TY - JOUR
T1 - Distinct Microbiome-Neuroimmune Signatures Correlate With Functional Abdominal Pain in Children With Autism Spectrum Disorder
AU - Luna, Ruth Ann
AU - Oezguen, Numan
AU - Balderas, Miriam
AU - Venkatachalam, Alamelu
AU - Runge, Jessica K.
AU - Versalovic, James
AU - Veenstra-VanderWeele, Jeremy
AU - Anderson, George M.
AU - Savidge, Tor
AU - Williams, Kent C.
N1 - Funding Information:
Funding This project was supported by the Health Resources and Services Administration of the US Department of Health and Human Services under cooperative agreement UA3 MC11054–Autism Intervention Research Network on Physical Health. This information or content and conclusions are those of the author and should not be construed as the official position or policy of, nor should any endorsements be inferred by, the Health Resources and Services Administration, Department of Health and Human Services, or the US Government. This work was conducted through the Autism Speaks Autism Treatment Network serving as the Autism Intervention Research Network on Physical Health. This work also was supported by Autism Speaks (GI and Neurobehavioral Processes grant 9455), the National Institute of Diabetes, Digestive, and Kidney Diseases (UH2 DK093990, UH3 DK083990, and DK56338), and the National Institute of Allergy and Infectious Diseases (RO1AI100914 and U01 AI124290-01).
Publisher Copyright:
© 2017 The Authors
PY - 2017/3/1
Y1 - 2017/3/1
N2 - Background & Aims Emerging data on the gut microbiome in autism spectrum disorder (ASD) suggest that altered host–microbe interactions may contribute to disease symptoms. Although gut microbial communities in children with ASD are reported to differ from individuals with neurotypical development, it is not known whether these bacteria induce pathogenic neuroimmune signals. Methods Because commensal clostridia interactions with the intestinal mucosa can regulate disease-associated cytokine and serotonergic pathways in animal models, we evaluated whether microbiome-neuroimmune profiles (from rectal biopsy specimens and blood) differed in ASD children with functional gastrointestinal disorders (ASD-FGID, n = 14) compared with neurotypical (NT) children with FGID (NT-FGID, n = 15) and without abdominal pain (NT, n = 6). Microbial 16S ribosomal DNA community signatures, cytokines, and serotonergic metabolites were quantified and correlated with gastrointestinal symptoms. Results A significant increase in several mucosa-associated Clostridiales was observed in ASD-FGID, whereas marked decreases in Dorea and Blautia, as well as Sutterella, were evident. Stratification by abdominal pain showed multiple organisms in ASD-FGID that correlated significantly with cytokines (interleukin [IL]6, IL1, IL17A, and interferon-γ). Group comparisons showed that IL6 and tryptophan release by mucosal biopsy specimens was highest in ASD children with abdominal pain, whereas serotonergic metabolites generally were increased in children with FGIDs. Furthermore, proinflammatory cytokines correlated significantly with several Clostridiales previously reported to associate with ASD, as did tryptophan and serotonin. Conclusions Our findings identify distinctive mucosal microbial signatures in ASD children with FGID that correlate with cytokine and tryptophan homeostasis. Future studies are needed to establish whether these disease-associated Clostridiales species confer early pathogenic signals in children with ASD and FGID.
AB - Background & Aims Emerging data on the gut microbiome in autism spectrum disorder (ASD) suggest that altered host–microbe interactions may contribute to disease symptoms. Although gut microbial communities in children with ASD are reported to differ from individuals with neurotypical development, it is not known whether these bacteria induce pathogenic neuroimmune signals. Methods Because commensal clostridia interactions with the intestinal mucosa can regulate disease-associated cytokine and serotonergic pathways in animal models, we evaluated whether microbiome-neuroimmune profiles (from rectal biopsy specimens and blood) differed in ASD children with functional gastrointestinal disorders (ASD-FGID, n = 14) compared with neurotypical (NT) children with FGID (NT-FGID, n = 15) and without abdominal pain (NT, n = 6). Microbial 16S ribosomal DNA community signatures, cytokines, and serotonergic metabolites were quantified and correlated with gastrointestinal symptoms. Results A significant increase in several mucosa-associated Clostridiales was observed in ASD-FGID, whereas marked decreases in Dorea and Blautia, as well as Sutterella, were evident. Stratification by abdominal pain showed multiple organisms in ASD-FGID that correlated significantly with cytokines (interleukin [IL]6, IL1, IL17A, and interferon-γ). Group comparisons showed that IL6 and tryptophan release by mucosal biopsy specimens was highest in ASD children with abdominal pain, whereas serotonergic metabolites generally were increased in children with FGIDs. Furthermore, proinflammatory cytokines correlated significantly with several Clostridiales previously reported to associate with ASD, as did tryptophan and serotonin. Conclusions Our findings identify distinctive mucosal microbial signatures in ASD children with FGID that correlate with cytokine and tryptophan homeostasis. Future studies are needed to establish whether these disease-associated Clostridiales species confer early pathogenic signals in children with ASD and FGID.
KW - Gastrointestinal disorders
KW - Microbiome
KW - Microbiome-Gut-Brain Axis
KW - Mucosa
KW - Serotonin
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U2 - 10.1016/j.jcmgh.2016.11.008
DO - 10.1016/j.jcmgh.2016.11.008
M3 - Article
AN - SCOPUS:85011589286
VL - 3
SP - 218
EP - 230
JO - CMGH Cellular and Molecular Gastroenterology and Hepatology
JF - CMGH Cellular and Molecular Gastroenterology and Hepatology
SN - 2352-345X
IS - 2
ER -