The Interplay Between Gut Microbiota, Inflammation, and Neurodevelopmental Disorders: A Focus on Autism Spectrum Disorder — The Association Specialists
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The Interplay Between Gut Microbiota, Inflammation, and Neurodevelopmental Disorders: A Focus on Autism Spectrum Disorder (22220)

Mohammed ALAMOUDI 1 , Samantha Matta 1 2 , Chalystha Yie Qin Lee 1 , Rachele Gore 1 3 , Edden SUBEJANO 3 , Mitra Mohsenipour 1 , Hithin VELAGAPUDI 3 , Peter J Crack 2 , Jennifer Wood 3 , Anya Shindler 3 , Ashley Franks 3 , Elisa L. Hill-Yardin 1 2
  1. School of Health and Biomedical Sciences, Royal Melbourne Institute of Technology , Bundoora, VIC, Australia
  2. The University of Melbourne, Parkville, VIC, Australia
  3. Department of Microbiology, Anatomy, Physiology and Pharmacology, School of Life Sciences, La Trobe University, Bundoora, VIC , Australia

Introduction: Autistic individuals commonly experience immune disorders and gastrointestinal (GI) symptoms and microbial dysbiosis. GI issues associated with altered gut microbiota may contribute to systemic inflammation and neurological dysfunction, potentially exacerbating core autism symptoms. We investigated impacts of acute inflammatory insult (dextran-sodium-sulphate-(DSS)-induced colitis), on the gut microbiome in Nlgn3R451C mice with an autism-associated variant in the Neuroligin-3 cell adhesion protein expressed at neuronal synapses, and in IFNAR1-/-mice (an immune-dysfunction mouse model).

Methods: 3%-DSS treatment for 7-days generated ulcerative colitis symptoms in 8-week-old Nlgn3R451C, IFNAR1-/-, Nlgn3R451CxIFNAR1-/-, and wild-type mice. We compared faecal microbial profiles using 16S rRNA sequencing.

Results: DSS treatment reduced microbial diversity in wild-type mice (P=0.004), particularly on Day-8 compared to SHAM-treated wild-type mice (P=0.03). Surprisingly, DSS-treated Nlgn3R451C samples showed similar microbial diversity and richness compared to SHAM whereas microbial-community evenness was reduced in DSS-treated wild-type and Nlgn3R451CxIFNAR1-/- mice. DSS treatment resulted in compositional dissimilarity of microbial communities in Nlgn3R451C mice. Overall, the genus Lachnospiraceae NK4A136-group dominated, however, upon DSS treatment, Clostridia UCG-014 and Clostridia vadinBB60_group increased on Day-4, and Romboutsia and Akkermansia increased on Day-8. Notably, Akkermansia was abundant in SHAM-treated Nlgn3R451C mice.

Conclusion: DSS-induced colitis reduced microbial diversity in Wild-type and Nlgn3R451CxIFNAR1-/- mouse models, however Nlgn3R451C samples were unchanged. DSS-treated caused compositional differences across genotypes except for IFNAR1-/- mice. In response to inflammatory insult, bacterial genera associated with gut mucosal repair increased in abundance including in Nlgn3R451C mice. Here we show that a nervous system mutation associated with autism impacts gut microbiota in response to inflammation.