The Immune System & Autism

The immune system has been implicated in the pathogenesis of autism spectrum disorders (ASD). Several studies have explored the relationship between immune dysfunction and ASD, providing evidence for immune system involvement in the development and progression of the disorder.

One study by Cohly & Panja (2005) reviewed the immunological findings in autism and highlighted the role of the immune system in ASD. They discussed the presence of autoimmunity, inflammation mediators, and immune system diseases in individuals with autism. The authors suggested that environmental pollutants and viral infections may contribute to immune dysregulation in ASD.

Another study by Dietert & Dietert (2008) focused on the potential for early-life immune insult, including developmental immunotoxicity, in ASD. They proposed that critical windows of immune vulnerability during pregnancy and early childhood may contribute to the development of ASD. The authors emphasized the impact of prenatal exposure to xenobiotics and environmental factors on immune system function and the subsequent risk of ASD.

Vargas et al. (2004) investigated neuroglial activation and neuroinflammation in the brains of individuals with autism. They found evidence of increased neuroglial and inflammatory reactions in autistic patients, suggesting a role for immune-mediated mechanisms in the pathogenesis of ASD. The study utilized immunocytochemistry, cytokine protein arrays, and enzyme-linked immunosorbent assays to assess the magnitude of immune reactions and cytokine expression profiles.

Autoimmune and gastrointestinal dysfunctions have also been linked to ASD. Brown & Mehl-Madrona (2011) conducted a literature review on the immunological and gastrointestinal aspects of autism. They found evidence of bacterial infections, autoantibodies, and food hypersensitivity in individuals with ASD, suggesting a broader connection between autoimmune and gastrointestinal dysfunctions in this population.

Furthermore, immune system dysregulation has been observed in individuals with ASD. Brigida et al. (2017) discussed the correlation between inflammatory state and neuro-immune alterations in ASD.

The role of mitochondria in immunity and its potential link to ASD was explored by (Napoli et al., 2014). They found deficits in bioenergetics and impaired immune response in granulocytes from children with autism, suggesting a connection between energy metabolism and immune dysfunction in ASD.

The gut microbiota has also been implicated in immune system dysregulation in ASD. Carpita et al. (2020) proposed an integrative model that considers the microbiome, immune system, and inflammation in ASD. They reviewed studies on the microbiota-gut-brain axis and its potential role in the pathogenesis of ASD.

In conclusion, multiple studies have provided evidence for immune system involvement in the development and progression of autism spectrum disorders. Immune dysfunction, including autoimmunity, inflammation, and gastrointestinal dysfunctions, has been observed in individuals with ASD. Prenatal exposure to environmental factors and early-life immune insult may contribute to the risk of ASD. Dysregulation of the endocannabinoid system, mitochondria, and gut microbiota has also been implicated in immune system dysfunction in ASD. Further research is needed to fully understand the complex relationship between the immune system and ASD.

Glycoimmunology & Autism

Glycoimmunology is a field of study that focuses on the interactions between glycans (carbohydrate molecules) and the immune system. It explores how glycans influence immune responses and how immune cells recognize and respond to glycan structures (Freeze et al., 2015). Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction, communication difficulties, and repetitive behaviors. The etiology of ASD is complex and involves both genetic and environmental factors (Rommelse et al., 2010).

Several studies have suggested a potential link between immune dysregulation and ASD. Neuroglial activation and neuroinflammation have been observed in the brains of individuals with autism (Vargas et al., 2004). Neuroglial cells, including microglia and astroglia, play crucial roles in neuronal activity, synaptic function, and brain development (Vargas et al., 2004). Additionally, gene-network analysis has identified an overrepresentation of genes related to glycobiology in individuals with autism, suggesting that alterations in glycan-related genes could contribute to the autism phenotype (Zwaag et al., 2009).

Autoimmune and gastrointestinal dysfunctions have also been associated with autism (Brown & Mehl-Madrona, 2011). A literature review found evidence of immunological and gastrointestinal abnormalities in individuals with autism (Brown & Mehl-Madrona, 2011). Furthermore, maternal infection during pregnancy has been linked to an increased risk of autism in offspring (Patterson, 2011). Infections can trigger immune responses that may affect fetal brain development and contribute to the development of autism (Patterson, 2011).

The immune system's role in autism is further supported by studies investigating cytokine profiles in individuals with autism. Cytokines are signaling molecules involved in immune responses. Plasma cytokine profiles have been found to be altered in individuals with autism, suggesting an abnormal immune response (Ashwood et al., 2010). Additionally, immune-based genes, such as human leukocyte antigen (HLA)-DRB1 and complement C4 alleles, have been associated with autism (Ashwood et al., 2006).

Glycosylation, the process of attaching glycans to proteins and lipids, is essential for proper cellular function. Dysregulation of glycosylation has been implicated in various neurological disorders, including autism (Freeze et al., 2015). Glycosylation disorders can lead to intellectual disability, epilepsy, and other neurological symptoms (Freeze et al., 2015). The specific role of glycosylation in autism is still being investigated, but it is hypothesized that alterations in glycan structures may affect neuronal development and function (Freeze et al., 2015).

In conclusion, glycoimmunology provides insights into the potential role of immune dysregulation and glycosylation in the pathogenesis of autism. Neuroglial activation, gene-network analysis, immune dysfunctions, and alterations in glycan-related genes all suggest a connection between the immune system and autism. Further research is needed to fully understand the mechanisms underlying this relationship and to develop potential therapeutic interventions.

Mannose Binding Lectin

One potential factor that has been studied in relation to autism is Mannose Binding Lectin (MBL), which is a protein involved in the innate immune system (Eisen, 2009). MBL is known to play a role in the recognition and clearance of pathogens, and deficiencies in MBL have been associated with increased susceptibility to infections (Eisen, 2009).

Several studies have investigated the relationship between MBL and autism. One study found that children with autism had significantly lower levels of MBL compared to typically developing children (Koch et al., 2001). Another study found that MBL deficiency was more common in children with autism compared to controls (Ruskamp et al., 2006). These findings suggest that MBL may be involved in the pathogenesis of autism, possibly through its role in immune function.

In addition to its role in immune function, MBL has also been implicated in other conditions. For example, MBL deficiency has been associated with an increased risk of respiratory tract infections (Eisen, 2009). It has also been linked to autoimmune diseases such as rheumatoid arthritis (Behairy et al., 2022). Furthermore, MBL has been shown to play a role in the complement system, which is involved in inflammation and immune responses (Asbeck et al., 2008).

Overall, the research suggests that MBL may be involved in the development of autism and other conditions. However, more studies are needed to fully understand the mechanisms underlying these associations. Further research could help to determine whether MBL deficiency is a risk factor for autism or if it is a consequence of the disorder. Additionally, investigating the role of MBL in the immune system and its interactions with other factors could provide insights into potential therapeutic targets for autism and related conditions.

Complement Deficiency

Complement deficiency has been increasingly implicated in neurodevelopmental disorders such as autism spectrum disorder (ASD) (Magdalon et al., 2020). The complement system, a key system for immune surveillance and homeostasis, plays a dual role in both homeostasis and disease (Ricklin et al., 2010). Dysfunction in the complement system has been associated with disorders of neurodevelopmental origin, including ASD (Gordon & Jaquiss, 2018). There is accumulating evidence suggesting a role of complement deficiency in the pathophysiology of ASD (Gordon & Jaquiss, 2018).

Microglia, the resident immune cells of the central nervous system, have been implicated in the development and pathogenesis of neurodevelopmental and psychiatric disorders, including autism (Schafer et al., 2012). Recent studies have suggested that abnormal microglial function and complement cascade activation may play a role in ASD (Stephan et al., 2012). The complement system has been found to have an unexpected role in synaptic pruning during development and disease, which may contribute to the pathogenesis of ASD (Stephan et al., 2012).

Transcriptomic analysis of the autistic brain has revealed convergent molecular pathology, indicating that there may be common underlying molecular pathways involved in ASD (Voineagu et al., 2011). The complement system has been identified as one of the pathways that may be perturbed in ASD (Voineagu et al., 2011). Additionally, genome-wide association studies and analyses of postmortem human brain tissue have suggested that abnormal microglial function and complement cascade activation may be involved in ASD and other psychiatric disorders (Stephan et al., 2012).

Furthermore, the complement system has been implicated in gene-environment interactions in the pathogenesis of schizophrenia (Nimgaonkar et al., 2017). It would be of interest to investigate whether individuals with complement deficiency have an elevated risk for schizophrenia (Nimgaonkar et al., 2017). The complement C4B gene null allele, which is associated with complement deficiency, has been found to be more frequent in individuals with autism (Ratajczak, 2011).

In conclusion, complement deficiency has been implicated in the pathophysiology of autism spectrum disorder. Dysfunction in the complement system, particularly in microglial function and complement cascade activation, may contribute to the development and pathogenesis of ASD. Further research is needed to fully understand the role of complement deficiency in neurodevelopmental disorders and its potential implications for diagnosis and treatment.

The Role of Sugar Chains in Autism

Recent research has suggested a potential link between sugar chains and ASD. Sugar chains, also known as glycans, are complex carbohydrates that play crucial roles in various biological processes, including cell-cell recognition, signal transduction, and infection (Shinchi et al., 2012).

Sugar Chains and Brain Development

The brain is rich in sugar chains, particularly sialic acids, which are nine-carbon sugars that terminate many glycans on cell surface glycoproteins and glycolipids (Schnaar et al., 2014). Sialic acids are involved in nervous system development, stability, disease, and regeneration. Alterations in sialic acid expression have been observed in various neurological disorders, including ASD. Studies have shown that changes in sialic acid levels can affect neuronal function and synaptic plasticity, potentially contributing to the pathogenesis of ASD (Schnaar et al., 2014).

Mitochondrial Dysfunction and Sugar Chains

Mitochondrial dysfunction has been implicated in the pathogenesis of ASD (Ghanizadeh et al., 2013). Mitochondria are responsible for energy production in cells, and disruptions in the mitochondrial electron transport chain can lead to oxidative stress and impaired ATP production. A systematic review suggests that targeting the mitochondrial electron transport chain could be a novel therapeutic approach for ASD (Ghanizadeh et al., 2013). Interestingly, sugar chains have been found to play a role in mitochondrial function. Glycosylation, the process of attaching sugar chains to proteins, is essential for maintaining the ordered social behavior of differentiated cells. Alterations in sugar chains can disrupt mitochondrial function and contribute to abnormal social behaviors observed in ASD (Kobata & Amano, 2005).

Glycosphingolipids and Brain Development

Glycosphingolipids (GSLs) are a class of sugar chains that are abundant in the brain and play critical roles in brain development and function (Yu et al., 2009). GSLs are involved in cell signaling, cell adhesion, and neuronal migration. Changes in the expression patterns of GSLs have been observed during brain development, suggesting their involvement in neurodevelopmental processes. Dysregulation of GSL metabolism has been implicated in various neurological disorders, including ASD (Yu et al., 2009). Further research is needed to elucidate the specific role of GSLs in ASD pathogenesis.

In conclusion, the relationship between sugar chains and ASD is a complex and emerging area of research. Sugar chains play critical roles in brain development, mitochondrial function, and cell signaling, all of which are implicated in ASD pathogenesis. Alterations in sugar chain expression and metabolism have been observed in individuals with ASD, suggesting their potential involvement in the disorder. Further research is needed to elucidate the specific mechanisms underlying the relationship between sugar chains and ASD and to explore potential therapeutic interventions targeting sugar chain metabolism.

Glycoimmunology and Glycosaminoglycans

Glycosaminoglycans (GAGs) are large complex carbohydrate molecules that play a crucial role in various physiological and pathological processes (Gandhi & Mancera, 2008). They interact with a wide range of proteins, including those involved in inflammation and immune responses (Taylor & Gallo, 2006). The field of glycosaminoglycan biology provides new insights into the initiation and modulation of inflammation, offering potential therapeutic approaches to human diseases (Taylor & Gallo, 2006).

In the context of glycoimmunology, mammalian and pathogen-derived glycans displayed on glycoproteins and other scaffolds are recognized by specific glycan-binding proteins (GBPs), leading to pro- and anti-inflammatory cellular responses (Bochner & Zimmermann, 2015). These interactions between glycans and GBPs are relevant to various aspects of immune responses, including hypersensitivity, neoplasms, and infectious diseases (Bochner & Zimmermann, 2015). Glycosaminoglycans, with their diverse structures, can act as targets for bacterial, viral, and parasitic virulence factors, contributing to attachment, invasion, and immune evasion (Schaefer et al., 2005).

Furthermore, glycosaminoglycans have been implicated in innate immune responses. For example, the accumulation of glycosaminoglycans, particularly heparan sulfate, can induce Toll-like receptor 4 (TLR4)-mediated innate immune responses (Parker & Bigger, 2018). This activation of the innate immune system is observed in mucopolysaccharide diseases, where the storage of undegraded substrates triggers aberrant innate immune responses, oxidative stress, and impaired autophagy (Fatoba et al., 2021).

The interactions between proteins and glycosaminoglycans are complex and can have diverse effects. For instance, glycosaminoglycans can modulate the binding of chemokines to their receptors, thereby influencing cellular responses (Kuschert et al., 1999). Additionally, glycosaminoglycans can interact with arterial wall glycosaminoglycans, affecting lipoprotein interactions and potentially contributing to atherosclerosis (Cardin & Weintraub, 1989).

Overall, the study of glycosaminoglycans and glycoimmunology provides valuable insights into the intricate interactions between carbohydrates and proteins in various physiological and pathological processes. Understanding these interactions can lead to the development of novel therapeutic strategies for inflammation, immune-related diseases, and other conditions (Taylor & Gallo, 2006; Bochner & Zimmermann, 2015; Schaefer et al., 2005; Fatoba et al., 2021; Cardin & Weintraub, 1989; Kuschert et al., 1999).

The Role of Glycosaminoglycans and Autism

The role of Glycosaminoglycans (GAGs) in autism spectrum disorder (ASD) has been a topic of interest in recent research. GAGs are a type of carbohydrate molecule that are involved in various biological processes, including cell signaling, tissue development, and immune response (David et al., 2016). Several studies have suggested a potential link between GAGs and ASD.

One study found that aberrant extracellular matrix GAG function localized to the subventricular zone of the lateral ventricles may be a biomarker for autism and potentially involved in the etiology of the disorder (Pearson et al., 2013). Another study reported increased excretion of GAGs, including Heparan Sulfate (HS), in the urine of patients with ASD, suggesting a possible connection between autism and HS (Pagan et al., 2021). Additionally, a meta-analysis of neuropsychological measures in children with high-functioning ASD found that executive dysfunctions, which are believed to contribute to the behavioral characteristics of autism, may interact with other cognitive dysfunctions to account for the core symptoms of autism (Lai et al., 2016).

Furthermore, there is evidence to suggest that GAGs play a role in immune modulation, which may be relevant to autism. Immunotherapeutic approaches targeting inflammation and the immune system, based on GAGs and vitamin D3, have shown positive outcomes in both cancer and autism (Ruggiero & Pacini, 2018). Additionally, GAGs have been identified as immune modulators that could be exploited in conditions such as autism (Peter & Ruggiero, 2017).

It is worth noting that GAGs are involved in various biological processes, and their dysregulation may contribute to the pathogenesis of multiple disorders, including autism. For example, lysosomal storage disorders characterized by impaired metabolism of GAGs have been associated with severe neurocognitive impairments (Potter et al., 2013). This suggests that GAGs may have a broader role in neurodevelopmental disorders beyond autism.

In conclusion, the role of GAGs in autism is an area of ongoing research. Evidence suggests that aberrant GAG function may be involved in the etiology of autism and that GAGs may play a role in immune modulation. Further research is needed to fully understand the mechanisms underlying the relationship between GAGs and autism and to explore potential therapeutic interventions targeting GAG pathways.

Glycoimmunology and the Gut-Brain Axis

The gut-brain axis refers to the bidirectional communication between the gut and the brain, which involves the gut microbiota, the enteric nervous system, and the central nervous system (Wang & Wang, 2016). Emerging evidence suggests that there is a close relationship between glycoimmunology and the gut-brain axis.

The gut microbiota, which is composed of trillions of microorganisms, plays a crucial role in the bidirectional communication of the gut-brain axis (Bravo et al., 2011). Studies have shown that ingestion of certain strains of Lactobacillus can regulate emotional behavior and central GABA receptor expression in mice via the vagus nerve (Bravo et al., 2011). This highlights the important role of bacteria in the gut-brain axis and suggests that certain organisms may have therapeutic potential in stress-related disorders such as anxiety and depression.

Extracellular vesicles (EVs) derived from the gut microbiota have also been implicated in the communication within the gut-brain-microbiota axis (Zhao et al., 2021). These EVs contain microRNAs that can regulate gene expression in recipient cells, including those in the gut and the brain. This provides a novel regulatory system for the bidirectional communication between the gut and the brain.

The gut microbiota affects the brain's physiological, behavioral, and cognitive functions, although the precise mechanisms are not yet fully understood (Strandwitz, 2018). It is well-recognized that the gut microbiota-brain axis plays a role in various aspects of brain function, including neurodevelopment, neurogenesis, and neurotransmitter modulation (Strandwitz, 2018). The gut microbiota forms a complex network with the enteric nervous system, the autonomic nervous system, and the neuroendocrine and neuroimmunity of the central nervous system, which is called the microbiota-gut-brain axis (Ding et al., 2020).

The gut-brain axis has also been implicated in various diseases, including irritable bowel syndrome (IBS) and gastrointestinal cancer (Sun et al., 2023; Di et al., 2019). Abnormal regulation of the nervous system, endocrine system, and immune system, as well as alterations in the gut microbiota, have been associated with the incidence of IBS (Sun et al., 2023).

In conclusion, glycoimmunology and the gut-brain axis are closely interconnected. The gut microbiota, through its interactions with the gut and the brain, plays a crucial role in the bidirectional communication of the gut-brain axis. Understanding the mechanisms underlying this communication is essential for developing therapeutic strategies for various diseases.

Mannose and the Gut-Brain Axis in Autism

Recent research has highlighted the role of the gut-brain axis in the pathophysiology of ASD. The gut-brain axis refers to the bidirectional communication between the gut microbiome and the central nervous system, involving neural, endocrine, and immune pathways (Lindefeldt et al., 2019). Dysbiosis, or disturbances in the gut microbiome, has been linked to neurological disorders, including autism, anxiety, and depression (Taniya et al., 2022).

Role of the Gut Microbiome in Autism

Several studies have investigated the role of the gut microbiome in autism. Dysregulation of the gut-brain axis has been implicated in the pathophysiology of neurological disorders, including autism (Kanhere et al., 2021). The gut microbiome plays a crucial role in regulating immune function, neurotransmitter production, and the metabolism of dietary components (Taniya et al., 2022). Alterations in the gut microbiome composition and diversity have been observed in individuals with autism (Taniya et al., 2022). These dysbiotic changes may contribute to the development and progression of ASD symptoms.

Mannose and the Gut-Brain Axis

Mannose, a monosaccharide, has gained attention for its potential role in modulating the gut-brain axis in autism. Mannose has been shown to have immunomodulatory effects and can influence the composition and function of the gut microbiome (Taniya et al., 2022). The gut microbiome produces various metabolites, including short-chain fatty acids (SCFAs), which have been implicated in neurodevelopment and behavior (Cryan et al., 2019). Mannose supplementation may promote the growth of beneficial bacteria in the gut, leading to the production of SCFAs that can positively influence brain function and behavior.

Therapeutic Potential of Mannose in Autism

Emerging evidence suggests that targeting the gut-brain axis through interventions such as mannose supplementation may have therapeutic potential in autism. Studies have shown that establishing a healthy gut ecosystem with probiotics and polyphenol-like compounds, including mannose, can positively impact gut-brain axis functionality and ameliorate autism symptoms (Sunand et al., 2021). Additionally, modulation of the gut microbiome using mannose or other interventions may help restore gut barrier integrity, reduce inflammation, and improve neurotransmitter balance, thereby alleviating ASD symptoms (Dera et al., 2021).

In conclusion, the gut-brain axis has emerged as a promising avenue for understanding the pathophysiology of autism spectrum disorder. Dysbiosis in the gut microbiome has been implicated in the development and progression of ASD symptoms. Mannose, a monosaccharide, has shown potential in modulating the gut-brain axis and improving autism symptoms. Further research is needed to elucidate the specific mechanisms by which mannose influences the gut microbiome and its impact on neurodevelopment and behavior in individuals with autism. Understanding the role of mannose in the gut-brain axis may pave the way for novel therapeutic interventions for autism spectrum disorder.

Glycoimmunology and Short-Chain Fatty Acids

SCFAs (short-chain fatty acids) have been extensively studied in the field of glycoimmunology. These metabolites are produced by gut microbiota through the fermentation of dietary fiber and have been found to play a crucial role in modulating immune responses and maintaining immune cell homeostasis (Schlatterer et al., 2021; Smith et al., 2013; Ratajczak et al., 2019; Gill et al., 2018; Kim, 2021; Corrêa-Oliveira et al., 2016). SCFAs interact with immune cells through receptor-dependent and receptor-independent mechanisms, influencing various aspects of the immune response (Schlatterer et al., 2021). One of the key receptors involved in SCFA signaling is GPR43 (also known as FFAR2), which is expressed on innate immune cells and mediates the resolution of inflammatory responses (Smith et al., 2013; Maslowski et al., 2009). SCFAs have been shown to regulate colonic Treg cell homeostasis through GPR43 signaling (Smith et al., 2013). Additionally, SCFAs affect intestinal immune cells and regulate immune responses through protein-inflammatory complexes (Li et al., 2021).

The immunomodulatory potential of SCFAs extends beyond the gut. SCFAs have been found to influence gut-brain communication, affecting neural functions such as sleep, appetite control, and circadian rhythm (Silva et al., 2020). Moreover, SCFAs have been investigated as potential therapeutic agents for gastrointestinal and inflammatory disorders (Gill et al., 2018).

The impact of SCFAs on immune cell function is well-established, although there are still some controversies in the literature (Corrêa-Oliveira et al., 2016). SCFAs act on various cell types to regulate important biological processes, including host metabolism, intestinal functions, and the immune system (Kim, 2021). They have been shown to stimulate the secretion of glucagon-like peptide-1 (GLP-1) through the GPR43 receptor, which has implications for glucose homeostasis and diabetes (Tolhurst et al., 2012).

In conclusion, SCFAs have emerged as key players in glycoimmunology, with their ability to modulate immune responses and maintain immune cell homeostasis. Through their interactions with receptors such as GPR43, SCFAs influence inflammatory responses, Treg cell homeostasis, and other immune cell functions. Further research is needed to fully understand the mechanisms underlying SCFA-mediated immunomodulation and to explore their therapeutic potential in various immune-related disorders.

The Role of Mannanoligosaccharides (MOS) in Autism

Recent research has suggested a potential link between the gut microbiome and ASD, highlighting the importance of investigating interventions that target the gut microbiota. One such intervention is the use of mannooligosaccharides (MOS), which have been shown to modulate the gut microbiota and improve gastrointestinal (GI) symptoms in children with ASD (Patusco & Ziegler, 2018).

Gut Microbiome and ASD

Several studies have reported alterations in the gut microbiota of individuals with ASD compared to neurotypical individuals (Vuong & Hsiao, 2017; Altimiras et al., 2021; Cao et al., 2021). These alterations include changes in microbial diversity, abundance of specific bacterial taxa, and metabolic pathways (Vuong & Hsiao, 2017; Altimiras et al., 2021; Cao et al., 2021). Dysbiosis of the gut microbiota has been associated with GI symptoms commonly observed in individuals with ASD, such as constipation, diarrhea, and abdominal pain (Patusco & Ziegler, 2018; Cao et al., 2021). Furthermore, emerging evidence suggests that the gut microbiota may influence brain development and behavior through the gut-brain axis (Vuong & Hsiao, 2017; Yarandi et al., 2016).

MOS and Gut Microbiome

MOS are prebiotic compounds that selectively stimulate the growth and activity of beneficial bacteria in the gut (Patusco & Ziegler, 2018). They are resistant to digestion in the upper gastrointestinal tract and reach the colon intact, where they serve as a substrate for the growth of beneficial bacteria (Patusco & Ziegler, 2018). Studies have shown that MOS supplementation can increase the abundance of beneficial bacteria, such as Bifidobacterium and Lactobacillus, while reducing the abundance of potentially harmful bacteria (Patusco & Ziegler, 2018). This modulation of the gut microbiota by MOS has been associated with improvements in GI symptoms and overall behavior in children with ASD (Patusco & Ziegler, 2018).

Clinical Evidence

A study by reported improvements in children with ASD who were given MOS supplementation (Kern et al., 2013). The authors observed a reduction in GI symptoms and improvements in behavior, suggesting a potential therapeutic role for MOS in ASD (Kern et al., 2013). Similarly, reviewed the use of probiotics, including MOS, in managing GI dysfunction in children with ASD and found that probiotic supplementation was associated with improvements in GI symptoms and overall quality of life (Patusco & Ziegler, 2018).

In conclusion, the gut microbiome has emerged as a potential target for interventions in ASD, and MOS supplementation has shown promise in modulating the gut microbiota and improving GI symptoms in children with ASD. However, further research is needed to elucidate the mechanisms underlying the effects of MOS on the gut microbiome and to determine the optimal dosage and duration of supplementation. Nonetheless, MOS represents a promising avenue for future research and may have the potential to improve the overall well-being of individuals with ASD.

The Role of Isomaltooligosaccharides (IMO) in Autism

IMO, a type of prebiotic, has gained attention for its potential role in modulating gut microbiota and improving gastrointestinal health. reported abnormal gut microbiota in individuals with ASDs and suggested a link between gut microbiome dysbiosis and ASD-like behaviors (Kang et al., 2019). They found that IMO supplementation led to long-term benefits in ASD symptoms and gut microbiota composition (Kang et al., 2019). Furthermore, IMO has been shown to promote the growth of beneficial bacteria such as Bifidobacterium and Prevotella (Kang et al., 2019).

Potential Therapeutic Benefits of IMO in ASDs

The gut-brain axis, which involves bidirectional communication between the gut microbiota and the central nervous system, has been implicated in the pathogenesis of ASDs (Hsiao et al., 2013). demonstrated that modulation of the gut microbiota through probiotic therapy improved gastrointestinal and behavioral symptoms of autism in a mouse model (Hsiao et al., 2013). Similarly, found that the gut microbiota regulates autism-like behavior by mediating vitamin B6 homeostasis (Liu et al., 2020). These studies suggest that targeting the gut microbiota, potentially through the use of prebiotics like IMO, may have therapeutic benefits in alleviating ASD symptoms.

In conclusion, the existing literature supports the association between gut microbiota dysbiosis and ASDs. IMO, as a prebiotic, shows promise in modulating gut microbiota composition and improving ASD symptoms. However, further research is needed to elucidate the underlying mechanisms and optimize the use of IMO in ASD management. Understanding the role of IMO in the gut-brain axis may provide new insights into the pathogenesis of ASDs and open avenues for novel therapeutic interventions.

The Role of Galactooligosaccharides (GOS) in Autism

Galactooligosaccharides (GOS) have been studied in relation to autism spectrum disorders (ASDs) and their potential impact on gut microbiota. One study conducted by (Grimaldi et al., 2018). investigated the effects of a Galactooligosaccharide prebiotic intervention in autistic children. The results showed that children on exclusion diets reported significantly lower scores of abdominal pain and bowel movement, as well as a lower abundance of Bifidobacterium spp (Grimaldi et al., 2018).

Another study by (Grimaldi et al., 2016). examined the influence of GOS on gut microbial ecology and metabolic function using fecal samples from autistic and non-autistic children in an in vitro gut model system. The study found that GOS had an impact on the composition and metabolic activity of gut bacteria in both autistic and non-autistic children (Grimaldi et al., 2016).

In addition, (Walton et al., 2019). conducted a study using an in vitro fermentation model of the equine large intestine to assess the effects of GOS on the microbial community. The study found that GOS had similar effects on the microbial community in vitro as observed in human studies (Walton et al., 2019).

Furthermore, Nicolucci & Reimer (2016) discussed the use of prebiotics, including GOS, in modulating the gut microbiota for host health benefits. They highlighted the ability of prebiotics to alter the gut microbiota in a way that confers benefits for host health (Nicolucci & Reimer, 2016).

Overall, the studies suggest that GOS may have beneficial effects on gastrointestinal symptoms and gut microbiota composition in autistic individuals. Further research is needed to fully understand the mechanisms underlying these effects and to determine the optimal dosage and duration of GOS supplementation in the context of autism.

The Role of Inulin Fructooligosaccharides (FOS) in Autism

Inulin fructooligosaccharides (FOS) have been the subject of research in various fields, including microbiology, nutrition, and aquaculture. Several studies have investigated the utilization and fermentation of FOS and inulin by different microorganisms. Rossi et al. (2005) conducted a comparative study on the fermentation of FOS and inulin by Bifidobacteria. They found that 55 strains of Bifidobacterium were able to utilize FOS and inulin, indicating their potential as prebiotics.

The effects of inulin and FOS supplementation on the viability, storage stability, and gastrointestinal tolerance of Lactiplantibacillus plantarum were investigated by (Parhi et al., 2021). They observed that the supplementation of inulin and FOS improved the viability and storage stability of Lactiplantibacillus plantarum in different sugar systems. This suggests that inulin and FOS can enhance the survival and functionality of probiotic bacteria.

Inulin-type fructans, including FOS and inulin, are natural components found in various fruits and vegetables (Bajic et al., 2023). These fructans have been shown to exert bifidogenic effects on the gut microbiota, promoting the growth of beneficial Bifidobacterium species (Bajic et al., 2023). This indicates that FOS and inulin can modulate the composition of the gut microbiota, which may have implications for conditions such as autism.

The prebiotic effects of FOS and inulin have been extensively studied. Roberfroid et al. (2010) reviewed the metabolic and health benefits of prebiotics and highlighted the potential of FOS and inulin in improving gastrointestinal health, immune function, and metabolic disorders. These findings suggest that FOS and inulin may have therapeutic potential in conditions such as autism, which are associated with gut dysbiosis and immune dysfunction.

In aquaculture, the effects of inulin and FOS on growth performance, body composition, and intestinal microbiota have been investigated in rainbow trout (Ortiz et al., 2012). The study found that inulin and FOS supplementation improved the growth performance and altered the intestinal microbiota of rainbow trout. This suggests that FOS and inulin can modulate the gut microbiota and improve the health of aquatic organisms.

In conclusion, research on inulin fructooligosaccharides (FOS) has demonstrated their potential as prebiotics that can modulate the gut microbiota and improve health outcomes. Studies have shown that FOS and inulin can be utilized and fermented by various microorganisms, including Bifidobacteria. Additionally, supplementation with FOS and inulin has been found to enhance the viability and storage stability of probiotic bacteria. These prebiotics have also been shown to exert bifidogenic effects on the gut microbiota and have potential metabolic and health benefits. Furthermore, in aquaculture, FOS and inulin supplementation has been found to improve growth performance and alter the intestinal microbiota of rainbow trout. Overall, these findings suggest that FOS and inulin may have therapeutic potential in conditions such as autism, which are associated with gut dysbiosis and immune dysfunction.

The Role of Xylooligosaccharides (XOS) in Autism

Xylooligosaccharides (XOS) are a type of oligosaccharide that have gained attention for their potential health benefits, including their role in improving gut microbiota composition and function (Pham et al., 2021). The gut microbiota has been implicated in various neurodevelopmental disorders, including autism spectrum disorder (ASD) (Pham et al., 2021). Research has shown that XOS can modulate the gut microbiota, leading to beneficial changes in microbial composition and activity (Pham et al., 2021). This suggests that XOS may have potential implications for neurodevelopmental disorders such as autism.

Xylooligosaccharides (XOS) have the potential to modulate the gut microbiota, which has been implicated in neurodevelopmental disorders such as autism Further research is needed to fully understand the mechanisms underlying the relationship between XOS and autism, as well as the role of sex chromosomes, epigenetics, and oxidative stress in the development of the disorder.

N-Linked Glycosylation

N-linked glycosylation is a crucial post-translational modification that plays a significant role in various biological processes. It involves the attachment of complex sugar molecules to proteins, which can affect protein folding, stability, trafficking, and function (Cantagrel et al., 2010). Disruption of N-linked glycosylation has been implicated in several disorders, including autism.

Autism is a neurodevelopmental disorder characterized by impaired social interaction, communication difficulties, and restricted and repetitive patterns of behavior. While the exact causes of autism are still not fully understood, there is growing evidence suggesting a link between N-linked glycosylation and the manifestation of behavioral symptoms in neurological disorders, including autism (Pradeep et al., 2023).

One study found that defects associated with the loss of N-linked glycosylation in Campylobacter jejuni, a bacterium commonly associated with gastrointestinal infections, resulted in the loss of glycoproteins and affected protein longevity (Oppy et al., 2019). This suggests that N-linked glycosylation is essential for protein stability and function.

Furthermore, mitochondrial dysfunction has been implicated as a potential trigger for autism. Mitochondria are responsible for energy production in cells, and disruptions in mitochondrial function can lead to oxidative stress and the production of reactive oxygen species (ROS). These mitochondrial mishaps, including oxidative stress and ROS production, have been linked to autism (Vellingiri et al., 2021). Interestingly, N-linked glycosylation has been shown to be involved in regulating mitochondrial function and maintaining mitochondrial homeostasis (Vellingiri et al., 2021). Therefore, it is possible that disruptions in N-linked glycosylation could contribute to mitochondrial dysfunction and subsequently contribute to the development of autism.

In addition to its role in protein stability and mitochondrial function, N-linked glycosylation has also been implicated in immune system regulation. The glycosylation of viral glycoproteins, such as the hemagglutinin glycoproteins of influenza viruses, can affect the immune response to viral infections (Wanzeck et al., 2011). Dysregulation of the immune system has been observed in individuals with autism, suggesting a potential link between immune dysfunction and the development of autism. Therefore, it is plausible that disruptions in N-linked glycosylation could contribute to immune dysregulation and the manifestation of autistic symptoms.

In conclusion, N-linked glycosylation is a critical post-translational modification that plays a role in protein stability, mitochondrial function, and immune system regulation. Disruptions in N-linked glycosylation have been implicated in various disorders, including autism. Further research is needed to fully understand the specific mechanisms by which N-linked glycosylation may contribute to the development of autism and to explore potential therapeutic interventions targeting this pathway.

O-Linked Glycosylation

Recent research has suggested a potential link between O-linked glycosylation and the development of ASD. O-linked glycosylation is a post-translational modification that involves the addition of sugar molecules to proteins.

Role of O-Linked Glycosylation in Autism

Several studies have highlighted the involvement of O-linked glycosylation in the pathophysiology of autism. Liu et al. (2022) found altered expression of glycan patterns and glycan-related genes in the medial prefrontal cortex of a rat model of autism. This study suggests that aberrant glycosylation may serve as potential biomarkers for autism diagnosis. Additionally, Dwyer (2016) discusses how insights into glycan susceptibility factors, obtained from studies on normal brain function and congenital disorders of glycosylation, can provide valuable information about the underlying mechanisms of autism.

Genetic Factors

Genetic studies have identified specific genes involved in O-linked glycosylation that are associated with autism. Pradeep et al. (2023) review the role of glycosylation in neurological disorders and highlight the importance of O-glycosylation in the manifestation of behavioral and neurological symptoms. They discuss how dysregulation of O-glycosylation can contribute to the development of neurodevelopmental disorders, including autism. Gao & Penzes (2015) suggest that common pathway perturbations in O-linked glycosylation may underlie the overlapping behavioral phenotypes observed in autism spectrum disorders and schizophrenia.

Congenital Disorders of Glycosylation

Congenital disorders of glycosylation (CDG) are a group of genetic disorders characterized by impaired glycosylation. Ravell et al. (2020) describe XMEN disease, a CDG that manifests as a combined immune deficiency. They highlight the role of MAGT1, a non-catalytic subunit of the oligosaccharyltransferase complex, in facilitating N-linked glycosylation. This suggests that disruptions in glycosylation processes can lead to immune dysfunction and potentially contribute to the development of autism.

Synaptic Abnormalities

Kelleher & Bear (2008) propose that synaptic abnormalities play a central role in autism. They discuss the identification of ASD-linked mutations in synaptic adhesion molecules and suggest that these mutations may disrupt normal synaptic function. While this study does not directly focus on O-linked glycosylation, it provides important insights into the broader mechanisms underlying autism.

In conclusion, the current literature suggests a potential role for O-linked glycosylation in the development of autism. Dysregulation of O-glycosylation processes may contribute to the manifestation of behavioral and neurological symptoms observed in individuals with autism. Further research is needed to elucidate the specific mechanisms by which O-linked glycosylation influences autism pathogenesis. Understanding these mechanisms may lead to the development of novel diagnostic tools and therapeutic interventions for individuals with autism.

Glycans as Master Regulators

Glycans, complex sugar molecules, play a crucial role in the regulation of the brain in autism. Glycans are involved in various biological processes, including cell adhesion, molecular trafficking, receptor activation, signal transduction, and endocytosis (Ohtsubo & Marth, 2006). In the brain, glycans have been found to exhibit diminished complexity compared to other tissues, suggesting tight regulation (Williams et al., 2022). The presence of specific glycans, such as the HNK-1 glycan on the core M2 of phosphacan/RPTPβ, has been identified as an important regulator of re-myelination in the brain (Endo, 2019).

Glycans also contribute to the proper development, maintenance, and health of the nervous system. Sialic acids, a type of glycan, are key regulatory components in the vertebrate brain. Gangliosides and polysialic acid, which contain sialic acids, are involved in nervous system development, stability, disease, and regeneration (Schnaar et al., 2014). Polysialic acid (PSA/polySia) and the synthesizing enzyme ST8SIA2 are particularly relevant in understanding mental disorders, as impairment of the fine-tuned glycan system affects molecules deeply involved in normal brain function (Sato & Hane, 2018).

In the context of autism, glycans have been implicated in the pathophysiology of the disorder. Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by impairments in communication, social interaction, and restricted interests and behaviors (Masi et al., 2017). Dysregulation of glycans has been associated with neurological diseases and disorders, including autism (Shajahan et al., 2017). Furthermore, neuroinflammation, which is observed in ASD, has been linked to glycan-related pathways (Kuo & Liu, 2018).

Overall, glycans serve as master regulators of the brain in autism, influencing various biological processes and contributing to the development and maintenance of the nervous system. Dysregulation of glycans has been implicated in the pathophysiology of autism, highlighting their importance in understanding and potentially targeting the disorder.

The Involvement of Glycans and Cortactin in Autism Spectrum Disorders

Recent research has suggested that glycans and the protein cortactin may play a role in the pathogenesis of ASD. Glycans are sugar molecules that are involved in various cellular processes, including cell signaling and adhesion. Cortactin is a cytoskeletal protein that regulates actin dynamics and is important for synaptic function.

Glycans and ASD

The glycosaminoglycan pathway has been proposed as a potential biomarker for ASD (David et al., 2016). Aberrant extracellular matrix glycosaminoglycan function localized to the subventricular zone of the lateral ventricle has been observed in individuals with ASD (David et al., 2016). Additionally, altered expression of glycan patterns and glycan-related genes has been found in the medial prefrontal cortex of a rat model of ASD (Liu et al., 2022). These findings suggest that dysregulation of glycans may contribute to the pathogenesis of ASD.

Cortactin and ASD

Cortactin has been implicated in the development and function of dendritic spines, which are specialized structures on neurons that play a crucial role in synaptic transmission (Szabo et al., 2021). Loss of the Shank3 protein, which is associated with ASD, leads to changes in forebrain spines and synapses (Szabo et al., 2021). Furthermore, the autism candidate gene DIP2A has been found to regulate spine morphogenesis via acetylation of cortactin (Ma et al., 2019). These findings suggest that cortactin may be involved in the synaptic dysfunction observed in ASD.

Potential Mechanisms

The exact mechanisms by which glycans and cortactin contribute to ASD are not fully understood. However, it has been suggested that dysregulation of glycans may disrupt cell signaling pathways involved in brain development and function (Schnaar et al., 2014). Additionally, alterations in cortactin-mediated actin dynamics may affect synaptic plasticity and impair the formation and maintenance of synapses (Szabo et al., 2021). Further research is needed to elucidate the specific roles of glycans and cortactin in ASD.

In conclusion, emerging evidence suggests that glycans and cortactin may be involved in the pathogenesis of ASD. Dysregulation of glycans and alterations in cortactin-mediated synaptic function may contribute to the synaptic dysfunction observed in individuals with ASD. Further research is needed to fully understand the mechanisms underlying the involvement of glycans and cortactin in ASD. Understanding these mechanisms may lead to the development of novel therapeutic strategies for individuals with ASD.

The Involvement of Cortactin and Shank Genes with Alterations of Glycans in Autism

Recent research has suggested that alterations in glycans, specifically proteoglycans (PGs), may play a role in the pathogenesis of ASD (Schwartz & Domowicz, 2018). Additionally, genetic studies have identified mutations in the Shank genes (SHANK1, SHANK2, and SHANK3) as significant contributors to ASD (Leblond et al., 2014; Ey et al., 2018; Han et al., 2013; Harris et al., 2016; Eltokhi et al., 2018). This paper aims to explore the involvement of Cortactin and Shank genes with alterations of glycans in autism.

Shank Genes and Autism

The Shank genes encode for postsynaptic scaffolding proteins that play a crucial role in synapse formation and function (Harris et al., 2016). Mutations in the Shank genes have been identified in patients with ASD, with a gradient of severity (Leblond et al., 2014; Ey et al., 2018). For instance, mutations in SHANK1 are rare and present in males with normal IQ and autism (Leblond et al., 2014). Mutations in SHANK2 are associated with mild intellectual disability (Leblond et al., 2014). Mutations in SHANK3 are more prevalent and are associated with moderate to profound intellectual disability (Leblond et al., 2014). These findings suggest that alterations in the Shank genes may contribute to the cognitive impairments observed in individuals with ASD.

Cortactin and Dendritic Spine Morphogenesis

Cortactin is a protein that interacts with Shank proteins and is involved in dendritic spine morphogenesis (Hering & Sheng, 2003; Chen & Hsueh, 2012). Dendritic spines are small protrusions on the dendrites of neurons that play a crucial role in synaptic transmission and plasticity. Research has shown that Cortactin is essential for dendritic spine formation and maintenance (Chen & Hsueh, 2012). The interaction between Cortactin and Shank proteins is thought to modulate the mobility of Cortactin and regulate dendritic spine development (Chen & Hsueh, 2012). Therefore, alterations in Cortactin function may contribute to the synaptic abnormalities observed in individuals with ASD.

Glycan Alterations in Autism

Abnormal glycan variants, including PGs, have been linked to ASD (Schwartz & Domowicz, 2018). PGs are a type of proteoglycan that are involved in various processes in the central nervous system, including cell plasticity, cell movement, and synaptogenesis (Schwartz & Domowicz, 2018). Dysregulation of PGs may disrupt synaptic connectivity and contribute to the pathogenesis of ASD. Although the specific mechanisms underlying the association between glycan alterations and ASD are not fully understood, it is hypothesized that abnormal glycan structures may affect neuronal signaling and synaptic function.

In conclusion, the involvement of Cortactin and Shank genes with alterations of glycans in autism suggests a complex interplay between genetic and molecular factors in the pathogenesis of ASD. Mutations in the Shank genes can lead to cognitive impairments observed in individuals with ASD, while Cortactin plays a role in dendritic spine morphogenesis and synaptic development. Abnormal glycan variants, including PGs, may further contribute to the synaptic abnormalities observed in ASD. Further research is needed to elucidate the precise mechanisms underlying these interactions and their implications for the development and treatment of ASD.

The Involvement of Glycans and SRC Kinase in Autism Spectrum Disorders

Recent research has highlighted the involvement of glycans and SRC kinase in the pathogenesis of ASDs. Glycans are complex sugar molecules that play crucial roles in cellular processes, including cell adhesion, signaling, and protein folding. SRC kinase is a non-receptor tyrosine kinase that regulates multiple signaling pathways involved in neuronal development and synaptic plasticity.

Glycans and ASDs

Several studies have implicated glycans in the pathogenesis of ASDs. Aberrant glycosylation patterns have been observed in the plasma and brain tissues of individuals with ASDs (Pivac et al., 2011; Dwyer, 2016; Liu et al., 2022). These alterations in glycan structures and composition may disrupt cellular processes critical for neurodevelopment and synaptic function. For example, the loss of UBE3A, an E3 ubiquitin ligase involved in protein degradation, has been linked to altered synaptic structure and ASDs (Gao & Penzes, 2015). Additionally, glycan-related genes have been found to be dysregulated in the medial prefrontal cortex of a rat model of autism (Liu et al., 2022). These findings suggest that aberrant glycosylation may contribute to the pathophysiology of ASDs.

SRC Kinase and ASDs

SRC kinase is a key regulator of neuronal development and synaptic plasticity. It is involved in multiple signaling pathways, including those mediated by N-methyl-D-aspartate (NMDA) receptors and postsynaptic density protein 95 (PSD-95) (Kelleher & Bear, 2008; Vistrup-Parry et al., 2020). Dysregulation of these pathways has been implicated in ASDs. Studies have shown that altered expression and phosphorylation of PSD-95, a scaffold protein critical for synaptic function, may disrupt synaptic protein synthesis and contribute to the pathogenesis of ASDs (Kelleher & Bear, 2008; Vistrup-Parry et al., 2020). Furthermore, the involvement of SRC kinase in the regulation of excitatory and inhibitory balance in the brain has been linked to both schizophrenia and ASDs (Gao & Penzes, 2015). These findings suggest that dysregulation of SRC kinase signaling pathways may contribute to the synaptic and neuronal abnormalities observed in ASDs.

In conclusion, the involvement of glycans and SRC kinase in the pathogenesis of ASDs highlights the complex molecular mechanisms underlying these neurodevelopmental disorders. Aberrant glycosylation patterns and dysregulation of SRC kinase signaling pathways may disrupt synaptic function, neuronal development, and cellular processes critical for neurodevelopment. Further research is needed to elucidate the specific molecular mechanisms by which glycans and SRC kinase contribute to ASDs. Understanding these mechanisms may provide insights into potential therapeutic targets for the treatment of ASDs.

The Relationship between SRC Kinase and Glycoimmunology in Autism

Recent research has focused on understanding the role of SRC kinase and glycoimmunology in the development of ASD. SRC kinase is a protein involved in cell signaling pathways, while glycoimmunology refers to the study of the interactions between the immune system and glycan structures.

SRC Kinase and Autism

SRC kinase is a member of the Src family of non-receptor tyrosine kinases and plays a crucial role in neuronal development and synaptic plasticity (Coley & Gao, 2018). Several studies have implicated SRC kinase in the pathogenesis of autism. For example, Reelin, a protein involved in neuronal migration and synaptic plasticity, has been shown to activate SRC kinase (Russo, 2017). Additionally, the binding of Reelin to its receptors results in the recruitment of SRC family tyrosine kinases (Tseng et al., 2009). These findings suggest that SRC kinase may be involved in the regulation of synaptic function and neuronal connectivity, which are disrupted in individuals with autism.

Glycoimmunology and Autism

Glycoimmunology refers to the study of the interactions between the immune system and glycan structures. Abnormalities in the immune system have been observed in individuals with autism, including altered cytokine levels and immune cell dysregulation (Pantazopoulos & Berretta, 2016). Glycans, which are complex sugar molecules, play a crucial role in immune cell signaling and function. Dysregulation of glycan structures has been implicated in various autoimmune and inflammatory disorders. Recent studies have suggested that abnormalities in glycan structures may contribute to the immune dysregulation observed in individuals with autism (Pantazopoulos & Berretta, 2016).

The Link between SRC Kinase and Glycoimmunology in Autism

Emerging evidence suggests a potential link between SRC kinase and glycoimmunology in the context of autism. SRC kinase has been shown to regulate immune cell function and cytokine production (Jelen et al., 2022). Additionally, glycan structures have been found to modulate SRC kinase activity and downstream signaling pathways (Pantazopoulos & Berretta, 2016). Therefore, it is plausible that dysregulation of SRC kinase and aberrant glycan structures may interact to contribute to the immune dysregulation observed in individuals with autism.

In conclusion, the relationship between SRC kinase and glycoimmunology in autism is an emerging area of research. SRC kinase has been implicated in the pathogenesis of autism, particularly in relation to synaptic function and neuronal connectivity. Abnormalities in glycan structures have also been observed in individuals with autism, suggesting a potential role for glycoimmunology in the etiology of the disorder. Further research is needed to elucidate the precise mechanisms underlying the relationship between SRC kinase and glycoimmunology in autism. Understanding these mechanisms may provide insights into the development of novel therapeutic interventions for individuals with autism.

The Involvement of Mannose Binding Lectin and SRC Kinase with the Immune Response in Autism

Recent research has suggested a potential involvement of the immune system in the pathogenesis of autism (Behairy et al., 2022).

One aspect of the immune response that has been implicated in autism is the lectin pathway, specifically mannose-binding lectin (MBL) (Fujita et al., 2004). MBL is a C-type lectin that plays a crucial role in the first line of host defense (Fujita et al., 2004). It is an important determinant of the innate immune response during an infection (Singh et al., 2008). MBL acts as a pattern recognition molecule, binding to pathogen-associated molecular patterns (PAMPs) on the surface of microorganisms, leading to activation of the lectin pathway of the complement system (Dommett et al., 2006). MBL deficiency has been associated with increased susceptibility to infections and autoimmune diseases (Behairy et al., 2022).

In addition to MBL, the involvement of Src kinase in the immune response in autism has also been suggested (Lowell, 2010). Src kinases are a family of non-receptor tyrosine kinases that play a crucial role in signaling pathways involved in immune cell activation and function (Lowell, 2010). Src kinases, such as Lck and Fyn, are involved in T-cell receptor proximal signaling, influencing T-cell activation, differentiation, and tolerance (Salmond et al., 2009). Src kinases have also been shown to play a pivotal role in the functional activation of macrophages, including the production of inflammatory cytokines/mediators (Byeon et al., 2012).

The interaction between MBL and Src kinase in the context of the immune response in autism is not well understood. However, both MBL and Src kinase are known to modulate immune cell function and contribute to the innate immune response. Further research is needed to elucidate the specific mechanisms by which MBL and Src kinase may be involved in the immune response in autism.

In conclusion, the lectin pathway, specifically MBL, and Src kinase have been implicated in the immune response in autism. MBL plays a crucial role in the innate immune response, acting as a pattern recognition molecule and activating the lectin pathway of the complement system. Src kinases are involved in signaling pathways that regulate immune cell activation and function. Further research is needed to fully understand the role of MBL and Src kinase in the immune response in autism and their potential contribution to the pathogenesis of the disorder.

The Role of Mannose and Neuroinflammation in Autism

Neuroinflammation has been implicated in the pathogenesis of autism spectrum disorders (ASD) (Vargas et al., 2004). Studies have shown evidence of neuroglial activation and neuroinflammation in the brains of individuals with autism (Vargas et al., 2004; Pardo et al., 2005). Neuroinflammation refers to the activation of immune cells in the central nervous system (CNS) and the release of pro-inflammatory molecules (Pardo et al., 2005). This neuroinflammatory response may both contribute to and result from abnormal CNS development and activity in autism (Vargas et al., 2004).

The role of neuroinflammation in autism is complex and not fully understood. It is believed that immune dysregulation and neuroinflammation may disrupt normal brain development and contribute to the behavioral and cognitive symptoms observed in individuals with autism (Pardo et al., 2005). Neuroinflammation in autism is characterized by the activation of glial cells, such as microglia and astrocytes, and the release of pro-inflammatory cytokines and chemokines (Pardo et al., 2005). These inflammatory molecules can affect neuronal function and synaptic connectivity, leading to the cognitive and behavioral impairments seen in autism (Pardo et al., 2005).

There is also evidence to suggest a link between neuroinflammation and immune system dysfunction in autism (Goines & Water, 2010). Autoantibodies targeting brain proteins have been found in both children with autism and their mothers, indicating an immune response against the brain (Goines & Water, 2010). This immune dysregulation may contribute to the neuroinflammatory processes observed in autism (Goines & Water, 2010).

In addition to neuroinflammation, there is growing interest in the role of mannose in autism. Mannose is a sugar molecule that plays a crucial role in glycosylation, a process involved in the modification of proteins and lipids (Shaffer et al., 2020). Glycosylation abnormalities have been reported in individuals with autism, and mannose supplementation has shown promise in improving symptoms in animal models of autism (Shaffer et al., 2020).

Mannose supplementation has been found to improve behavioral abnormalities, reduce neuroinflammation, and restore synaptic function in animal models of autism (Shaffer et al., 2020; Bozkurt et al., 2022). These findings suggest that mannose may have therapeutic potential for the treatment of autism.

In conclusion, neuroinflammation appears to play a significant role in the pathogenesis of autism. The activation of glial cells and the release of pro-inflammatory molecules contribute to abnormal brain development and function in individuals with autism. Mannose supplementation shows promise in ameliorating neuroinflammation and improving symptoms in animal models of autism. Further research is needed to fully understand the mechanisms underlying neuroinflammation in autism and to explore the therapeutic potential of mannose in the treatment of this complex disorder.

Suppressing Proinflammatory Cytokines with Mannose

Cytokines are signaling molecules that play a crucial role in the immune response and inflammation (Zimmer et al., 2003). Mannose, a monosaccharide, has been found to have various effects on cytokine production and immune regulation.

One study found that D-mannose supplementation in mice led to a decrease in the production of proinflammatory cytokines such as RANKL, IL-6, IL-17, and TNF-α in the bone marrow (Liu et al., 2020). This suggests that mannose may have anti-inflammatory effects by suppressing the production of these cytokines.

Another study demonstrated that interleukin-4 (IL-4), a Th2 cytokine, enhances the activity of the macrophage mannose receptor (MMR) (Stein et al., 1992). The MMR is an important phagocytic receptor involved in the binding and ingestion of microorganisms with surface mannose residues. This suggests that IL-4 can enhance the immune response mediated by the MMR.

Furthermore, mannose has been shown to stimulate cytokine expression and activate dendritic cells through a calcium-dependent mannose-receptor binding (Ragupathy et al., 2014). This indicates that mannose can modulate the immune response by promoting cytokine production and activating immune cells.

In addition, mannose has been found to induce the differentiation of regulatory T cells (Tregs) (Zhang et al., 2017). Tregs play a crucial role in immune regulation and suppressing immunopathology. The activation of Tregs by mannose is mediated by the upregulation of integrin αβ and reactive oxygen species generated by increased fatty acid oxidation. This suggests that mannose can promote immune tolerance and suppress excessive immune responses.

Overall, these studies demonstrate that mannose can modulate cytokine production and immune regulation. It has anti-inflammatory effects by suppressing proinflammatory cytokines, enhances the activity of phagocytic receptors, stimulates cytokine expression, activates immune cells, and promotes the differentiation of regulatory T cells. These findings highlight the potential therapeutic applications of mannose in immune-related disorders.

Proinflammatory Cytokines and Glycoimmunology

Proinflammatory cytokines play a crucial role in the immune response and inflammation. They are involved in various physiological and pathological processes, including infection, autoimmune diseases, and cancer. Glycoimmunology, on the other hand, focuses on understanding how immune responses are mediated by glycans and their interaction with glycan-binding proteins called lectins (Colomb et al., 2019). Glycosylation, the process of attaching sugar molecules to proteins and lipids, has been shown to have a significant impact on the function and activity of proinflammatory cytokines (Marth & Grewal, 2008).

Glycosylation of proinflammatory cytokines can affect their stability, secretion, receptor binding, and signaling pathways. For example, glycosylation of interleukin-6 (IL-6) has been shown to modulate its biological activity and receptor binding affinity (Chan et al., 2019). Additionally, glycosylation of tumor necrosis factor-alpha (TNF-α) has been found to influence its stability and bioactivity (McCarthy et al., 2014).

Furthermore, glycosylation can also regulate the interaction between proinflammatory cytokines and their receptors. For instance, glycosylation of the Fc region of immunoglobulin G (IgG) antibodies can modulate their binding to Fc receptors on innate immune effector cells, leading to the induction of proinflammatory responses (Albert et al., 2008). This interaction is particularly relevant in autoimmune diseases, where IgG autoantibodies are responsible for chronic inflammation and tissue destruction (Albert et al., 2008).

In addition to its impact on proinflammatory cytokines, glycosylation has been implicated in the regulation of inflammation itself. Changes in glycosylation patterns have been observed in various inflammatory diseases, including rheumatoid arthritis, lupus erythematosus, and pancreatitis (Gornik & Lauc, 2008). These alterations in glycosylation can affect the function and activity of proteins involved in inflammation, such as acute phase proteins and serum glycoproteins (McCarthy et al., 2014; Gornik & Lauc, 2008).

Moreover, glycosylation has been linked to the aging process and age-related inflammation, known as inflammaging. Changes in glycosylation patterns of immunoglobulin G (IgG) have been identified as biomarkers of biological aging and longevity (Krištić et al., 2013; Dall’Olio et al., 2013). The age-related accumulation of aberrantly glycosylated IgG can contribute to inflammaging by activating the immune system and exacerbating inflammation (Dall’Olio et al., 2013).

Overall, glycosylation plays a critical role in the regulation of proinflammatory cytokines and inflammation. Understanding the glycoimmunology of proinflammatory cytokines can provide insights into the development of therapeutic strategies for inflammatory diseases and immune-related disorders.

The Role Proinflammatory Cytokines and Glycoimmunology in Autism

In recent years, there has been growing interest in the role of proinflammatory cytokines and glycoimmunology in the pathogenesis of ASD.

Proinflammatory Cytokines in Autism

Several studies have reported elevated levels of proinflammatory cytokines in individuals with ASD. Vargas et al. (2004) found that both proinflammatory cytokines (e.g., IL-6) and anti-inflammatory cytokines (e.g., IL-10) were markedly elevated in the autistic cortex. Xu et al. (2015) reported reduced cytotoxic activity and elevated levels of proinflammatory cytokines, such as tumor necrosis factor (TNF-α) and IL-1β, in children with ASD. These findings suggest that dysregulation of the immune system, specifically an imbalance between proinflammatory and anti-inflammatory cytokines, may contribute to the pathogenesis of ASD.

Glycoimmunology and Autism

Glycoimmunology, the study of the interactions between glycans and the immune system, has emerged as a promising field in understanding the pathogenesis of various diseases, including ASD. Wang et al. (2019) demonstrated that proinflammatory cytokines, particularly IL-6 and IL-17a, play a role in the development of ASD induced by maternal immune activation (MIA) in animal models. This suggests that immune dysregulation during pregnancy, leading to increased proinflammatory cytokines, may contribute to the risk of ASD in offspring.

Potential Biomarkers and Therapeutic Targets

The identification of biomarkers for ASD is crucial for early diagnosis and intervention. Croonenberghs et al. (2002) suggested that the hyperproduction of proinflammatory cytokines in ASD may be indicative of an underlying autoimmune disorder or chronic viral infection. Furthermore, Tsilioni et al. (2019) found that the anti-inflammatory cytokine IL-37 is increased in the brains of children with ASD, suggesting its potential as a therapeutic target.

Implications for Future Research

While the role of proinflammatory cytokines and glycoimmunology in ASD is becoming increasingly recognized, there is still much to be explored. Naik et al. (2011) highlighted the need for further research on innate and adaptive immune responses in children with ASD. Dietert & Dietert (2008) emphasized the importance of studying critical windows of immune vulnerability during early development. Patterson (2011) suggested that maternal infection and immune activation may contribute to the neuropathology and behavioral features of ASD in offspring.

In conclusion, the evidence suggests that dysregulation of proinflammatory cytokines and glycoimmunology may play a role in the pathogenesis of ASD. Imbalances between proinflammatory and anti-inflammatory cytokines, as well as immune dysregulation during pregnancy, have been implicated in the development of ASD. Further research is needed to elucidate the underlying mechanisms and potential therapeutic targets in order to improve early diagnosis and intervention for individuals with ASD.

Overall, the evidence suggests that immune system dysfunction and glycan-related abnormalities may contribute to the development of autism.

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