Research focus
We use different animal model systems to understand the contribution of genetic factors, impact of early adverse life experience (e.g., stress, infections), and gene-environment interactions on the development of motor, affective and cognitive functions, which are impaired in ADHD and ASD. In parallel, we conduct human studies using several cohorts of infants and children (e.g., infants with elevated likelihood of developing ASD, children with ASD and a population-based Swedish twin cohort).
Our work is performed in collaboration with clinicians and psychologists at the Astrid Lindgren Children's Hospital and Karolinska Institutet Center of Neurodevelopmental Disorders (KIND). This optimizes the opportunities for iterative translation from basic to clinical research and back to more fundamental mechanistic studies.
Key subjects of interest
- Potential role of gut microbiota on early aspects of motor, social and cognitive development in humans
- Influence of gut-derived microbial molecules such as “bacterial peptidoglycan fragments” on typical and atypical brain development
- Role of bacterial peptidoglycans and their sensing molecules in brain and behavior across the life span.
- Potential beneficial effects of psychobiotic diet in early life on motor, social and cognitive development
There are multiple direct and indirect pathways through which gut microbiota may influence the brain, including signals carried by neuronal circuits [e.g., bidirectional vagus nerve-to-brain communication, the enteric nervous system and neuropods; (1)], the production of bacterial fermentation metabolic by-products, such as short chain fatty acids (2), tryptophan metabolites and neurotransmitters (3), release of cytokines by immune cells (4), and gut hormone signaling (5). The gut microbiota has been shown to influence various neurodevelopmental processes such as microglial maturation and function, blood brain barrier formation and integrity, myelination and neurogenesis (7). For more details, see Gonzalez-Santana A, Diaz Heijtz R, Trends Mol Med 2020 08;26(8):729-743.
Recent Scientific Discoveries
Autism Spectrum Disorder (ASD) is now understood to be a multifactorial neurodevelopmental condition, involving genetic susceptibility, environmental risk factors, and gene-environmental interactions. One such risk factor is having a sibling with ASD, with studies consistently demonstrating a higher prevalence among siblings and in families with a history of ASD.
In a recent prospective longitudinal study published in Translational Psychiatry, we found pronounced alterations in the gut microbiota composition of infants at elevated likelihood (EL) of developing ASD (i.e., siblings of children with ASD) compared to low-likelihood (LL) infants (i.e., infants without a family history of ASD) at five months of age (see Figure 1). Specifically, infants in the EL group harbored less beneficial Bifidobacterium species (B. bifidum, B. longum and B. Bifidobacterium kashiwanohense) and more Clostridium (C. bolteae, C. difficile, C. clostridioforme, C. neonatale) species compared to infants in the LL group. On the other hand, Clostridium species have been previously been with linked to ASD, are considered pathobionts and responsible for inflammation when homeostasis is disturbed.
