Autism Spectrum Disorder (ASD) with and without Mental Regression is Associated with Changes in the Fecal Microbiota

Abstract

New microbiome sequencing technologies provide novel information about the potential interactions among intestinal microorganisms and the host in some neuropathologies as autism spectrum disorders (ASD). The microbiota–gut–brain axis is an emerging aspect in the generation of autistic behaviors; evidence from animal models suggests that intestinal microbial shifts may produce changes fitting the clinical picture of autism. The aim of the present study was to evaluate the fecal metagenomic profiles in children with ASD and compare them with healthy participants. This comparison allows us to ascertain how mental regression (an important variable in ASD) could influence the intestinal microbiota profile. For this reason, a subclassification in children with ASD by mental regression (AMR) and no mental regression (ANMR) phenotype was performed. The present report was a descriptive observational study. Forty-eight children aged 2–6 years with ASD were included: 30 with ANMR and 18 with AMR. In addition, a control group of 57 normally developing children was selected and matched to the ASD group by sex and age. Fecal samples were analyzed with a metagenomic approach using a next-generation sequencing platform. Several differences between children with ASD, compared with the healthy group, were detected. Namely, Actinobacteria and Proteobacteria at phylum level, as well as, Actinobacteria, Bacilli, Erysipelotrichi, and Gammaproteobacteria at class level were found at higher proportions in children with ASD. Additionally, Proteobacteria levels showed to be augmented exclusively in AMR children. Preliminary results, using a principal component analysis, showed differential patterns in children with ASD, ANMR and AMR, compared to healthy group, both for intestinal microbiota and food patterns. In this study, we report, higher levels of Actinobacteria, Proteobacteria and Bacilli, aside from Erysipelotrichi, and Gammaproteobacteria in children with ASD compared to healthy group. Furthermore, AMR children exhibited higher levels of Proteobacteria. Further analysis using these preliminary results and mixing metagenomic and other “omic” technologies are needed in larger cohorts of children with ASD to confirm these intestinal microbiota changes.

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

“…They also identified that 2 distinct dietary patterns were associated with unique microbial profiles in children with ASD [29]. Similarly, differential patterns in food and microbiota were also seen in children with ASD in the study by Plaza-Diaz et al [15]. The vast majority of studies did not collect details on diet or assess dietary impact on the gut microbiota.…”

“…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.…”

“…Of the included studies, the majority (n = 11) were from the United States, 6 from Europe [15,20,22,35,39,42] and 3 from Australia [34,40,41]. The remaining 8 studies were from Asia [30,37].…”

“…The majority used 1 month as a cut-off. Eight studies did not address antibiotic use [15,17,19,21,25,28,39,41]. The 3 remaining studies did not exclude participants based on antibiot-ics but did collect data [31,40,42].…”

“…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…”