Analysis of the Fecal Microbiome & Metabolome in Pitt Hopkins Syndrome

This repository holds the Jupyter Notebooks containing our analysis. Our manuscript, "The Fecal Microbiome and Metabolome of Pitt Hopkins Syndrome, a Severe Autism Spectrum Disorder" is published in mSystems. We have reproduced the abstract below for your convenience.

Authors: Amanda H Dilmore^1,#, Daniel McDonald^1,#, Tanya T Nguyen^2,3,#, James B Adams⁴, Rosa Krajmalnik-Brown^5,6, Emmanuel Elijah⁷, Pieter C Dorrestein^7,8,9, Rob Knight^1,9,10,11,*

Affiliations:

¹ Department of Pediatrics, School of Medicine, University of California, San Diego, California, USA

² Department of Psychiatry, UC San Diego, San Diego, California, USA

³ Sam and Rose Stein Institute for Research on Aging, UC San Diego, San Diego, California, USA

⁴ School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, Arizona, USA

⁵ Biodesign Center for Health Through Microbiomes, Arizona State University, Tempe, Arizona, USA

⁶ School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe, Arizona, USA

⁷ Pharmaceutical Sciences, University of California, San Diego, California, USA

⁸ Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and

⁹ Center for Microbiome Innovation, Jacobs School of Engineering, University of California, San Diego, California, USA

¹⁰ Department of Computer Science, Jacobs School of Engineering, University of California, San Diego, California, USA

¹¹ Department of Bioengineering, University of California, San Diego, California, USA

^* corresponding author

^# co-first authors

Abstract:

Alterations to the gut microbiome have been reported between children with autism spectrum disorders (ASD) and typically developing (TD) children. Characterizing these differences has led to the proposal of new treatments for ASD, such as probiotic interventions and fecal matter transplants. However, no study to date has characterized the gut microbiome nor metabolome in Pitt Hopkins syndrome (PTHS), a severe ASD with high incidence of gastrointestinal (GI) disturbance such as constipation. Here, we surveyed the gut microbiome and metabolome in a cohort of PTHS individuals and their unaffected parents. We focused our analysis on C. bolteae, a microbe previously associated with ASD known to chemically modify bile acids in the gut. PTHS individuals carry a higher load of C. bolteae than their parents as well as both ASD- and non-ASD individuals from the American Gut cohort. Specific metabolites were associated with PTHS, including bile acids and sphingosines. With a metadata reanalysis tool, we found that PTHS-associated metabolites have previously been identified in inflammatory bowel disease and obesity patients. These results suggest microbial involvement in PTHS, but further research must be performed to clarify the exact mechanisms which microbes may act through. Furthermore, new associations between PTHS-specific metabolites and other conditions may lead to additional therapeutic options for PTHS individuals.

Importance:

GI disturbances in ASD such as severe constipation can be medically significant and often require medication. This is especially true for individuals with PTHS, suggesting that the gut microbiome may be involved in PTHS’s pathology. Revealing associations between specific gut microbes and PTHS may allow for the development of new therapeutics or application of existing therapeutics to ease day to day challenges encountered by PTHS individuals. In this study, we characterized an association between C. bolteae and PTHS, in addition to metabolites linked with both PTHS and C. bolteae. We also identified other microbiome-involved medical conditions where PTHS-associated metabolites have been isolated. Utilizing common metabolites to identify conditions with similar phenotypes may suggest new therapeutic options for GI-related symptoms.