









































Pa
ge

 
1



Pa
ge

 
24

American Journal of  Medical 
Science and Innovation (AJMSI) 

The Gut-Brain Connection: Investigating the Correlation between Autism Disorder and 
Gut Bacterium

Wafa Manaf1, Nageena Dileep2*, Haifa Manaf3, Nadiya Dileep4, Azhar Liyakath5

Volume 4 Issue 1, Year 2025
ISSN: 2836-8509 (Online)

DOI: https://doi.org/10.54536/ajmsi.v4i1.3818
https://journals.e-palli.com/home/index.php/ajmsi

Article Information ABSTRACT

Received: September 22, 2024
Accepted: October 25, 2024
Published: January 24, 2024

Autism Spectrum Disorder (ASD) is a type of  developmental disability which results in 
social and communication difficulties besides exhibiting stereotyped or repetitive use of  
objects and bodies. ASD is becoming increasingly prevalent as a significant public health 
issue, impacting 1 in 100 children globally and showing an apparent increase in cases inter-
nationally. Up to 80% of  children with ASD experience gastrointestinal (GI) dysfunction, in-
dicating a potential connection between gut microbiota and the development of  ASD. This 
study aims to define the link between gut dysbiosis and ASD and look into the effectiveness 
of  the therapies which use the microbiota, including probiotics, prebiotics, and MTT. A 
literature review was carried out to identify literature published on Scopus, MEDLINE, 
and PubMed that focused on paediatric population, and the types of  interventions included 
dietary changes and FMT. Growing evidence for the changed gut microbiota of  children 
with ASD reveals the higher level of  Clostridium and the lower level of  Bifidobacterium pop-
ulation. Supplements of  other types of  microbes such as probiotics had mixed outcomes in 
impacting ASD behaviours but positively impacted the gastrointestinal manifestations. The 
research identifies changes in the gut bacterial makeup of  children with ASD, showing in-
creased levels of  Clostridium and Sutterella, which play a significant role in gastrointestinal and 
behavioral issues. Therapies aimed at the microbiota, such as probiotics and dietary changes, 
and fecal microbiota transplantation (FMT) demonstrated the ability to enhance symptoms 
associated with GI issues and ASD. 

Keywords
Autism, Gut-Brain Axis, 
Gut Microbiome, Microbiota, 
Neurodevelopment 

1 Ras Al Khaimah Medical and Health Sciences University, United Arab Emirates
2 Mohammed Bin Rashid University of  Medicine and Health Sciences, Dubai, United Arab Emirates
3 Neonatology Department, Travancore Medical College, Kollam, Kerala, India
4 Private Clinic: United Ambulances Services, Abu Dhabi, United Arab Emirates
5 Department of  Pediatrics, GIMS, Greater Noida, Uttar Pradesh, India
* Corresponding author’s e-mail: nadiyadileep2796@gmail.com

INTRODUCTION
Autism Spectrum Disorder (ASD) is recognised as 
a neurodevelopmental disorder, and impairments in 
interaction, social communication, and the occurrence 
of  repetitive behaviors distinguish it (Namocot, 2023). 
Gastrointestinal (GI) issues affect up to 80% of  
children with ASD, suggesting a possible link between 
gut microbiota as well as ASD development (Yu et al., 
2024). ASD affects 1 in 100 children worldwide, and 
its prevalence remains varied across studies and regions 
(Chiarotti & Venerosi, 2020). Symptoms often manifest 
in early childhood but may go undiagnosed until later, 
and this condition ranges from mild to severe, with some 
individuals living independently and others requiring 
lifelong care (Hodges et al., 2020). Conditions such as 
epilepsy, anxiety, and ADHD often occur alongside 
autism spectrum disorder; evidence-based psychosocial 
interventions improve outcomes, but societal support 
is also critical for accessibility and quality of  life (Lai 
et al., 2020). However, (Fattorusso et al., 2019) study 
emphasised that children with ASD display imbalances 
in gut microbiota, which could contribute to both GI and 
behavioral symptoms. 
The gut-brain axis, otherwise referred to as the body’s 
microbiome, was an issue of  significant interest due to its 
potential influence implying the role of  the microbiome 

in ASD. The microbiota comprises trillions of  microbes 
that influence immune response, digestion, and even brain 
function, with modulation through neural, immune, and 
metabolic pathways such as antibodies and metabolites, 
including short-chain fatty acids (Dupont et al., 2020). 
However, (Iglesias-Vázquez et al., 2020) study explained 
that a change in gut microbiota may be linked with the 
emergence and the severity of  ASD symptoms including 
gastrointestinal abnormalities. As a result, it has been 
established that children with ASD have different bacterial 
composition in their gut, reduced bacterial diversity and 
some pathogenic genera according to (Coretti et al., 2018). 
These imbalances could be beneficial in the conditions of  
enclave GI problems and anxiety, irritability, and other 
repetitive behavioral disorders. The treatments that affect 
such microbiota are the use of  probiotics and prebiotics, 
and dietary management as these help to eliminate these 
symptoms (Cunningham et al., 2021). The purpose of  this 
study is to determine a connection between functional 
abnormalities in the gut microbiota and autism signs, as 
well as to review new findings concerning the gut-brain 
axis and neurodevelopmental and behavioral changes 
elicited by an imbalance in the bacterial flora. This work 
aims at assessing new interventions such as probiotics 
and diet modulations in children with ASD believed to 
have an impaired gut brain connection.



Pa
ge

 
25

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 4(1) 24-34, 2025

MATERIALS AND METHODS
Research Strategy 
A systematic approach was chosen to investigate the link 
between gut microbiome health and Autism Spectrum 
Disorders (ASD) in children. An extensive literature 
search was conducted across various databases, including 
Scopus, MEDLINE, and PubMed. Key MeSH terms 
such as “Autism Spectrum Disorder,” “Gut Microbiota,” 
“Pediatric Population”, “Kids OR “kid”, “Child*”, 
“Microbiome Therapy,” “Fecal Microbiota Transplant,” 
and “Neurodevelopment “NOT “adults” were used 
to identify relevant studies. The study combines these 
primary and secondary keywords using Boolean operators 
like AND, OR, and NOT. 

Inclusion and Exclusion Criteria
In inclusion, articles published in the last 10 years were 
prioritised to ensure up-to-date findings. However, this 
study includes papers from the previous two or three 
decades to cover the maximum amount of  research and 
provide broader research on ASD and gut microbiota. 
This study only selected peer-reviewed papers and 
papers published on governmental and federal sites 
to ensure the authenticity of  the research. Inclusion 
criteria also focused on studies with precise data on gut 
microbiome and ASD in pediatric populations (children 
aged 2–18 years). Articles examining interventions such 
as probiotics, dietary changes, or microbiome transplants 
were included, provided a control group and quantified 
both microbial changes and behavioral outcomes in 
children with ASD. Some research models on animal 
studies are also evidenced in this paper. 
Exclusion criteria include omitted studies with 
inconclusive findings, those with no control groups, 
and articles not focused on the gut-brain axis. Those 
studies involving adults or populations with overlapping 
conditions like Down syndrome were excluded. The 
exclusion was justified to maintain focus on children and 
eliminate unrelated co-morbidities. 

Study Selection
The studies were filtered through inclusion and exclusion 
criteria for relevance and quality of  the final research 
papers selected. Only articles published in the last 10 
years were selected to provide a recent understanding of  
the link between the gut and brain in children with ASD. 
Earlier and highly influenced studies were incorporated 
to give background information. Peer-reviewed articles 
and research extracted from secure official government 
sources were used to ensure the authenticity of  the data 
collected. Exclude studies did not include control groups, 
targeted adults only, or reported on related disorders such 
as Down’s syndrome. This may confound results because 
the review aimed to include only pediatric patients and 
the gut-brain axis.

Data Analysis
In this research, data analysis was confined to articles 

published in academic and peer-reviewed journals. 
Specialists in the subject review scholarly reviewed 
articles, thus the efficiency of  the techniques and 
recommendations made. Through such articles, this 
investigation ensures that sorting comprises only the 
most robust studies on the gut microbiome and ASD 
in children. Studies include the findings of  microbial 
alteration, behavioral impacts, and effectiveness of  the 
strategies (e.g., probiotics, fecal microbiota transplants) 
published by peer-reviewed journals. This approach 
is justified because it gives a better and more accurate 
account of  the constituents of  the gut-brain axis in 
pediatric ASD patients to arrive at definite conclusions 
(Bozkurt et al., 2019).

RESULT AND DISCUSSION
Gut Dysbiosis in ASD
As mentioned earlier impaired gut microbial called 
dysbiosis is now linked to ASD (Pulikkan et al., 2019). 
Many children with ASD have different GI issues, and 
a disruption of  the gut microbiota causes far worse 
GI and behavioral symptoms. (Navarro et al., 2016), 
they noted that reduced level of  some friendly bacteria 
(Bifidobacterium) and overgrown pathogenic bacteria 
(Clostridia) have been found commonly described in 
children with ASD. (Roussin et al., 2020) research 
indicates that gut dysbiosis plays a critical role in the 
pathophysiology of  ASD. However, studies have 
identified significant differences in gut microbiota 
between individuals with ASD and neurotypical controls, 
revealing an altered bacterial composition that could affect 
the neurodevelopmental and behavioral characteristics 
associated with ASD (Fattorusso et al., 2019; Ye et al., 
2021). Although Clostridium species have been reported at 
higher levels in individuals with ASD, this genus produces 
neurotoxins and metabolites that can disrupt the gut-
brain axis while contributing to the gastrointestinal and 
neurological ASD observed symptoms (Fattorusso et al., 
2019; Liu et al., 2022). Clostridia overgrowth in patients 
diagnosed with ASD leads to a “leaky gut” through which 
toxic byproducts infiltrate the bloodstream and thereby 
affect brain function (Doroszkiewicz et al., 2021). Also, 
the elevation of  Sutterella, which exists in children with 
ASD, can stimulate gastrointestinal inflammation that 
may influence the neurodevelopment of  ASD children 
and increase ASD symptoms (Bezawada et al., 2020; 
Doroszkiewicz et al., 2021). The specific role is still under 
investigation, but Sutterella is believed to contribute to 
inflammation and immune dysregulation factors that 
are often seen in ASD individuals. However, (Iglesias-
Vázquez et al., 2020) illustrated that Sutterella’s presence 
is associated with gastrointestinal disturbances, which are 
commonly reported in ASD patients and can exacerbate 
behavioral symptoms. Besides, Clostridium and Sutterella 
show imbalances in other bacterial genera such as 
Bacteroides and Prevotella. These bacteria are associated with 
maintaining gut homeostasis and supporting immune 
function.



Pa
ge

 
26

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 4(1) 24-34, 2025

Further, the study by (Strati et al., 2017) demonstrates 
considerable shifts in gut microbiota and microbiota 
in subjects of  severe ASD with elevated Firmicutes/
Bacteroidetes ratios and particular bacterial disruptions. 
A reduction in their levels in individuals with ASD 
may contribute to dysregulation of  gut immunity and 
exacerbate systemic inflammation. In the review, (Hughes 
et al., 2018) study suggested that changes in the gut 
microbial composition could impact ASD and neuro more 
than development and behavior. These findings show 
potential for gut-targeted therapies such as probiotics and 
dietary interventions to alleviate some symptoms of  ASD 
by addressing the underlying dysbiosis, so the connection 
between gut health and ASD is represented as a critical 
area of  ongoing research (De Sales-Millán et al., 2023; Liu 
et al., 2022).

Variation of  Gut Bacterial Composition between 
Patients with ASD and Neurotypical Individuals
Individuals with ASD show distinct variations of  
gut bacterial composition compared to neurotypical 
individuals. In individuals with ASD, Firmicutes make 
up approximately 60.9% of  the gut microbiota, while 
Bacteroidota accounts for 17.1%, Actinobacteriota for 
15.4%, and Proteobacteria for 4% (De Sales-Millán et 
al., 2024). Conversely, neurotypical individuals have 

different profiles, with Firmicutes at 59.6%, Bacteroidota 
at 15.1%, Actinobacteriota at 17.2%, and Proteobacteria at 
3.6%. Notably, Blautia levels are significantly lower in 
individuals with ASD (3.46%) compared to neurotypical 
individuals (9.80%) as shown in Table 1, while Prevotella 
is more abundant in those with ASD (2.54% vs. 0.71%). 
Other differences in genus level include variations in 
Clostridium species, with ASD individuals having higher 
levels of  Clostridium_XI but lower levels of  Clostridium_
XVIII. However, the study by (De Sales-Millán et al., 
2024) focused that Megamonas appear uniquely present 
in females with ASD but are absent in both neurotypical 
groups, and these compositional differences in gut 
bacteria suggest potential links between microbiome 
diversity and ASD. In addition to the noted differences 
in Bacteroidetes and Firmicutes, individuals with ASD have 
shown higher proportions of  other bacteria and increased 
Clostridium species (Table 1). Patients diagnosed with ASD 
present changes in microbiota in the gastrointestinal tract 
with increased presence of  such bacteria as Clostridium, 
Desulfovibrio, and Sutterella. (Hughes et al., 2018) results 
showed that carcinogenic sulfur compounds formation 
by Desulfovibrio might affect gut microbiota composition, 
contributing to dysbiosis and elevated Sutterella 
concentration, which is associated with gut inflammation 
exacerbation and ASD manifestation.

Table 1: Gut Microbiota Genera Involved in Autism Spectrum Disorder (ASD), Characteristics, Classification, and 
Functional Role in ASD Development (Bezawada et al., 2020)
Genus Characteristics Bacterial 

Classification
Function in ASD Development

Bacteroides Gram-negative, 
anaerobic, non-
spore-forming

Bacteroidetes Levels observed to be higher As compared to children 
diagnosed with ASD. It also plays a role in breaking 
down complex carbohydrates though it forms neurotoxic 
metabolites that interfere with communication between 
the gut and the brain which can alter gastrointestinal and 
behavioral conditions (Coretti et al., 2018).

Clostridium Gram-positive, 
anaerobic, 
spore-forming

Firmicutes Probiotic imbalance; overgrowth of  specific bacteria such as 
Clostridium bolteae identified as associated with ASD. These 
include neurotoxins like propionic acids that might interfere 
with signals within the brain leading to behavioral disorders 
and oversupply of  antibiotics (Rose et al., 2018).

Prevotella Gram-negative, 
anaerobic, non-
spore-forming

Bacteroidetes The AChE levels were reduced in the present study in 
comparison to the control in the ASD group. SCFAs are also 
produced by fiber that it is believed to enhance the health 
of  the gastrointestinal tract. Their deficiency might also 
adversely affect gut structural components and increase the 
inflammatory response (Strati et al., 2017).

Bifidobacterium Gram-positive, 
anaerobic, non-
motile

Actinobacteria Involved in regulation of  immune response and also in 
the regulation of  intestinal permeability. Its lack may cause 
elevated gut permeability leading to the appearance of  
“leaky gut” wherein toxic by-products are allowed entry into 
circulation, as well as hinder brain development (Berding & 
Donovan, 2018).



Pa
ge

 
27

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 4(1) 24-34, 2025

Brain Axis Influence on ASD
The gut microbiome plays an important role in brain 
formation because it is associated with neurological 
disorders and with communication between the CNS and 
the macrobiotics through immune, neurotransmitter, and 
hormonal pathways (Suganya & Koo, 2020). Microbial 
metabolites like SCFAs or short-chain fatty acids modulate 
gut immunity and reinforce the intestinal barrier, which 
prevents harmful pathogen invasion that triggers 
neuroinflammation in conditions like autism spectrum 
disorder (ASD) as mention in Table 2. Doroszkiewicz 
et al. (2021) study analysed that dysbiosis can cause gut 
permeability (leaky gut), allowing harmful bacteria into 
circulation and aggravating neurodevelopmental issues. 
However, the Gut microbiome also affects the migration 
of  immune cells like IFNγ+ NK cells and IgA+ 
plasma cells to the CNS, regulating neuroinflammation 
and guarding the developing brain against infections 
(Moradi et al., 2021). Under certain conditions, cells 
migrate and induce inflammation, demonstrating gut 
microbiota’s dual role in maintaining CNS homeostasis 
or contributing to neurodevelopmental disorders like 
ASD, and its balance depends on it (Table 2). According 
to (Azhari et al., 2019), gut microbiotas have a profound 
role in neurodevelopment through cell wall components 
and systemic cytokine regulation. 
Derived from bacterial cell walls, peptidoglycan can 
cross the blood-brain barrier and activate pattern 
recognition receptors (PRRs) in the brain, and this 
activation influences synaptogenesis in areas such as the 
prefrontal cortex and cerebellum, which are crucial for 

social behavior and stress responses linked to autism 
spectrum disorders (Oummadi, 2023). In addition to 
peptidoglycan, cytokines are circulating to the CNS; 
these molecules impact processes like neurogenesis, 
glycogenesis, and neuronal migration while making them 
critical to neurodevelopmental disorders (NDDs) (Wang 
et al., 2023). Maternal immune activation (MIA) has 
garnered attention for the association of  inflammatory 
cytokines such as IL-16 and IL-6 with increased risk 
for NDDs in offspring (Bergdolt & Dunaevsky, 2019). 
In pregnant females, if  IL-6 is elevated, it will further 
boost IL-17 production while directly affecting neurons 
through synaptogenesis, which will disrupt hippocampal 
connectivity (Mohebalizadeh et al., 2023; Wang et al., 
2023)) analysed that microglia are resident immune 
cells of  the brain that play a pivotal role in modulating 
neurodevelopment by pruning synapses, regulating neural 
progenitor cells, and influencing myelination. However, 
(Otero & Antonson, 2022) emphasised that disruptions 
in microglial functions, including their synaptic pruning 
activity via the complement system, are linked to NDDs, 
as gut microbiota impacts microglial maturation and 
function with microbial metabolites such as SCFAs. 
Furthermore, microbial-derived aryl hydrocarbon 
receptor (AHR) agonists also control microglial 
synthesis of  anti-inflammatory factors TGFα and 
cerebrovascular endothelial growth factor VEGF-B 
amplifying the relationship between gut microbiota and 
brain inflammation (Wang et al., 2023). It generates a 
variety of  neurotransmitters that shape brain activity, 
such as serotonin and dopamine, which are among 

Lactobacillus Gram-positive, 
facultative 
anaerobe

Firmicutes Used less in ASD but is recognised for its capability to 
produce lactic acid, to regulate Gut pH and to support healthy 
gut. A deficiency may lead to dysbiosis and impaired COM 
obtained communication affecting their neurodevelopment, 
and behavior (Pulikkan et al., 2018).

Desulfovibrio Gram-negative, 
sulfate-reducing 
bacteria (SRB)

Proteobacteria Desulfovibrio is increased in ASD and it forms hydrogen 
sulfide which is known to be toxic to the epithelial cells of  
the gut leading to inflammation and a leaky gut. Dysbiosis 
may lead to increased permeability of  the gut wall and permit 
neurotoxic metabolites to enter the brain and modulate ASN 
symptomology (Tomova et al., 2015).

Parabacteroides Gram-negative, 
anaerobic, non-
spore-forming

Bacteroidetes It is increased in some persons with ASD and influences 
neurotransmission and inflammation. They are connected 
with higher immune activation and neuroinflammation that 
lead to ASD symptoms (Garcia-Gutierrez et al., 2020).

Collinsella Gram-positive, 
anaerobic, non-
spore-forming

Actinobacteria It has a break down role for the aspect of  complex 
carbohydrates and has a responsibility in the aspect of  
gut health in ASD. Its decrease probably affects both 
metabolic and immune processes, likely being involved in 
the gastrointestinal disorder which is manifested in most 
children suffering from ASD (Srikantha & Mohajeri, 2019).

Sutterella Gram-negative, 
anaerobic, non-
spore-forming

Proteobacteria Increased rate of  ASD with inflammation and gastrointestinal 
abnormalities. If  so, its increase might be associated with 
changes in gut integrity and immune regulation, which clearly 
affects ASD development (Hiippala et al., 2016).



Pa
ge

 
28

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 4(1) 24-34, 2025

these metabolites (Table 2). However, there are two 
metabolites, taurine and 5-amino valeric acid, that help 
enhance social activity and reduce stereotypic movements 
in an ASD model. The gut microbiota also affects the 
hypothalamic-pituitary-adrenal (HPA) axis, the hormones 
of  which get deleteriously altered in a context that can 
cause increased stress hormone cortisol, which is seen in 
individuals with ASD (Rusch et al., 2023). However, some 
bacterial strains can reduce social stress by normalising 
glucocorticoid concentrations. These findings illuminate 
vast bidirectional communication between the Brain and 
gut with modulation into the Vogus nerve. 
ASD is marked by deficits in social interaction and 
communication and varying degrees of  repetitive behavior. 
It is also associated with genetic and environmental factors. 
(Borrego-Ruiz & Borrego, 2024) identified different genes 
related to ASD through large-scale genetic analyses, 
and yet, it is important to consider infections, diet, and 
toxicity. Recent focus has been devoted to relationships 
between GI dysfunction in ASD and dysbiosis as research 
has revealed variations in microbial profiles in children 
with ASD compared to TD in Table 2.  One notable 
example is the elevated presence of  Clostridioides genus 
in ASD individuals. The research illustrated that microbial 
metabolites like 4-EP(S) and p-Cresol sulfate are derived 
from aromatic amino acids and have been implicated in 
processes like neuroinflammation. Further elaborated by 
(Zheng et al., 2021), serotonin dysregulation observed in 
ASD also points to gut-brain interactions with research 
emphasising the abnormal metabolism of  tryptophan in 
autistic individuals. 
A range of  therapeutic approaches for the microbiota-

gut-brain axis encompassing prebiotics, probiotics, 
and fecal microbiota transplantation (FMT) has shown 
potential. Probiotics like Lactobacillus reuteri and Bacteroides 
fragilis have confirmed improvements in ASD-related 
behaviors and gut permeability in murine models 
(Wang et al., 2023). As shown in Table 2, FMT restores 
microbial diversity and improves GI and behavioural 
symptoms in small-scale clinical studies, but factors 
like donor-recipient compatibility and administration 
methods remain critical challenges for FMT. Alterations 
in microbial composition, such as increased Bifidobacterium 
and Bacteroidaceae and reduced abundance of  certain taxa, 
have been associated with ADHD symptoms. However, 
(Song et al., 2022) elaborated that transplanting ADHD-
associated microbiota into mice led to ADHD-like 
behaviors that point out potential causal gut-brain axis 
roles. Probiotics and omega-3 polyunsaturated fatty acids 
(PUFAs) confirmed therapeutic promise in ADHD by 
modulating the immune response and intestinal barrier 
stability (Table 2). For instance, Rett Syndrome (RTT) 
is a severe NDD that predominantly affects females 
and has also been linked to gut microbiota alterations. 
These RTT patients show reduced microbial diversity 
in taxa like Bifidobacterium and Lactobacillus (Borghi & 
Vignoli, 2019). These findings have revealed a significant 
attendance of  FMT to improve microbial imbalance 
and gastrointestinal and behavioral manifestations of  
ASD. Also, gut dysbiosis observed in ADHD children, 
including increased Bifidobacterium count, has been 
associated with ADHD symptoms, suggesting a causal 
connection of  the gut-brain axis in neurodevelopmental 
disorders, including Rett Syndrome.

Table 2: Mechanisms Linking Gut Microbiota to Autism Spectrum Disorder (ASD) Development
Mechanism Gut Microbes 

Involved
Effect on ASD 
Development

Pathophysiological Impact

Gut-Brain Axis 
Disruption

Clostridium, 
Bacteroides

Microbes produce 
neurotoxic metabolites 
(e.g., propionic acid) that 
can alter brain function 
and behavior.

Disruption in neurotransmission, increased 
production of  neuroactive compounds, and 
imbalanced synaptic activity contribute to 
abnormal behaviors and cognitive dysfunction 
in ASD (Coretti et al., 2018).

Altered Immune 
Response

Desulfovibrio, 
Sutterella

Dysbiosis triggers 
chronic gut inflammation, 
which activates systemic 
immune responses and 
neuroinflammation.

Heightened inflammatory responses in the gut 
increase pro-inflammatory cytokines like IL-6 
and TNF-α, promoting neuroinflammation 
and neural circuit disruptions involved in ASD 
(Kang et al., 2017).

Leaky Gut and 
Gut Permeability

Bifidobacterium, 
Lactobacillus

Reduced beneficial 
bacteria compromise gut 
barrier integrity, increasing 
permeability ("leaky gut").

Toxins and bacterial metabolites enter the 
bloodstream, potentially crossing the blood-
brain barrier, impacting neurodevelopment, and 
increasing ASD symptom severity, including 
GI disturbances (Berding & Donovan, 2018)

Short-Chain 
Fatty Acid 
(SCFA) 
Deficiency

Prevotella, 
Bifidobacterium

Reduced SCFA production 
affects gut health, 
immune balance, and 
neurotransmitter synthesis, 
all crucial for brain health.

SCFAs regulate immune responses and 
maintain gut epithelial integrity. Reduced levels 
lead to increased inflammation, impair brain 
development, and affect signaling pathways 
linked to ASD (Coretti et al., 2018).



Pa
ge

 
29

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 4(1) 24-34, 2025

Contribution of  Gut Microbiota in the Development 
of  ASD
The gut microbiota’s potential contribution to the 
development of  (ASD) has gained attention for its 
association between gastrointestinal disturbances and 
neurodevelopmental disorders. (Yu et al., 2024) research 
emphasised that children with ASD have distinct gut 
microbiota composition compared to neurotypical 
individuals, bacterial taxa being differentially abundant, 
and there are disruptions in the gut-brain axis. However, 
(ERSÖZ ALAN & Gülerman, 2019)finding highlighted 
that individuals with ASD tend to have fewer beneficial 
bacteria such as Bifidobacterium and Collinsella, which belong 
to the Actinobacteria Phylum. On the other hand, higher 
abundance levels of  Proteobacteria have been reported, 
particularly from the family of  Enterobacteriaceae, 
which are considered to foster inflammation in the gut 
in individuals with ASD (Gomaa, 2020). Other bacterial 
taxa observed in disproportionately high amounts are 
Prevotellaceae and Parabacteroides from the Bacteroidota, 
which may be associated with gastrointestinal complaints 
that most ASD patients exhibit (Peralta-Marzal et al., 
2024). These outcomes stress that microbial dysbiosis 
may play a role in ASD pathogenesis, and modulating 
microbial ecology, including by use of  probiotics or 
fecal microbiota transfer, may provide one of  the 
reasons for ameliorating gastrointestinal and behavioural 
manifestations in children with ASD. However, (Peralta-
Marzal et al., 2024) research shows that gut microbiota is 
crucial for the bidirectional gut-brain axis, especially in 
patients diagnosed with ASD. Some of  these mechanisms 
include modulation of  immune responses, generation of  
neuroactive metabolites, and effects on the barrier in the gut.
Moreover, the presence of  particular microbial genera 
in ASD individuals, including a reduced amount of  
Bifidobacterium and Collinsella and increased Prevotellaceae 
and Parabacteroides that, are thought to affect neurological 
signaling (Berding & Donovan, 2018). This communication 
between the gut and brain is believed to affect behavior, 
thinking, and even feelings. Although, (Chernikova et al., 
2021) study highlighted the alteration of  gut microbiota 
by probiotics or fecal microbiota transplantation can be 
therapeutic targets for AS-designated gastrointestinal and 
neurological manifestations of  ASD.

Dietary Interventions
Parents of  children with ASD often favor gluten- 
and casein-free diets (GFCF), grounded in the belief  
that certain peptides from these foods might worsen 
symptoms. The Gluten-Free Casein-Free (GFCF) diet 
has been investigated as a potential treatment for (ASD) 
because of  the possible connections between gluten, 
casein, and brain function (Christison & Ivany, 2006). 
However, the study by (Knivsberg et al., 2003) suggested 
that eliminating casein and gluten could reduce autism-
like symptoms by preventing the formation of  opioid-like 
peptides from these proteins which may cross intestinal 
and blood-brain barriers. Studies like (Knivsberg et al., 
2003) reported reduced autistic behaviors following 
the GFCF diet, while others, like (Elder et al., 2006) 
identified no significant behavioral improvements after 
6 weeks on a diet. Further, (Mari-Bauset et al., 2014) 
study demonstrated that parents observed reductions 
in gastrointestinal symptoms and repetitive behaviors in 
their children on the GFCF diet. (Whiteley et al., 2010) 
argued that longer durations of  6 months or more may be 
necessary to see effects, though this remains contested. 
However, (Başpinar & Yardimci, 2020) study supported 
that elimination diets should be considered only when 
there’s a known intolerance to gluten or casein. It 
indicates that a low GFCF diet might lessen autism-like 
behaviors in certain children; other research has shown 
only mild effects. Long-term beneficial results, especially 
in regard to digestion and compulsive behaviors might 
be observed; however, elimination diets should only be 
attempted if  certain pathologies involving intolerances 
are confirmed.

Probiotics
Probiotic strains such as Lactobacillus and Bifidobacterium, 
are proposed to balance gut microbiota in individuals 
with ASD (Sanlier & Kocabas, 2023). (Sivamaruthi et al., 
2020)study randomised controlled trial (RCT) proposed 
that probiotics improved GI symptoms and marginally 
enhanced social responsiveness in ASD patients but 
the overall impact on core ASD behaviors remains 
inconsistent. (Patel et al., 2022)review emphasised that 
probiotics and gut microbiota in children with (ASD) 
has produced mixed findings. According to (Buffington 

Neurotransmitter 
Dysregulation

Bacteroides, 
Clostridium

Gut microbiota modulates 
serotonin, dopamine, 
and GABA levels, crucial 
for regulating mood and 
behavior.

Imbalances in neurotransmitter production 
linked to the altered microbial composition 
may contribute to ASD-related behaviors 
like anxiety, repetitive behaviors, and social 
impairments (Strati et al., 2017).

Oxidative Stress Desulfovibrio, 
Clostridium

Overgrowth of  certain 
microbes increases 
oxidative stress markers, 
exacerbating brain 
inflammation and damage.

Increased oxidative stress in the gut and 
brain leads to mitochondrial dysfunction 
and neuronal damage, which is commonly 
observed in individuals with ASD, worsening 
cognitive and behavioral symptoms (Dargenio 
et al., 2023).



Pa
ge

 
30

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 4(1) 24-34, 2025

et al., 2016)research, animal studies demonstrated that 
probiotic supplementation could improve ASD-like 
symptoms and social behavior in mice, but human studies 
are less conclusive. A meta-analysis by (He et al., 2023) 
investigated the effect of  probiotics such as Lactobacillus 
plantarum and Bifidobacterium longum on ASD symptoms. 
Probiotics did help alleviate gastrointestinal (GI) 
symptoms in other research, and multi-strain probiotics 
such as blends containing Lactobacillus reuteri appeared to 
show better outcomes than single strains in improving 
behavior in children with ASD (Buffington et al., 2016; 
Wang et al., 2023). Despite these promising insights, (He et 
al., 2023)suggested that high-quality clinical trials are still 
required to substantiate probiotics’ therapeutic impact on 
ASD-related behavioral symptoms. The findings from the 
current literature review indicate that only a few clinical 
trials on the effects of  probiotics on people with ASD 
are published. Those studies demonstrate improvements 
in gastrointestinal symptoms when using probiotics 
and multi-strain blends but cannot conclude consistent 
benefits on the core ASD symptoms.
 
Microbiota Transfer Therapy (MTT)
MTT refers to transplantation to the subjects with ASD 
of  a microbiota sourced from healthy individuals for its 
normalising impact on the gut. A study conducted by 
(Kang et al., 2017) illustrated that Microbiota Transfer 
Therapy (MTT) demonstrated there was a notable 
enhancement in gastrointestinal (GI) symptoms as well 
as autism symptoms among children with ASD. After 
a treatment regimen that included antibiotics bowel 
cleanses, and fecal microbiota transplants (FMT), 
included participants experienced an 80% reduction 
in GI symptoms like constipation and diarrhea, and 
behavioral improvements in ASD symptoms were also 
observed and both GI and ASD improvements persisted 
8 weeks post-treatment (Tan et al., 2021). Increased 
microbial diversity including abundance of  beneficial 
bacteria like Bifidobacterium and Prevotella was also noted 
by (Adams et al., 2019; Kang et al., 2019) study also 
demonstrated promising results in children with ASD 
after MTT a procedure involving the transfer of  a healthy 
donor’s fecal microbiota to the patient and an open-label 
study showed that after two years, 45% of  children saw a 
reduction in core ASD symptoms by 50% while their GI 
symptoms improved by 58%. Further, (Kang et al., 2019) 
analysed that long-term follow-up shows intervention 
had sustained effects with changes in microbial diversity 
resembling that of  neurotypical individuals. Nevertheless, 
the lack of  control groups in some MTT studies may limit 
the robustness of  these findings to some extent. 

Microbiota Transfer and Other Therapies in ASD
ASD has prompted microbiota transfer therapy (MTT) 
and other gut-targeted interventions including use of  
probiotics and changes in diet (Adams et al., 2019). (Kang 
et al., 2019)research exploring the gut-brain axis in ASD 
has shown interest in microbiota transfer therapy (MTT), 

probiotics, and dietary interventions. However, (Kang 
et al., 2017) suggested that gut microbiota influence 
ASD symptoms by altering the gut-brain axis through 
several mechanisms for instance, microbial imbalances 
cause increased gut permeability allowing inflammatory 
molecules to reach the brain, which affects neural 
pathways tied to behavior. Also, (Taniya et al., 2022) study 
elaborated that microbes may also produce neuroactive 
compounds like serotonin or GABA impacting social 
behavior and repetitive actions and these imbalances can 
disrupt digestion leading to gastrointestinal disturbances 
commonly seen in ASD.

Discussion
The discussion emphasised the microbiota in relation to 
ASD has attracted much interest with different studies 
indicating the role of  gut bacteria in the development 
of  the brain and behaviour. The exact mechanisms and 
clinical relevance of  these findings are not yet cleared 
and are calling for a more critical evaluation of  current 
evidence. Navya (Bezawada et al., 2020) study elaborated 
that ASD children are seen frequently exhibit altered gut 
microbiota characterised by an increase in certain bacteria 
like Clostridium and Sutterella and a reduction in beneficial 
species such as Prevotella. However, one major limitation 
in current research is heterogeneity in methodologies like 
inconsistent use of  controls varying diagnostic criteria for 
ASD and differences in sample collection and sequencing 
techniques. Without controlling for these factors, there 
is a gap to conclude that microbial differences are 
intrinsically linked to ASD. Although, (Loth et al., 2016) 
study conducted on the link between autism spectrums 
disorder (ASD) and gut microbiota as the scientific 
community aims to use this association for identification. 
Lacking precisely validated gut-based biomarkers 
diagnosing ASD, several arising methodologies exist.
However, (Ye et al., 2021) study identified that there 
is a low concentration of  better bacteria, especially 
Bifidobacterium, and a higher chance of  pathology. Apart 
from traditional stool analysis, modern techniques are 
available such as Metagenomic sequencing to determine 
the gene content of  these microbes, which assists in 
establishing a direct relationship between particular 
microbes and ASD. (Eicher & Mohajeri, 2022) study 
approach focuses on microbial metabolites being the 
chemical output of  these bacteria, some of  which are 
likely to be shifted in autistic patients. To model the risk 
of  ASD based on gut microbiome data, active machine 
learning algorithms are being trained and will soon be 
available; these methods are relatively new in diagnosing, 
giving hope for the future of  diagnosing persons with ASD. 
However, (Zou et al., 2020) study illustrated that the 
mechanisms by which the gut-brain axis influences 
these CNS functions via short-chain fatty acids, 
neurotransmitters, and the immune system or which guts 
dysbiosis affect the core signs of  ASD. Although, as per 
(Oh & Cheon, 2020) research, propionic acid, a short-
chain fatty acid synthesised by some gut bacteria has been 



Pa
ge

 
31

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 4(1) 24-34, 2025

found to cause ASD-like behaviors in animal models, 
but direct extrapolation to humans is difficult due to 
the complexity of  neurodevelopment and many genetic 
factors underlying ASD. Some gut pathologies arising 
from microbiota imbalance, including the overgrowth 
of  Clostridium and Desulfovibrio, produce neurological 
toxins, including propionic acid, which interferes with 
neurotransmission and may help explain behaviors seen in 
ASD (Coretti et al., 2018). MacFabe (2015) argued that the 
disintegration of  the communication between the gut and 
the brain, combined with the increase of  the permeability 
of  the intestinal barrier leads to the introduction of  toxins 
from the bloodstream into the brain. However, Liwinski 
and Elinav (2020) noted that causality of  microbiota 
for the development of  ASD remains ambiguous 
since, according to many investigations, they show only 
coexistence. Despite the positive outcomes observed 
from the clinical studies, variability in the results obtained 
across the human trials has necessitated more rigorous 
research using better-quality interventions. 
Furthermore, it is still doubtful whether microbiota-
targeted interventions such as prebiotics, probiotics, or 
fecal microbiota transplantation can be used as therapeutic 
options. The study by Settanni et al. (2021) highlighted 
significant reductions in gastrointestinal and behavioral 
symptoms, but the durability and safety of  these 
treatment procedures are questionable. The possibility of  
the placebo effect, small sample sizes, and the absence 
of  keen, controlled trials hampers these findings. 
Further, Liwinski and Elinav (2020) study examined 
the therapeutic efficacy of  targeting gut microbiota in 
ASD and answered whether such interventions can 
be anything more than treatment of  symptom(s). Zhu 
et al. (2022) study suggested that ABA and OT are 
identified as evidence-based for enhancing functional 
and adaptive communication, daily living, and social, and 
motor development. Other dietary interventions, such 
as omega-3 fatty acids, benefit behavior, though these 
findings are inconclusive. In addition, Awaad (2022) 
study discussed that sensory integration therapy (SIT) 
is useful for helping children with sensory processing, 
hyperbaric oxygen therapy (HBOT) and acupuncture give 
limited assistance. Anxiety can be controlled and treated 
with Cognitive Behavioral Therapy also known as CBT 
for people with higher intellectual capacity. This study 
identified that more and more interest has been gain to 
the gut- brain axis and its relationship to ASD, the specific 
processes are not yet well understood. Literature shows 
that gut–brain axis contributes to neurodevelopment 
and behaviour but there is a limit focus on the quality of  
research. Compared with antibiotics, antibiotic-associated 
microbiota-targeted therapies such as probiotics and fecal 
microbiota transplantation provide evidence of  efficacy 
but their effect and safety in the long-term are abilities 
more research. If  the patient’s problem is severe enough, 
dietary and behavioral practices, together with medical 
treatments, can be the most effective ASD intervention.

CONCLUSION
It can be concluded that the increasing fascination 
with the gut-brain connection is a potential contributor 
to changes in ASD symptoms. A substantial body of  
evidence suggests gut dysbiosis has a significant role 
in both behavioral and gastrointestinal symptoms 
among children with ASD. While microbiota-targeted 
interventions such as fecal microbiota transplantation 
or probiotics show therapeutic promise, several critical 
questions remain unanswered regarding their safety, 
effectiveness, mechanisms of  action, and the longevity 
of  their effects. The research emphasises that there is 
a pressing need for further extensive studies to develop 
individualised reproducible microbiota-based therapies, 
considering the wide variability of  symptoms among ASD 
patients. The review further emphasises the need to apply 
microbial health findings to managing ASD. It suggests 
the need for larger clinical trials to establish microbiota 
and neurodevelopmental disorders such as ASD.

REFERENCES 
Adams, J. B., Borody, T. J., Kang, D.-W., Khoruts, A., 

Krajmalnik-Brown, R., & Sadowsky, M. J. (2019). 
Microbiota transplant therapy and autism: lessons 
for the clinic. Expert Review of  Gastroenterology & 
Hepatology, 13(11), 1033-1037. 

Awaad, Y. (2022). Management of  Spasticity and Cerebral 
Palsy Update. In Cerebral Palsy-Updates. IntechOpen. 

Azhari, A., Azizan, F., & Esposito, G. (2019). A systematic 
review of  gut‐immune‐brain mechanisms in Autism 
Spectrum Disorder. Developmental psychobiology, 61(5), 
752-771. 

BAŞPINAR, B., & YARDIMCI, H. (2020). Gluten-Free 
Casein-Free Diet for Autism Spectrum Disorders: 
Can It Be Effective in Solving Behavioural and 
Gastrointestinal Problems? Eurasian Journal of  
Medicine, 52(3). 

Berding, K., & Donovan, S. M. (2018). Diet can impact 
microbiota composition in children with autism 
spectrum disorder. Frontiers in neuroscience, 12, 515. 

Bergdolt, L., & Dunaevsky, A. (2019). Brain changes 
in a maternal immune activation model of  
neurodevelopmental brain disorders. Progress in 
neurobiology, 175, 1-19. 

Bezawada, N., Phang, T. H., Hold, G. L., & Hansen, 
R. (2020). Autism spectrum disorder and the gut 
microbiota in children: a systematic review. Annals of  
Nutrition and Metabolism, 76(1), 16-29. 

Borghi, E., & Vignoli, A. (2019). Rett syndrome and 
other neurodevelopmental disorders share common 
changes in gut microbial community: A descriptive 
review. International Journal of  Molecular Sciences, 20(17), 
4160. 

Borrego-Ruiz, A., & Borrego, J. J. (2024). 
Neurodevelopmental disorders associated with gut 
microbiome dysbiosis in children. Children, 11(7), 796. 

Bozkurt, A., Koseoglu, S., & Singh, L. (2019). An analysis 



Pa
ge

 
32

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 4(1) 24-34, 2025

of  peer reviewed publications on openness in 
education in half  a century: Trends and patterns in the 
open hemisphere. Australasian Journal of  Educational 
Technology, 35(4). 

Buffington, S. A., Di Prisco, G. V., Auchtung, T. A., 
Ajami, N. J., Petrosino, J. F., & Costa-Mattioli, M. 
(2016). Microbial reconstitution reverses maternal 
diet-induced social and synaptic deficits in offspring. 
Cell, 165(7), 1762-1775. 

Chernikova, M. A., Flores, G. D., Kilroy, E., Labus, J. S., 
Mayer, E. A., & Aziz-Zadeh, L. (2021). The brain-
gut-microbiome system: pathways and implications 
for autism spectrum disorder. Nutrients, 13(12), 4497. 

Chiarotti, F., & Venerosi, A. (2020). Epidemiology of  
autism spectrum disorders: a review of  worldwide 
prevalence estimates since 2014. Brain sciences, 10(5), 
274. 

Christison, G. W., & Ivany, K. (2006). Elimination diets 
in autism spectrum disorders: any wheat amidst the 
chaff? Journal of  Developmental & Behavioral Pediatrics, 
27(2), S162-S171. 

Coretti, L., Paparo, L., Riccio, M. P., Amato, F., Cuomo, 
M., Natale, A., Borrelli, L., Corrado, G., De Caro, 
C., & Comegna, M. (2018). Gut microbiota features 
in young children with autism spectrum disorders. 
Frontiers in microbiology, 9, 3146. 

Cunningham, M., Azcarate-Peril, M. A., Barnard, A., 
Benoit, V., Grimaldi, R., Guyonnet, D., Holscher, 
H. D., Hunter, K., Manurung, S., & Obis, D. (2021). 
Shaping the future of  probiotics and prebiotics. Trends 
in microbiology, 29(8), 667-685. 

Dargenio, V. N., Dargenio, C., Castellaneta, S., De 
Giacomo, A., Laguardia, M., Schettini, F., Francavilla, 
R., & Cristofori, F. (2023). Intestinal barrier 
dysfunction and microbiota–gut–brain axis: Possible 
implications in the pathogenesis and treatment of  
autism spectrum disorder. Nutrients, 15(7), 1620. 

De Sales-Millán, A., Aguirre-Garrido, J. F., González-
Cervantes, R. M., & Velázquez-Aragón, J. A. (2023). 
Microbiome–Gut–Mucosal–Immune–Brain Axis 
and Autism Spectrum Disorder (ASD): A Novel 
Proposal of  the Role of  the Gut Microbiome in ASD 
Aetiology. Behavioral Sciences, 13(7), 548. 

De Sales-Millán, A., Reyes-Ferreira, P., Aguirre-Garrido, J. 
F., Corral-Guillé, I., Barrientos-Ríos, R., & Velázquez-
Aragón, J. A. (2024). Comprehensive Analysis of  Gut 
Microbiota Composition and Functional Metabolism 
in Children with Autism Spectrum Disorder and 
Neurotypical Children: Implications for Sex-Based 
Differences and Metabolic Dysregulation. International 
journal of  molecular sciences, 25(12), 6701. 

Doroszkiewicz, J., Groblewska, M., & Mroczko, B. (2021). 
The role of  gut microbiota and gut–brain interplay 
in selected diseases of  the central nervous system. 
International Journal of  Molecular Sciences, 22(18), 10028. 

Dupont, H. L., Jiang, Z.-D., Dupont, A. W., & Utay, N. 
S. (2020). The intestinal microbiome in human health 
and disease. Transactions of  the American Clinical and 

Climatological Association, 131, 178. 
Eicher, T. P., & Mohajeri, M. H. (2022). Overlapping 

mechanisms of  action of  brain-active bacteria and 
bacterial metabolites in the pathogenesis of  common 
brain diseases. Nutrients, 14(13), 2661. 

Elder, J. H., Shankar, M., Shuster, J., Theriaque, D., Burns, 
S., & Sherrill, L. (2006). The gluten-free, casein-free 
diet in autism: results of  a preliminary double blind 
clinical trial. Journal of  autism and developmental disorders, 
36, 413-420. 

Ersoy Alan, B., & Gülerman, F. (2019). The role of  
gut microbiota in autism spectrum disorder. Turk 
Psikiyatri Dergisi, 30(3). 

Fattorusso, A., Di Genova, L., Dell’Isola, G. B., Mencaroni, 
E., & Esposito, S. (2019). Autism spectrum disorders 
and the gut microbiota. Nutrients, 11(3), 521. 

Garcia-Gutierrez, E., Narbad, A., & Rodríguez, J. M. 
(2020). Autism spectrum disorder associated with gut 
microbiota at immune, metabolomic, and neuroactive 
level. Frontiers in neuroscience, 14, 578666. 

Gomaa, E. Z. (2020). Human gut microbiota/
microbiome in health and diseases: a review. Antonie 
Van Leeuwenhoek, 113(12), 2019-2040. 

He, X., Liu, W., Tang, F., Chen, X., & Song, G. (2023). 
Effects of  probiotics on autism spectrum disorder 
in children: a systematic review and meta-analysis of  
clinical trials. Nutrients, 15(6), 1415. 

Hiippala, K., Kainulainen, V., Kalliomäki, M., Arkkila, 
P., & Satokari, R. (2016). Mucosal prevalence 
and interactions with the epithelium indicate 
commensalism of  Sutterella spp. Frontiers in microbiology, 
7, 1706. 

Hodges, H., Fealko, C., & Soares, N. (2020). Autism 
spectrum disorder: definition, epidemiology, causes, 
and clinical evaluation. Translational pediatrics, 9(Suppl 
1), S55. 

Hughes, H. K., Rose, D., & Ashwood, P. (2018). The 
gut microbiota and dysbiosis in autism spectrum 
disorders. Current neurology and neuroscience reports, 18, 
1-15. 

Iglesias-Vázquez, L., Van Ginkel Riba, G., Arija, V., & 
Canals, J. (2020). Composition of  gut microbiota in 
children with autism spectrum disorder: a systematic 
review and meta-analysis. Nutrients, 12(3), 792. 

Kang, D.-W., Adams, J. B., Coleman, D. M., Pollard, E. 
L., Maldonado, J., McDonough-Means, S., Caporaso, 
J. G., & Krajmalnik-Brown, R. (2019). Long-term 
benefit of  Microbiota Transfer Therapy on autism 
symptoms and gut microbiota. Scientific Reports, 9(1), 
5821. 

Kang, D.-W., Adams, J. B., Gregory, A. C., Borody, T., 
Chittick, L., Fasano, A., Khoruts, A., Geis, E., 
Maldonado, J., & McDonough-Means, S. (2017). 
Microbiota transfer therapy alters gut ecosystem and 
improves gastrointestinal and autism symptoms: an 
open-label study. Microbiome, 5, 1-16. 

Knivsberg, A.-M., Reichelt, K.-L., Høien, T., & Nødland, 
M. (2003). Effect of  a dietary intervention on 



Pa
ge

 
33

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 4(1) 24-34, 2025

autistic behavior. Focus on autism and other developmental 
disabilities, 18(4), 248-257. 

Lai, M.-C., Anagnostou, E., Wiznitzer, M., Allison, C., 
& Baron-Cohen, S. (2020). Evidence-based support 
for autistic people across the lifespan: Maximising 
potential, minimising barriers, and optimising the 
person–environment fit. The Lancet Neurology, 19(5), 
434-451. 

Liu, J., Gao, Z., Liu, C., Liu, T., Gao, J., Cai, Y., & Fan, X. 
(2022). Alteration of  gut microbiota: new strategy for 
treating autism spectrum disorder. Frontiers in cell and 
developmental biology, 10, 792490. 

Liwinski, T., & Elinav, E. (2020). Harnessing the 
microbiota for therapeutic purposes. American Journal 
of  Transplantation, 20(6), 1482-1488. 

Loth, E., Murphy, D. G., & Spooren, W. (2016). Defining 
precision medicine approaches to autism spectrum 
disorders: concepts and challenges. Frontiers in 
psychiatry, 7, 188. 

MacFabe, D. F. (2015). Enteric short-chain fatty acids: 
microbial messengers of  metabolism, mitochondria, 
and mind: implications in autism spectrum disorders. 
Microbial ecology in health and disease, 26(1), 28177. 

Mari-Bauset, S., Zazpe, I., Mari-Sanchis, A., Llopis-
González, A., & Morales-Suarez-Varela, M. (2014). 
Evidence of  the gluten-free and casein-free diet in 
autism spectrum disorders: a systematic review. Journal 
of  child neurology, 29(12), 1718-1727. 

Mohebalizadeh, M., Babapour, G., Maleki Aghdam, 
M., Mohammadi, T., Jafari, R., & Shafiei-Irannejad, 
V. (2023). Role of  maternal immune factors in 
neuroimmunology of  brain development. Molecular 
Neurobiology, 1-13. 

Moradi, K., Ashraf-Ganjouei, A., Tavolinejad, H., Bagheri, 
S., & Akhondzadeh, S. (2021). The interplay between 
gut microbiota and autism spectrum disorders: A 
focus on immunological pathways. Progress in Neuro-
Psychopharmacology and Biological Psychiatry, 106, 110091. 

Namocot, M. L. L. (2023). The Use of  One-Part 
Directives in Developing Play Skills in Children with 
Autism during Trial-Based Instructions. Journal of  
Tertiary Education and Learning, 1(1), 12-15. 

Navarro, F., Liu, Y., & Rhoads, J. M. (2016). Can probiotics 
benefit children with autism spectrum disorders? 
World journal of  gastroenterology, 22(46), 10093. 

Oh, D., & Cheon, K.-A. (2020). Alteration of  gut 
microbiota in autism spectrum disorder: An overview. 
Journal of  the Korean Academy of  Child and Adolescent 
Psychiatry, 31(3), 131. 

Otero, A. M., & Antonson, A. M. (2022). At the crux 
of  maternal immune activation: Viruses, microglia, 
microbes, and IL‐17A. Immunological Reviews, 311(1), 
205-223. 

Oummadi, A. (2023). Evaluation of  the effects of  inflammation 
and combined exposure to environmental toxicants during 
the perinatal period: a potential etiological factor of  
neurodegenerative pathologies? Université d’Orléans; 
Macquarie University (Sydney, Australie)]. 

Patel, M., Atluri, L. M., Gonzalez, N. A., Sakhamuri, N., 
Athiyaman, S., Randhi, B., Gutlapalli, S. D., Pu, J., 
Zaidi, M. F., & Khan, S. (2022). A Systematic Review 
of  Mixed Studies Exploring the Effects of  Probiotics 
on Gut-Microbiome to Modulate Therapy in Children 
With Autism Spectrum Disorder. Cureus, 14(12). 

Peralta-Marzal, L. N., Rojas-Velazquez, D., Rigters, D., 
Prince, N., Garssen, J., Kraneveld, A. D., Perez-Pardo, 
P., & Lopez-Rincon, A. (2024). A robust microbiome 
signature for autism spectrum disorder across 
different studies using machine learning. Scientific 
Reports, 14(1), 814. 

Pulikkan, J., Maji, A., Dhakan, D. B., Saxena, R., Mohan, 
B., Anto, M. M., Agarwal, N., Grace, T., & Sharma, V. 
K. (2018). Gut microbial dysbiosis in Indian children 
with autism spectrum disorders. Microbial ecology, 76, 
1102-1114. 

Pulikkan, J., Mazumder, A., & Grace, T. (2019). Role of  the 
gut microbiome in autism spectrum disorders. Reviews 
on Biomarker Studies in Psychiatric and Neurodegenerative 
Disorders, 253–269. 

Rose, D. R., Yang, H., Serena, G., Sturgeon, C., Ma, 
B., Careaga, M., Hughes, H. K., Angkustsiri, K., 
Rose, M., & Hertz-Picciotto, I. (2018). Differential 
immune responses and microbiota profiles in 
children with autism spectrum disorders and co-
morbid gastrointestinal symptoms. Brain, behavior, and 
immunity, 70, 354-368. 

Roussin, L., Prince, N., Perez-Pardo, P., Kraneveld, 
A. D., Rabot, S., & Naudon, L. (2020). Role of  the 
gut microbiota in the pathophysiology of  autism 
spectrum disorder: clinical and preclinical evidence. 
Microorganisms, 8(9), 1369. 

Rusch, J. A., Layden, B. T., & Dugas, L. R. (2023). Signalling 
cognition: the gut microbiota and hypothalamic-
pituitary-adrenal axis. Frontiers in endocrinology, 14, 
1130689. 

Sanlier, N., & Kocabas, Ş. (2023). The effect of  probiotic, 
prebiotic and gut microbiota on ASD: a review and 
future perspectives. Critical Reviews in Food Science and 
Nutrition, 63(15), 2319-2330. 

Settanni, C. R., Bibbò, S., Ianiro, G., Rinninella, E., Cintoni, 
M., Mele, M. C., Cammarota, G., & Gasbarrini, 
A. (2021). Gastrointestinal involvement of  autism 
spectrum disorder: focus on gut microbiota. Expert 
Review of  Gastroenterology & Hepatology, 15(6), 599-622. 

Sivamaruthi, B. S., Suganthy, N., Kesika, P., & Chaiyasut, 
C. (2020). The role of  microbiome, dietary 
supplements, and probiotics in autism spectrum 
disorder. International Journal of  Environmental Research 
and Public Health, 17(8), 2647. 

Song, W., Zhang, M., Teng, L., Wang, Y., & Zhu, L. 
(2022). Prebiotics and probiotics for autism spectrum 
disorder: a systematic review and meta-analysis of  
controlled clinical trials. Journal of  Medical Microbiology, 
71(4), 001510. 

Srikantha, P., & Mohajeri, M. H. (2019). The possible role 
of  the microbiota-gut-brain-axis in autism spectrum 



Pa
ge

 
34

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 4(1) 24-34, 2025

disorder. International Journal of  Molecular Sciences, 20(9), 
2115. 

Strati, F., Cavalieri, D., Albanese, D., De Felice, C., Donati, 
C., Hayek, J., Jousson, O., Leoncini, S., Renzi, D., & 
Calabrò, A. (2017). New evidences on the altered gut 
microbiota in autism spectrum disorders. Microbiome, 
5, 1-11. 

Suganya, K., & Koo, B.-S. (2020). Gut–brain axis: role 
of  gut microbiota on neurological disorders and how 
probiotics/prebiotics beneficially modulate microbial 
and immune pathways to improve brain functions. 
International journal of  molecular sciences, 21(20), 7551. 

Tan, Q., Orsso, C. E., Deehan, E. C., Kung, J. Y., Tun, 
H. M., Wine, E., Madsen, K. L., Zwaigenbaum, L., & 
Haqq, A. M. (2021). Probiotics, prebiotics, synbiotics, 
and fecal microbiota transplantation in the treatment 
of  behavioral symptoms of  autism spectrum 
disorder: A systematic review. Autism Research, 14(9), 
1820-1836. 

Taniya, M. A., Chung, H.-J., Al Mamun, A., Alam, S., 
Aziz, M. A., Emon, N. U., Islam, M. M., Hong, S.-
T. s., Podder, B. R., & Ara Mimi, A. (2022). Role of  
gut microbiome in autism spectrum disorder and its 
therapeutic regulation. Frontiers in Cellular and Infection 
Microbiology, 12, 915701. 

Tomova, A., Husarova, V., Lakatosova, S., Bakos, J., 
Vlkova, B., Babinska, K., & Ostatnikova, D. (2015). 
Gastrointestinal microbiota in children with autism in 
Slovakia. Physiology & behavior, 138, 179-187. 

Wang, Q., Yang, Q., & Liu, X. (2023). The microbiota–

gut–brain axis and neurodevelopmental disorders. 
Protein & Cell, 14(10), 762-775. 

Whiteley, P., Shattock, P., Carr, K., Hooper, M., & Todd, 
L. (2010). How could a gluten- and casein-free 
diet ameliorate symptoms associated with autism 
spectrum conditions? Autism Insights, 2. 

Ye, F., Gao, X., Wang, Z., Cao, S., Liang, G., He, D., Lv, 
Z., Wang, L., Xu, P., & Zhang, Q. (2021). Comparison 
of  gut microbiota in autism spectrum disorders and 
neurotypical boys in China: A case-control study. 
Synthetic and Systems Biotechnology, 6(2), 120-126. 

Yu, R., Hafeez, R., Ibrahim, M., Alonazi, W. B., & Li, 
B. (2024). The Complex Interplay Between Autism 
Spectrum Disorder and Gut Microbiota in Children: 
A Comprehensive Review. Behavioural Brain Research, 
115177. 

Zheng, Y., Bek, M. K., Prince, N. Z., Peralta Marzal, L. N., 
Garssen, J., Perez Pardo, P., & Kraneveld, A. D. (2021). 
The role of  bacterial-derived aromatic amino acids 
metabolites relevant in autism spectrum disorders: 
a comprehensive review. Frontiers in neuroscience, 15, 
738220. 

Zhu, M., Liu, X., Ye, Y., Yan, X., Cheng, Y., Zhao, L., 
Chen, F., & Ling, Z. (2022). Gut microbiota: a novel 
therapeutic target for Parkinson’s disease. Frontiers in 
immunology, 13, 937555. 

Zou, R., Xu, F., Wang, Y., Duan, M., Guo, M., Zhang, 
Q., Zhao, H., & Zheng, H. (2020). Changes in the 
gut microbiota of  children with autism spectrum 
disorder. Autism Research, 13(9), 1614-1625.


