The Role Of Oral Microbiota In Autism Spectrum Disorders

Autism spectrum disorder(ASD)is a heterogeneous neurodevelopmental disorder involving social communication and interaction deficits and repetitive stereotyped behaviors.The prevalence of ASD grows fast worldwide,and the etiology is unknown,making it difficult to diagnose and cure.Mounting studies have shown that intestinal microbiota plays an important role in the pathogenesis of ASD.The oral microbiota,as the reservoir of gut microbiota,have gradually attracted attention in recent years for their role in systemic diseases.Herein,this paper firstly summarizes and reviews the overseas and domestic research status on oral microbes and ASD,attempting to provide a reference for the subsequent exploration of the relationship between oral microbes and ASD and its potential etiological role in ASD.In order to initially explore the oral health status of ASD patients,we recruited144 children with ASD and 228 unrelated children with typical development(TD)aged3-16 years old from China.Through data collected using parent-reported questionnaires,the oral status of children with and without ASD was analyzed.The results shows that children with ASD had worse oral health status than children with TD.Oral symptoms were more prevalent in the ASD group,especially halitosis,food impaction,and oral lesions,than the TD group.The rate of damaging oral habits,including mouth breathing,drooling and object biting,was also high in the ASD group.Compared with the TD group,more children with ASD did not brush their teeth independently and frequently,had difficulty accessing dental care,and reported unpleasant dental experiences.The presence of ASD was associated with decreased oral health-related quality of life in these children and their families,especially in older children.Next,on the basis of the microbial dysbiosis detected in the oral cavity of children with ASD as compared with TD children in our previous studies,we introduced animal experiments to elucidate whether the oral microbiota contributes to the pathogenesis of ASD.By transferring oral microbiota from donors with ASD and TD into an antibioticmediated microbiota-depleted mouse model,we found that the ASD microbiota is sufficient to induce ASD-like behaviors,such as impaired social behavior.Mice receiving oral microbiota from the ASD donor showed significantly different microbiota structures in their oral cavity and intestinal tract as compared with those receiving TD microbiota and those not receiving any bacterium.The prefrontal cortex of ASD microbiota recipient mice displayed an alternative transcriptional profile with significant upregulation of serotonin-related gene expression,neuroactive ligandreceptor interaction,and TGF-β signaling pathway relative to that in TD microbiota recipient mice.The expression of serotonin-related genes was significantly increased in ASD microbiota recipient mice and was associated with selective autistic behaviors and changes in abundance of specific oral microbiota,including species of Bacteroidetes[G-7],Porphyromonas,and Tannerella.Machine learning based on the causal inference method confirmed a contributing role of Porphyromonas sp.HMT 930 in ASD.Taken together,we demonstrate that there were differences in oral health status between children with and without ASD in China.Children with ASD showed a high prevalence of oral manifestation such as halitosis,oral lesions and mouth breathing.These children also lack oral hygiene practices and dental care.The oral microbiota of children with ASD is disturbed,and its transplantation into recipient mice results in ASD-like behaviors,changes in microbiota composition,abnormal expression of ASDrelated genes,and dysfunction of neuronal signaling activities in mice.Porphyromonas may affect the etiopathogenesis of ASD by promoting serotonin-related gene expression and neural signaling activity.This work suggests that dental team should be aware of the oral health dilemma of ASD patients and make efforts to develop novel strategies to provide proper oral care to this special-needs population,and highlights the mouth-microbial-brain connections in the development of neuropathology and provides a novel strategy to fully understand the etiologic mechanism of ASD.In the finality,the problems requiring further studies are briefly discussed this paper.