Oral microbiota and autism

I am a big believer that an altered gut microbiota is associated with autism spectrum disorders and so do many others.  Recently, a group of scientists reported that it may be possible to diagnose autism, not on behaviors, eye contact, or repetitive movements, but instead on SALIVA!

The growing evidence of gut bacterial, viral and fungal abnormalities as a key to autism,  is not a crazy concept.  To think that a MEDICAL test rather than simply an OBSERVATIONAL one, could show a BIOLOGICAL mechanism, would be helpful in diagnosing and treating autism. 

Here is that study: Alterations of oral microbiota distinguish children with autism spectrum disorders from healthy controls  

 ....we demonstrated that the salivary and dental microbiota of ASD patients were highly distinct from those of healthy individuals. Lower bacterial diversity was observed in ASD children compared to controls, especially in dental samples.....pathogens such as Haemophilus in saliva and Streptococcus in plaques showed significantly higher abundance in ASD patients, whereas commensals such as Prevotella, Selenomonas, Actinomyces, Porphyromonas, and Fusobacterium were reduced....The distinguishable bacteria were also correlated with clinical indices, reflecting disease severity and the oral health status

Available twin studies showed that environmental factors are more important than genetic predisposition6. Among such factors, microbial dysbiosis is of increasing interest, with accumulating reports in animal models and human epidemiologic studies linking disruptive alterations in the gut microbiota to ASD symptomology7,8,9,10,11,12. 

The enrolled ASD subjects were between 7 and 14 years of age, with no previous medical treatment (except for rehabilitation training) or antibiotic/antifungal use within 3 months of sample collection.  Stopping here to say that I wondered if antibiotics could affect the results, as the controls did not have antibiotics (or antifungals), so did some research and it looks like the oral microbiome is not altered like the gut when it comes to antibiotics.

ASD was associated with increased abundance rates of Streptococcus (FDR Q = 0.02 in plaques) and Haemophilus (FDR Q = 0.007 in saliva), and decreased rates of Prevotella(FDR Q = 0.009 in plaques), Selenomonas (FDR Q = 0.042 in plaques), Actinomyces (FDR Q = 0.002 in saliva), Porphyromonas (FDR Q = 0.03 in saliva), and Fusobacterium (FDR Q = 0.011 and 0.025 in plaques and saliva, respectively). ...

 ASD was not only associated with decreased richness of commensals, but also related to reduced mutual effects within these bacteria. Among these commensals, an interesting finding was the obvious reduction of Prevotellaceae co-occurrence network patterns in dental samples, including Prevotella and Alloprevotella clusters (Fig. 4b). In contrast, the OTUs in ASD groups formed smaller clusters and were less interconnected. Two ASD-enriched shared OTUs, including OTU139 (Rothia aeria) and OTU285 (Streptococcus mutans), and saliva-specific OTUs, i.e. OTU159, OTU189, and OTU361, which were all annotated to Haemophilus, were negatively correlated with control-enriched OTUs, suggesting unknown antagonistic or mutually exclusive relationships. Moreover, clusters containing 9 OTUs belonging to Actinomyces, Solobacterium, Alloprevotella, Leptotrichia, Peptostreptococcus and Peptostreptococcacea [XI][G-1], were all enriched in both salivary and dental samples from healthy controls but not in the ASD groups....A separation was found between control- and ASD-enriched OTUs based on ABC scores, which are used to preliminarily determine the severity of ASD27. Notably, most ASD-enriched phylotypes, such as Haemophilus sp. (OTU159, R = 0.445, p < 0.001) and Rothia aeria (OTU139, R = 0.381, P = 0.004), were positively correlated to the ABC score...

The family Prevotellaceae, including the genera Prevotella and Alloprevotella, also showed a relatively low abundance in children with ASD. This was evident in dental samples as demonstrated in the co-occurrence network (Fig. 4). In agreement with these findings, Finegold et al. recorded a depletion of Prevotella in the gut of autistic patients compared to sibling controls38.  Meanwhile, Kang et al. reported that Prevotella, as the most significantly altered genus between autistic and neurotypical subjects, decreases dramatically in abundance in stool samples from autistic patients12.   A low abundance of Prevotella was also detected in feces from patients with Parkinson’s disease and untreated Multiple Sclerosis, supporting the relevance of this bacterium in CNS disorders 40, 41.  Prevotella is a commensal microorganism in multiple human habitats, including the intestine and oral cavity; it does not only interact with the immune system but also plays a key role in degrading a broad spectrum of saccharides42,43.44.  Interestingly, it was reported that autistic children may have deficiencies in saccharide metabolism and impaired carbohydrate digestion36,45.  Prevotella species also have essential genes for the biosynthesis of vitamins44, which were reported to mitigate ASD symptoms46.47.  Future studies are warranted to further interrogate the role of Prevotellaceae, also evaluating its therapeutic potential for ASD.

This finding is interesting and pertinent for my daughter and probably many more as PANDAS , also on the rise, with or without an autism diagnosis, has its epicenter with STREP infections.  The authors here report : Another putative pathogen showing overgrowth in dental samples was Streptococcus, a potent immunogenic trigger that was reported to affect the risk of CNS dysfunction such as Tourette Syndrome (another neurodevelopmental illness), Sydenham chorea and bacterial meningitis 55,56.  Indeed, Streptococcus was recorded to cause neurological damage by producing neurotoxins such as streptomycin, streptodornase, and streptokinase57. Studies of the intestinal microbiota indicated that Streptococcus might be responsible for bacterial infection in Parkinson’s disease and liver cirrhosis, probably originating from the mouth57,58,59. This finding indicated that specific oral bacteria could invade the gut and subsequently influence remote organs.

Connecting some more dots here related to TREATMENT as we look at bacterial infections.  I recently reported this important and pertinent study.  STREPTOCOCCUS  seems to be an important factor in these increasing neuropsychiatric, medical disorders.  Knowing that it can be in both the gut and in saliva may help in treatments.

The conclusion of this saliva study - In the present study, the MIA ["microbial index of ASD"] diagnosis model based on oral microbial biomarkers was proposed and achieved 96.3% accuracy, showing a great potential for improved diagnostic sensitivity and specificity. Compared to the gut microbiota usually collected from feces or biopsies, the oral microbiota is easier to sample and potentially mirrors the ASD-associated microbiota profile in situ. 

To sum up - 

    • A new test to diagnose autism is being discussed based on saliva.
    • Research shows that the oral microbiome of those diagnosed with autism, seems to mirror the gut of those diagnosed with autism.  Both show many pathogenic bacteria and less beneficial bacteria.
    • Streptococcus bacteria showed up in "significantly higher abundance" in the ASD group.
    • Prevotella, a commensal microorganism found in both the intestine and oral cavity, is lacking in ASD individuals.
    • The more pathogens and less commensals indicated a more severe autism in the child based on an ABC score (Aberrant Behavior Checklist).

The importance of this type of research can't be stressed enough, in both diagnosing and treating individuals. As far as prevention, especially as we see the physical and emotional pain of severe autism , the studies are indeed showing that the influence of the microbiome on the human body is significant. Knowing the factors that can disturb the microbiome is then key, as it is known that both the typical age of an asd diagnosis and the age in which the gut microbiome is developed, do seem to overlap:

"Human microbial colonization begins at birth and continues to develop and modulate in species abundance for about 3 years, until the microbiota becomes adult-like. During the same time period, children experience significant developmental changes that influence their health status as well as their immune system....Modern changes in lifestyle, including improved sanitization, cesarean sections, antibiotic usage, and immunizations are among some of the factors that can shift the microbiota, and are being studied as potential drivers of the sudden increase in immune-mediated diseases in the developed world.....


By Teresa Conrick / Science Editor to Age of Autism
(Source: ageofautism.com; February 19, 2018; http://bit.ly/2EREU3u)
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