Gut microbiota variations and dysbiosis are linked to ASD. However, the microbiota’s role in the development of ASD as a result of host genetic predisposition is uncertain. A study aimed to examine the interaction between host genetic variation and gut microbiota in ASD children from a systematic standpoint. To identify single nucleotide variations (SNVs) in individuals with ASD, whole-exon sequencing was used on 26 children with ASD and 26 age- and sex-matched control subjects. For this group, prior research demonstrated an altered gut microbiota and a disrupted metabolic activity in ASD. To assess whether SNVs were associated with the gut microbiota and their components, the study sequenced the bacteria. Bioinformatic analyses were also carried out to investigate the link between SNVs and gut microbiota as well as their by-products. The genes involved with the innate immune system, protein glycosylation processing, and retrograde axonal transport were significantly overrepresented in the ASD SNVs. These SNVs were linked to the microbiome composition as well as a variety of microbial functions, particularly metabolism. Furthermore, the presence of a large number of metabolites linked to neurotransmitter metabolic networks was found to be causally related to particular SNVs and microorganisms. In the study, it was suggested that host genotype and intestinal microbes may play an important role in immune and metabolism homeostasis in ASD. The research may help scientists learn more about the connection between host genetic variations and the gut microbiota in the development of ASD.