Abstract
A large number of children in the autism spectrum disorder suffer from gastrointestinal (GI) conditions, such as constipation and diarrhea. Clostridium bolteae is a part of a set of pathogens being regularly detected in the stool samples of hosts affected by GI and autism symptoms. Accompanying studies have pointed out the possibility that such microbes affect behaviour through the production of neurotoxic metabolites in a so-called, gut-brain connection. As an extension of our Clostridium difficile polysaccharide (PS)-based vaccine research, we engaged in the discovery of C. bolteae surface carbohydrates. So far, studies revealed that C. bolteae produces a specific immunogenic PS capsule comprised of disaccharide repeating blocks of mannose (Manp) and rhamnose (Rhap) units: α-D-Manp-(1→[-4)-β-D-Rhap-(1→3)-α-D-Manp-(1→]n. For vaccinology and further immunogenic experiments, a method to produce C. bolteae PS conjugates has been developed, along with the chemical syntheses of the PS non-reducing end linkage, with D-Rha or L-Rha, α-D-Manp-(1→4)-α-D-Rhap-(1→O(CH2)5NH2 and α-D-Manp-(1→4)-α-L-Rhap-(1→O(CH2)5NH2, equipped with an aminopentyl linker at the reducing end for conjugation purposes. The discovery of C. bolteae PS immunogen opens the door to the creation of non-evasive diagnostic tools to evaluate the frequency and role of this microbe in autistic subjects and to a vaccine to reduce colonization levels in the GI tract, thus impeding the concentration of neurotoxins.
Highlights
Autism is a neurological disorder clinically defined by social and communication impairments with repetitive and restricted patterns of interests and behaviours [1]
Clostridium bolteae is a part of a set of pathogens being regularly detected in the stool samples of hosts affected by GI and autism symptoms
We discovered that C. bolteae produces a specific capsule PS immunogen that so far seems to be shared by C. bolteae strains: α-D-Manp-(1→[-4)-β-D-Rhap-(1→3)α-D-Manp-(1→]n
Summary
Autism is a neurological disorder clinically defined by social and communication impairments with repetitive and restricted patterns of interests and behaviours [1]. 6342 Current Medicinal Chemistry, 2019, Vol 26, No 35 diversity is due to the disease or vice-versa Along these lines, it has been observed that ASD patients have abnormal GI bacterial flora compared to developmentally normal children [6]. In a 2004 study, it was noticed that another Clostridia specie, C. clostridioforme, was present in ASD patients (with late-onset autism) but was not observed in stool samples from the control group [17, 20]. Given that Clostridia species, such as C. bolteae, may be associated with ASDs, a vancomycin treatment was attempted in a small sampling of children presenting regressive late-onset autism [21]. Increasing our knowledge base about microbes putatively involved in GI illnesses, and associated behavioural traits, perhaps antibiotic-free treatment options can be advanced Microbes, such as bacteria, expose complex carbohydrates, polysaccharides (PS), as the outer-most decoration on their cell wall. It may be feasible to generate PSbased products to help detect and control C. bolteae, preventing the accumulation of high levels of neurotoxic metabolites
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