The Brain-Gut-Microbiome Axis: What role might the microbiome play in our current ASD epidemic in the Western world?

As a pediatrician, I recall having seen one bona fide case of “autism” (as this clinical phenotype was defined at that time) in a 4-year-old boy, out of perhaps 10,000 patients with whom I had direct, or indirect, contact during the 1960s-70s. Now, one of my sons who teaches 5th-6th-grade science says “about one-third of his students (N = about 26) each year, have the diagnosis of ASD” (“autism spectrum disorder”). Thus, just like Obesity, the frequency of ASD has skyrocketed in Western society during the past several decades. This rate of increase … FAR exceeds any explanation via genetic changes (DNA mutations) and must be based on epigenetics and environment.

Admittedly, the “diagnosis of ASD” has been dramatically expanded from its specific definition 40-50 years ago. Also, perhaps clinicians also have become more aware in recent decades. However, what is it––in the environment of Western society––that is causing this incredible rise in behavioral defects among children? Maybe it’s the early exosure to television and (rapid-flickering) computer games, or mothers often on prescription drugs to fight “stress” during pregnancy?

Alternatively, we recently have learned that, of the total DNA isolated in a human body, ~92% of this DNA is derived from bacteria from our gastrointestinal (GI) system. In my humble opinion, the environment of children today is vastly different from that of 40-50 years ago: helicopters parents, sterile environment, emphasis on prevention of exposure of small children to everything, etc. Could striking changes in the gut microbiota be responsible for this rise in ASD? Perhaps a large cohort of ASD (vs non-ASD) children, and their mothers, should be studied with regard to their GI tract bacteria, metabolomics, etc. The questions I have posed (above) … center more on the CAUSE, rather than treatment, of ASD. WHY has this enormous increase in ASD occurred in recent decades?

The two attached reviews summarize the state-of-this-field at the moment. The Luna et al review summarizes interactions between the central nervous system, GI system, and microorganisms that live in the GI tract. Exploring these interactions provides a rationale for why GI disorders are commonly seen in children with ASD. Signs of altered brain-gut interactions that are closely associated with functional GI disorders (FGIDs) commonly occur in children with ASD. Studies of the Microbiome in ASD suggest that changes in the gut microbiome may be associated with ASD and with GI disorders in children with ASD. Further studies into the brain-gut-microbiome axis could lead to new techniques for identifying GI disorders in children with ASD and novel therapies for treating ASD behaviors.

The human “gut microbiota” normally assemble during the early post-natal years of life. This evolution-driven process has been shown to contribute to developmental programming of epithelial barrier function, gut homeostasis, and angiogenesis––as well as development and function of the immune system. Research over the past few years has revealed that actions of the gut microbiota have much wider effects on host physiology and development than originally believed, including the modulation of brain development and behavior. The review article by R.Diaz Heijtz briefly discusses recent findings on impact of the gut microbiota on brain development, and how disturbances in the assembly and maturation of the gut microbiota may affect development of motor, social, and cognitive functions. The potential link between the Microbiome and metabolic requirements of the developing brain is also considered.

Curr Dev Disord Rep  2016 Mar; 3: 75-81

Semin Fetal Neonatal Med  2016 May 30; doi: 10.1016/j.siny.2016.04.012.     PMID:  27255860

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