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APC Scientists Uncover Novel Role for Gut Bacteria in Autism Spectrum Disorder

By Dr Anna Golubeva, Postdoctoral scientist, APC Microbiome Ireland

Autism Spectrum Disorders (ASD) are among the most prevalent neurodevelopmental disorders characterised by impaired social skills and repetitive patterns of behaviour. A strikingly high percentage of subjects with ASD also suffer from gastrointestinal symptoms such as bloating, diarrhoea, cramps and constipation. More recently, the gut microbiota has emerged as an important player with multiple studies having observed altered gut microbiota and mycobiota (fungi) of individuals with ASD.  However, we have very little knowledge on how intestinal bacteria can affect gut-brain axis signalling and gastrointestinal symptoms in autism.

APC scientists have now shed new light on how the gut microbiota can contribute to the gastrointestinal symptoms and deficits in social behaviours in mice with ASD-like symptoms.

The group has shown that a reduction in the abundance of particular intestinal bacteria is associated with gastrointestinal distress and impaired social communication. In particular, the scientists found that the microbiota in these mice is substantially depleted in specific bacteria which are involved in the metabolism of bile acids and tryptophan. In total, 18 out of 44 bacterial genera/groups tested were found to be altered with significant reduction in the relative abundance of Blautia and Bifidobacterium genera observed. These changes are linked to increased permeability of the intestine (“leaky” gut) and delayed movement of faecal matter along the intestine in the mice, as well as reduced sociability and increased engagement in compulsive behaviours.

Understanding these mechanisms is a crucial step toward the development of microbiota-based interventions for both the gastrointestinal and behavioural symptoms in ASD. These findings identify specific bacteria that may trigger changes in gut physiology and modulate the onset of autistic behaviours, at least in mice. This opens new perspectives in targeted manipulation of the gut microbiota for reversing gastrointestinal and behavioral symptomatology in autism.

The research was carried out by a postdoctoral scientist  Anna Golubeva in John Cryan’s group in collaboration with  Susan Joyce,  Cormac Gahan, Ted Dinan and Catherine Stanton and their colleagues at the APC Microbiome Ireland, University College Cork and Teagasc Food Research Centre, Cork, Ireland.

“This is a fascinating discovery” said John Cryan. “For too long the underlying biology of gastrointestinal dysfunction in ASD has been relatively ignored. However, we need to stress that this is in an animal model and is early-stage research. Nonetheless it does offer some specific insights into targeting the gut microbiome for the gastrointestinal and perhaps even the behavioural symptoms of autism”.

The study was published in the EBioMedicine, a new open access journal under the umbrella of Cell Press and The Lancet covering cutting-edge translational and clinical research to facilitate the effective translation of insights gained from biomedical research into improved human health.  The research was featured on the journal cover and was also the subject of a Commentary.

Full reference:

Anna V. Golubeva, Susan A. Joyce, Gerard Moloney, Aurelijus Burokas, Eoin Sherwin, Silvia Arboleya, Ian Flynn, Dmitry Khochanskiy, Angela M. Pérez, Veronica Peterson, Kieran Rea, Kiera Murphy, Olga Makarova, Sergey Buravkov, Niall P. Hyland, Catherine Stanton, Gerard Clarke, Cormac G.M. Gahan, Timothy G. Dinan and John F. Cryan (2017) “Microbiota-Related Changes in Bile Acid & Tryptophan Metabolism Are Associated with Gastrointestinal Dysfunction in a Mouse Model of Autism” EBioMedicine http://www.ebiomedicine.com/article/S2352-3964(17)30374-2/fulltext

Commentary in the journal by We-Li Wu  http://www.ebiomedicine.com/article/S2352-3964(17)30400-0/fulltext