Therapeutic Effects of the In Vitro Cultured Human Gut Microbiota as Transplants on Altering Gut Microbiota and Improving Symptoms Associated with Autism Spectrum Disorder

Role of the Gut Microbiota in the Pathophysiology of Autism Spectrum Disorder: Clinical and Preclinical Evidence

“…Although the nature of the dysbiosis is very different among the different models, there are a few similarities. Firstly, a decrease in α-diversity has been described in Shank3 KO, BTBR, MIA and MHFD mice and VPA rats [53,55,[58][59][60][61]. However, other studies in Shank3B KO, NL3 R451C , BTBR, MIA and VPA mice did not observe any change in α-diversity [52,54,57,62,63].…”

“…First, studies on germ-free animals prove that the microbiota is important for maturation of the immune system and helps maintain immune homeostasis [93]. Plus, as previously mentioned, an immune challenge during pregnancy in the MIA model results in a dysbiosis in the offspring along with altered communication, social and repetitive behaviors and cortical defects similar to ASD [48,60,94]. Immune alterations similar to those seen in ASD patients were observed in MIA offspring, such as an increase in IL-6 and IL-17 pro-inflammatory cytokines, and higher proportion of Th17 cells [54,95].…”

“…Another recent study performed FMT in the MIA mouse model, using pooled stools from three healthy human donors [60]. Mice received microbiota either directly after collection from the donors or after an in vitro culture step.…”

“…All of the studies included in Table A1 and Table A2 that assessed β-diversity observed a difference between controls and model animals, except for Hsiao et al (2013) [ 54 ]. At the phylum level, an increase in Bacteroidetes and a decrease in Firmicutes was observed in BTBR and MIA mice, and in male VPA rats [ 53 , 59 , 60 , 61 ]. This is in agreement with the elevated Bacteroidetes/Firmicutes ratio in ASD patients described in a meta-analysis previously mentioned [ 17 ].…”

“…However, Coretti et al (2017) [ 52 ] found increased Lactobacillus in male BTBR mice. The Prevotella genus, which has been found to be decreased in ASD patients by Kang et al (2013) [ 65 ], was also decreased in Shank3 KO mice [ 58 ] but was increased in MIA and BTBR mice [ 52 , 59 , 60 ]. Although changes in proportion of Clostridium species seem to be recurrent in ASD patients, they were only observed in BTBR mice by Newell et al (2016) [ 59 ], who found decreased and increased levels of various Clostridium species in cecal contents and feces, respectively.…”