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Abstract
From birth until around age 3, a child's microbiome begins to develop.
Using antibiotics during these formative years can disrupt the development of immune-mediated, metabolic, and neurological diseases (Arrieta et al., 2014).
Antibiotics significantly alter the microbial composition by inhibiting the growth of pathogenic microbes (Ahmed et al., 2013a; Ahmed et al., 2013b; Ahmed et al., 2014).
Early and uncontrolled doses of antibiotics may lead to loss of predominant microbial phyla, loss of diversity, change in metabolic activity, and colonization of pathogens (Bourassa et al., 2016; Chen et al., 2017).
Antibiotic treatment during the 1–2 years of life can crucially impact the maturation of the immune system and have a detrimental effect on typical microbiota establishment with severe long-term consequences, such as inflammation, immune dysregulation, allergies, infections, and GI diseases such as Crohn’s, inflammatory bowel disease (IBD), constipation, and diarrhea (Jernberg et al., 2007; Yang et al., 2009; Ubeda et al., 2010; Ni et al., 2017; Warner, 2018).
Further cohort studies performed using antibiotics during infancy and early childhood showed significant alterations in gut microbiota, which could be directly responsible for turning on or off specific genes.
Early use and overuse of antibiotics lead to microbial dysbiosis and may turn on the autism gene.
This affects the gut-brain axis by causing epigenetic modification, which potentially facilitates the pathogenesis of ASD (Eshraghi et al., 2018).
Conclusions, Current Challenges, and Future Perspectives
Recapitulating all mounting evidence elucidates the association between the gut–brain axis and ASD (Sanders et al., 2013).
Several factors leading to ASD were identified, mainly early colonization on infant health development and the effect of early microbiota dysbiosis in the gestation period, mode of delivery, uncontrolled usage of antibiotics, and stress.
These factors eventually lead to gut microbiome dysbiosis and colonization of pathogenic microbes, which impact the CNS function by the production of neurotoxins. The presence of these pathogenic bacteria, such as Clostridium found in the colon of children, shows the possibility of developing ASD.
Studies also indicated the importance of two SCFA produced from microbial formation of dietary fiber, including butyrate and propionate. Butyrate improves brain function by inhibiting histone deacetylases, whereas propionate impacts brain function, leading to changes in behavior and aggressiveness in ASD patients.
According to many studies on the gut microbiome, MTT can potentially treat autism-like symptoms, including the restoration of healthy gut microbiome composition in the gestation period and early stage of infancy.
Most studies have been conducted in experimental animal models.
Some studies have small sample sizes, especially studies performed using human volunteers. The majority of them lacked randomization or control groups. Significant limitations in these studies eventually reduced the validity of the results. Recently, scientists have carried out several clinical trials to investigate the efficacy of MTT on children who have ASD, and the results obtained were satisfactory, showing remarkable improvement in GI symptoms with minimal adverse effects due to pre-treatment with vancomycin (Kang et al., 2017).
An increasing number of news articles and science media are featuring the successes of microbiome research and its promising therapeutics regime. The general population is excited to learn that the gut microbiome is linked to the progression of various diseases and is also essential for healthy organ development. Based on the forecasted information regarding the success of microbial therapeutics in clinical trials, people are hopeful that this treatment will be a better alternative compared to conventional medicinal practices (Bik, 2016).
In 2019, the Food and Drug Administration (FDA) recognized microbial transplant therapy and labeled it “fast-track” for ASD treatment after observing successful clinical trials using long-term microbial transplant therapy on autistic children (Adams et al., 2019). Further research should be conducted to determine whether findings in animal studies and clinical trials can be successfully implemented with similar efficacy rates in different populations of ASD patients across various geographical locations and exhibit promising results among the patients. Furthermore, more follow-up studies are required with accurate methodologies and optimized dosage of antibiotics and microbial suspensions to increase the efficacy of the treatment to support the validity, reliability, and precision of past research. In addition, genomic analysis of the gut microbiome of the donor and recipient should further define specific strains, better pathways, and regimens to provide optimum supplements and treatment in this particular population (Gondalia et al., 2012; Sanders et al., 2013; Xu, 2015; Li et al., 2019; Nitschke et al., 2020; Yadav and Chauhan, 2021).
There is an increase in demand to find a substitute for microbial transplant therapy and reduce the dependency on the harness beneficial microbiota from a healthy human, which can be achieved by culturing a specific combination of bacteria for transplantation (Adams et al., 2019).
Microbiome research has made much progress in recent years from animal studies to clinical trials, with satisfactory results and better efficacy in MTT treatment. In the next couple of years, FDA-approved pills, probiotics, and metabolites might be commercially available to establish a suitable bacterial composition to treat and regulate ASD.
Our review investigations strongly imply exploring the underlying molecular mechanism of the gut microbiome in the pathogenesis and advancement of ASD and finding promising therapeutic agents/drugs that will deliver new hope for the treatment and management of ASD soon.
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