The results of a small study carried out by scientists at Hong Kong Polytechnic University, and The Chinese University of Hong Kong suggest that children with autism spectrum disorder (ASD) may have a distinctive and underdeveloped range and volume of gut bacteria that isn’t related to their diet.
The team’s findings indicated that children with ASD have significantly fewer bacteria linked to neurotransmitter activity, but also exhibit five species of bacteria that typically are not found in the guts of children without ASD. The researchers say the results suggest that there may be a characteristic microbial profile for ASD, which could pave the way for developing early treatments.
Reporting their findings in Gut, Siew C Ng, PhD, at The Chinese University of Hong Kong, and Ruth Chan, PhD, at The Hong Kong Polytechnic University, and colleagues, concluded, “We identified novel bacterial markers for prediction of ASD and demonstrated persistent underdevelopment of the gut microbiota in children with ASD which lagged behind their respective age-matched peers.”
Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions that begins in early life and is characterised by impaired social communication and interactions as well as stereotyped, repetitive behavior, the authors explained. Prevalence of the condition in children and adolescents has been estimated at 0.36% in Asia, and 1.85% in western countries, and the incidence of ASD in China has also increased from 2.8 per 10,000 in 2000, to 63 per 10,000 in 2015, the team continued.
While genetic research has pointed to the importance of de novo mutations in ASD, no single gene has been identified as substantially increasing the risk of ASD. In addition, the researchers pointed out, “Apart from genetic factors, the gut microbiota has been suggested to play a role in ASD”. Indeed, evidence suggests that the gut-brain axis has a profound effect on social behaviors, they noted. “The community of microorganisms in the gastrointestinal (GI) tract is known to influence brain physiology and social-behavior via a diverse set of pathways, including immune activation, production of microbial metabolites and peptides and production of various neurotransmitters and neuromodulators.” But while changes in fecal bacteria have been reported in children with ASD, “… causality is yet to be established in humans .. data on gut microbiome development during early age in children with ASD are lacking.”
Diagnosing autism spectrum disorder can be difficult, because there is no definitive medical test and diagnosis is based on physician assessment. So, potential fecal biomarkers could be of key interest, the scientists suggested; “Potential fecal bacteria biomarkers used to predict ASD can therefore facilitate early treatment and intervention.”
For their newly reported studies, the investigators evaluated whether three to six year-olds with autism might harbor a microbiome that differs significantly from that of typically developing children. To do this, they compared the range, volume, and associated functions of bacteria in the stool samples of 128 Chinese children, including 64 children diagnosed with autism spectrum disorder and 64 children without evidence of ASD.
Their results suggested that the factors most strongly and independently associated with microbiome composition in the stool samples were age, autism, and weight (BMI). Interestingly, diet wasn’t an influential factor, but the stool samples of children with ASD displayed a greater variety of microbes than those matched for age and weight who didn’t have the condition. More specifically, Clostridium, Dialister and Coprobacillus bacteria were enriched in children with autism, while numbers of Faecalibacterium bacteria were significantly decreased.
Several species of clostridia enriched in children with autism closely interacted with each other and formed a connected group, the team pointed out. “Clostridia species have been linked with ASD via production of clostridial toxins which have pathological effects in the central nervous system.”
Overall, the gut microbiome composition in children with ASD differed substantially from that of children without the condition, with five bacterial species largely accounting for the difference. “These species-level compositional differences were largely attributed to five bacterial species including Alistipes indistinctus, candidate division_TM7_isolate_TM7c, Streptococcus cristatus, Eubacterium limosum and Streptococcus oligofermentans …” they stated.
These differences were further confirmed in a separate group of 18 children, eight with autism and 10 without. And importantly, bacteria associated with neurotransmitter activities were substantially reduced in children with autism. “Altogether, our data show that the microbiome functionalities associated with neurotransmitter synthesis were markedly reduced in children with ASD which may have profound functional consequences on the psychiatric abnormalities in ASD,” they wrote. “Since neurotransmitters enable signal transmission across synapses to nerve cells where synaptic dysfunction is thought to contribute to the pathophysiology of ASD, these results suggest that the role of gut microorganisms in ASD is related to amino acid metabolism.”
Some 26 age-related bacterial species were identified as proxies of typical development of the gut microbiome by age. But these associations were absent in children with autism, suggesting abnormal development of the gut microbiome during the early life of these children, the researchers suggested. They further suggested their collective results “indicate that compositional differences in gut microbiota between TD [typically developing] children and children with ASD could serve as a non-invasive screening tool for ASD.”
While the reported observational study was small, and the gut microbiome can vary according to geographical region, the researchers nevertheless concluded, “Our study shows for the first time that the gut microbiota of children with [autism] is abnormally developed and lags that of age-matched peers … As development of microbial communities within the [gastrointestinal] tract during childhood represents a critical window of human growth and health, shifts in the gut microbiota during early life development may have important functional roles in the pathogenesis of [autism spectrum disorder] and thus warrants extensive investigation.”
And they further suggested, “Future therapeutics targeting reconstitution of gut microbiota in early life and increasing abundance of neurotransmitter-synthesized bacteria such as Faecalibacterium should be explored for ASD.”