Gut Microbial Dysbiosis in Indian Children with Autism Spectrum Disorders

Abstract

Autism spectrum disorder (ASD) is a term associated with a group of neurodevelopmental disorders. The etiology of ASD is not yet completely understood; however, a disorder in the gut-brain axis is emerging as a prominent factor leading to autism. To identify the taxonomic composition and markers associated with ASD, we compared the fecal microbiota of 30 ASD children diagnosed using Childhood Autism Rating Scale (CARS) score, DSM-5 approved AIIMS-modified INCLEN Diagnostic Tool for Autism Spectrum Disorder (INDT-ASD), and Indian Scale for Assessment of Autism (ISAA) tool, with family-matched 24 healthy children from Indian population using next-generation sequencing (NGS) of 16S rRNA gene amplicon. Our study showed prominent dysbiosis in the gut microbiome of ASD children, with higher relative abundances of families Lactobacillaceae, Bifidobacteraceae, and Veillonellaceae, whereas the gut microbiome of healthy children was dominated by the family Prevotellaceae. Comparative meta-analysis with a publicly available dataset from the US population consisting of 20 ASD and 20 healthy control samples from children of similar age, revealed a significantly high abundance of genus Lactobacillus in ASD children from both the populations. The results reveal the microbial dysbiosis and an association of selected Lactobacillus species with the gut microbiome of ASD children.

An approach to gut microbiota profile in children with autism spectrum disorder

“…The present systematic review found a lower abundance of Bilophila in American (Berding and Donovan, ) and Italian (Strati et al ., ) children with ASD compared to HC, therefore, further research is needed regarding the implications of this bacterial genus in ASD. Regarding the Bacteroidetes/Firmicutes ratio in the GI tract of children with ASD, it is characterized by a lower Bacteroidetes/Firmicutes ratio in Italian, Slovakian and Indian children with ASD compared to their heterogeneous control groups (De Angelis et al ., ; Tomova et al ., ; Strati et al ., ; Pulikkan et al ., ). However, according to Coretti et al .…”

“…Phylogenetic map of bacterial populations (Phyla, families, genera and species level) in ASD. Note: [A = Williams et al ., ; B = Gondalia et al ., ; C = Kang et al ., ; D = Wang et al ., ; E = De Angelis et al ., ; F = Son et al ., ; G = Tomova et al ., ; H = Inoue et al ., ; I = Strati et al ., ; J = Iovene et al ., ; K= Luna et al ., ; L = Finegold et al ., ; M = Kushak et al ., ; N = Shaaban et al ., ; O = Gora et al ., ; P = Kang et al ., ; Q = Pulikkan et al ., ; R = Rose et al ., ; S = Coretti et al ., ; T = Zhang et al ., ; U = Berding and Donovan, ]. …”

“…Specifically, at the phylum level: Proteobacteria (Coretti et al ., ) were found to have a statistically significant higher abundance in children with ASD compared to their control groups. At family level: Lactobacillaceae, Enterococcaceae, Erysipelotrichaceae and Desulfovibrionaceae (Pulikkan et al ., ), Peptostreptococcaceae (Berding and Donovan, ), Bacteroidaceae, Lachnospiraceae and Ruminococcaceae (Rose et al ., ), and presumptive Enterobacteriaceae (De Angelis et al ., ) were found to have statistically significant higher abundance in children with ASD compared to their control groups. At genus level: Porphyromonas , presumptive Bacteroides , Porphyromonas and Prevotella , Caloromator , Sarcina , Anaerofilum , presumptive Pseudomonas and Aeromonas , and Shigella (De Angelis et al ., ), Ruminococcus and Lachnospira (Coretti et al ., ), Collinsella (Strati et al ., ), Mitsuokella and Megasphaera (Pulikkan et al ., ), Burkholderia (Kushak et al ., ), Roseburia (De Angelis et al ., ; Berding and Donovan, ; Coretti et al ., ), Peptostreptococcus and Ralstonia (Kushak et al ., ), and Candida (Iovene et al ., ; Strati et al ., ) were found to have statistically significant higher abundance in children with ASD compared to their control groups.…”

“…At family level: Lactobacillaceae, Enterococcaceae, Erysipelotrichaceae and Desulfovibrionaceae (Pulikkan et al ., ), Peptostreptococcaceae (Berding and Donovan, ), Bacteroidaceae, Lachnospiraceae and Ruminococcaceae (Rose et al ., ), and presumptive Enterobacteriaceae (De Angelis et al ., ) were found to have statistically significant higher abundance in children with ASD compared to their control groups. At genus level: Porphyromonas , presumptive Bacteroides , Porphyromonas and Prevotella , Caloromator , Sarcina , Anaerofilum , presumptive Pseudomonas and Aeromonas , and Shigella (De Angelis et al ., ), Ruminococcus and Lachnospira (Coretti et al ., ), Collinsella (Strati et al ., ), Mitsuokella and Megasphaera (Pulikkan et al ., ), Burkholderia (Kushak et al ., ), Roseburia (De Angelis et al ., ; Berding and Donovan, ; Coretti et al ., ), Peptostreptococcus and Ralstonia (Kushak et al ., ), and Candida (Iovene et al ., ; Strati et al ., ) were found to have statistically significant higher abundance in children with ASD compared to their control groups. At species level: Bilophila wadsworthia , Flavonifractor plautii , Roseburia intestinalis , Lachnoclostridium boltae , Lachnoclostridium hathewayi , Oscillospira valericigenes , Clostridium lituseburense and Clostridium aldenense (Luna et al ., ), Ruminococcus gnavus and Ruminococcus torques (Wang et al ., ), Lactobacillus ruminis (Pulikkan et al ., ) and Akkermansia muciniphila (De Angelis et al ., ) were found to have statistically significant higher abundance in children with ASD compared to their control groups.…”

Effects of early life NICU stress on the developing gut microbiome

“…Additionally, the presence of Proteobacteria pathobionts species has been shown to profoundly influence vulnerability to gut pathology (Chow et al, 2011;Langgartner et al, 2017). In humans, connections are emerging between the gut microbiota and brain health (Jiang et al, 2018;Pulikkan et al, 2018;Shen et al, 2018;Winter, Hart Robert, Charlesworth Richard, & Sharpley Christopher, 2018). As research continues to elucidate the microbiota-brain-gut axis (Foster, Rinaman, & Cryan, 2017), it will be important to understand how early life environmental stress exposure and dysbiosis effect preterm infant short-and long-term neurodevelopment (Groer et al, 2014).…”