Weight*
  • Brain-Gut Axis / physiology
  • Disease Models, Animal
  • Female
  • Gastrointestinal Microbiome*
  • Humans
  • Male
  • Mice

Grants and funding

ZM, KG, ALR, and ACE were supported by NIH U42 OD010918. ZM was also supported by NIH T32 GM008396. KG was also supported by NIH T32 OD011126.