Human epidemiologic studies linking gut microbiota changes to ASD symptomology
| Publication | Cohort Population | Type of Analysis and/or Treatment | Major Finding |
|---|---|---|---|
| Gondalia et al. (2012) | ASD children without GI dysfunction (n = 23); ASD children with GI dysfunction (n = 28); neurotypical siblings (n = 53) | • bEFAP was performed on the stool samples from all three groups. | • Firmicutes (70%), Bacteroidetes (20%), and Proteobacterias (4%) comprised the major microbiota present in the stool regardless of disease state and sociodemographic features. |
| • No evidence was found linking gut disease, dysbiosis, and ASD symptoms. | |||
| Song et al. (2004) | ASD children (n = 15); nonrelated controls (n = 8) | • Group and species-specific primers were designed to target the 16S rRNA genes for qRT-PCR analysis on the stool samples. | • C. bolteae and clusters I and XI were elevated in the stool of ASD children. |
| Finegold et al. (2002) | ASD children (n = 13); nonrelated controls (n = 8) | • Bacterial cultures were performed on the stool samples. | • Nine species of Clostridium were present in ASD but not the control children, where three unique species were identified. |
| • Non-spore-forming anaerobes and microaerophilic bacteria were abudant in ASD but lacking in the control children. | |||
| Parracho et al. 2005) | ASD children (n = 58); control siblings (n = 12); nonrelated controls (n = 10) | • FISH analysis was performed on the stool samples. | • C. histolyticum (Clostrium clusters I and II) was abundant in ASD children. |
| • Nonautistic siblings possess intermediate levels of this intestinal microbe. | |||
| Finegold et al. (2010) | ASD children (n = 33); control siblings (n = 7); nonrelated controls (n = 8) | • bEFAP procedure was used to analyze the stool samples. | • Phyla changes: Bacteroidetes and Protebacteria were increased in ASD children; whereas Firmcutes and Actinobacteria were less abundant in the stool of this group. |
| • Genus changes: Delsufovibrio, Bacteroides, Alkaliflexus, Acetanaerobacterium, and Parabacteroides were elevated in ASD children, whereas Clostridum, Weissella, Turicibacter, Anaerofilum, Pseudoramibacter, Ruminococcus, and Streptococcus were decreased in this group. | |||
| Tomova et al. (2015) | ASD children (n = 10); control siblings (n = 9); nonrelated controls (n = 10) | • qRT-PCR analysis was performed on the stool samples. | • ASD children showed significant reduction in the Bacteroidetes/Firmcutes ratio but increased amount of Lactobacillus spp. |
| • Probiotic supplementation of one Children Dophilus capsule, which contains three strains of Lactobacillus (60%), two strains of Bifidumbacteria (25%), and one strain of Streptococcus (15%) was provided orally to the ASD group 3 times a day for 4 months. | • Delsulfovibrio spp. showed a trend to be increased in this group, especially with increasing autistic severity. | ||
| • Clinical severity of GI symptoms was positively correlated with autism severity. | |||
| • Probiotic supplementation of the autistic children corrected the imbalanced Bacteroidetes/Firmicutes ratio, suppressed Delsufovibrio spp., and increased the amount of Bifidobacterium spp. present in the stool. | |||
| Williams et al. (2011) | ASD children with GI dysfunction (n = 15); nonrelated controls with GI symptoms only (n = 7) | • qRT-PCR with human mRNA samples for SI, MGAM, LCT, SGLT1, GLUT2, Vilin, and CDX2. | • ASD children exhibited decreased expression of disaccharidases, hexose transporters, and the transcription factor CDX2. |
| • Pyrosequencing of intestinal microbiota. | • The host transcriptomic changes correlated with the degree of gut dysbiosis observed in this ASD child cohort. | ||
| • qRT-PCR of Bacteroidete and Firmicute 16s rRNA genes from intestinal biopsies. | • ASD children showed decrease amounts of Bacteroidetes and ratio of Bacteroidetes to Firmcutes, and greater preponderance of Betaproteobacteria in the intestinal biopsy samples. | ||
| Wang et al. (2013) | ASD children (n = 23); control siblings (n = 22); nonrelated controls (n = 9) | • qPCR on the stool samples. | • ASD children with and without GI disorders showed high amounts of fecal Sutterella spp. |
| • Ruminococcus torques was elevated in the stool of children with ASD and GI symptoms compared with those without any such disorders. | |||
| De Angelis et al. (2013) | ASD children (n = 10); nonrelated controls (n = 10) | • bEFAP procedure was used to analyze the stool samples. | • Phylum changes were evident in Bacteroidetes, Firmicutes, Fusbobacteria, and Verrucomicrobia in ASD compared with health children. |
| • Measurement of free amino acid and volatile organic compounds in the stool samples. | • Caloramator, Sarcina, and Clostridium genera were greater in ASD children. | ||
| • Variations within the Lachnospracease family were observed. | |||
| • ASD children possessed greater amounts of fecal Bacteroidetes genera, select Alistipes and Akkermansia species, but Sutterellaceae, Enterobacteriaceae, Eubacteriaceae and Bifidobacterium species were reduced in this group. | |||
| • Levels of free amino acids and volatile organic compounds within the stool were affected in this group. | |||
| Wang et al. (2011) | ASD children (n = 23); control siblings (n = 22); nonrelated controls (n = 9) | • qPCR on the stool samples. | • Bifidobacteria species was reduced and mucolytic bacterium, Akkermansia muciniphilia, was increased in the stool of ASD children. |
| Williams et al. (2012) | ASD children with GI dysfunction (n = 15); nonrelated controls with GI symptoms only (n = 7) | • Pyrosequencing and qPCR of ileal and cecal biopsies. | • Sutterella spp. (wadsworthensis and stercoicanis) predominated in the gut microbiota of ASD children with concurrent GI dysfunction, but these species were absent in children with GI symptoms only. |
| Kang et al. (2013) | ASD children (n = 20); nonrelated controls (n = 20) | • Pyrosequencing of the stool samples. | • The presence of ASD rather than GI symptoms was a better predictor of a less diverse gut microbiota composition. |
| • The genera Prevotella, Coprococcus, and unclassified Veillonellaceae were reduced in the stool of ASD children. | |||
| Adams et al. (2011) | ASD children (not on probiotic supplement and those taking a daily probiotic, n = 58); nonrelated controls (n = 39) | • Bacterial culture of the stool samples. | • There was a positive correlation with GI symptoms and ASD clinical severity. |
| • Concentrations of Lysozyme, lactoferrin, secretory IgA, elastase, SCFAs were measured in the stool. | • Decreased number of SCFAs, specifically acetate, propionate, and valerate were identified in ASD children, especially those consuming a daily probiotic. | ||
| • The stool of ASD children contained less Bifidobacter but greater amounts of Lactobacillus. | |||
| • Lysozyme was suppressed in ASD children. | |||
| Sandler et al. (2000) | Regressive-onset autistic children (n = 11) | • The children received a 12-week treatment of oral vancomycin (125 mg 4 times a day for a daily dose of 500 mg). | • The vancomycin treatment improved the behavioral scores of ASD children, but the beneficial effects were transient with the behavioral symptoms recurring upon discontinuation of the antibiotic. |
| • Once antibiotic treatment was discontinued, the children received probiotic supplementation with a mixture of L. acidophilus, L. bulgaricus, and B. bifidum (40 × 109 CFU/ml). | |||
| • Psychologic evaluations were performed before and after the antibiotic treatment. | |||
| Wang et al. (2012) | ASD children (n = 23); nonrelated controls (n = 31) | • Concentrations of SCFAs, phenols, and ammonia were measured in the stool samples. | • Fecal SCFAs were significantly higher in ASD children. |
| • Acetic, butyric, isobutryic, valeric, and isovaleric acids were elevated in the stool of ASD children, whereas caproic acid was reduced. | |||
| • The ASD group had greater ammonia concentration in the stool. | |||
| Yap et al. (2010) | ASD children (n = 39 with 35 males and 4 females); control siblings (n = 28 with 14 males and 14 females); nonrelated controls (n = 34 with 17 males and 17 females) | • H NMR spectroscopy and pattern recognition methods were used to measure the concentration of free amino acids and bacterial metabolites in the urine. | • The free amino acids glutamate and taurine were elevated in the urine of ASD children. |
| • Disturbances in the patterns of bacterial metabolites dimethylamine, hippurate, and phenylacetylglutamine were also observed in this group. | |||
| Kalużna-Czaplńnska and Blaszczyk (2012) | ASD children with GI dysfunction (n = 22) | • Concentrations of DA, LA, and the ratio of DA/LA in the urine were determined by capillary gas chromatography/mass spectrometry before and after probiotic therapy. | • The concentration of DA in the urine was higher in ASD children compared with controls before and after probiotic supplementation. |
| • The children were provided an oral probiotic capsule containing L. acidophilus twice daily for 2 months (strain Rosell-11, containing 5 × 109 CFU/gram). | • The probiotic therapy appeared to partially improve the elevated urinary concentrations of DA and ratio of DA/LA, and there was noticeable improvement in the behaviors of ASD children, particularly in concentration ability and carrying out orders. |
bEFAP, bacterial tag encoded FLX amplicon pyrosequencing; CFU, colony forming unit; FISH, fluorescent in situ hybridization; LA, L-arabinitol; qRT-PCR, quantitative real-time polymerase chain reaction.