Proceedings of the Texas A&M Medical Student Grand Rounds

The role of Candida albicans, Clostridium spp., and lack of diversity in the gut microbiome during development in the pathogenesis of Autism Spectrum Disorders

October 4, 2017 Madelyn Ricco

Madelyn Ricco

Introduction: Autism spectrum disorders have increased in incidence nearly seven-fold from 1970 to today1. This increase cannot be attributed solely to an increase in diagnostic awareness1. While no one cause has been implicated in the development of autism, the role of the gut microbiome and the microbiome-gut-brain axis has been studied in relation to the development of Autism spectrum disorders. Autism is characterized by verbal difficulties, repetitive behaviors, decreased social skills, social withdrawal, and heightened response to stimuli. 1 This disorder is diagnosed on a spectrum, using either CARS or ADOS screening, and a higher score equates to an increase in severity of symptoms.2 Patients diagnosed with autism have also proven to have a high rate of gastrointestinal co-morbidities.1 The gut microbiome contributes to the development of the immune system as well as aid in nutrient absorption.3 It can also impact the central nervous system.3 Methods: The gut microbiome was analyzed in patients with autism as well as control patients.4 Gut microbiota was assessed and species were sequenced using stool samples.4 Peripheral blood mononuclear cells were also analyzed in patients diagnosed with autism.5 A mouse model was also analyzed.6 One group of mice was fed a high fat diet and were bred, and their offspring were compared to the offspring of a control group of mice fed a regular diet.6 The microbiota and behaviors of both groups of offspring were observed and analyzed. In this study, the offspring of the high fat diet mice were made to cohabitate with the regular diet mice, and their microbiota and behavior was analyzed again. In addition, the offspring of the high fat diet mice were given a fecal transplant from offspring of normal diet mice.6 Results: Upon analysis, the interferon signaling pathway genes were increased in expression among the peripheral blood mononuclear cells of patients with autism.5 This can lead to chronic inflammation, which can result in dysbiosis of the microbiome and a loss of microbiome homeostasis.5 The microbiome of patients with autism was shown to have an overgrowth of Candida albicans,4 an increase in Clostridium spp., and a lack of diversity among the microbes7. Conclusions: Treatment of autism could include options to treat gut microbiome abnormalities. In mice, restoration of the microbiome resulted in normalization of their social behavior.6 Antifungals and probiotics can be used to balance the microbiome.7 Fecal transplants could be an option in restoring the microbiome and altering behavior.6

  1. Currenti SA. Understanding and determining the etiology of autism. Cellular and molecular neurobiology. 2010;30(2):161-171. http://www-ncbi-nlm-nih-gov.lib-ezproxy.tamu.edu:2048/pubmed/19774457. doi: 0.1007/s10571-009-9453-8.
  2. Strati F, Cavalieri D, Albanese D, et al. New evidences on the altered gut microbiota in autism spectrum disorders. Microbiome. 2017;5(1). http://search.proquest.com.lib-ezproxy.tamu.edu: 2048/docview/ 1874317881.doi:10.1186/s40168-017-0242-1.
  3. Petra AI, Panagiotidou S, Hatziagelaki E, Stewart JM, Conti P, Theoharides TC. Gut-microbiota-brain axis and its effect on neuropsychiatric disorders with suspected immune dysregulation. Clin Ther. 2015;37(5):984-995.
  4. Kantarcioglu A, Kiraz N, Aydin A. Microbiota–Gut–Brain axis: Yeast species isolated from stool samples of children with suspected or diagnosed autism spectrum disorders and in vitro susceptibility against nystatin and fluconazole. Mycopathologia.2016;181(1):1-7.http://www-ncbi-nlm-nih-gov.lib-ezproxy.tamu.edu:2048/ pubmed/26442855. doi:10.1007/s11046-015-9949-3.
  5. Inoue R, Sakaue Y, Sawai C, et al. A preliminary investigation on the relationship between gut microbiota and gene expressions in peripheral mononuclear cells of infants with autism spectrum disorders. Bioscience, Biotechnology, and Biochemistry.2016;80(12):2450-2458. http://www.tandfonline.com.lib-ezproxy.tamu. edu:2048/doi/abs/10.1080/09168451.2016.1222267.10.1080/09168451.2016.1222267
  6. Buffington SA, Di Prisco GV, Auchtung TA, Ajami NJ, Petrosino JF, Costa-Mattioli M.Microbial reconstitution reverses maternal diet-induced social and synaptic deficits inoffspring. Cell. 2016;165(7):1762-1775. http://www-ncbi-nlm-nih-gov.lib-ezproxy.tamu.edu:2048/pubmed/27315483. doi: 10.1016/j.cell.2016.06. 001.
  7. Iovene MR, Bombace F, Maresca R, et al. Intestinal dysbiosis and yeast isolation in stool of subjects with autism spectrum disorders. Mycopathologia. 2016;182(3-4):349.http://search.proquest.com.lib-ezproxy.tamu. edu:2048/docview/ 1875685785.10.1007/s11046-016-0068-6.

 

Microbiology Neuroscience
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