Altered gut microbiota and short chain fatty acids in Chinese children with autism spectrum disorder

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is characterized by impairments in social interactions and communication, restricted interests and repetitive behaviors. Several studies report a high prevalence of gastrointestinal (GI) symptoms in autistic individuals. Cumulative evidence reveals that the gut microbiota and its metabolites (especially short-chain fatty acids, SCFAs) play an important role in GI disorders and the pathogenesis of ASD. However, the composition of the gut microbiota and its association with fecal SCFAs and GI symptoms of autistic children remain largely unknown. In the present study, we sequenced the bacterial 16S rRNA gene, detected fecal SCFAs, assessed GI symptoms and analyzed the relationship between the gut microbiome and fecal SCFAs in autistic and neurotypical individuals. The results showed that the compositions of the gut microbiota and SCFAs were altered in ASD individuals. We found lower levels of fecal acetic acid and butyrate and a higher level of fecal valeric acid in ASD subjects. We identified decreased abundances of key butyrate-producing taxa (Ruminococcaceae, Eubacterium, Lachnospiraceae and Erysipelotrichaceae) and an increased abundance of valeric acid associated bacteria (Acidobacteria) among autistic individuals. Constipation was the only GI disorder in ASD children in the present study. We also found enriched Fusobacterium, Barnesiella, Coprobacter and valeric acid-associated bacteria (Actinomycetaceae) and reduced butyrate-producing taxa in constipated autistic subjects. It is suggested that the gut microbiota contributes to fecal SCFAs and constipation in autism. Modulating the gut microbiota, especially butyrate-producing bacteria, could be a promising strategy in the search for alternatives for the treatment of autism spectrum disorder.

Autism Spectrum Disorder and the Gut Microbiota in Children: A Systematic Review

“…Increased Lachnospiraceae and Ruminococcaceae were also seen in ASD children with GI symptoms when compared to control children with similar symptoms in Rose et al [33]. Pulikkan et al [37] also noted an increase in Ruminococcaceae in their analysis whereas Liu et al [23] found Ruminococcaceae to be significantly reduced in ASD.…”

“…Among the 28 studies, 19 studied the difference between ASD and unaffected, unrelated children [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33], 4 studies looked at the difference between ASD and unaffected siblings [34][35][36] or blood relatives [37] and 5 studies considered all 3 groups [38][39][40][41][42] (Table 2). The number of enrolled patients in a single study ranged from 12 to 104 participants and all were aged between 2 and 18 years.…”

“…Pulikkan et al [37] 2018 * -* * ** -* -6 Rose et al [33] 2018 * * -* ** -* -6 Zhang et al [25] 2018 * * * * * -* -6 Li et al [26] 2019 * * * ---* -4 Liu et al [23] 2019 * * * * ** -* -7 Ma et al [24] 2019 * * * * ** -* -7 Plaza-Diaz et al [15] 2019 * * * * ** -* -7 Wang et al [28] 2019 -* * ---* -5 Zhai et al [27] 2019 * * * * ** -* -7…”

“…The analyses of the gut microbiota did not however always take symptoms into account. Five studies described distinct microbiota profiles in ASD with and without GI symptoms [20,23,33,40,41]. Two studies found no association [26,28].…”

Gut microbiota profiles of autism spectrum disorder and attention deficit/hyperactivity disorder: A systematic literature review.

“…Finally, 24 original articles were included in this systematic review. These articles included 20 articles investigating ASD [45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64] and 4 investigating ADHD 65- (Figure 1, supplementary data 1). None Table 1.…”