scholarly journals Autism-Associated Variant in the SLC6A3 Gene Alters the Oral Microbiome and Metabolism in a Murine Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Gabriella E. DiCarlo ◽  
Samuel J. Mabry ◽  
Xixi Cao ◽  
Clara McMillan ◽  
Tiffany G. Woynaroski ◽  
...  
Keyword(s):  
Body Fat ◽  
The United States ◽  
Autism Spectrum ◽  
Oral Microbiome ◽  
Oral Microbiota ◽  
Gastrointestinal Function ◽  
Metabolic Function ◽  
Functional Changes ◽  
16S Rna ◽  
The Impact

Background: Altered dopamine (DA) signaling has been associated with autism spectrum disorder (ASD), a neurodevelopmental condition estimated to impact 1 in 54 children in the United States. There is growing evidence for alterations in both gastrointestinal function and oral microbiome composition in ASD. Recent work suggests that rare variants of the SLC6A3 gene encoding the DA transporter (DAT) identified in individuals with ASD result in structural and functional changes to the DAT. One such recently identified de novo mutation is a threonine to methionine substitution at position 356 of the DAT (DAT T356M). The DAT T356M variant is associated with ASD-like phenotypes in mice homozygous for the mutation (DAT T356M+/+), including social deficits, hyperactivity, and impaired DA signaling. Here, we determine the impact of this altered DA signaling as it relates to altered oral microbiota, and metabolic and gastrointestinal dysfunction.Methods: In the DAT T356M+/+ mouse, we determine the oral microbiota composition, metabolic function, and gastrointestinal (GI) function. We examined oral microbiota by 16S RNA sequencing. We measured metabolic function by examining glucose tolerance and we probed gastrointestinal parameters by measuring fecal dimensions and weight.Results: In the DAT T356M+/+ mouse, we evaluate how altered DA signaling relates to metabolic dysfunction and altered oral microbiota. We demonstrate that male DAT T356M+/+ mice weigh less (Wild type (WT) = 26.48 ± 0.6405 g, DAT T356M+/+ = 24.14 ± 0.4083 g) and have decreased body fat (WT = 14.89 ± 0.6206%, DAT T356M+/+ = 12.72 ± 0.4160%). These mice display improved glucose handling (WT = 32.60 ± 0.3298 kcal/g, DAT T356M+/+ = 36.97 ± 0.4910 kcal/g), and an altered oral microbiota. We found a significant decrease in Fusobacterium abundance. The abundance of Fusobacterium was associated with improved glucose handling and decreased body fat.Conclusions: Our findings provide new insights into how DAT dysfunction may alter gastrointestinal function, composition of the oral microbiota, and metabolism. Our data suggest that impaired DA signaling in ASD is associated with a number of metabolic and gastrointestinal changes which are common in individuals with ASD.

scholarly journals Transitions in oral and gut microbiome of HPV+ oropharyngeal squamous cell carcinoma following definitive chemoradiotherapy (ROMA LA-OPSCC study)

2021 ◽  
Author(s):  
Marc Oliva ◽  
Pierre H. H. Schneeberger ◽  
Victor Rey ◽  
Matthew Cho ◽  
Rachel Taylor ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Taxonomic Composition ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Oral Microbiome ◽  
Metagenomic Sequencing ◽  
Α Diversity ◽  
16S Rna ◽  
The Impact

Abstract Background Oral and gut microbiomes have emerged as potential biomarkers in cancer. We characterised the oral and gut microbiomes in a prospective observational cohort of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) patients and evaluated the impact of chemoradiotherapy (CRT). Methods Saliva, oropharyngeal swabs over the tumour site and stool were collected at baseline and post-CRT. 16S RNA and shotgun metagenomic sequencing were used to generate taxonomic profiles, including relative abundance (RA), bacterial density, α-diversity and β-diversity. Results A total of 132 samples from 22 patients were analysed. Baseline saliva and swabs had similar taxonomic composition (R2 = 0.006; p = 0.827). Oropharyngeal swabs and stool taxonomic composition varied significantly by stage, with increased oral RA of Fusobacterium nucleatum observed in stage III disease (p < 0.05). CRT significantly reduced the species richness and increased the RA of gut-associated taxa in oropharyngeal swabs (p < 0.05), while it had no effect in stool samples. These findings remained significant when adjusted by stage, smoking status and antibiotic use. Conclusions Baseline oral and gut microbiomes differ by stage in this HPV+ cohort. CRT caused a shift towards a gut-like microbiome composition in oropharyngeal swabs. Stage-specific features and the transitions in oral microbiome might have prognostic and therapeutic implications.

scholarly journals Is There a Link between Oropharyngeal Microbiome and Schizophrenia? A Narrative Review

2022 ◽  
Vol 23 (2) ◽  
pp. 846
Author(s):  
Stanislas Martin ◽  
Audrey Foulon ◽  
Wissam El Hage ◽  
Diane Dufour-Rainfray ◽  
Frédéric Denis
Keyword(s):  
Periodontal Disease ◽  
Research Team ◽  
Oral Microbiome ◽  
Oral Microbiota ◽  
Future Studies ◽  
The Subject ◽  
The Moment ◽  
The Impact ◽  
The Brain

The study aimed to examine the impact of the oropharyngeal microbiome in the pathophysiology of schizophrenia and to clarify whether there might be a bidirectional link between the oral microbiota and the brain in a context of dysbiosis-related neuroinflammation. We selected nine articles including three systemic reviews with several articles from the same research team. Different themes emerged, which we grouped into 5 distinct parts concerning the oropharyngeal phageome, the oropharyngeal microbiome, the salivary microbiome and periodontal disease potentially associated with schizophrenia, and the impact of drugs on the microbiome and schizophrenia. We pointed out the presence of phageoma in patients suffering from schizophrenia and that periodontal disease reinforces the role of inflammation in the pathophysiology of schizophrenia. Moreover, saliva could be an interesting substrate to characterize the different stages of schizophrenia. However, the few studies we have on the subject are limited in scope, and some of them are the work of a single team. At this stage of knowledge, it is difficult to conclude on the existence of a bidirectional link between the brain and the oral microbiome. Future studies on the subject will clarify these questions that for the moment remain unresolved.

scholarly journals Did the Brain and Oral Microbiota Talk to Each Other? A Review of the Literature

2020 ◽  
Vol 9 (12) ◽  
pp. 3876
Author(s):  
Yoann Maitre ◽  
Pierre Micheneau ◽  
Alexis Delpierre ◽  
Rachid Mahalli ◽  
Marie Guerin ◽  
...  
Keyword(s):  
Mental Health ◽  
Mental Disorders ◽  
Bipolar Disorders ◽  
Down’S Syndrome ◽  
Mental Health Disorders ◽  
Autism Spectrum ◽  
Oral Microbiome ◽  
Oral Microbiota ◽  
Health Disorders

This systematic review aims to investigate the role of the oral microbiome in the pathophysiology of mental health disorders and to appraise the methodological quality of research of the oral–brain axis which is a growing interest area. The PRISMA guideline was adopted, to carry out an electronic search through the MEDLINE database, to identify studies that have explored the role of the oral microbiome in the pathophysiology of mental health disorders published from 2000 up to June 2020. The search resulted in 140 records; after exclusions, a total of 22 papers were included in the present review. In accordance with the role of the oral microbiome in the pathophysiology of mental disorders, four mental disorders were identified: Alzheimer’s disease, dementia, and cognitive disorders; autism spectrum disorder; Down’s syndrome and mental retardation; and Bipolar disorders. Studies argue for correlations between oral microbiota and Alzheimer’s disease, autism spectrum disorders, Down’s syndrome, and bipolar disorders. This field is still under-studied, and studies are needed to clarify the biological links and interconnections between the oral microbiota and the pathophysiology of all mental health disorders. Researchers should focus their efforts to develop research on the oral–brain axis in the future.

The Impact of Culture on Parental Perceptions about Autism Spectrum Disorders: Striving for Culturally Competent Practices

2018 ◽  
Vol 14 (1) ◽  
Author(s):  
Brenda L. Barrio ◽  
Yun-Ju Hsiao ◽  
Nydia Prishker ◽  
Callie Terry
Keyword(s):  
Linguistically Diverse ◽  
The United States ◽  
Autism Spectrum ◽  
Culturally And Linguistically Diverse ◽  
Culturally Competent ◽  
Number Of Children ◽  
Wide Range ◽  
Diverse Backgrounds ◽  
Parental Perspectives ◽  
The Impact

AbstractDespite the increasing number of children from culturally and linguistically diverse (CLD) backgrounds in the United States, limited research exists synthesizing what is known about the prevalence and diagnosis of autism spectrum disorder (ASD) in these communities. Children from culturally and linguistically diverse backgrounds are disproportionately diagnosed with ASD and, there is a need for practitioners and educators to be culturally competent at addressing challenges and practices related to ASD for children and youth. The purpose of this paper is to review the literature related to parental perspectives on ASD, in children from a wide range of culturally diverse backgrounds to provide information and resources to practitioners about the importance to strive for cultural competence in practice-related work.

scholarly journals Brief Report: Impact of COVID-19 on Individuals with ASD and Their Caregivers: A Perspective from the SPARK Cohort

2021 ◽  
Author(s):  
L. Casey White ◽  
◽  
J. Kiely Law ◽  
Amy M. Daniels ◽  
Jaimie Toroney ◽  
...  
Keyword(s):  
United States ◽  
Autism Spectrum Disorder ◽  
The United States ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Autism Research ◽  
The Impact ◽  
Family Distress ◽  
Minimal Benefit

AbstractThe impact of the 2019 coronavirus pandemic (COVID-19) in the United States is unprecedented, with unknown implications for the autism community. We surveyed 3502 parents/caregivers of individuals with an autism spectrum disorder (ASD) enrolled in Simons Powering Autism Research for Knowledge (SPARK) and found that most individuals with ASD experienced significant, ongoing disruptions to therapies. While some services were adapted to telehealth format, most participants were not receiving such services at follow-up, and those who were reported minimal benefit. Children under age five had the most severely disrupted services and lowest reported benefit of telehealth adaptation. Caregivers also reported worsening ASD symptoms and moderate family distress. Strategies to support the ASD community should be immediately developed and implemented.

scholarly journals Investigation of the impact of commonly used medications on the oral microbiome of individuals living without major chronic conditions

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261032
Author(s):  
Vanessa DeClercq ◽  
Jacob T. Nearing ◽  
Morgan G. I. Langille
Keyword(s):  
Thyroid Hormones ◽  
Relative Abundance ◽  
Beta Diversity ◽  
Chronic Conditions ◽  
Oral Microbiome ◽  
Rrna Gene ◽  
Oral Microbiota ◽  
Shannon Diversity ◽  
Significant Difference ◽  
The Impact

Background Commonly used medications produce changes in the gut microbiota, however, the impact of these medications on the composition of the oral microbiota is understudied. Methods Saliva samples were obtained from 846 females and 368 males aged 35–69 years from a Canadian population cohort, the Atlantic Partnership for Tomorrow’s Health (PATH). Samples were analyzed by 16S rRNA gene sequencing and differences in microbial community compositions between nonusers, single-, and multi-drug users as well as the 3 most commonly used medications (thyroid hormones, statins, and proton pump inhibitors (PPI)) were examined. Results Twenty-six percent of participants were taking 1 medication and 21% were reported taking 2 or more medications. Alpha diversity indices of Shannon diversity, Evenness, Richness, and Faith’s phylogenetic diversity were similar among groups, likewise beta diversity as measured by Bray-Curtis dissimilarity (R2 = 0.0029, P = 0.053) and weighted UniFrac distances (R2 = 0.0028, P = 0.161) were non-significant although close to our alpha value threshold (P = 0.05). After controlling for covariates (sex, age, BMI), six genera (Saprospiraceae uncultured, Bacillus, Johnsonella, Actinobacillus, Stenotrophomonas, and Mycoplasma) were significantly different from non-medication users. Thyroid hormones, HMG-CoA reductase inhibitors (statins) and PPI were the most reported medications. Shannon diversity differed significantly among those taking no medication and those taking only thyroid hormones, however, there were no significant difference in other measures of alpha- or beta diversity with single thyroid hormone, statin, or PPI use. Compared to participants taking no medications, the relative abundance of eight genera differed significantly in participants taking thyroid hormones, six genera differed in participants taking statins, and no significant differences were observed with participants taking PPI. Conclusion The results from this study show negligible effect of commonly used medications on microbial diversity and small differences in the relative abundance of specific taxa, suggesting a minimal influence of commonly used medication on the salivary microbiome of individuals living without major chronic conditions.

scholarly journals Association of Bitter Taste Receptor T2R38 Polymorphisms, Oral Microbiota, and Rheumatoid Arthritis

2021 ◽  
Vol 43 (3) ◽  
pp. 1460-1472
Author(s):  
Vivianne Cruz de Jesus ◽  
Manu Singh ◽  
Robert J. Schroth ◽  
Prashen Chelikani ◽  
Carol A. Hitchon
Keyword(s):  
Rheumatoid Arthritis ◽  
Relative Abundance ◽  
Bitter Taste ◽  
Bacterial Species ◽  
Taste Receptor ◽  
Oral Microbiome ◽  
Rrna Gene ◽  
Oral Microbiota ◽  
Microbial Composition ◽  
The Impact

The association of taste genetics and the oral microbiome in autoimmune diseases such as rheumatoid arthritis (RA) has not been reported. We explored a novel oral mucosal innate immune pathway involving the bitter taste G protein-coupled receptor T2R38. This case–control study aimed to evaluate whether T2R38 polymorphisms associate with the buccal microbial composition in RA. Genomic DNA was obtained from buccal swabs of 35 RA patients and 64 non-RA controls. TAS2R38 genotypes were determined by Sanger sequencing. The buccal microbiome was assessed by Illumina MiSeq sequencing of the V4-16S rRNA gene. Bacterial community differences were analyzed with alpha and beta diversity measures. Linear discriminant analysis effect size identified taxa discriminating between RA versus non-RA and across TAS2R38 genotypes. TAS2R38 genotype frequency was similar between RA and non-RA controls (PAV/PAV; PAV/AVI; AVI/AVI: RA 42.9%; 45.7%; 11.4% versus controls 32.8%; 48.4%; 18.8%, chi-square (2, N = 99) = 2.1, p = 0.35). The relative abundance of Porphyromonas, among others, differed between RA and non-RA controls. The relative abundance of several bacterial species also differed across TAS2R38 genotypes. These findings suggest an association between T2R38 polymorphisms and RA buccal microbial composition. However, further research is needed to understand the impact of T2R38 in oral health and RA development.

scholarly journals A human TSC1 mutation screening platform in GABAergic cortical interneurons for Genotype to Phenotype assessments

2020 ◽  
Author(s):  
Dean Wundrach ◽  
Luis E Martinetti ◽  
April M Stafford ◽  
Stephanie M Bilinovich ◽  
Kartik Angara ◽  
...  
Keyword(s):  
Mutation Screening ◽  
Cell Types ◽  
Autism Spectrum ◽  
Functional Changes ◽  
Missense Variants ◽  
Multiple Organs ◽  
Physiological Properties ◽  
Screening Platform ◽  
The Impact

AbstractTuberous Sclerosis Complex is a complex syndrome that affects multiple organs and is caused by dysfunction of either the TSC1 or TSC2 genes. One of the least understood features of TSC is the impact of TSC1&2 variants on brain phenotypes, including elevated rates of autism spectrum disorder and seizures. Moreover, while a great deal of work has uncovered how loss of either gene can alter various neural cell types, the impact of many variants in TSC and on these cell types is poorly understood. In particular, missense variants that cause minor changes in the proteins are expected to cause functional changes that differ from a complete loss of the protein. Herein, we examined how some missense variants in TSC1 impacted the development of cortical inhibitory interneurons, a cell type whose molecular, cellular and physiological properties are known to be altered after loss of mouse Tsc1. Importantly, we found that most missense variants complemented phenotypes caused by loss of Tsc1 and resulting in elevated MTOR activity as well as several cell intrinsic physiological properties. However, distinct variants showed deficits in complementing an increase in parvalbumin levels, which is observed after loss of Tsc1 and demonstrated smaller amplitudes of after hyperpolarizations. These data suggest subtle but sensitive phenotypes can be detected by some TSC1 missense variants and provide an in vivo system in which to better assess TSC variants.

scholarly journals Effect of Different Sweeteners on the Oral Microbiota and Immune System of Sprague Dawley Rats

2020 ◽  
Author(s):  
Xi Cheng ◽  
Xiurong Guo ◽  
Feihong Huang ◽  
Hui Lei ◽  
Quan Zhou ◽  
...  
Keyword(s):  
Immune System ◽  
High Throughput Sequencing ◽  
Pure Water ◽  
Oral Microbiome ◽  
Oral Microbiota ◽  
Metabolic Function ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Structure And Functions

Abstract Sucrose, xylose, and saccharin are common beverage additives used by humans. Long-term consumption of beverages containing these substances will inevitably affect the oral immune system and the composition of healthy oral microbiomes. In this study, we used 24 Sprague Dawley rats and divided them into four groups. Each group was fed water containing a specific dose of sucrose, saccharin, xylose, or pure water 12 hours a day for eight weeks. To determine the changes in composition, community structure, and functions of the oral microbiomes of rats, we collected oral microbiome samples and subjected them to high-throughput sequencing at the end of eight weeks. Meanwhile, ELISA was performed using the saliva samples from rats to estimate the concentrations of salivary immunoglobulin, to reveal the effect of sweetener on the oral immune system. Sequencing results showed that Firmicutes and Proteobacteria, were the predominant phyla in all the groups. In additions, we found that the oral microbial diversity of rats drinking sucrose water was significantly higher than that of rats in the other groups. Our results indicate that drinking water containing sweeteners could influence oral immunity as well as the composition, metabolic function, and diversity of the oral microbiota, thereby disrupting the original oral micro-ecosystem.

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