Genetic analyses suggest selected gut microbial taxa and metabolite pathways may be linked to ASD susceptibility, with Prevotellaceae and Lachnospiraceae the most persistent risk signals.
Evidence
This study used gut microbiota GWAS instruments from 18,340 people and ASD GWAS data from 14,759 cases and 155,327 controls, with metabolite-adjusted and reverse analyses.
Caveat
MR depends on genetic-instrument assumptions, and most microbial associations weakened after neurotransmitter and amino acid metabolite adjustment.
Simplified
Recent studies have illuminated a significant relationship between the gut microbiota and the development and progression of autism spectrum disorder (ASD), mediated through the complex gut-brain axis, where metabolic pathways are crucial. Nevertheless, the exact causal link remains to be elucidated. This study aims to assess the potential causal relationship between the gut microbiota, metabolites, and ASD, utilizing methodology. The exposure variable of gut microbiota was ascertained using instrumental variables derived from a genome-wide association study that included a cohort of 18,340 individuals. The outcome variable comprised genome-wide association study data from 14,759 individuals diagnosed with ASD and 1,55,327 controls. The primary method of analysis was the inverse-variance weighted method. Multivariable multiple regression analysis was conducted to examine the impact of gut microbial metabolites on the established correlations. Inverse-variance weighted analyses revealed that Methanobacteria[c] (odds ratio [OR] = 1.17 [1.03-1.33]), Methanobacteriaceae[f] (OR = 1.17 [1.03-1.33]), Prevotellaceae[f] (OR = 1.29 [1.04-1.60]), Holdemania[g] (OR = 1.23 [1.03-1.45]), Lachnospiraceae[g] (OR = 1.29 [1.06-1.57]), Ruminiclostridium[g] (OR = 1.63 [1.27-2.10]), Terrisporobacter[g] (OR = 1.28 [1.00-1.63]), Methanobacteriales[o] (OR = 1.17 [1.03-1.33]), and Euryarchaeota[p] (OR = 1.16 [1.02-1.32]) serve as risk factors for ASD, while Eisenbergiella[g] (OR = 0.80 [0.68-0.94]) and Ruminococcaceae[g] (OR = 0.79 [0.63-1.00]) exhibit protective roles against ASD. Adjustments for neurotransmitter and amino acid metabolites effects diminished these associations. However, Prevotellaceae and Lachnospiraceae remained significantly associated with increased ASD risk. Reverse Mendelian randomization analyses did not establish a causal relationship between ASD and gut microbiota composition. Sensitivity tests showed no evidence of heterogeneity or pleiotropy. Alterations in metabolites induced by the gut microbiota may contribute to ASD susceptibility. Prevotellaceae and Lachnospiraceae are implicated as potential risk factors. Investigating these associations further could unveil novel therapeutic targets and provide deeper insights into ASD's etiological mechanisms.
Key numbers
1.63
Increased Risk -
for Ruminiclostridium associated with risk.
1,70,086
Total Study Cohort Size
Cohort size includes 14,759 patients and 1,55,327 controls.
13
Gut Microbiota Species Identified
Total species identified in the analysis related to .
Full Text
We can’t show the full text here under this license.
Gut-Brain Axis