**6. Existing and emerging therapeutic strategies in autism targeting the gutbrain axis and gut microbiome: Role of individual microbes and dietary amino acids in maintaining gut-brain homeostasis**

Existing therapies targeting the gut microbiome include diet, antibiotics, and probiotics. Dietary restriction, including the removal of dairy casein-containing products, wheat and gluten sources, sugar, chocolate, preservatives, and food coloring have all been found to be therapeutic in autism. Interestingly, dairy casein-containing products stimulate ghrelin (a hunger hormone) and reduce CCK (a satiety agent) production in the periphery and in the brain. Gastrointestinal problems in autism appear to respond to antimicrobial agents. Treat‐ ments targeting Candida, and probiotics have been used to reduce disbiosis and control gut permeability (Kidd, 2002). Other strategies include the removal of heavy metals (including mercury) by chelation and sulfur-sulphydryl repletion. Supplementation with dimethylgly‐ cine, vitamin B6, magnesium, vitamin B3, C, folic acid, calcium and zinc, cod liver, digestive enzymes, all appear to be beneficial in a number of autistic children (Kidd, 2002). Immune therapies, including pentoxifyllin, immunoglobulin, transfer factors and colostrums appear to work in a limited number of cases,

The initial promising use of secretin, a triggering factor for digestion, in the treatment of autism has been more recently disclaimed. In multiple randomized controlled trials secretin offered no significant benefit (Krishnaswami et al., 2011; Williams et al., 2012).

Abnormalities in the primary pathway for carbohydrate digestion and transporters, involving disaccharidases and hexose transporters, have been reported and found to be accompanied by dysbiosis as evidenced by a decrease in Bactoroidetes and an increase in the ratio of Firmicutes to Bacteroidetes (Williams et al., 2011). These abnormalities respond to probiotic and dietary responses (Williams et al., 2011). Probiotic therapy appears to influence microbiome compo‐ sition, intestinal barrier function and mucosal immune responses (Critchfield et al., 2011). There is evidence to support alterations of fecal microbiome in autism, and in the majority of cases treatment with vancomycin, an antibiotic that targets gram positive anaerobes and is minimally absorbed by the gut, can improve symptoms (Sandler et al., 2000).

Recently therapies targeting the gut microbiome are emerging as a viable strategy in the treatment of CNS disorders (Forsythe et al., 2010). Preclinical studies of selected probiotics in healthy volunteers (Messaoudi et al., 2011) provided encouraging results for further studies exploring the concept of microbial targeting of the GIT under pathological conditions includ‐ ing autism. Individually tailored probiotic formulations, enriched in specific strains of gut bacteria, could one day be used in treatments of ASD even as an adjuvant to other treatments.

several organs outside the brain. While the systemic endogenous ghrelin exerts a tonic stimulating effect on hypothalamic CRH (Rucinski et al., 2012), its function in the brain includes the modulation of membrane excitability, control of neurotransmitter release, neuronal gene

It has been reported that ghrelin of GIT origin interacts with bacterial toxins (Tiaka et al., 2011) and exerts a protective role in experimental colitis; is it possible that the ghrelin of brain origin plays a protective role as well? If so, changes in the level of brain-derived ghrelin could

**6. Existing and emerging therapeutic strategies in autism targeting the gutbrain axis and gut microbiome: Role of individual microbes and dietary**

Existing therapies targeting the gut microbiome include diet, antibiotics, and probiotics. Dietary restriction, including the removal of dairy casein-containing products, wheat and gluten sources, sugar, chocolate, preservatives, and food coloring have all been found to be therapeutic in autism. Interestingly, dairy casein-containing products stimulate ghrelin (a hunger hormone) and reduce CCK (a satiety agent) production in the periphery and in the brain. Gastrointestinal problems in autism appear to respond to antimicrobial agents. Treat‐ ments targeting Candida, and probiotics have been used to reduce disbiosis and control gut permeability (Kidd, 2002). Other strategies include the removal of heavy metals (including mercury) by chelation and sulfur-sulphydryl repletion. Supplementation with dimethylgly‐ cine, vitamin B6, magnesium, vitamin B3, C, folic acid, calcium and zinc, cod liver, digestive enzymes, all appear to be beneficial in a number of autistic children (Kidd, 2002). Immune therapies, including pentoxifyllin, immunoglobulin, transfer factors and colostrums appear to

The initial promising use of secretin, a triggering factor for digestion, in the treatment of autism has been more recently disclaimed. In multiple randomized controlled trials secretin offered

Abnormalities in the primary pathway for carbohydrate digestion and transporters, involving disaccharidases and hexose transporters, have been reported and found to be accompanied by dysbiosis as evidenced by a decrease in Bactoroidetes and an increase in the ratio of Firmicutes to Bacteroidetes (Williams et al., 2011). These abnormalities respond to probiotic and dietary responses (Williams et al., 2011). Probiotic therapy appears to influence microbiome compo‐ sition, intestinal barrier function and mucosal immune responses (Critchfield et al., 2011). There is evidence to support alterations of fecal microbiome in autism, and in the majority of cases treatment with vancomycin, an antibiotic that targets gram positive anaerobes and is

Recently therapies targeting the gut microbiome are emerging as a viable strategy in the treatment of CNS disorders (Forsythe et al., 2010). Preclinical studies of selected probiotics in

no significant benefit (Krishnaswami et al., 2011; Williams et al., 2012).

minimally absorbed by the gut, can improve symptoms (Sandler et al., 2000).

expression, and neuronal survival and proliferation (Ferrini et al., 2009).

**amino acids in maintaining gut-brain homeostasis**

be detrimental to the developing brain.

70 Recent Advances in Autism Spectrum Disorders - Volume I

work in a limited number of cases,
